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Tumor cells require high levels of cholesterol for membrane biogenesis for rapid proliferation during development. Beyond the acquired cholesterol from low-density lipoprotein (LDL) taken up from circulation, tumor cells can also biosynthesize cholesterol. The molecular mechanism underlying cholesterol anabolism in esophageal squamous cell carcinoma (ESCC) and its effect on patient prognosis are unclear. Dysregulation of lipid metabolism is common in cancer. Lysophosphatidylcholine acyltransferase 1 (LPCAT1) has been implicated in various cancer types; however, its role in esophageal squamous cell carcinoma (ESCC) remains unclear. In this study, we identified that LPCAT1 is highly expressed in ESCC and that LPCAT1 reprograms cholesterol metabolism in ESCC. LPCAT1 expression was negatively correlated with patient prognosis. Cholesterol synthesis in ESCC cells was significantly inhibited following LPCAT1 knockdown; cell proliferation, invasion, and migration were significantly reduced, along with the growth of xenograft subcutaneous tumors. LPCAT1 could regulate the expression of the cholesterol synthesis enzyme, SQLE, by promoting the activation of PI3K, thereby regulating the entry of SP1/SREBPF2 into the nucleus. LPCAT1 also activates EGFR leading to the downregulation of INSIG-1 expression, facilitating the entry of SREBP-1 into the nucleus to promote cholesterol synthesis. Taken together, LPCAT1 reprograms tumor cell cholesterol metabolism in ESCC and can be used as a potential treatment target against ESCC.

Landslides are dramatic and complex surface processes that can result in extensive casualties and property damage. The broadband seismic signals generated by landslides provide datasets essential for understanding time-dependent sliding processes. However, traditional methods for computing Green’s functions based on wavenumber integration converge very slowly for surface sources, especially at high frequencies. Usually, long-period synthetic waves with a cutoff k-integral for an approximated near-surface source are adopted for landslide studies, which may lead to artifacts. Thus, the development of efficient methods for computing the broadband Green’s functions of surface sources is important. The generalized reflection and transmission method with the peak-trough averaging technique can overcome the difficulties in wavenumber integration for surface sources, quickly converging even for high-frequency calculations. We use this improved method to compute Green’s functions for surface single-force sources and invert the force histories of the 2017 devastating Xinmo landslide in different frequency bands. The results indicate that the complex sliding process of this drastic event can be revealed by broadband signals (0.02–0.5 Hz), and that the initiation stage of this event shows a dominant frequency up to 0.2 Hz.

Waterlogging represents a serious abiotic stress for plants that retards crop growth and reduces production. Therefore, exploration of effective ways to alleviate the impacts of waterlogging has important theoretical and practical applications. This study investigated the responses of seedlings of two sorghum cultivars with different waterlogging tolerances to exogenous foliar treatment with melatonin (MT) and nitrogen (N) under waterlogged conditions. The chlorophyll fluorescence, photosynthetic capabilities, and antioxidant enzyme activities of these seedlings were measured after treatments with waterlogging and either exogenous application of MT, N, or both. The results showed that waterlogging severely limited sorghum growth and reduced dry matter accumulation in both cultivars. However, the negative effects of waterlogging were mitigated by spaying MT and N on leaves, especially of the waterlogging sensitive cultivar. Notably, exogenous foliar spraying of MT and N enhanced the chlorophyll content and improved the maximal quantum yield of photosystem II photochemistry (Fv/Fm), resulting in higher rates of photosynthesis. In addition, exogenous spraying of MT and N markedly decreased the malondialdehyde (MDA) content by upregulating antioxidant enzyme activities. The results also show that the combined effects of MT and N were better than the application of either alone and that exogenous foliar spraying of MT and N significantly increased the soluble protein content of leaves of sorghum. Overall, these results indicate the beneficial roles of MT and N in alleviating waterlogging stress in sorghum and show that their application may represent a strategy to mitigate waterlogging stress during agricultural production.

A series of new β-carboline derivatives containing an imidazolium moiety were designed and synthesized via the reaction of β-carboline-1-carboxaldehydes, acetyl chloride, primary amine, and formaldehyde. The antitumor activity of the synthesized compounds was examined against lung carcinoma (A549), gastric carcinoma (BGC-823), murine colon carcinoma (CT-26), liver carcinoma (Bel-7402) and breast carcinoma (MCF-7) cells. The results indicated that most compounds exhibited significant antiproliferative activity, in some cases greater than that of cisplatin, and compound 3z was found to be the most potent antiproliferative agent against A549, BGC823, CT-26, Bel-7402 and MCF-7 cell lines with an IC(50) value of 2.7 ± 0.4, 2.7 ± 0.6, 2.4 ± 0.2, 3.2 ± 0.2, and 5.6 ± 0.3 μM, respectively. Combined with favorable in vitro potency, the antitumor efficacies of the selected compounds in mice were also evaluated. Compound 3z exhibited potent antitumor activity with a tumor inhibition rate of 48.6% in sarcoma 180 models. Preliminary investigations on the mechanisms of action revealed that compound 3z could dramatically inhibit EA.hy926 cell tube formation in a dose-dependent manner. Further investigation of the preliminary mechanism of action demonstrated that compound 3z had obvious angiogenesis inhibitory effects in the chicken chorioallantoic membrane (CAM) assay. The results of the docking study showed a good fitting of the new compounds 3o and 3z to the active site of VEGFR-2 with a docking score energy of −11.31 kcal per mole and −11.26 kcal per mole, respectively.

Introduction. Baicalein has been shown to have antitumor activities in several cancer types. However, its acting mechanisms remain to be further investigated. This work is aimed at exploring the functional long noncoding RNA (lncRNA)/microRNA (miRNA)/messenger RNA (mRNA) triplets in response to baicalein in hepatocellular carcinoma (HCC) cell to understand the mechanisms of baicalein in HCC. Methods. Differentially expressed lncRNAs (DELs) and miRNAs (DEMs) in HCC cell treated with baicalein were first screened using GSE95504 and GSE85511, respectively. miRNA targets for DELs were predicted and intersected with DEMs, after which the miRNA expression was validated using ENCORI and its prognostic value was assessed using Kaplan-Meier plotter. Potential miRNA targets were predicted by 3 prediction tools, after which expression level was validated at UALCAN and Human Protein Atlas. Kaplan-Meier plotter was used to evaluate the effects of these genes on overall survival and recurrence-free survival of HCC patients. Enrichment analyses for these genes were performed at DAVID. Results. Here, we identified 14 overlapping DELs and 26 overlapping DEMs in the baicalein treatment group than those in the DMSO treatment group. Subsequently, by analyzing expression and clinical significance of miRNAs, hsa-miR-4443 was found as a highly potential miRNA target. Then, targets of hsa-miR-4443 were predicted and analyzed, and we found AKT1 was the most potential target for hsa-miR-4443. Hence, the lncRNAs-hsa-miR-4443-AKT1 axis that can respond to baicalein was established. Conclusion. Collectively, we elucidated a role of lncRNAs-hsa-miR-4443-AKT1 pathway in response to baicalein treatment in HCC, which could help us understand the roles of baicalein in inhibiting cancer progression and may provide novel insights into the mechanisms behind HCC progression.

