Melanin Nanoparticle-Modified Probiotics for Targeted Synergistic Therapy of Ulcerative Colitis.

Ulcerative colitis (UC) is a recurrent chronic mucosal inflammation disease whose most significant pathological characteristics are intestinal inflammation and damaged mucosal barrier induced by reactive oxygen/nitrogen species, abnormal immune microenvironment, and intestinal microecological imbalance. Oral probiotics are a living therapy for intestinal diseases, but their clinical application is hindered by poor bacterial biological activity and insufficient intestinal retention. Here, we developed a targeted oral formulation, functionalized probiotic Lf@MPB, with Lactobacillus fermentum (Lf) as the core and modified melanin nanoparticles (MNPs) on its surface through a click reaction of tricarboxyphenylboronic acid for synergistic therapy of UC. In vitro experiments showed that Lf@MPB not only possessed strong free radical scavenging ability, reduced cellular mitochondrial polarization, and inhibited apoptosis but also significantly enhanced the viability of Lf probiotics in simulated gastrointestinal fluid. Fluorescence imaging in vivo revealed the high accumulation of Lf@MPB at the site of intestinal inflammation in dextran sulfate sodium-induced UC mice. Moreover, in vivo results demonstrated that Lf@MPB effectively alleviated oxidative stress and inflammatory response and restored the intestinal barrier. In addition, 16S rRNA gene sequencing verified that Lf@MPB could increase the abundance and diversity of intestinal microbial communities and optimize microbial composition to inhibit the progression of UC. This work combines effective antioxidant and anti-inflammatory strategies with the oral administration of functionalized probiotics to provide a promising alternative for UC treatment.

Silicon-van der Waals heterointegration for CMOS-compatible logic-in-memory design.

Silicon CMOS-based computing-in-memory encounters design and power challenges, especially in logic-in-memory scenarios requiring nonvolatility and reconfigurability. Here, we report a universal design for nonvolatile reconfigurable devices featuring a 2D/3D heterointegrated configuration. By leveraging the photo-controlled charge trapping/detrapping process and the partially top-gated energy band landscape, the van der Waals heterostacking achieves polarity storage and logic reconfigurable characteristics, respectively. Precise polarity tunability, logic nonvolatility, robustness against high temperature (at 85°C), and near-ideal subthreshold swing (80 mV dec-1) can be done. A comprehensive investigation of dynamic charge fluctuations provides a holistic understanding of the origins of nonvolatile reconfigurability (a trap level of 1013 cm-2 eV-1). Furthermore, we cascade such nonvolatile reconfigurable units into a monolithic circuit layer to demonstrate logic-in-memory computing possibilities, such as high-gain (65 at Vdd = 0.5 V) logic gates. This work provides an innovative 3D heterointegration prototype for future computing-in-memory hardware.

Classical prescription Huanglian Decoction relieves ulcerative colitis via maintaining intestinal barrier integrity and modulating gut microbiota.

BACKGROUND: 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. PURPOSE: This study aimed to investigate the therapeutic effect and underlying mechanism of HLD in dextran sodium sulfate (DSS)-induced colitis mice. METHODS: 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. RESULTS: 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 ß-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. CONCLUSION: This study demonstrates that HLD may present a potential remedy for UC treatment, providing evidence for further developing Chinese classical prescriptions.

Targeted delivery of Chinese herb pair-based berberine/tannin acid self-assemblies for the treatment of ulcerative colitis.

INTRODUCTION: Ulcerative colitis (UC) is a chronic recurrent idiopathic disease characterized by damage to the colonic epithelial barrier and disruption of inflammatory homeostasis. At present, there is no curative therapy for UC, and the development of effective and low-cost therapies is strongly advocated. OBJECTIVES: Multiple lines of evidence support that tannic acid (TA) and berberine (BBR), two active ingredients derived from Chinese herb pair (Rhei Radix et Rhizoma and Coptidis Rhizoma), have promising therapeutic effects on colonic inflammation. This study aims to develop a targeted delivery system based on BBR/TA-based self-assemblies for the treatment of UC. METHODS: TA and BBR self-assemblies were optimized, and hyaluronic acid (HA) was coated to achieve targeted colon delivery via HA-cluster of differentiation 44 (CD44) interactions. The system was systematically characterized and dextran sodium sulfate (DSS)-induced mouse colitis model was further used to investigate the biodistribution behavior, effect and mechanism of the natural system. RESULTS: TA and BBR could self-assemble into stable particles (TB) and HA-coated TB (HTB) further increased cellular uptake and accumulation in inflamed colon lesions. Treatment of HTB inhibited pro-inflammatory cytokine levels, restored expression of tight junction-associated proteins and recovered gut microbiome alteration, thereby exerting anti-inflammatory effects against DSS-induced acute colitis. CONCLUSION: Our targeted strategy may provide a convenient and powerful platform for UC and reveal new modes of application of herbal combinations.

Turmeric-derived nanovesicles as novel nanobiologics for targeted therapy of ulcerative colitis.

