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Macrophage infiltration and activation is a critical step during acute colitis. Redox-mediated activation of NLRP3 inflammasomes in macrophages plays a critical role in mediating colonic inflammatory responses. Rhein isolated from the rhizome of rhubarb exhibits anti-inflammatory effects in various diseases. However, its role in regulating acute colonic inflammation is unexplored. Here, we investigated the protective mechanisms of rhein during acute gut inflammation and its regulation of macrophage activation.Inhibitory effects of rhein on NLRP3 inflammasomes were evaluated in activated macrophages and a mouse model of colitis. Expression of inflammatory mediators, inflammasome complex and redox-related signalling were analysed by ELISA, Western blots, immunofluorescence staining, and qRT-PCR. The phenotype of macrophages was assessed by flow cytometry. Colonic inflammation was evaluated by histological analysis.Rhein significantly decreased IL-1β secretion via NLRP3 inflammasomes by disturbing their assembly in macrophages. Rhein also activated the Nrf2-HO1-NQO1 pathway and inhibited expression of Nox2 subunits and translocation to regulate redox balance. Moreover, rhein attenuated inflammatory responses by mediating macrophage polarization from M1 to M2 phenotype. NF-κB, AP-1, and MAPK signalling were also involved in improving inflammatory conditions by rhein. In mice with acute intestinal inflammation, rhein treatment attenuated clinical features and reduced macrophage infiltration into damaged tissue to alleviate colonic inflammation.Rhein regulated redox-mediated NLRP3 inflammasome activation to protect against acute colitis, by interfering with macrophage accumulation and polarization. These findings provide a promising strategy of novel compounds for regulating mucosal inflammation in gastrointestinal disorders.

The organic field-effect transistors (OFETs) have developed rapidly in recent years. However, compared with the p-type OFETs, the n-type devices always show poorer performance due to their hard electron injection and low stability. It is necessary to further improve the charge injection properties of n-type OFETs. In this work, indium (In) layers, as an interlayer above contacts, were adopted for electron injection improvement in the n-type poly((N, $\text{N}^{\prime }$ -bis(2-octyldodecyl)-1,4,5,8-naphthalenedicarboximide-2,6-diyl)-alt-5, $5^{\prime }$ -(2, $2^{\prime }$ -bithiophene)) (N2200) OFETs. The injection barrier, such as Schottky barrier, at the metal/semiconductor interface was effectively weakened with the In interlayers thickness ( ${T}_{In}$ ) increasing from 0 to 6 nm. The mechanism of electron injection changed from thermionic emission to tunneling, as the ${T}_{In}$ reaching 6 nm. It results in a marked improvement in electrical properties for N2200 OFETs. The mobility increased from 0.09 to 0.29 cm ${}^{2}\cdot \text{V}^{-1}\cdot \text{s}^{-1}$ while the subthreshold swing decreased from 2.7 to 0.8 $\text{V}\cdot $ dec−1 with the ${T}_{In}$ . This work provides an efficient approach for the electron injection improvement in n-type OFETs.

In general, self-powered photodetectors are tedious and costly. Here, high-performance self-powered visible photodetectors based on MAPbI3 films were fabricated by using asymmetric Au electrodes. For this construction of photodetector, the illumination passing through the translucent MAPbI3 film can reduce the Schottky barrier between the lower electrode and perovskite, and the Au particles doping into the MAPbI3 at the contact areas between the upper electrode and films can also change the Schottky barrier, which leads to the formation of built-in potential. Without an applied bias, the photodetectors exhibit an ultralow dark current of $\sim 3$ pA. At the power intensity of 2.92 mW/cm2 under 635 nm illumination, a decent responsivity of 10 mAW−1, a high specific detectivity of $3.3 \times 10^{11}$ cmHz1/2W−1, and an external quantum efficiency of 2.1% are obtained. The on/off ratio reaches 104 and the response speed is less than 50 ms. Our results pave a new design concept to form a self-powered perovskite-based photodetector.