Porous nitrogen–doped-carbon-coated nano-Si/graphite ternary composites were prepared by liquid-phase stirring, high-temperature calcination, and acid etching. At the Si and graphite mass ratio of 1:5 in the ternary composites, porous nitrogen–doped-carbon-coated nano-silicon particles were uniformly distributed into the graphite framework, which not only acts as active material for lithium storage but also provides high conductivity for Si particles. The porous amorphous nitrogen–doped carbon shells could further enhance both lithium ion and electrical conductivity of the composite and could also effectively relieve the volume expansion. The composite anode exhibited a highly stable specific capacity of 500 mAh g−1 after 1000 cycles with the capacity retention of 95.5% at a high current density of 2000 mA g−1. It also delivered a good rate performance of 739, 662, 589, and 507 mAh g−1 at the current densities of 300, 500, 1000, and 2000 mA g−1, respectively.

Porous carbon nitride nanosheets with carbon and nitrogen double vacancies have been synthesized by a soft template-supported one-pot method. Besides their highly defined and unambiguous structure, they also show minimal thickness and high crystallinity. This porous carbon nitride exhibits great enhancement in photocatalytic hydrogen evolution activity (297.6 μmol h−1), which is 9.6 times higher than 31.2 μmol h−1 of the pristine one. An apparent quantum yield of 12.7% at 420 nm for hydrogen production can be achieved over these porous nanosheets. The detailed investigation suggests that there are carbon vacancies along with nitrogen vacancies. Besides nitrogen vacancies, carbon vacancies also play a positive role in the improvement of hydrogen evolution. In addition, the photocatalytic performance especially hydrogen evolution increases with the increase of the C/N ratio.

Plant disease seriously threatens the global food security. However, an effective and sustainable control strategy is lacking. In this study, foliar application with 10 mg/L nitrogen doped carbon dots (N-CDs) suppressed bacterial wilt in tomatoes, statistically decreased disease severity by 71.19%, and increased the fresh biomass of tomato shoot by 55.86%. The disease control efficacy with N-CDs was 1.56-fold greater than the pure CDs (P-CDs). Mechanistically, 1) nitrogen doping enhanced reactive oxygen species (ROS) scavenging ability of P-CDs, and then exhibited higher oxidative stress alleviation in tomatoes; 2) N-CDs activated the salicylic acid and jasmonic acid dependent systemic acquired resistance (SAR) in tomatoes, with subsequent inhibition in vivo pathogens growth; 3) N-CDs activated the antioxidative enzyme activity in tomatoes, and then reduced the pathogen induced oxidative stress. Polyacrylic acid modification eliminated the disease control ability of N-CDs because the modification decreased the direct physiochemical process (e.g., ROS scavenging) and indirect resistance activation (e.g., SAR activation) of N-CDs in tomatoes. Metabolomics analysis suggested that N-CDs also significantly promoted the tricarboxylic acid cycle and fatty acid synthesis in tomatoes. The findings demonstrate the important role of N-CDs in promoting disease suppression for sustainable agriculture.

Osteoporosis is a bone metabolic disease caused by the imbalance between osteoblasts and osteoclasts due to excess osteoclastogenesis, manifesting in the decrease of bone density and bone strength. Scutellariae Radix shows good anti-osteoporosis activity, but the effective component is still unclear. Cell membrane chromatography (CMC) is a biological affinity chromatography with membrane immobilized on a silica carrier as the stationary phase. It can realize a dynamical simulation of interactions between drugs and receptors on cell membrane, which is suitable for screening active compounds from complex systems. In this study, the components of Scutellariae Radix with potential anti-osteoporosis activity through inhibiting the differentiation from bone marrow mononuclear cells (BMMCs) to osteoclast were screened by a BMMC/CMC analytical system. Firstly, a new 3-mercaptopropyltrimethoxysilane (MPTS)-modified BMMC/CMC stationary phase was developed to realize covalent binding with cell membrane fractions. By investigating the retention time (tR) of the positive drug, the life span of the MPTS-modified CMC columns was significantly improved from 3 to 12 days. Secondly, 6 components of Scutellariae Radix were screened to show affinity to membrane receptors on BMMCs by a two-dimensional BMMC/CMC–TOFMS analytical system. Among them, tectochrysin demonstrated the best anti-osteoporosis effect in vitro, which has never been reported. We found that tectochrysin could inhibit the differentiation of BMMCs into osteoclasts induced by receptor activator of nuclear factor-κΒ ligand (RANKL) and macrophage colony-stimulating factor (M-CSF) in a concentration-dependent manner in vitro. In vivo, it significantly reduced the loss of bone trabeculae in ovariectomized mice, and decreased the level of C-terminal cross-linking telopeptides of type 1 collagen (CTX-1), tartrate-resistant acid phosphatase 5b (TRAP-5b), interleukin 6 (IL-6) in serum. In conclusion, tectochrysin serves as a potential candidate in the treatment of osteoporosis. The proposed two-dimensional MPTS-modified BMMC/CMC-TOFMS analytical system shows the advantages of long-life span and fast recognition ability, which is very suitable for infrequent cell lines., Graphical abstract To screen anti-osteoporosis components from Scutellariae Radix, 2D BMMC/CMC-TOFMS analytical system was established and the column life span was significantly prolonged by MPTS modification on silica stationary phase. Tectochrysin was screened out with good anti-osteoporosis activity for the first time.Image 1

Cell membrane chromatography (CMC) has been widely used for characterizing the interaction between drugs and membrane receptors to screen target components from herbal medicines. However, the column life, stability, and the efficiency cannot meet the needs of high-throughput screening purpose. In this study, a P-glycoprotein immobilized cell membrane stationary phase (P-gp/CMSP) was prepared with a simple and mild two-step aldehyde modification, realizing the covalent bonding between cell membrane and stationary phase. The column life and stability were significantly enhanced compared with the unmodified columns. The P-gp/CMC column was equipped into a comprehensive 2D P-gp/CMC/Capcell-C18/TOFMS system, which actualizes the automated and high-throughput analytical process and rapid identification of complex chemical samples with no data loss. Five compounds with significant retention were screened out and unambiguously identified by the comprehensive 2D analytical system. Baicalin was confirmed as a P-gp inhibitor with ATP depletion inhibition ratio of 83.4%. Moreover, the reversal index of baicalin on DOX significantly increased to 11.13 when its concentration reached 25 μM, revealing that baicalin could effectively reverse the MDR cell model induced by DOX. The integrated system is a practical drug discovery platform and could be applied to other transmembrane protein models.

