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The interlayer electronic coupling is responsible for the electronic structure evolution from monolayer graphene to graphite and for the moiré potential in twisted bilayer graphene. Here we demonstrate that the interlayer transfer integral (hopping parameter) increases nearly 40% with a quite moderate pressure of ∼3.5 GPa, manifested by the resonance peak shift in the infrared spectra of all 2–10 L graphene. A simple model based on the Morse potential enabled us to establish the relationship between the transfer integral and pressure. Our work provides fundamental insights into the dependence of the electronic coupling on the interlayer distance.

ABSTRACTIntroductionHMGB1 is a non-histone chromatin protein released or secreted in response to tissue damage or infection. Extracellular HMGB1, as a crucial immunomodulatory factor, binds with several different receptors to innate inflammatory responses that aggravate acute and chronic liver diseases. The increased levels of HMGB1 have been reported in various liver diseases, highlighting that it represents a potential biomarker and druggable target for therapeutic development.Areas coveredThis review summarizes the current knowledge on the structure, function, and interacting receptors of HMGB1 and its significance in multiple liver diseases. The latest patented and preclinical studies of HMGB1 inhibitors (antibodies, peptides, and small molecules) for liver diseases are summarized by using the keywords ‘HMGB1,’ ‘HMGB1 antagonist, HMGB1-inhibitor,’ ‘liver disease’ in Web of Science, Google Scholar, Google Patents, and PubMed databases in the year from 2017 to 2023.Expert opinionsIn recent years, extensive research on HMGB1-dependent inflammatory signaling has discovered potent inhibitors of HMGB1 to reduce the severity of liver injury. Despite significant progress in the development of HMGB1 antagonists, few of them are approved for clinical treatment of liver-related diseases. Developing safe and effective specific inhibitors for different HMGB1 isoforms and their interaction with receptors is the focus of future research.

Atmospheric particulate matter (PMs) pollution has raised increasing public concerns, especially with the outbreak of COVID-19. The preparation of high-performance membranes for air filtration is of great significance. Herein, the biosynthetic polymer poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV) was adopted to create a hierarchical structure and biodegradable nonwoven membrane for PMs filtration through a facile directly electrospinning method. The as-prepared membranes with hierarchical structure contain abundant nanowires (5–100 nm) and microfibers (2–5 μm) with different diameter (1000–5000 nm). We have achieved realization of formation mechanisms of such bimodal micro- and nanofibers, which stem from the branching of microfiber at early stage of electrospinning. The PHBV membranes exhibit a very high PM0.3removal efficiency of 99.999% and PM2.5removal efficiency of 100% with 0.077% standard atmospheric pressure in the air flow speed of 5.3 cm/s. More importantly, the PHBV membranes can be completely disintegrated within 1 week under composted conditions, indicating the great biodegradability of PHBV membranes. Our work provides insights for the development of biodegradable, high performance air filters for pollutants, molds, bacteria, and viruses.

At present, the distribution network fault self-healing method based on deep learning in smart grid work often has problems such as low accuracy and insufficient feature extraction ability. To overcome this, the authors propose a method of fault self-healing in a distribution network based on robot patrol and deep learning in a cloud edge architecture. Firstly, the data collected by the robot fault collection system is preprocessed by using one-hot coding and normalization methods to prevent data flooding. Secondly, they propose an improved bi-directional short-term memory (BiLSTM) fault location method which combines the advantages of both BiLSTM and attention mechanism, adjusts attention weight, filters, or weakens redundant information. Finally, the I-BiLSTM network and the U-BiLSTM network are trained, respectively, and the fault section can be accurately located based on the data of each node of the robot fault collection system topology. Experimental results show that this method has achieved accuracy scores of 0.928, 0.933, 0.948, and 0.942, respectively, in four fault types, namely single-phase grounding, two-phase grounding, phase-to-phase short circuit, and three-phase short circuit, which outperform those in previous literature. The proposed method is well suited for applications in smart grid work because of its desirable fault self-healing ability.