Inflammatory bowel disease (IBD) is a chronic intestinal disease with painful clinical manifestations and high risks of cancerization. With no curative therapy for IBD at present, the development of effective therapeutics is highly advocated. Drug delivery systems have been extensively studied to transmit therapeutics to inflamed colon sites through the enhanced permeability and retention (EPR) effect caused by the inflammation. However, the drug still could not achieve effective concentration value that merely utilized on EPR effect and display better therapeutic efficacy in the inflamed region because of nontargeted drug release. Substantial researches have shown that some specific receptors and cell adhesion molecules highly expresses on the surface of colonic endothelial and/or immune cells when IBD occurs, ligand-modified drug delivery systems targeting such receptors and cell adhesion molecules can specifically deliver drug into inflamed sites and obtain great curative effects. This review introduces the overexpressed receptors and cell adhesion molecules in inflamed colon sites and retrospects the drug delivery systems functionalized by related ligands. Finally, challenges and future directions in this field are presented to advance the development of the receptor-mediated targeted drug delivery systems for the therapy of IBD., Graphical abstract When inflammatory bowel disease occurs, some specific receptors and cell adhesion molecules, like mannose receptor, CD98, CD44 and ICAM-1, are overexpressed on the colonic epithelial cells and/or immune cells. Drug delivery systems superficially modified with related ligands can specifically bind to receptors on inflamed cells and deliver drug into target area.Image 1

Ulcerative colitis (UC) is an autoimmune disease afflicting an increasing number of patients and increasing demands towards the development of efficacious and safe drugs. Recently, with increasing interest in alternative medicines, natural resources have become a hotspot for drug discovery against UC. In addition to being consumed as a food and spice, ginger is also widely used as a well-recognized gastrointestinal herbal medicine. With a long history in the treatment of digestive disorders, the potential of ginger in alleviating UC has been documented in several experimental models and clinical trials. However, as a major active constituent of ginger, ginger polysaccharides (GP) and its effect on UC has yet to be reported. In this study, GP was firstly separated and characterized. In a dextran sulfate sodium (DSS)-induced colitis mouse model, GP alleviated UC symptoms by inhibiting pro-inflammatory cytokines levels to regulate intestinal inflammation, repairing the intestinal barrier as indicated by occludin-1 and ZO-1, as well as regulating gut microbiota. Taking these results together, we believe GP could be an innovative option in developing functional foods or therapeutic agents for UC management.

Van der Waals layered indium selenide (InSe) is an emerging star of the 2D semiconducting materials because of its excellent fundamental properties, such as ultrahigh carrier mobility, layer-tunable bandgap, large elastic deformability, and rich polytypes. In addition, 2D layered indium selenide has demonstrated outstanding device performance including photodetector, field-effect transistor, memory and synapse, mechanical and gas sensor, which has offered a new chance to next-generation electrical and optoelectronic devices. This review presents a comprehensive summary of recent progress in 2D layered indium selenide. The novel fundamental properties and synthetic methods are summarized. Also, the indium selenide-based state-of-the-art electronic/optoelectronic devices, such as a functional field-effect transistor, photodetector, and mechanical and gas sensors are systematically summarized. The techniques to enhance the performances of devices are also discussed. Finally, a brief discussion on the challenges and future opportunities as a guideline for this field is provided. This work was financially supported by the Natural Science Foundation of Shanghai (Grant No. 19ZR1473400), the NSAF Foundation of China (Grant No. U1830130), and the young scientist project of MOE innovation platform (Fudan University).

Ulcerative colitis (UC) has affected an increasing number of people globally, with still limited clinical success. Huanglian Decoction (HLD) is a famous classical prescription documented for alleviating gastrointestinal disorders with unexplored therapeutic effects and mechanisms.This study aimed to investigate the therapeutic effect and underlying mechanism of HLD in dextran sodium sulfate (DSS)-induced colitis mice.The efficacy and safety of HLD were evaluated in a well-established DSS-induced colitis mice model. Disease progression was monitored via clinical symptoms, histopathological examination, biochemical assays, and epithelial barrier function evaluation.HLD alleviated DSS-induced colitis symptoms, reversed colon length reduction, reduced histological injury, downregulated the level of pro-inflammatory cytokines, maintained the tight distribution of ZO-1/occludin-1 and the normal level of β-catenin, concurrent with apoptosis reduction in the colonic epithelium. After HLD treatment, the DSS-induced gut dysbiosis was modulated, and the gut microbiota achieved a new equilibrium state.This study demonstrates that HLD may present a potential remedy for UC treatment, providing evidence for further developing Chinese classical prescriptions.