Psoralea corylifolia (P corylifolia) has been popularly applied in traditional Chinese medicine decoction for treating osteoporosis and promoting fracture healing since centuries ago. However, the bioactive natural components remain unknown. In this study, applying comprehensive two‐dimensional cell membrane chromatographic/C18 column/time‐of‐flight mass spectrometry (2D CMC/C18 column/TOFMS) system, neobavaisoflavone (NBIF), for the first time, was identified for the bioaffinity with RAW 264.7 cells membranes from the extracts of P corylifolia. Here, we revealed that NBIF inhibited RANKL‐mediated osteoclastogenesis in bone marrow monocytes (BMMCs) and RAW264.7 cells dose dependently at the early stage. Moreover, NBIF inhibited osteoclasts function demonstrated by actin ring formation assay and pit‐formation assay. With regard to the underlying molecular mechanism, co‐immunoprecipitation showed that both the interactions of RANK with TRAF6 and with c‐Src were disrupted. In addition, NBIF inhibited the phosphorylation of P50, P65, IκB in NF‐κB pathway, ERK, JNK, P38 in MAPKs pathway, AKT in Akt pathway, accompanied with a blockade of calcium oscillation and inactivation of nuclear translocation of nuclear factor of activated T cells cytoplasmic 1 (NFATc1). In vivo, NBIF inhibited osteoclastogenesis, promoted osteogenesis and ameliorated bone loss in ovariectomized mice. In summary, P corylifolia‐derived NBIF inhibited RANKL‐mediated osteoclastogenesis by suppressing the recruitment of TRAF6 and c‐Src to RANK, inactivating NF‐κB, MAPKs, and Akt signalling pathways and inhibiting calcium oscillation and NFATc1 translocation. NBIF might serve as a promising candidate for the treatment of osteoclast‐associated osteopenic diseases.

Angelica sinensis (AS; Dang Gui), a traditional Chinese herb, has for centuries been used for the treatment of bone diseases, including osteoporosis and osteonecrosis. However, the effective ingredient and underlying mechanisms remain elusive. Here, we identified guaiacol as the active component of AS by two‐dimensional cell membrane chromatography/C18 column/time‐of‐flight mass spectrometry (2D CMC/C18 column/TOFMS). Guaiacol suppressed osteoclastogenesis and osteoclast function in bone marrow monocytes (BMMCs) and RAW264.7 cells in vitro in a dose‐dependent manner. Co‐immunoprecipitation indicated that guaiacol blocked RANK‐TRAF6 association and RANK‐C‐Src association. Moreover, guaiacol prevented phosphorylation of p65, p50, IκB (NF‐κB pathway), ERK, JNK, c‐fos, p38 (MAPK pathway) and Akt (AKT pathway), and reduced the expression levels of Cathepsin K, CTR, MMP‐9 and TRAP. Guaiacol also suppressed the expression of nuclear factor of activated T‐cells cytoplasmic 1(NFATc1) and the RANKL‐induced Ca2+ oscillation. In vivo, it ameliorated ovariectomy‐induced bone loss by suppressing excessive osteoclastogenesis. Taken together, our findings suggest that guaiacol inhibits RANKL‐induced osteoclastogenesis by blocking the interactions of RANK with TRAF6 and C‐Src, and by suppressing the NF‐κB, MAPK and AKT signalling pathways. Therefore, this compound shows therapeutic potential for osteoclastogenesis‐related bone diseases, including postmenopausal osteoporosis.

Osteoarthritis (OA), a highly prevalent chronic joint disease, involves a complex network of inflammatory mediators that not only triggers pain and cartilage degeneration but also accelerates disease progression. Traditional Chinese medicinal shenjinhuoxue mixture (SHM) shows anti-inflammatory and analgesic effects against OA with remarkable clinical efficacy. This study explored the mechanism underlying anti-OA properties of SHM and evaluated its efficacy and safety via in vivo experiments. Through network pharmacology and published literature, we identified the key active phytochemicals in SHM, including β-sitosterol, oleanolic acid, licochalcone A, quercetin, isorhamnetin, kaempferol, morusin, lupeol, and pinocembrin; the pivotal targets of which are TLR-4 and NF-κB, eliciting anti-OA activity. These phytochemicals can enter the active pockets of TLR-4 and NF-κB with docking score ≤ − 3.86 kcal / mol , as shown in molecular docking models. By using surface plasmon resonance assay, licochalcone A and oleanolic acid were found to have good TLR-4-binding affinity. In OA rats, oral SHM at mid and high doses (8.72 g/kg and 26.2 g/kg) over 6 weeks significantly alleviated mechanical and thermal hyperalgesia ( P < 0.0001 ). Accordingly, the expression of inflammatory mediators (TLR-4, interleukin (IL-) 1 receptor-associated kinase 1 (IRAK1), NF-κB-p65, tumor necrosis factor (TNF-) α, IL-6, and IL-1β), receptor activator of the NF-κB ligand (RANKL), and transient receptor potential vanilloid 1 (TRPV1) in the synovial and cartilage tissue of OA rats was significantly decreased ( P < 0.05 ). Moreover, pathological observation illustrated amelioration of cartilage degeneration and joint injury. In chronic toxicity experiment of rats, SHM at 60 mg/kg demonstrated the safety. SHM had an anti-inflammatory effect through a synergistic combination of active phytochemicals to attenuate pain and cartilage degeneration by inhibiting TLR-4 and NF-κB activation. This study provided the experimental foundation for the development of SHM into a more effective dosage form or new drugs for OA treatment.

Nonspherical anisotropic particles, as basic building blocks, have been catching much attention in recent decades. However, it is still a challenge to produce nonspherical particles by traditional approaches. Here, we reported a facile method to fabricate hexagonal particles via the double-solvent swelling method. When the crystal arrays were immersed in the double-solvent system of N,N-dimethylformamide (DMF) and tetraethyl orthosilicate (TEOS), the particles were swollen and squeezed into hexagonal particles. The concave size of hexagonal particles was controlled by tuning the mass ratio of the solvent and the swelling time. In addition, the particles with novel morphology were also prepared by swelling the arrays with a distinct lattice structure. The monodispersed particle possesses a well-defined hexagonal morphology and the liquid crystal phenomenon, which has promising applications in the fields of photonics, optical devices, and toners.

In flowering plants, pollen wall is a specialized extracellular cell-wall matrix surrounding male gametophytes and acts as a natural protector of pollen grains against various environmental and biological stresses. The formation of pollen wall is a complex but well-regulated process, which involves the action of many different genes. However, the genetic and molecular mechanisms underlying this process remain largely unknown. In this study, we isolated and characterized a novel rice male sterile mutant, defective pollen wall3 (dpw3), which displays smaller and paler anthers with aborted pollen grains. DPW3 encodes a novel membrane-associated alpha integrin-like protein conserved in land plants. DPW3 is ubiquitously expressed in anther developmental stages and its protein is localized to the plasma membrane, endoplasmic reticulum (ER) and Golgi. Anthers of dpw3 plants exhibited unbalanced anther cuticular profile, abnormal Ubisch bodies, disrupted callose deposition, defective pollen wall formation such as abnormal microspore plasma membrane undulation and defective primexine formation, resulting in pollen abortion and complete male sterility. Our findings revealed a novel and vital role of alpha integrin-like proteins in plant male reproduction.

Screening of bioactive ligands for a certain protein target from medicinal herbs is a highly important yet challenging task during drug discovery process. In this study, a surface plasmon resonance biosensor-based active ingredient recognition system (SPR-AIRS) was applied to screen p38 mitogen-activated protein kinase (p38) ligands from herbal extracts. After p38 protein was immobilized on a SPR chip and the suitability of SPR-AIRS was validated, thirty-four p38-related medicinal herbs were selected and pre-screened. Two medicinal herbs having high response signal with p38-immobilized chip, Folium Ginkgo and Herba Artemisiae Scopariae, were injected into SPR system for ligand fishing. Among them, two active compounds, eupatilin (EPT) and ginkgolide B (GKB), were identified as p38 ligands, and then the KD values of EPT and GKB were measured as 21.68 ± 2.21 and 44.71 ± 1.80 μM, respectively. They can inhibit p38 activities significantly and bind to the ATP binding site on p38. Furthermore, EPT and GKB can inhibit cell proliferation (IC50 = 30.31 ± 6.84 and 42.97 ± 0.83 μM), induce apoptosis and G2/M cell cycle arrest against K562 cell line. This is the first time that EPT and GKB are reported as effective p38 binding ligands. These results prove that SPR-AIRS could be an effective method to screen active compounds acting on a specific protein from complex systems.