Developing manufacturing methods that are scalable and compatible with a roll-to-roll process with low waste of material has become a pressing need to transfer organic photovoltaics (OPVs) to a viable renewable energy source. For this purpose, various spray printing methods have been proposed. Among them, electrospray (ES) is an attractive option due to its negligible material waste, tunable droplet size, and tolerance to the substrate defects and roughness. Conventional ES with a circular spray footprint often makes the droplets well separated and unlikely to merge, giving rise to “coffee rings” which cause a rough and flawed film morphology. Here, a quadrupole electrode is introduced to generate a compressing electric field that squeezes the conical ES profile into the shape of a thin sheet. The numerical simulation and experimental data of the trajectories of sprayed droplets show that the quadrupole apparatus can effectively increase the long axis to short axis ratio of the oval spray footprint and hence bring droplets closer to each other and make the merging more likely for the deposited droplets. By promoting the merging of droplets, individual coffee rings are also suppressed. Thus, the quadrupole ES offers untapped opportunities for effectively reducing voids and improving the flatness of the ES-printed active layer. The devices with a PM6:N3 active layer printed by the sheet ES exhibited the highest power conversion efficiency (PCE) of up to 15.98%, which is a noticeable improvement over that (14.85%) of counterparts fabricated by a conventional conical ES. This is the highest PCE reported for ES-printed OPVs and is one of the most efficient spray-deposited OPVs so far. In addition, the all-spray-printed devices reached a PCE of 14.55%, which is also among the most efficient all-spray-printed OPVs.

For the optimum use of soyasaponins isolated from soybean cake and to explore the potential anti-inflammatory agents from pentacyclic triterpenes as natural food supplements, microbial transformation of soyasapogenol A was carried out. Four strains of microbes, including Bacillus megateriumCGMCC 1.1741, Penicillium griseofulvumCICC 40293, Bacillus subtilisATCC 6633, and Streptomyces griseusATCC 13273, showed robust catalytic capacity to the substrate. Preparative biotransformation and column chromatographic purification led to the isolation of 10 novel and 1 reported metabolites. The structure elucidation was performed using 1D/2D NMR and HR-ESI-MS analytical method. Several novel tailoring reactions, such as allyl oxidation, C–C double bond rearrangement, hydroxylation, dehydrogenation, and glycosylation, were observed in the biotransformation. In the follow-up bioassay, most of the metabolites exhibited low cytotoxicity and potent inhibitory activity against the production of nitric oxide (NO) in RAW 264.7 cells stimulated by lipopolysaccharide. Especially compound 6(3-oxo-11α,21β,22β,24-tetrahydroxy-olean-12-ene) showed comparable activity to the positive control of quercetin with an IC50value of 16.70 μM. These findings provided an experimental approach to achieve the derivatization of natural aglycons in soybeans through microbial transformation for developing potent anti-inflammatory food supplements.

Low-grade heat (<100°C) is abundant and ubiquitous but is generally discarded owing to a lack of cost-effective recovery technologies. Emerging liquid-state thermocells (thermogalvanic cells or thermo-electrochemical cells), with advantages such as low cost, scalability, flexibility, and intrinsic high thermopower, may be a promising thermoelectric technology for low-grade heat harvesting. In the past decade, extensive efforts have been directed toward the performance enhancement of thermocells and their modules; however, they still suffer from challenges such as a low conversion efficiency and power density of single cells and stability issues (e.g., leakage, freezing or boiling of electrolytes) in devices working over a wide temperature window. From this perspective, we first summarize the advances in thermocells regarding their electrodes, electrolytes, and devices. Then, we highlight the critical challenges and determine future research directions toward more cost-effective thermocells with higher robustness, simpler fabrication, and wider applications in low-grade heat harvesting, temperature detection, cooling, and beyond.

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Aptamers are nucleic acid-based affinity reagents that are isolated via an in vitroprocess known as systematic evolution of ligands by exponential enrichment (SELEX). Despite their great potential for a wide range of analytical applications, there are relatively few high-quality small-molecule binding aptamers, especially for “challenging” targets that have low water solubility and/or limited moieties for aptamer recognition. The use of libraries containing chemically modified bases may improve the outcome of some SELEX experiments, but this approach is costly and yields inconsistent results. Here, we demonstrate that a thoughtfully designed SELEX procedure with natural DNA libraries can isolate aptamers with high affinity and specificity for challenging small molecules, including targets for which such selections have previously failed. We first isolate a DNA aptamer with nanomolar affinity and high specificity for (−)-trans-Δ9-tetrahydrocannabinol (THC), a target previously thought to be unsuitable for SELEX with natural DNA libraries. We subsequently isolate aptamers that exhibit high affinity and cross-reactivity to two other challenging targets, synthetic cannabinoids UR-144 and XLR-11, while maintaining excellent specificity against a wide range of non-target interferents. Our findings demonstrate that natural nucleic acid libraries can yield high-quality aptamers for small-molecule targets, and we outline a robust workflow for isolating other such aptamers in future selection efforts.