The simulation of human brain neurons by synaptic devices could be an effective strategy to break through the notorious "von Neumann Bottleneck" and "Memory Wall". Herein, opto-electronic synapses based on layered hafnium disulfide (HfS

Dachuanxiong Formula (DCXF) is a classical Chinese medicine prescription and is composed of dried rhizomes from Ligusticum striatum DC. (Chuanxiong Rhizoma) and Gastrodia elata Bl. (Gastrodiae Rhizoma) at the ratio of 4:1 (w/w). It has been used as Chinese medicine prescription for thousands of years. DCXF is used traditionally to treat many diseases, including migraine, atherosclerosis and ischemic stroke.This study aimed to investigate the effects of DCXF on pain response in migraine mice, and the underlying mechanisms using proteomics and bioinformatics analyses.DCXF extract was prepared by mixing Chuanxiong Rhizoma and Gastrodiae Rhizoma at a mass ratio of 4:1 (w/w). After extraction, the extract was filtered prior to high performance liquid chromatography (HPLC) analysis. Nitroglycerin (NTG) was used to establish a mouse migraine model, and a behaviour study was conducted by hot plate test. In addition, proteomics and bioinformatics studies were conducted to investigate the mechanisms of DCXF-mediating anti-migraine treatment.Our results showed that there were significant differences in the latencies between NTG-treated and DCXF low dose- and high doses-treated groups at 30 min after NTG injection, this suggested that DCXF could ameliorate pain response in migraine mice. Besides, the plasma levels of endothelin-1 were also measured. NTG group significantly enhanced the endothelin-1 level compared to the control group. In contrast, DCXF low dose and high dose groups significantly reduced this level compared to NTG group. In addition, the underlying mechanisms were also investigated. Our results demonstrated that the anti-migraine treatment of DCXF was highly associated with fatty acid synthesis, suggesting that DCXF ameliorated pain response through reducing endothelin-1 level and regulating fatty acid synthesis.The present study revealed the anti-migraine effect of DCXF in migraine mice and provided insights into the mechanisms of DCXF-mediating anti-migraine treatment.

Chemotherapy outcomes for the treatment of glioma remains unsatisfactory due to the inefficient drug transport across the blood—brain barrier (BBB) and insufficient drug accumulation in the tumor region. Although many approaches, including various nanosystems, have been developed to promote the distribution of chemotherapeutics in the brain tumor, the delivery efficiency and the possible damage to the normal brain function still greatly restrict the clinical application of the nanocarriers. Therefore, it is urgent and necessary to discover more safe and effective BBB penetration and glioma-targeting strategies. In the present study, menthol, one of the strongest BBB penetration enhancers screened from traditional Chinese medicine, was conjugated to casein, a natural food protein with brain targeting capability. Then the conjugate self-assembled into the nanoparticles to load anti-cancer drugs. The nanoparticles were characterized to have appropriate size, spheroid shape and high loading drug capacity. Tumor spheroid penetration experiments demonstrated that penetration ability of menthol-modified casein nanoparticles (M-CA-NP) into the tumor were much deeper than that of unmodified nanoparticles. In vivo imaging further verified that M-CA-NPs exhibited higher brain tumor distribution than unmodified nanoparticles. The median survival time of glioma-bearing mice treated with HCPT-M-CA-NPs was significantly prolonged than those treated with free HCPT or HCPT-CA-NPs. HE staining of the organs indicated the safety of the nanoparticles. Therefore, the study combined the advantages of traditional Chinese medicine strategy with modern delivery technology for brain targeting, and provide a safe and effective approach for glioma therapy., Graphical abstract Chemotherapy for the treatment of glioma remains to be unsatisfactory due to inefficient drug transport across the blood—brain barrier and insufficient accumulation in the tumor region. The prepared menthol-modified casein nanoparticles combined the advantages of traditional Chinese medicine strategy with modern drug delivery technology for brain tumor.fx1

The simulation of human brain neurons by synaptic devices could be an effective strategy to break through the notorious "von Neumann Bottleneck" and "Memory Wall". Herein, opto-electronic synapses based on layered hafnium disulfide (HfS2) transistors have been investigated. The basic functions of biological synapses are realized and optimized by modifying pulsed light conditions. Furthermore, 2 × 2 pixel imaging chips have also been developed. Two-pixel visual information is illuminated on diagonal pixels of the imaging array by applying light pulses (λ = 405 nm) with different pulse frequencies, mimicking short-term memory and long-term memory characteristics of the human vision system. In addition, an optically/electrically driven neuromorphic computation is demonstrated by machine learning to classify hand-written numbers with an accuracy of about 88.5%. This work will be an important step toward an artificial neural network comprising neuromorphic vision sensing and training functions.