Background/Objective:Forkhead Box M1 (FOXM1) is frequently activated in tumors. We studied the expression and the possible mechanism of FOXM1 and evaluated the effects of thiostrepton in an endometriotic rat model.Methods and Material:This was a randomized study in a rat model of endometriosis. Fifty female Wistar rats were surgically induced with endometriosis. After 4 weeks of observation, twenty and thirty rats were randomly allocated to an ovariectomized (OVX) group and a treatment group, respectively. The OVX group was ovariectomized and randomly divided into an OVX-estrogen group and a control (OVX -oil) group. All rats were allowed a resting period of 3 days prior to any operation. The rats in the estrogen group were given estradiol (20 µg/kg, 0.1 ml /d), while the control group was treated with an equivalent amount of sesame oil. Every group was injected with subcutaneous injection for 7 days. The treatment group was randomly divided into three groups to receive the following: TST at 150 mg/kg, ip.; TST at 250 mg/kg, ip.; or sterile normal saline, ip. The groups received these dosages every 2 days for 2 weeks. Lesion growth, histological examination, and protein expression were subsequently analyzed using caliper measurement, histology, immunostaining, and Western blot after each rat received an injection in its own group.Results:Our results showed that FOXM1 is enriched in nucleus of an ectopic endometrium when compared with a eutopic uterus. Furthermore, we found that an ERK/FOXM1/matrix metalloproteinase-9 (MMP9) signaling pathway might result in the establishment and development of endometriosis. Finally, a thiostrepton concentration dependently reduced the expression of FOXM1, MMP9 and Bcl-2 in endometriotic lesions of the treated rats. Statistical significance was accepted for a value of P < 0.05.Conclusion:We postulate that thiostrepton could inhibit the endometriotic lesions, at least in part, by decreasing the FOXM1 expression and exerting a pro-apoptotic effect. We reported for the first time that FOXM1 expresses in experimental endometriosis rat and thiostrepton may also be suitable for the administration of endometriosis by inhibiting the growth of endometriotic implants. More studies are needed to further evaluate thiostrepton’s effect.

Necroptosis, a form of programmed cell death, plays a critical role in various diseases, including inflammatory, infectious, and degenerative diseases. We previously identified N-(7-cyano-6-(4-fluo...

Non-iridescent structural colors with wide viewing angles are produced by amorphous photonic structure (APS) and have received increasing attention. However, it is still a challenge to fabricate of non-iridescent, crack-free and functional structural colors, simultaneously. Here, the flexible lamellar nanostructures of graphene oxide (GO) are introduced as a black additive to fabricate amorphous, crack-free structural colors. The color hue and spectral purity of APS film can be easily tuned by adjusting the diameter of spheres and concentration of GO. Furthermore, after reduction treatment, the APS film possesses excellent visibility, flexibility and conductivity, paving the way toward their practical applications in flexible sensors, solar cells and full-color paper-like displays.

Angiogenesis is central to a wide range of physiological and pathological processes including wound healing, macular degeneration, and cancer. Excessive or inappropriate vascular supply of tumors is one of the main targets for cancer therapy. Recently, critical and selective transcriptional factors such as yes-associated protein (YAP) that control the expression of angiogenesis factors have gained increasing attention in antiangiogenic therapy. In this study, we have identified and characterized a novel inhibitor of YAP, gambogic acid (GA), which exerted striking antiangiogenic effects both in vitro and in vivo. We demonstrated that GA remarkably inhibited a variety of vascular endothelial growth factor-induced angiogenesis processes including proliferation, migration, sprouting, and tube formation of endothelial cells in vitro. In addition, GA resulted in decreased neo-vessel formation in Matrigel plugs of mice and chick chorioallantoic membrane. More importantly, we showed that GA limited tumor growth via preventing tumor angiogenesis and vascular maturation. Further mechanistic studies illustrated that GA directly targeted YAP/STAT3 signaling axis, which is critical for the transcriptional regulation of a series of angiogenic factors. Taken together, these preclinical findings suggest that GA significantly repressed tumor angiogenesis and may serve as a promising drug candidate against cancer.

A polyoxometalate cluster integrating a photothermal and catalytic center is used to synergistically enhance olefin oxidation., A strategy integrating near infrared (NIR) photothermal and catalytic effects within one active center beyond ultraviolet and visible light is proposed without the combination of separated photothermal transformation components. A giant polyoxomolybdate, which has high NIR photothermal conversion efficiency, is selected as the model catalyst, while a cationic β-cyclodextrin is used to cover its negatively charged surface electrostatically. Under NIR light radiation, the designed catalyst increases catalytic activity of cyclohexene oxidation under O2 atmosphere in water. The conversion reaches about pentaploid of the reaction without NIR radiation. By excluding heating effect from the external heater at the same temperature, about twice as much enhancement, which can be attributed to the sole photothermal action, is still observed. While the catalytic center is shielded by the organic porous layer, the surface cavity allows the integrated catalyst to conduct a selective catalysis by screening the molecules in size over the surface channel.

Summary Panicle architecture is a key determinant of grain yield in cereals, but the mechanisms governing panicle morphogenesis and organ development remain elusive. Here, we have identified a quantitative trait locus (qPA1) associated with panicle architecture using chromosome segment substitution lines from parents Nipponbare and 9311. The panicle length, branch number and grain number of Nipponbare were significantly higher than CSSL‐9. Through map‐based cloning and complementation tests, we confirmed that qPA1 was identical to SD1 (Semi Dwarf1), which encodes a gibberellin 20‐oxidase enzyme participating in gibberellic acid (GA) biosynthesis. Transcript analysis revealed that SD1 was widely expressed during early panicle development. Analysis of sd1/osga20ox2 and gnp1/ osga20ox1 single and double mutants revealed that the two paralogous enzymes have non‐redundant functions during panicle development, likely due to differences in spatiotemporal expression; GNP1 expression under control of the SD1 promoter could rescue the sd1 phenotype. The DELLA protein SLR1, a component of the GA signalling pathway, accumulated more highly in sd1 plants. We have demonstrated that SLR1 physically interacts with the meristem identity class I KNOTTED1‐LIKE HOMEOBOX (KNOX) protein OSH1 to repress OSH1‐mediated activation of downstream genes related to panicle development, providing a mechanistic link between gibberellin and panicle architecture morphogenesis.