Erythrodiol, a typical pentacyclic triterpenic diol in olive oil and its byproduct, olive pomace, frequently appears in food additives for the prevention of cardiovascular diseases because of its antioxidation, anti-inflammatory, and antitumor activities. To develop new derivatives of erythrodiol (1), preparative biotransformations were investigated through Streptomyces griseusATCC 13273, Penicilium griseofulvumCICC 40293, and Bacillus subtilisATCC 6633, and ten new (1a–1j) and one known metabolites were isolated. Their structures were elucidated by high resolution electrospray ionization mass spectrometry (HR-ESI-MS) and one-dimensional (1D) and two-dimensional (2D) nuclear magnetic resonance (NMR) spectroscopy. Furthermore, relative to 1, most metabolites exhibited lower toxicity and more potent inhibitory activities against nitric oxide (NO) production in lipopolysaccharide (LPS)-stimulated RAW 264.7 cells. In particular, the glycosylated metabolite 1kshowed a dramatically increased inhibitory effect with an IC50value of 2.40 μM, which is even lower than that of quercetin. Thus, biotransformation of erythrodiol is a viable strategy for discovering new triterpenes as food supplements with anti-inflammatory properties.

This paper presents a new framework for efficient and accurate analysis of transient elastodynamic cracks by using the generalized finite difference method (GFDM). The method first discretizes the solution domain into a set of overlapping small subdomains, and then in each of the subdomains, the unknown functions and their derivatives are approximated by using the local Taylor series expansions and moving-least square approximation. The degree of the Taylor series used in the local subdomain is increased automatically in the regions near the crack-tips, in order to appropriately describe the local asymptotic behavior of near-tip displacement and stress fields. The path-independent J-integral and sub-domain technique are adopted to compute the dynamic stress intensity factors (SIFs) of the cracked bodies. Preliminary numerical experiments for dynamic SIFs with both uniform and variable loading conditions are given to show the efficient and accuracy of the present method for transient elastodynamic crack analysis.

14–3–3ζ protein, the key target in the regulation and control of integrin β3 outside-in signaling, is an attractive new strategy to inhibit thrombosis without affecting hemostasis. In this study, 4′-O-methylbavachalconeB (4-O-MB) in Psoraleae Fructus was identified as a 14–3–3ζ ligand with antithrombosis activity by target fishing combined with ultra-high performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UHPLC-Q-TOF-MS) analysis. The competitive inhibition analysis showed that 4-O-MB targeted 14–3–3ζ and blocked the 14–3–3ζ/integrin β3 interaction with inhibition constant (Ki) values of 9.98 ± 0.22 μM. Molecular docking and amino acid mutation experiments confirmed that 4-O-MB specifically bound to 14–3–3ζ through LSY9 and SER28 to regulate the 14–3–3ζ/integrin β3 interaction. Besides, 4-O-MB affected the integrin β3 early outside-in signal by inhibiting AKT and c-Src phosphorylation. Meanwhile, 4-O-MB could inhibit ADP-, collagen-, or thrombin-induced platelet aggregation function but had no effect on platelet adhesion to collagen-coated surfaces in vivo. Administration of 4-O-MB could significantly inhibit thrombosis formation without disturbing hemostasis in mice. These findings provide new prospects for the antithrombotic effects of Psoraleae Fructus and the potential application of 4-O-MB as lead compounds in the therapy of thrombosis by targeting 14–3–3ζ.

Paeonia suffruticosaAndr. is a well-known landscape plant worldwide and also holds significant importance in China due to its medicinal and dietary properties. Previous studies have found that Cortex Moutan (CM), the dried root bark of P. suffruticosa, showed antiplatelet and cardioprotective effects, although the underlying mechanism and active compounds remain to be revealed. In this study, protein disulfide isomerase (PDI) inhibitors in CM were identified using a ligand-fishing method combined with the UHPLC-Q-TOF-MS assay. Further, their binding sites and inhibitory activities toward PDI were validated. The antiplatelet aggregation and antithrombotic activity were investigated. The results showed that two structurally similar compounds in CM were identified as the inhibitor for PDI with IC50at 3.22 μM and 16.73 μM; among them Mudanpioside C (MC) is the most effective PDI inhibitor. Molecular docking, site-directed mutagenesis, and MST assay unequivocally demonstrated the specific binding of MC to the b′-x domain of PDI (Kd= 3.9 μM), acting as a potent PDI inhibitor by interacting with key amino acids K263, D292, and N298 within the b′-x domain. Meanwhile, MC could dose-dependently suppress collagen-induced platelet aggregation and interfere with platelet activation, adhesion, and spreading. Administration of MC can significantly inhibit thrombosis formation without disturbing hemostasis in mice. These findings present a promising perspective on the antithrombotic properties of CM and highlight the potential application of MC as lead compounds for targeting PDI in thrombosis therapy.