Reactive oxygen species (ROS) are chemically reactive species that are produced in cellular aerobic metabolism. They mainly include superoxide anion, hydrogen peroxide, hydroxyl radicals, singlet oxygen, ozone, and nitric oxide and are implicated in many physiological and pathological processes. Bilirubin, a cardinal pigment in the bile, has been increasingly investigated to treat cancer, diabetes, ischemia-reperfusion injury, asthma, and inflammatory bowel diseases (IBD). Indeed, bilirubin has been shown to eliminate ROS production, so it is now considered as a promising therapeutic agent for ROS-mediated diseases and can be used for the development of antioxidative nanomedicines. This review summarizes the current knowledge of the physiological mechanisms of ROS production and its role in pathological changes and focuses on discussing the antioxidative effects of bilirubin and its application in the experimental studies of nanomedicines. Previous studies have shown that bilirubin was mainly used as a responsive molecule in the microenvironment of ROS overproduction in neoplastic tissues for the development of anticancer nanodrugs; however, it could also exert powerful ROS scavenging activity in chronic inflammation and ischemia-reperfusion injury. Therefore, bilirubin, as an inartificial ROS scavenger, is expected to be used for the development of nanomedicines against more diseases due to the universality of ROS involvement in human pathological conditions.

Liposomes have been widely used for targeted drug delivery. However, nonselective distribution, low blood-brain barrier penetration, and the disadvantages of cholesterol greatly limit the application of conventional liposomes in the treatment of brain tumors. In the present study, we aimed to develop a multifunctional ginsenoside Rg3-based liposomal system (Rg3-LPs). Compared to cholesterol liposomes (C-LPs), Rg3-LPs not only significantly improved cellular uptake and penetration across glioma spheroids in vitro, but also remarkably enhanced active glioma targeting and intratumoral diffusion capability in vivo. Paclitaxel-loaded Rg3-LPs (Rg3-PTX-LPs) exhibited a substantially stronger anti-proliferation effect on C6 glioma cells than paclitaxel-loaded C-LPs and re-educated tumor-associated macrophages from the protumor M2 phenotype to the antitumor M1 phenotype in vivo. Rg3-PTX-LPs significantly prolonged median survival time of intracranial C6-bearing mice/rats by activating the immune microenvironment in glioma, facilitating T-cell immune responses with expansion of the CD8+ T-cell population, increasing the M1/M2 ratio, and decreasing regulatory T and myeloid-derived suppressor cells. Together, the results demonstrated that ginsenoside Rg3 is a good alternative for cholesterol in drug delivery liposomes and has a synergistic effect with loaded anticancer drugs. Rg3-PTX-LPs can serve as a multifunctional potential drug for the treatment of glioma.

Understanding how the temperature affects the structural and electronic properties for two-dimensional (2D) semiconductors could promote the application and development of the nanoelectronic devices. Here, temperature dependence of lattice structure for indium selenide (InSe) nanosheet and the corresponding electronic properties of 3-nm-indium-deposited InSe field-effect transistor (FET) are systematically demonstrated. Analyses of Raman spectra suggest that the difference of phonon frequency ($\Delta\omega$) for A$_{1g}^{2}$ mode is found to be 3.14 cm$^{-1}$, which is larger than that of the E$_{2g}^{1}$ mode due to the stronger electron-phonon coupling for A$_{1g}^{2}$ mode. The device performance based on indium-deposited InSe is systematically explained by the Kelvin probe force microscopy (KPFM) and the predicted energy band structure. Furthermore, FETs based on temperature and the thickness variable InSe flakes as the applicable devices are designed. Our findings are fundamental importance to explain the underlying physics in intrinsic InSe transistor and improve further applications.