Sorghum [Sorghum bicolor (L.) Moench] seed germination is sensitive to salinity, and seed priming is an effective method for alleviating the negative effects of salt stress on seed germination. However, few studies have compared the effects of different priming agents on sorghum germination under salt stress. In this study, we quantified the effects of priming with distilled water (HP), sodium chloride (NaCl), potassium chloride (KCl), calcium chloride (CaCl2), and polyethylene glycol (PEG) on sorghum seed germination under 150 mM NaCl stress. The germination potential, germination rate, germination index, vigor index, root length, shoot length, root fresh weight, shoot fresh weight, root dry weight, and shoot dry weight were significantly reduced by salt stress. Different priming treatments alleviated the germination inhibition caused by salt stress to varying degrees, and 50 mM CaCl2 was the most effective treatment. In addition, the mitigation effect of priming was stronger on root traits than on shoot traits. Mitigation efficacy was closely related to both the type of agent and the concentration of the solution. Principal component analysis showed that all concentrations of CaCl2 had higher scores and were clearly distinguished from other treatments based on their positive effects on all germination traits. The effects of the other agents varied with concentration. The priming treatments were divided into three categories based on their priming efficacy, and the 50, 100, and 150 mM CaCl2 treatments were placed in the first category. The 150 mM KCl, 10% PEG, HP, 150 mM NaCl, 30% PEG, and 50 mM KCl treatments were placed in the second category, and the 100 mM NaCl, 100 mM KCl, 20% PEG, and 50 mM NaCl treatments were least effective and were placed in the third category. Choosing appropriate priming agents and methods for future research and applications can ensure that crop seeds germinate healthily under saline conditions.

Lianhuaqingwen (LHQW) capsule, a herb medicine product, has been clinically proved to be effective in coronavirus disease 2019 (COVID-19) pneumonia treatment. However, human exposure to LHQW components and their pharmacological effects remain largely unknown. Hence, this study aimed to determine human exposure to LHQW components and their anti-COVID-19 pharmacological activities. Analysis of LHQW component profiles in human plasma and urine after repeated therapeutic dosing was conducted using a combination of HRMS and an untargeted data-mining approach, leading to detection of 132 LHQW prototype and metabolite components, which were absorbed via the gastrointestinal tract and formed via biotransformation in human, respectively. Together with data from screening by comprehensive 2D angiotensin-converting enzyme 2 (ACE2) biochromatography, 8 components in LHQW that were exposed to human and had potential ACE2 targeting ability were identified for further pharmacodynamic evaluation. Results show that rhein, forsythoside A, forsythoside I, neochlorogenic acid and its isomers exhibited high inhibitory effect on ACE2. For the first time, this study provides chemical and biochemical evidence for exploring molecular mechanisms of therapeutic effects of LHQW capsule for the treatment of COVID-19 patients based on the components exposed to human. It also demonstrates the utility of the human exposure-based approach to identify pharmaceutically active components in Chinese herb medicines., Graphical abstract This study provides chemical and biochemical evidence of LHQW capsule for the treatment of COVID-19 patients based on the components exposed to human.Image 1

Background Protection of pancreatic islet cells against dysfunction or death by regulating autophagy is considered to be an effective method for treatment of type 2 diabetes mellitus (T2DM). Morus alba leaves (mulberry leaves), a popular herbal medicine, have been used for prevention of T2DM since ancient times. Purpose This study aimed to clarify whether Morus alba leaves ethanol extract (MLE) could protect islet cells in vivo and in vitro by regulating autophagy in T2DM, and explore the possible mechanism of action. Methods The main chemical constituents in MLE were analyzed by HPLC. The T2DM rat model was induced via high-fat diet combined with peritoneal injection of low-dose streptozotocin, and MLE was administered by oral gavage. Fasting blood glucose (FBG) and plasma insulin were measured, and homeostatic model assessment of β cell function (HOMA-β) and insulin resistance (HOMA-IR) were determined. The histomorphology of pancreas islets was evaluated by haematoxylin and eosin staining. In palmitic acid (PA)-stressed INS-1 rat insulinoma cells, cell viability was assayed by an MTT method. Expression of the autophagy-related proteins LC3 I/II, p62, p-AMPK and p-mTOR in islet tissues and INS-1 cells was evaluated by western blotting or immunohistochemistry analysis. Results The four main chemical constituents in MLE were identified as chlorogenic acid, rutin, isoquercitrin and quercitrin. MLE ameliorated hyperglycemia, insulin resistance and dyslipidemia of T2DM rats with prominent therapeutic effect. Further study indicated that MLE observably improved islet function, alleviated islet injury of T2DM rats, and inhibited PA-induced INS-1 cell death. On the other hand, MLE significantly induced autophagy in islet cells both in vivo and in vitro, and autophagy inhibitors abolished its therapeutic effect on T2DM rats and protective effect on islet cells. Apart from this, MLE markedly activated the AMPK/mTOR pathway in INS-1 cells, and the AMPK inhibitor prevented the autophagy induction ability of MLE. Conclusion Together, MLE could protect islet cells against dysfunction and death by inducing AMPK/mTOR-mediated autophagy in T2DM, and these findings provide a new perspective for understanding the treatment mechanism of Morus alba leaves against T2DM.

A novel surface plasmon resonance–based P-gp ligand screening system (SPR-PLSS) combined with lentiviral particle (LVP) stabilization strategy was constructed to screen out potential P-gp inhibitors from natural products. Firstly, we constructed LVPs with high and low expression levels of P-gp. The LVPs can ensure the natural conformation of P-gp based on the principle that LVPs germinated from packaging cells will contain cell membrane fragments and P-gp they carry. Then the LVPs with high P-gp expression for active channel and LVPs with low P-gp expression for reference channel were immobilized on CM5 chip respectively. The affinity detection was thus carried out with the signal reduction on the two channels. The P-gp inhibitors, Valspodar (Val) and cyclosporin (CsA), as positive compounds, were detected to characterize the chip’s activity, and the KD of Val and CsA were 14.09 μM and 16.41 μM, respectively. Forty compounds from natural product library were screened using the SPR CM5 chip, and magnolol (Mag), honokiol (Hon), and resveratrol (Res) were screened out as potential P-gp ligands, showing a significant response signal. This work presented a novel P-gp ligand screening system based on LVP-immobilized biosensor to rapidly screen out P-gp ligands from natural product library. Compared with traditional cell experiments which the screening time may take up to several days, our method only takes several hours. Furthermore, this study has also provided solid evidences to support that some complicated membrane proteins would apply to the lentivirus-based SPR screening system.

The development of switchable molecular units is a challenging task of modern synthetic and supramolecular chemistry. In the present study, alkyl bridged bis(catecholketone) ligands are introduced in order to obtain helicates which cation triggered show some spring type dynamics. The preparation of the ligands as well as of the complexes and corresponding switching processes are described.

Screening active components from Chinese traditional medicine is an effective approach to discover new drugs or active structures. Cell membrane chromatography (CMC), developed rapidly because of its high sensitivity and effectiveness, has achieved a wide application in screening active components on pathological cells or tissues. However, it is hard to clarify the selectivity between pathological and normal tissues through simply using pathological cells. In this study, a novel comparative two-dimensional (2D) cell membrane chromatography system was established. Briefly, hepatic carcinoma HepG2 CMC columns and normal hepatic L02 CMC columns were simultaneously loaded to screen potential selective antitumor components from Scutellariae Radix by comparing the retention behaviors on two kinds of cells. Totally 13 components in Scutellariae Radix retained on both HepG2/ CMC and L02/ CMC columns. Among them, three components, oroxylin A, wogonin and chrysin, were screened out to perform stronger affinity on HepG2 columns, and in further cell proliferation assay, IC50 of these three compounds of HepG2 cells were 9.66 μM, 66.77 μM and 36.26 μM respectively, while of L02 cells, IC50 of chrysin was 59.10 μM and over 200 μM of the other two components. On the whole, the toxity of these three compounds to hepatoma cells was stronger than to normal cells. It can be supposed that oroxylin A, wogonin, and chrysin own the potential to be developed as selective anti-hepatoma active components, which expects further research to validate.