Background: To construct and assess a computed tomography (CT)-based deep learning radiomics nomogram (DLRN) for predicting the pathological grade of bladder cancer (BCa) preoperatively. Methods: We retrospectively enrolled 688 patients with BCa (469 in the training cohort, 219 in the external test cohort) who underwent surgical resection. We extracted handcrafted radiomics (HCR) features and deep learning (DL) features from three-phase CT images (including corticomedullary-phase [C-phase], nephrographic-phase [N-phase] and excretory-phase [E-phase]). We constructed predictive models using 11 machine learning classifiers, and we developed a DLRN by combining the radiomic signature with clinical factors. We assessed performance and clinical utility of the models with reference to the area under the curve (AUC), calibration curve, and decision curve analysis (DCA). Results: The support vector machine (SVM) classifier model based on HCR and DL combined features was the best radiomic signature, with AUC values of 0.953 and 0.943 in the training cohort and the external test cohort, respectively. The AUC values of the clinical model in the training cohort and the external test cohort were 0.752 and 0.745, respectively. DLRN performed well on both data cohorts (training cohort: AUC = 0.961; external test cohort: AUC = 0.947), and outperformed the clinical model and the optimal radiomic signature. Conclusion: The proposed CT-based DLRN showed good diagnostic capability in distinguishing between high and low grade BCa.

Colorimetric aptamer-based sensors offer a simple means of on-site or point-of-care analyte detection. However, these sensors are largely incapable of achieving naked-eye detection, because of the poor performance of the target-recognition and signal-reporting elements employed. To address this problem, we report a generalizable strategy for engineering novel multimodule split DNA constructs termed “CBSAzymes” that utilize a cooperative binding split aptamer (CBSA) as a highly target-responsive bioreceptor and a new, highly active split DNAzyme as an efficient signal reporter. CBSAzymes consist of two fragments that remain separate in the absence of target, but effectively assemble in the presence of the target to form a complex that catalyzes the oxidation of 2,2′-azino-bis(3-ethylbenzthiazoline)-6-sulfonic acid, developing a dark green color within 5 min. Such assay enables rapid, sensitive, and visual detection of small molecules, which has not been achieved with any previously reported split-aptamer-DNAzyme conjugates. In an initial demonstration, we generate a cocaine-binding CBSAzyme that enables naked-eye detection of cocaine at concentrations as low as 10 μM. Notably, CBSAzyme engineering is straightforward and generalizable. We demonstrate this by developing a methylenedioxypyrovalerone (MDPV)-binding CBSAzyme for visual detection of MDPV and 10 other synthetic cathinones at low micromolar concentrations, even in biological samples. Given that CBSAzyme-based assays are simple, label-free, rapid, robust, and instrument-free, we believe that such assays should be readily applicable for on-site visual detection of various important small molecules such as illicit drugs, medical biomarkers, and toxins in various sample matrices.

The heat transfer efficiency during the pyrolysis process is a key factor to be considered in the design of pyrolysis reactors. In this study, the average apparent heat transfer characteristics of molten plastic pyrolysis in a vertical falling film reactor were explored by experiments and numerical simulation and the apparent heat transfer coefficients were determined. In addition, the temperature distribution and the thickness of the liquid film in the reactor were predicted and the influences of pyrolysis temperatures on the average apparent heat transfer coefficients were discussed.

Thermogalvanic cells (TGC) are promising devices for directly converting heat into a stable electric output. The practical applications of TGCs are presently significantly hindered by the low voltage (millivolt level) generated from a limited temperature difference. One general strategy for improving the voltage is to alternately connect n-type and p-type redox units in series. However, the number of the possible redox species is limited, hindering the optimization of the series stacking of devices. In this work, we report a novel concept that enables p-n conversion for the iodide/triiodide (I-/I3-) redox couple induced by poly (N-isopropylacrylamide) (PNIPAM) thermo-sensitive nanogels, with the Seebeck coefficient changing from 0.71 mV K−1to − 1.91 mV K−1. The results prove that the nanogels enable selective capture of I3-at the hot side followed by the release of I3-at the cold side, yielding a concentration gradient of the free I3-, resulting in the p-n inversion. Furthermore, we designed a wearable device consisting of alternating I-/I3-and I-/I3-/nanogels unites in series that generated the open-circuit voltage of approximately 1 V and output power of approximately 9 μW by utilizing body heat. This work developed a new method for inverting the Seebeck effect of redox couples and is highly important for extending the library of possible redox species in TGCs.