The unsatisfactory therapeutic outcome for glioma is mainly due to the poor blood-brain barrier (BBB) permeability and inefficient accumulation in the glioma area of chemotherapeutic agents. The existing drug delivery strategies can increase drug transport to the brain but are restricted by side effects and/or poor delivery efficiency. In this study, potent brain penetration enhancers were screened from the active components of aromatic resuscitation drugs used in traditional Chinese medicine. A novel glioma-targeting system based on enhancer-modified albumin nanoparticles was developed to safely and efficiently deliver drugs to the glioma regions in the brain. The nanoparticles improved the transport of nanoparticles across brain capillary endothelial cell (BCEC) monolayer by increasing endocytosis in endothelial cells and causing BBB disruption. In vivo imaging studies demonstrated that the systems could enter the brain and subsequently accumulate in glioma cells with a much higher targeting efficiency than that of transferrin-modified albumin nanoparticles. Of note, the nanoparticles could be captured and penetrate through endothelial cells fenestrae in pineal gland, which is suggestive of an effective way to deliver a nanosystem to the brain by bypassing the BBB. The nanoparticles showed good biocompatibility and negligible cytotoxicity. The results reveal an efficient and safe strategy for brain drug delivery in glioma therapy.

Neuromorphic electronics with two-dimensional van der Waals materials meet the ever-increasing demands of both the semiconductor industry and biological engineering, such as miniaturization, structure flexibility, multifunctionality, and low power consumption. However, the majority of reported electronic devices achieve multifarious memory storage states or synaptic plasticity through regulation of an electrical or an optical signal. Herein, we propose an innovative touch-modulated device based on an indium selenide/hexagonal boron nitride/graphene van der Waals heterostructure coupled with a triboelectric nanogenerator. The device is prepared utilizing a simple copper grid shadow mask instead of the expensive and cumbersome electron beam lithography process, exhibits high mobility of 829 cm2 V−1 s−1, low voltage, and low power consumption. Nonvolatile memory with self-writing power, durability and multibit data storage is achieved through mechanical modulation without an additional gate-voltage supply. Moreover, by adjusting the distance between the two friction layers, essential synaptic plasticity, including short-term and long-term potentiation/depression and paired-pulse facilitation/depression, are successfully imitated in the device. Most importantly, we achieve ultralow power consumption of 165 aJ in tribotronic synapses owing to the ultra-high mobility of InSe. Our tribotronic synapse with self-writing power has great potential to simulate the low-power-consuming neuromorphic bioelectronic devices with multiple functions and lays the foundation for future advanced neuromorphic systems and artificial intelligence.

Exploiting cells as vehicles combined with nanoparticles combined with therapy has attracted increasing attention in the world recently. Red blood cells, leukocytes and stem cells have been used for tumor immunotherapy, tissue regeneration and inflammatory disorders, and it is known that neutrophils can accumulate in brain lesions in many brain diseases including depression. N-Acetyl Pro–Gly–Pro (PGP) peptide shows high specific binding affinity to neutrophils through the CXCR2 receptor. In this study, PGP was used to modify baicalein-loaded solid lipid nanoparticles (PGP-SLNs) to facilitate binding to neutrophils in vivo. Brain-targeted delivery to the basolateral amygdala (BLA) was demonstrated by enhanced concentration of baicalein in the BLA. An enhanced anti-depressant effect was observed in vitro and in vivo. The mechanism involved inhibition of apoptosis and a decrease in lactate dehydrogenase release. Behavioral evaluation carried out with rats demonstrated that anti-depression outcomes were achieved. The results indicate that PGP-SLNs decrease immobility time, increase swimming time and climbing time and attenuate locomotion in olfactory-bulbectomized (OB) rats. In conclusion, PGP modification is a strategy for targeting the brain with a cell–nanoparticle delivery system for depression therapy., Graphical abstract PGP was used to modify solid lipid nanoparticles (PGP-SLNs) loaded with baicalein for binding to neutrophils in vivo. Cell–nanoparticle brain-targeted delivery to the basolateral amygdala and increased anti-depressant effect was obtained in vitro and in vivo. The mechanism involved inhibition of apoptosis induced by mitochondria and reduction of lactate dehydrogenase release.fx1