Crystal-induced kidney injury (CIKI) is the fundamental pathological change during nephrolithiasis, although the molecular mechanism is still unclear. Pyrrosia calvata (Bak.) Ching has been used in folk medicine to treat urolithiasis for years. To clarify the pharmacodynamic substances and the mechanism of its antiurolithiasis effects, in this study, a novel, stop-flow, comprehensive, two-dimensional (2D) HK-2 and HK-2/CIKI cell membrane chromatography (CMC) comparative analysis system was developed to screen for the potential active ingredients from Pyrrosia calvata (Bak.) Ching against CIKI. The comprehensive 2D CMC comparative analysis system showed satisfactory selectivity, and eight ingredients were screened and identified by this system. Among them, mangiferin exhibited higher affinity for the HK-2/CIKI CMC column than the HK-2 CMC column and was selected for further efficacy verification. Cell proliferation assays showed that mangiferin could protect HK-2 cell viability after stimulation with sodium oxalate (NaOX). Additionally, in a rodent model of CIKI, mangiferin decreased the deposition of calcium oxalate (CaOX) crystals in mouse kidneys, alleviated the pathological damage to kidney tissue, and inhibited the upregulation of OPN, MCP1, and CD44 expression caused by CaOX crystals. The established comprehensive 2D CMC comparative analysis system can be applied to screen active ingredients with disease specificity from traditional Chinese medicine (TCM) and is suitable for other cell models.

Catechol ligands with aldehyde, ketone or ester groups attached in 3-position form, in the presence of titanium(IV) triscatecholate, titanium(IV) complexes. If lithium cations are the counterions, they can bind in a successive step to the salicylate units of the complex and form a dimeric triple-lithium-bridged dinuclear helicate. In solution, the dimer is in equilibrium with the monomer and the thermodynamics of the dimerization can be easily evaluated. Thus, the hierarchically assembled titanium(IV) helicates represent a lithium-dependent molecular switch. The investigation of different derivatives of the complex allows for an estimation of the influence of side chain functionalities on the energetics of the dimerization. Thus, the hierarchically assembled helicates can be used as a kind of molecular balance to determine weak interaction energies (solvophobic effects and even dispersive effects). In addition, tethering of two ligands leads to "classical" helicates. Removal or addition of lithium cations allows for a reversible switching between a compressed and expanded state, which in the case of chiral ligands can be even performed stereospecifically.

Salvianic acid A sodium (SAAS), derived from a well-known herbal medicine Danshen (Salvia miltiorrhiza), is a new drug involved in phase I clinical trials in China for the treatment of coronary heart disease and stable angina pectoris. However, the direct binding protein(s) of SAAS are not understood and the broader cardioprotective effects as well as the underlying mechanisms remain to be further elucidated. In this study, Sprague-Dawley rats were subjected to left anterior descending artery ligation to investigate the cardioprotective effect of SAAS against myocardial infarction (MI). Moreover, a human proteome microarray was used to identify the direct binding proteins of SAAS, which was further verified by metabolomic profiling of rat serum after MI using an ultra-performance liquid chromatography/quadrupole time-of-flight mass spectrometry (UPLC-QTOF-MS) based approach. Our results demonstrated that SAAS significantly improved cardiac function and protected against MI-induced injury. In total, 370 proteins were identified to specifically bind SAAS and strikingly enriched in metabolic pathways. Rat serum metabolomic profiling identified 26 potential biomarkers including various glycerophospholipids (GPLs) and an array of fatty acids. Metabolic pathway analysis found increased phospholipid catabolism, sphingolipid metabolism and linoleic acid metabolism, decreased tryptophan metabolism, and impaired glycerophospholipid metabolism and primary bile acid biosynthesis in MI animals, while SAAS remarkably reversed these metabolic changes. SAAS may protect against myocardial infarction in rats by reversing multiple metabolic changes-induced by MI injury. Our findings will shed light on the cardioprotective mechanism of SAAS and aid its clinical use. Moreover, the SAAS-binding proteins identified by the proteome microarray are expected to be a valuable resource for its greater development.

Root function plays a vital role in maintaining crop production. However, the role of deep roots in yield production and their effects on photosynthetic performance in sorghum remain unclear. This study aimed to provide theoretical supports for establishing highly efficient root systems of sorghum to achieve more yield under certain conditions. In this study, two sorghum (Sorghum bicolor L. Moench) cultivars, Jiza127 and Jiza305, were cultivated in soil columns as experimental materials. Three treatments (no roots removed, CK, roots removed at 30 cm underground, R30, roots removed at 60 cm underground, R60) were carried out under drought conditions during the filling stage. The root bleeding intensity, endogenous substances in the root bleeding sap, photosynthetic characteristics, dry matter accumulation, and yield were measured. The results showed that R30 and R60 significantly reduced yield in both sorghum cultivars, and the effect of R30 on yield was greater than that of R60. The contributions of roots below 30 cm to the yield of both sorghum hybrids were notably higher than those below 60 cm. R30 significantly reduced the dry matter weights (DMWs) of leaves, stems, sheaths, and panicles. R60 significantly reduced the DMW of panicles but had no significant effect on the DMWs of leaves and stems. R30 significantly reduced the photosynthetic level and PSII reaction center activity, however, the effect of R60 was not significant. Although both R30 and R60 significantly reduced root activity and the soluble sugar, amino acid, gibberellin (GA3), and abscisic acid (ABA) contents of the root bleeding sap, some of the above indicators in R60 were significantly higher than those in R30 during the filling stage, indicating that the deeper roots (below 30 cm) had a critical regulatory effect on the physiological processes of the aerial parts in sorghum, which resulted in a stronger effect on yield, especially under drought conditions. In brief, the deep roots of sorghum played a key role in yield production, but the roots in different soil depths regulated yield production in different ways. Our results indicate that deep roots of sorghum deserve consideration as a potential trait for yield improvement especially under drought conditions.