Flexible Zn-based batteries with intrinsic safety, non-toxicity and biocompatibility are promising power sources for wearable electronics. To meet practical applications, they need to be durable, robust and stable. However, inevitable self-discharge and interface delamination between electrodes and hydrogel electrolytes often cause serious capacity fading or even failure for flexible Zn-based batteries. Here, inspired from nature, we report hydrogel diodes with strong and tunable interfacial adhesion by attaching oppositely charged hydrogels together. The high adhesion energy is stemmed from strong coulombic interaction and effectively dissipating energy of hydrogel matrix. The adhesion is facilely tuned by narrowing the depletion region in hydrogel diodes. Subsequently we design Hook&Loop-like Cu-Zn batteries by using hydrogel diodes as electrolytes, which are robust, stable and durable and capable for powering wearable electronics. The batteries can eliminate self-discharge and maintain their capacity by splitted into two half cells during long-term storage and easily reattaching together at working stage. Further, the batteries are ultra-stable during 2000 stretching and bending cycles because of their robust interfacial adhesion. It is believed the hydrogel-electrolyte platforms can be utilized to harness issues including interface contact, stability, durability and safety for flexible power sources.

Two new acylated β-hydroxynitrile glycosides, ribemansides A (1) and B (2), were isolated from the aerial parts of Ribes manshuricum. Their structures were elucidated by comprehensive spectroscopic analysis. Ribemansides A and B inhibited transforming growth factor β1 (TGF-β1)-induced expression of α-smooth muscle actin, fibronectin release, and changes in cell morphology in the human proximal tubular epithelial cell line (human kidney-2, HK-2). Further biological evaluation demonstrated that both 1and 2inhibit the activity of canonical transient receptor potential cation channel 6 (TRPC6), with IC50values of 24.5 and 25.6 μM, respectively. The antifibrogenic effect of these compounds appears to be mediated through TRPC6 inhibition, since the TRPC6 inhibitor, SAR7334, also suppressed TGF-β1-induced fibrogenesis in HK-2 cells.

Compound Danshen Dripping Pills (CDDPs) are a Chinese herbal medicinal preparation composed of Salviae miltiorrhizaeRadix and two other Chinese medicines, Notoginseng Radix and Borneolum. The main components of CDDPs are protocatechuic aldehyde, danshensu, salvianolic acid A, rosmarinic acid, ginsenoside Rg1, ginsenoside Rb1, l-(−)-borneol and isoborneol. The complex composition of CDDPs, which contains phenolic acids, ginseng saponins and borneols, makes quantitative analysis by traditional methods difficult. Therefore, a fast and accurate 1H qNMR method was established that can simultaneously determine the eight main components of CDDPs. The qNMR method was well validated and successfully applied in the determination of ten sample batches. The vector cosine angle method was used for further analysis of the results to evaluate the sample quality. The results indicate that the qNMR method is suitable for the quality control of CDDPs and has potential as an easy alternative for the analysis of other complex Traditional Chinese Medicines (TCMs) that require two or more traditional instruments for comprehensive quantitative analysis.

The number of Chinese oldest-old (aged 80+) is growing rapidly and some studies have shown that the health status is unequal among older persons in different regions. However, to the best of our knowledge, no study to date has analyzed health inequalities among the oldest-old in urban and rural areas in China. This study therefore aimed to examine the correlation between health inequalities among the oldest-old in urban and rural areas of China. From the 8th wave of the Chinese Longitudinal Health Longevity Survey (CLHLS), we selected 8124 oldest-old participants who met the requirements of the study. Chi-square tests were used to analyze the distribution characteristics of indicators and a logistic model was performed to determine the factors associated with different self-rated health (SRH). The Fairlie model was adopted to decompose the causes and related contributions to health inequality. Our results found that of the Chinese oldest-old, 46.57% were in good health. Urban residents reported significantly better SRH than rural residents (50.17% vs. 45.13%). Variables associated with good and poor SRH had different distribution characteristics. The logistic model suggested that marital status, alcohol consumption, and annual income were important factors underlying the SRH differences. Our decomposition analysis indicated that 76.64% of the SRH differences were caused by observational factors, and validated that the difference in SRH between urban and rural areas was significantly (P<0.05) associated with exercise status (45.44%), annual income (37.64%), social activity status (3.75%), age (-5.27%), and alcohol consumption (-2.66%). Therefore, socioeconomic status and individual lifestyle status were the main factors underlying the health inequality between urban and rural Chinese oldest-old.