Current chemotherapeutics for glioma are not sufficiently effective due to their low tolerance and poor blood–brain barrier (BBB) permeability. Energy restriction based on co-delivery of albendazole (Abz) and nano-silver has been proven to suppress tumor growth without adverse effects. Accordingly, menthol was conjugated to BSA (MeB) to overcome the BBB-permeability issue. In this study, Abz-loaded MeB-silver nanoparticles (MBS-Abz) were developed by self-assembly of MeB, albendazole and nano silver for glioma targeting therapy. The nanoparticle entered the brain across the BBB and specifically accumulated in the glioma region. MeB delivered the nanoparticles across the brain capillary endothelial cell monolayer by promoting internalization and BBB disruption. MBS-Abz hindered ATP generation via the inhibition of glycolytic and mitochondrial pathways both in vitro and in vivo. The anti-glioma mechanisms of energy restriction were related to the cytotoxicity, proliferation inhibition, cell cycle arrest, and apoptosis induced by ATP exhaustion, and the effects of MBS-Abz were significantly better than those induced by monotherapy nanoparticles or unmodified nanoparticles. These results demonstrated that by combining the energy restriction effect of albendazole and nano silver, as well as the BBB penetration ability of menthol, MBS-Abz achieves superior anti-glioma efficacy and can be an effective strategy for glioma therapy. Nanoparticles that can deliver drugs to cancerous cells in the brain have been developed by researchers in China. Gliomas are tumors that can form in the brain, the spine or elsewhere in the central nervous system. Combining silver nanoparticles with a drug called albendazole is known to suppress the growth of these cancerous cells by inhibiting energy metabolism. However, the membrane that separates the brain from the blood prevents injected drugs from reaching the gliomas. Jianming Liang from Fudan University, Shanghai, and co-workers used menthol-modified bovine serum albumin as a drug delivery system, because of its ability to disrupt the the brain–blood barrier. The menthol-modified albumin carried both albendazole and silver nanoparticles through the barrier in mice and accumulated at the glioma without any noticeable toxic effects elsewhere. This study examined the efficiency of co-delivering albendazole (Abz) and silver nanoparticles in suppressing glioma growth. For this purpose, we conjugated menthol, shown to relax the BBB, to bovine serum albumin loaded the complex with Abz and silver nanoparticles. The nanoparticles efficiently crossed the BBB, and specifically accumulated in glioma regions, where they induced glioma cell apoptosis. This effect was mediated by BBB disruption and internalization, and further by blocking ATP generation via inhibition of the glycolytic and mitochondrial pathways. The anti-glioma mechanisms of the nanoparticles involved cytotoxicity, proliferation inhibition, cell cycle arrest, and apoptosis induced by ATP depletion.

Ethnopharmacological relevance Astragali Radix (AR, Huangqi in Chinese), the dried root of Astragalus membranaceus (Fisch.) Bge. var. mongholicus (Bge.) Hsiao or A. membranaceus (Fisch.) Bge., possesses diverse therapeutic effects against fatigue, dyspepsia, diarrhea, heart diseases, hepatitis, and anemia. In recent years, increasing evidence has indicated the multiple immunomodulatory activities of AR in preclinical and clinical studies. Aim of the review This review attempts to elaborate the immunomodulatory effects of AR and its potential application in the treatment of immune related diseases. Materials and methods A comprehensive literature search AR was carried out using multiple internationally recognized databases (including Web of Science, Google Scholar, PubMed, ScienceDirect, Wiley, ACS, Springer, Taylor & Francis, and CNKI). Results The immunomodulatory effects of AR are closely attributed to its active constituents such as polysaccharides, saponins, and flavonoids. We also demonstrate that AR can be used as a potential therapeutic intervention for immune related diseases through regulating immune organs, mucosal immune, and immune system (innate immunity and acquired immunity). Conclusion AR promotes the development of immune organs, enhances mucosal immune function, increases the quantity and phagocytic capacity of innate immunity, promotes the maturation and differentiation of acquired immunity cells, and improves the expression of antibodies in acquired immunity. We believe that AR has a broad research space in the adjuvant treatment of immune related diseases, which could be a breakthrough point to improve the application value of AR.