Cell membrane chromatography, which has been used to build an in vitro screening model, has become a practical method to screen active ingredients of traditional Chinese medicine (TCM) or study the interaction between drugs and receptors. In this paper, the development of cell membrane chromatography and its preparation methods, the optimization of the system and methodological for stability and other issues were reviewed, as well the unique advantages on the selection of active ingredients of TCM. On this basis, the future development trend of cell membrane chromatography technique was discussed to provide ideas for the further development of cell membrane chromatography and its further application in the field of drug high throughput screening

Background/Aims: Multidrug resistance (MDR) is the most common cause of chemotherapy failure. Upregulation of P-glycoprotein (P-gp) is one of the main mechanisms underlying MDR. Methods: In this study, we developed a targeted drug and small interfering (si)RNA co-delivery system based on specific aptamer-conjugated grapefruit-derived nanovectors (GNVs) that we tested in MDR LoVo colon cancer cells. The internalization of nanovectors in cancer cells was tested by fluorescence microscopy and flow cytometry. The anti-cancer activity in vitro was determined by colony formation and cell apoptosis assays. The biodistribution of nanovectors was analyzed by live imaging and the anti-cancer activity in vivo was observed. Results: GNVs loaded with aptamer increased doxorubicin (Dox) accumulation in MDR LoVo cells, an effect that was abolished by pretreatment with DNase. The LA1 aptamer effectively promoted nanovector internalization into cells at 4°C and increased the targeted delivery of Dox to tumors. Constructs harboring Dox, LA1, and P-gp siRNA more effectively inhibited proliferation and enhanced apoptosis in cultured MDR LoVo cells while exhibiting more potent anti-tumor activity in vivo than free Dox or GNVs loaded with Dox alone or in conjunction with LA1, an effect that was associated with downregulation of P-gp expression. Conclusion: This GNV-based system may be an effective strategy for overcoming MDR in clinical settings.

A novel "Prediction and Confirmation" (PC) strategy was proposed for characterizing phosphodiesterase-5 inhibitor (PDE-5) derivatives in botanical dietary supplements (BDSs) for on-site detection. Discovery Studio (DS) and density functional theory (DFT) calculations were used for the "Prediction" step in order to estimate PDE-5 derivative structures and theoretical Raman shifts without synthesizing the derivatives. After 11 potentially bioactive sildenafil derivatives were acquired through DS, 32 common calculated Raman shifts were obtained through DFT. The mean absolute wavenumber deviation (δ, peak range) of the major bands and the minimum number (τ) of Raman spectral peaks matching the calculated common shifts were optimized, so that a positive result of an unknown sample could be reasonably produced. In this study, δ was set at ±10 cm-1 and the corresponding τ was set at 4-5 after optimization. Surface plasmon resonance (SPR) biosensor and surface-enhanced Raman scattering (SERS) detection were the "Confirmation" step to validate the reliability and accuracy of DS and DFT in the "Prediction" step, respectively. The optimized δ and τ criteria were used as indexes for on-site SERS detection after thin-layer chromatographic (TLC) separation of six real-world samples, one of which was preliminarily identified as "suspected positive samples." This strategy allows for a quick determination of the BDSs adulterated with sildenafil or its derivatives, independent of any standard materials.

A surface plasmon resonance (SPR) biosensor-based active ingredients recognition system (SPR-AIRS) was developed, validated, and applied to screen signal transducer and activator of transcription 3 (STAT3) ligands. First, features of the screening system were investigated in four aspects: (1) specificity of the STAT3-immobilized chip, it shows that the chip could be applied to screen STAT3 ligands from complex mixture; (2) linearity and limit of detection (LOD) of the system, the minimum recovery cycle number was determined as 5 cycles; (3) saturability of the chip, the results indicate that it is necessary to select a proper concentration based on the compound's Kd value; (4) robustness of the system, it indicates that inactive compounds in the matrix could not interfere with active compounds in the process of screening. Next, SPR-AIRS was applied to screen STAT3 ligands from medicinal herbs. Nine candidate compounds were fished out. Then SPR assay and molecular docking were performed to verify the interplay between STAT3 and candidate compounds. Apoptosis assay and luciferase report assay were performed to investigate the drug effect of candidate compounds on STAT3 activity. Western blot results indicated that neobaicalein and polydatin could inhibit the phosphorylation of STAT3. As far as we know, this is the first time that neobaicalein and polydatin are reported as effective STAT3 ligands. In a conclusion, we have systemically demonstrated the feasibility of SPR biosensor-based screening method applying to complex drug systems, and our findings suggest that SPR-AIRS could be a sensitive and effective solution for the discovery of active compounds from a complex matrix.

Gandi capsule (GDC) has been used clinically for years for treatment of vascular lesions caused by diabetes. However, its comprehensive ingredients, especially those that can be absorbed, remain unclear. In this study, we developed a simple and fast ultra-high performance liquid chromatography–quadrupole time-of-flight mass spectrometry (UHPLC–Q-TOFMS) method to identify the ingredients of GDC extract, as well as those that can permeate the Caco-2 monolayer cell model. Firstly, 52 components were rapidly identified in GDC extract. Then, a total of 17 components were able to pass across Caco-2 cells from the apical side to the basolateral side with the apparent permeability coefficients (Papp) > 1.0 × 10−5 cm/s, which indicate good intestinal permeability and bioavailability. Furthermore, 14 of the 17 penetrative components were definitely detected and identified in rat plasma. These results confirmed that the combination of Caco-2 monolayer cell absorption model and UHPLC–Q-TOFMS is suitable for fast screening of the ingredients entering the blood circulation. Our results will serve as a foundation for further evaluation of the pharmacological efficacy of GDC in the clinical treatment of diabetic vascular disease.

Rhizoma corydalis and Radix Angelicae Dahurica (Yuanhu–Baizhi) herbal medicine pair has been used for thousands of years and has been reported to be potentially active in recent cancer therapy. But the exact active components or fractions remain unclear. In this study, a new comprehensive two-dimensional (2D) 3-aminopropyltriethoxysilane (APTES)-decorated MCF7-cell membrane chromatography (CMC)/capcell-C18 column/time-of-flight mass spectrometry system was established for screening potential active components and clarifying the active fraction of Yuanhu–Baizhi pair. APTES was modified on the surface of silica, which can provide an amino group to covalently link cell membrane fragments with the help of glutaraldehyde in order to improve the stability and column life span of the MCF7 CMC column. The comprehensive 2D MCF7-CMC system showed good separation and identification abilities. Our screen results showed that the retention components are mainly from the alkaloids in Yuanhu (12 compounds) and the coumarins (10 compounds) in Baizhi, revealing the active fractions of Yuanhu–Baizhi herbal medicine pair. Oxoglaucine, protopine, berberine, osthole, isopimpinellin and palmitic acid were selected as typical components to test the effects on cell proliferation and their IC50 were calculated as 38.17 μM, 29.45 μM, 45.42 μM, 132.7 μM, 156.8 μM and 90.5 μM respectively. Cell apoptosis assay showed that the drug efficacy was obtained mainly through inducing cell apoptosis. Furthermore, a synergistic assay results demonstrated that oxoglaucine (representative of alkaloids from Yuanhu) and isopimpinellin (representative of coumarins from Baizhi) showed significant synergistic efficacy with GFT, indicating that these components may act on other membrane receptors. The proposed 2D CMC system could also be equipped with other cells for further applications. Besides, the follow-up in-vitro experimental strategy using cell proliferation assay, cell apoptosis assay and synergistic assay proved to be a practical way to confirm the active fractions of herbal medicine. Keywords: Cell membrane chromatography, Comprehensive two-dimensional chromatography, Herbal medicine, Rhizoma corydalis and Radix Angelicae Dahurica, Anti-breast-cancer components

Flexible electronics is booming and attracts considerable interest in monitoring physiological activities and health conditions. The development of human-friend flexible electronics with both excellent human movement monitoring and flexible electrode functions at a wide working range remains highly challenging. Herein, we report a biomimetic double-layered multifunctional flexible electronic device composed of a stretchable, tough elastomer covalently coupled with a conductive, double-network hydrogel for monitoring physiological motions. The introduction of optimal physical crosslinking including hydrogen bond and metal coordination in the covalently cross-linked polyurethane elastomer effectively provides favorable flexibility and stretchability. The elastomer-hydrogel integration (EHI) shows ultra-fast responsiveness (10 ms) and resilience (246 ms) as a skin sensor and could effectively detect diverse muscle and joint movements in a highly sensitive and signal waveform-interpreting manner. Further, such a polymer integration with skin shape-adaptive hydrogel and low contact impedance enables real-time high-quality detection of electrocardiogram (ECG) by serving as flexible electrode compared to commercial Ag/AgCl electrodes, and was successfully applied to measure electrooculogram (EOG) and electromyogram (EMG). EHI-based electrodes were feasible and effective for electroencephalogram (EEG) signal detection in brain-computer interfaces (BCI) system. Altogether, this biomimetic EHI electronic device provides an advanced platform for the design of next-generation flexible healthcare diagnostic monitors and soft robots.