Antibacterial modification is a chemical-free method to mitigate biofouling, but surface accumulation of bacteria shields antibacterial groups and presents a significant challenge in persistently preventing membrane biofouling. Herein, a great synergistic effect of electrorepulsion and quaternary ammonium (QA) inactivation on maintaining antibacterial activity against biofouling has been investigated using an electrically conductive QA membrane (eQAM), which was fabricated by polymerization of pyrrole with QA compounds. The electrokinetic force between negatively charged Escherichia coliand cathodic eQAM prevented E. colicells from reaching the membrane surface. More importantly, cathodic eQAM accelerated the detachment of cells from the eQAM surface, particularly for dead cells whose adhesion capacity was impaired by inactivation. The number of dead cells on the eQAM surface was declined by 81.2% while the number of live cells only decreased by 49.9%. Characterization of bacteria accumulation onto the membrane surface using an electrochemical quartz crystal microbalance revealed that the electrorepulsion accounted for the cell detachment rather than inactivation. In addition, QA inactivation mainly contributed to minimizing the cell adhesion capacity. Consequently, the membrane fouling was significantly declined, and the final normalized water flux was promoted higher than 20% with the synergistic effect of electrorepulsion and QA inactivation. This work provides a unique long-lasting strategy to mitigate membrane biofouling.

Spermatogonial stem cells (SSCs) are unique stem cells in adult body that can transmit genetic information to the next generation. They have self-renewal potential and can continuously support spermatogenesis throughout life of a male animal. However, the SSC population is extremely small, isolation and purification of the SSCs is challenging, especially for livestock animals. It has been confirmed that CDH1 (cadherin-1, also known as E-cadherin) can be expressed in undifferentiated SSCs of mouse and rats, but it has not been verified in sheep. Here, CDH1 was found as a novel surface marker for sheep SSCs. In this paper, sheep anti-CDH1 polyclonal antibodies were prepared and its activity was checked. Using the obtained antibodies and immunohistochemistry analysis, we confirmed that CDH1 can be expressed by SSCs in sheep testis.

Emerging thermocells have the commercialized potential for directly harvesting low-grade heat. Although a huge progress in p-type thermocells, their n-type counterpart has seriously lagged, becoming a major bottleneck for practical utilization of their integrated devices. Here, we developed a novel Cu-based thermosensitive crystallization and 3D multi-structured electrodes to synergistically boost the thermodynamic and kinetic characteristics of the n-type thermocell. As a result, the optimized Cu/Cu2+-based system achieved an exceptionally high value for the Seebeck coefficient (1.66 mV K–1) and the power density (3.5 W m–2), accompanied with a much competitive cost-performance metric (~$3.28 W–1), all of which were superior to the p-type benchmark. Furthermore, a high-performance p-n junction of thermocells was demonstrated with a 14.5 times enhancement of output, paving the way for advancing the integrated devices.

Tissue factor (TF), the primary initiator of the coagulation cascade, plays a critical role in hemostasis and thrombosis, and inhibition of TF activity appears to be an attractive target for the treatment of cardiovascular diseases. However, few selective small-molecule inhibitors of TF are available, and the present assays for measuring TF activity are relatively expensive and complex. The authors present a simple and high-throughput chromogenic assay for screening TF inhibitors based on using commercial human prothrombin complex instead of purified coagulation factors, reducing the dosage, and performing with a one-stage procedure. In the optimized assay, <45 µL cell lysates was incubated with Tris-CaCl2buffer (pH 7.3) containing human prothrombin complex at 37°C for 15 min in 96-well or 384-well plates. Tris-EDTA buffer (pH 8.4) containing chromogenic substrate Xa was then added and the absorbance measured at 405 nm. This simplified assay was more sensitive or precise than some reported methods for TF procoagulant activities. Two known active compounds (curcumin and simvastatin) inhibiting TF activity were tested by the simplified assay to validate the screening method. Furthermore, berberine and cryptotanshinone suppressed TF activity induced by lipopolysaccharides in human monocytes by this assay and might be promising new TF inhibitors.

Our previous results suggested that ruscogenin inhibited tumor necrosis factorα(TNF-α)–induced leukocyte adhesion, which correlated with its suppression of intercellular adhesion molecule-1 (ICAM-1) expression in endothelial cells. In the present studies, we further examined its effects on the main signaling pathways involved in upregulation of ICAM-1 induced by TNF-αin human umbilical vein endothelial cells (HUVECs). The results showed that ruscogenin significantly suppressed p65 phosphorylation, IκB-αphosphorylation and degradation, and inhibited IκB kinaseα(IKKα) and IKKβactivation induced by TNF-α. However, it exerted weak effects on TNF-α–induced phosphorylations of p38, JNK, ERK1/2, and Akt. Overall, our results indicated that downregulation of ICAM-1 expression by ruscogenin in HUVECs might be mediated by nuclear factor-κB (NF-κB), but not by mitogen-activated protein kinase (MAPK) and Akt signaling pathways.