Human epidermal growth factor receptor 2 (HER2) is a powerful target for cancer immune therapy. The development of anti-HER2 monoclonal antibodies targeting different domains of HER2 is quite effective. However, the selection and production of multivalent antibodies are complicated. In this study, a mimivirus-based designed ankyrin repeat protein (DARPin) targeting HER2 was selected from an artificial library by bacteria surface display. The selection was performed on HER2-positive B16BL6/E2 melanoma cells and HER2-nagative cells. DARPin selected from the library could be expressed in soluble form with a yield of 70 mg/L. After purified by two continuous and easy steps, the purity of DARPin was 90% as established by SDS-PAGE and RP-HPLC. Selected DARPin showed significant HER2-targeting ability with an affinity of 1.05 ± 0.47 µM. MTT assay demonstrated that at the concentration of 640 nM, the selected DARPin dimer could inhibit the SK-BR-3 growth at a rate of 36.63 and 46.34% in 48 and 72 hr incubation separately, which was similar to trastuzumab (43.12 and 49.14% separately). These findings suggested that it was an effective method to select antibody mimetic DARPin by bacteria surface display combined with live cells sorting and provided a drug candidate for cancer therapy.

Acidic mine drainage(AMD) containing acidity and a broad range of heavy metal ions is classified as hazardous, and must be properly treated. The removal mechanism of heavy metal ions in acidic mine drainage containing Cu2+, Fe2+, and Zn2+ with biological method was studied here. Using 20 mmol/L ethanol as carbon source, Desulfovibrio marrakechensis, one of sulfate reducing bacteria(SRB) species, grew best at 35 °C and pH=6.72 with concentrations of 10, 55 and 32 mg/L for Cu2+, Fe2+ and Zn2+, respectively. The removal efficiency for each ion mentioned above was 99.99%, 87.64% and 99.88%, respectively. The mineralogy and surface chemistry of precipitates were studied by means of energy dispersive spectrometer(EDS), X-ray photoelectron spectroscopy(XPS), X-ray diffraction(XRD) combined with control tests. The experimental results demonstrate that the removal mechanism of heavy metal ions by Desulfovibrio marrakechensis is comprehensive function of chemical precipitation, adsorption and bioprecipitation. The biogenic iron sulfide solid was characterized as greigite(Fe3S4), while the zinc sulfide solid was characterized as sphalerite(ZnS).

Li Zhang,1,* Mengchu Yao,2,3,* Wei Yan,4,* Xiaoning Liu,5 Baofei Jiang,6 Zhaoye Qian,2,3 Yong Gao,2,3 Xiao-jie Lu,7 Xiaofei Chen,2 Qi-long Wang2,3,5 1Department of Hematology, 2Department of Clinical Oncology, 3Huai’an Key Laboratory of Esophageal Cancer Biobank, 4Department of Gastroenterology, 5Department of Central Laboratory, 6Department of Gastrointestinal Surgery, Huai’an First People’s Hospital, Nanjing Medical University, Huai’an, 7Liver Transplantation Center, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China *These authors contributed equally tothis work Abstract: Low toxicity and high efficacy are the key factors influencing the real-world clinical applications of nanomaterial-assisted drug delivery. In this study, novel hollow carbon spheres (HCSs) with narrow size distribution were developed. In addition to demonstrating their ease of synthesis for large-scale production, we also demonstrated in vitro that the HCSs possessed high drug-loading capacity, lower cell toxicity, and optimal drug release profile at low pH, similar to the pH in the tumor microenvironment. The HCSs also displayed excellent immunocompatibility and could rapidly distribute themselves in the cytoplasm to escape lysosomal clearance. More importantly, the HCSs could efficiently deliver doxorubicin (a representative chemotherapeutic drug) to tumor sites, which resulted in significant inhibition of tumor growth in an esophageal xenograft cancer model. This also prolonged the circulation time and altered the biodistribution of the drug. In conclusion, this study revealed a novel drug delivery system for targeted tumor therapy. Keywords: hollow carbon spheres, drug delivery, doxorubicin, esophagus carcinoma

Diaryl formation is achieved by coupling phenols and (hetero)aryl halides under the catalysis of CuI/N,N'-bis(2-phenylphenyl) oxalamide (BPPO) or CuI/N-(2-phenylphenyl)-N'-benzyl oxalamide (PPBO) at 90 °C using DMF or MeCN as the solvent. Only 0.2-2 mol % CuI and ligand are required for complete conversion, which represents the lowest catalytic loadings for a general Cu/ligand-catalyzed diaryl ether formation.

Membrane proteins (MPs) are playing important roles in several biological processes. Screening new candidate compounds targeting MPs is important for drug discovery. However, it remains challenging to characterize the interactions between MPs and small-molecule ligands in a label-free method. In this study, a surface plasmon resonance (SPR)-based membrane protein-targeted active ingredients recognition strategy was constructed. This strategy contains two major modules: affinity detection module and ligand screening module. Through the combination of these two functional modules, it is feasible to screen small molecular ligands targeting MPs from herbal medicines. First, we have constructed high/low comparative C-X-C chemokine receptor type 4 (CXCR4)-expressed lentiviral particles (LVPs) models and characterized the expression levels. Then we immobilized LVPs on CM5 chips and detected the affinity between AMD3100 and CXCR4 by using affinity detection module. The KD of AMD3100 was 32.48 ± 3.17 nM. Furthermore, the suitability and robustness of the ligand screening module were validated by using AMD3100 as a positive compound. Subsequently, this module was applied in the screening of CXCR4 small molecular ligands from herbal medicine extracts. Senkyunolide I was screened out from Chuanxiong extract. The affinity constant between senkyunolide I and CXCR4 was 2.94 ± 0.36 μM. The Boyden chamber assay revealed that senkyunolide I could inhibit cell migration process. In conclusion, an SPR-based small molecular ligand recognition strategy combined with virus-based membrane protein stabilization method was constructed. The SPR-based membrane protein-targeted active ingredients recognition strategy will be an effective tool to screen target components from complex systems acting on MPs.

European journal of organic chemistry 2020(32), 5161-5172 (2020). doi:10.1002/ejoc.202000843, Published by Wiley-VCH Verl., Weinheim