Scalable and roll-to-roll compatible processing methods have become pressing needs to transfer organic solar cells (OSCs) to realistic energy sources. Herein a new fabrication method of flexible microcomb printing is proposed. The microcomb is based on a PET sheet micromachined into comb teeth by a laser marker. A computational fluid mechanics simulation shows that the fluid flow around the microcomb teeth induces high shear as well as extensional strain rates, which enhance the molecular alignment and lateral mass transport. The PTQ10:Y6-BO OSCs printed by the flexible microcomb demonstrate a substantially increased degree of crystallinity and phase separation with a suitable domain size. Devices printed by the flexible microcomb in air achieve PCEs of up to 15.93%, higher than those of control devices spin-coated in the N2glovebox. The flexibility of the PET film makes the microcomb teeth contact directly with the substrate without a suspended liquid meniscus, thus facilitating printing on soft or curved substrates. Printing of flexible OSCs and large-area devices are demonstrated. The flexible OSCs exhibit PCEs of up to 13.62%, which is the highest for flexible OSCs made by scalable printing techniques to date. These results make flexible microcomb printing a feasible and promising strategy toward the manufacture of efficient OSCs.

We examined the effects of ruscogenin glycoside (Lm‐3), isolated from Liriope muscari, on lymphocyte adhesion to extracellular matrix. Adhesion of Jurkat cells activated by anti‐CD3 to type I collagen was inhibited by Lm‐3 in a concentration‐ and time‐dependent manner. Lm‐3 also inhibited the cell attachment to fibronectin and laminin. However, the saponin did not influence anti‐CD3‐induced cell proliferation and Mn2+‐induced adhesion. Protein kinase C activator, phorbol 12, 13‐dibutyrate, significantly enhanced, while its inhibitor, chlorpromazine, almost completely blocked, the adhesion of anti‐CD3‐activated Jurkat cells to collagen. Against phorbol 12,13‐dibutyrate‐activated Jurkat cells, Lm‐3 treatment, either before or after activation, significantly inhibited the cell adhesion to collagen. Lm‐3 also inhibited the adhesion activated by both anti‐CD3 and phorbol 12,13‐dibutyrate. Similar inhibition by Lm‐3 of the phorbol 12,13‐dibutyrate‐induced adhesion to collagen was also observed in lymphocytes freshly isolated from mice with contact dermatitis. Furthermore, Lm‐3 significantly decreased the leucocyte accumulation in an animal model of experimental pleurisy. These results suggest that the blockade of lymphocyte adhesion to extracellular matrix through interference with the protein kinase C pathway may be one of the mechanisms by which Lm‐3 exerts anti‐inflammatory activity.

We examined the effects of ruscogenin glycoside (Lm-3), isolated from Liriope muscari, on lymphocyte adhesion to extracellular matrix. Adhesion of Jurkat cells activated by anti-CD3 to type I collagen was inhibited by Lm-3 in a concentration- and time-dependent manner. Lm-3 also inhibited the cell attachment to fibronectin and laminin. However, the saponin did not influence anti-CD3-induced cell proliferation and Mn2+-induced adhesion. Protein kinase C activator, phorbol 12, 13-dibutyrate, significantly enhanced, while its inhibitor, chlorpromazine, almost completely blocked, the adhesion of anti-CD3-activated Jurkat cells to collagen. Against phorbol 12,13-dibutyrate-activated Jurkat cells, Lm-3 treatment, either before or after activation, significantly inhibited the cell adhesion to collagen. Lm-3 also inhibited the adhesion activated by both anti-CD3 and phorbol 12,13-dibutyrate. Similar inhibition by Lm-3 of the phorbol 12,13-dibutyrate-induced adhesion to collagen was also observed in lymphocytes freshly isolated from mice with contact dermatitis. Furthermore, Lm-3 significantly decreased the leucocyte accumulation in an animal model of experimental pleurisy. These results suggest that the blockade of lymphocyte adhesion to extracellular matrix through interference with the protein kinase C pathway may be one of the mechanisms by which Lm-3 exerts anti-inflammatory activity.

The effects of ruscogenin 1-O-[β-d-glucopyranosyl(1 → 2)] [β-d-xylopyranosyl(1 → 3)]-β-d-fucopyranoside (Lm-3) and its aglycone, ruscogenin, on liver injury induced in mice by delayed-type hypersensitivity to picryl chloride have been investigated. Lm-3 and ruscogenin significantly decreased liver injury when given during the effector phase of the delayed-type hypersensitivity reaction. The pretreatment of nonparenchymal cells, but not hepatocytes, with Lm-3 or ruscogenin in-vitro caused a concentration- and time-dependent inhibition against the damage. Lm-3 showed a stronger inhibition against the damage than ruscogenin (IC50: Lm-3 6.3 times 10−10m, ruscogenin 3.9 times 10−7m). However, neither Lm-3 nor ruscogenin blocked the hepatotoxic potential of CCl4, when used to pretreat hepatocytes. Moreover, Lm-3 and ruscogenin inhibited concanavalin A-induced lymphocyte proliferation only at high concentrations. These results suggested that Lm-3 and ruscogenin improved the immunological liver injury by selectively causing dysfunction of the liver-infiltrating cells rather than by protecting hepatocyte membranes. Such characteristics would be significant for treating immunologically related liver diseases as well as for developing new drugs.

The effects of ruscogenin 1‐O‐[β‐d‐glucopyranosyl(1 → 2)] [β‐d‐xylopyranosyl(1 → 3)]‐β‐d‐fucopyranoside (Lm‐3) and its aglycone, ruscogenin, on liver injury induced in mice by delayed‐type hypersensitivity to picryl chloride have been investigated. Lm‐3 and ruscogenin significantly decreased liver injury when given during the effector phase of the delayed‐type hypersensitivity reaction. The pretreatment of nonparenchymal cells, but not hepatocytes, with Lm‐3 or ruscogenin in‐vitro caused a concentration‐ and time‐dependent inhibition against the damage. Lm‐3 showed a stronger inhibition against the damage than ruscogenin (IC50: Lm‐3 6.3 times 10−10m, ruscogenin 3.9 times 10−7m). However, neither Lm‐3 nor ruscogenin blocked the hepatotoxic potential of CCl4, when used to pretreat hepatocytes. Moreover, Lm‐3 and ruscogenin inhibited concanavalin A‐induced lymphocyte proliferation only at high concentrations. These results suggested that Lm‐3 and ruscogenin improved the immunological liver injury by selectively causing dysfunction of the liver‐infiltrating cells rather than by protecting hepatocyte membranes. Such characteristics would be significant for treating immunologically related liver diseases as well as for developing new drugs.

Immunohistochemical staining is the important method for the identification of protein expression in mammal ovaries, in particular in the follicles with the potential to develop into cumulus-oocyte complexes (COCs), which are able to support oocyte maturation regardless of in vivo or in vitro. Here, we reported an advanced immunohistochemical method based on an artificial structure gathering multiple COCs by paraffin embedding for rapid and highly sensitive detection of co-expressed proteins in ovine COCs rather than ovaries. Compared with the conventional immunohistochemistry on ovine ovaries, the advanced COC paraffin sectioning technique showed the better immunostaining effect and featured the higher generation rate for COCs, the distincter cumulus layers, and the more simplified procedures. These results indicate that the COC paraffin sectioning technique is highly effectively applied for identification of protein expression in ovine COC.

Ginsenoside Rb1, a bioactive component isolated from the Panax ginseng, acts as a remedy to prevent myocardial injury. However, it is obscure whether the cardioprotective functions of Rb1 are related to the regulation of endogenous metabolites, and its potential molecular mechanism still needs further clarification, especially from a comprehensive metabolomics profiling perspective.

Two new C27-steroidal glycosides were isolated from the fibrous roots of Ophiopogon japonicus. The spectral analysis and chemical evidence revealed their chemical structures to be (25R)-spirost-5,14-dien-3β-yl-O-α-l-rhamnopyranosyl-(1→2)-β-d-xylopyranosyl-(1→4)-β-d-glucopyranoside (1) and ophiogenin 3-O-β-d-glucopyranoside (2).

Saponins have significant bioactivities in treating cardiovascular disease. Whereas there is a lack of in-depth knowledge about how saponins prevent cardiovascular disease. Tissue factor (TF) is the major initiator of the coagulation cascade and plays an important role in hemostasis and thrombosis. However structure–activity relationships (SARs) of saponins inhibiting TF activity have not been discussed in detail at present. To further clarify the relationships between saponins and TF, in this study, 10 representative saponins were selected to study the inhibitory effect on TF procoagulant activity of monocytes by an improved chromogenic substrate method, and the possible SARs were preliminarily analyzed. Furthermore, molecular docking analysis suggested that 4 representative saponins had a good affinity with TF/FVIIa. In addition, a representative saponin, ruscogenin, decreased both messenger ribonucleic acid and protein levels of TF in human monocytes partly due to its downregulation of nuclear factor kappa-light-chain-enhancer of activated B cells and c-Jun N-terminal kinase pathways. In conclusion, this study provides further explanation for the cardiovascular protection of saponins, and the analysis of SARs between inhibiting TF activity and saponins will be helpful to explore the therapeutic TF inhibitors.

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.