Rationale: Ulcerative colitis (UC), a typical kind of inflammatory bowel disease (IBD), is an idiopathic chronic intestinal inflammation. Conventional therapeutic strategies mainly focus on the rebalance of pro-inflammation and anti-inflammation cytokines, whereas targeting damaged intestinal barriers, imbalanced intestinal microbiota and dysregulated mucosal immune responses in UC remain a big challenge. The objective of this study was to develop turmeric-derived nanovesicles (TNVs) for alleviation of colitis and explore the underlying mechanisms. Methods: TNVs were isolated and purified through differential centrifugation. The targeted ability was evaluated on the dextran sulfate sodium (DSS)-induced mouse model by IVIS imaging system. The anti-inflammation efficacy was studied in lipopolysaccharide (LPS)-induced macrophages and DSS-induced acute and chronic colitic mouse model. In addition, the influence of TNVs on the intestinal microbiota was investigated via 16S rRNA microbiome sequence and the condition of macrophage polarization after TNVs treatment was analyzed by flow cytometry. Results: TNVs were isolated and characterized as nano-size spheroids. The IVIS imaging experiment indicated that orally administrated TNVs could accumulate in the inflamed colon sites and exhibited superior anti-inflammatory activity both in vitro and in vivo. The 16S rRNA sequencing suggested the important role of TNVs in the regulation of gut microbiota. Further, TNVs could promote the transformation of M1 phenotype to M2 macrophages and restore the damaged intestinal epithelium barrier to exert the anti-colitis efficacy. Conclusion: Collectively, oral administration of TNVs exhibited excellent anti-inflammatory efficacy through restoring the damaged intestinal barrier, regulating the gut microbiota and reshaping the macrophage phenotype. This study sheds light on the application of natural exosome-like nanovesicles for the treatment of UC.

A polyphenol-assisted IL-10 mRNA delivery system for ulcerative colitis.

With the development of synthesis technology, modified messenger RNA (mRNA) has emerged as a novel category of therapeutic agents for a broad of diseases. However, effective intracellular delivery of mRNA remains challenging, especially for its sensitivity to enzymatic degradation. Here, we propose a polyphenol-assisted handy delivery strategy for efficient in vivo delivery of IL-10 mRNA. IL-10 mRNA binds to polyphenol ellagic acid through supramolecular binding to yield a negatively charged core, followed by complexing with linear polyetherimide and coating with bilirubin-modified hyaluronic acid to obtain a layer-by-layer nanostructure. The nanostructure specifically up-regulated the level of IL-10, effectively inhibited the expression of inflammatory factors, promoted mucosal repair, protected colonic epithelial cells against apoptosis, and exerted potent therapeutic efficacy in dextran sulfate sodium salt-induced acute and chronic murine models of colitis. The designed delivery system without systemic toxicity has the potential to facilitate the development of a promising platform for mRNA delivery in ulcerative colitis treatment.

Ginger polysaccharides relieve ulcerative colitis via maintaining intestinal barrier integrity and gut microbiota modulation.

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.

Classical prescription Dachuanxiong Formula delays nitroglycerin-induced pain response in migraine mice through reducing endothelin-1 level and regulating fatty acid biosynthesis.

ETHNOPHARMACOLOGICAL RELEVANCE: 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. AIM OF THE STUDY: This study aimed to investigate the effects of DCXF on pain response in migraine mice, and the underlying mechanisms using proteomics and bioinformatics analyses. MATERIALS AND METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Rhein regulates redox-mediated activation of NLRP3 inflammasomes in intestinal inflammation through macrophage-activated crosstalk.

BACKGROUND AND PURPOSE: 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. EXPERIMENTAL APPROACH: 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. KEY RESULTS: Rhein significantly decreased IL-1ß 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. CONCLUSION AND IMPLICATIONS: 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.

Optically Modulated HfS2-Based Synapses for Artificial Vision Systems.

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.

Receptor-mediated targeted drug delivery systems for treatment of inflammatory bowel disease: Opportunities and emerging strategies.

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.

Shikonin promotes ubiquitination and degradation of cIAP1/2-mediated apoptosis and necrosis in triple negative breast cancer cells.

BACKGROUND: Shikonin (SKO) is a natural naphthoquinone derived from Chinese herbal medicine Arnebiae Radix with high development potentials due to its anti-inflammatory and anti-tumor activities. Overwhelming evidences have indicated that SKO can induce both necrosis and apoptosis in cancer cells, while the mechanisms for triple negative breast cancer cells is still need to be disclosed. METHODS: In this study, kinds of molecular biological technologies, including flow-cytometry, Western blot, immunoprecipitation, enzyme-linked immunosorbent assay (ELISA) as well as real-time quantitative PCR (RT-qPCR), were applied for investigation on the underlying mechanisms of SKO induced necrosis and apoptosis for MDA-MB-231 cells. Inhibitors were also used for validation ofthe key signaling pathways involved in SKO triggered necrosis and apoptosis. RESULTS: We found that SKO significantly triggered necrosis and apoptosis of MDA-MB-231 cells in both a concentration- and time-dependent manner. Mechanism studies demonstrated that SKO significantly promoted the autoubiquitination levels and facilitated the proteasome dependent degradation of cellular inhibitor of apoptosis protein 1 (cIAP1) and cIAP2 in MDA-MB-231 cells. Autoubiquitination and degradation of cIAP1 and cIAP2 induced by SKO further led to significant decreased ubiquitination and inactivation of RIP1, which played an important role in inhibition of pro-survival and accelerating of necrosis of MDA-MB-231 cells. Treatment with proteasome inhibitor lactacystin significantly rescued the cell viability induced by treatment of SKO. CONCLUSIONS: Our results demonstrate that SKO promotes the autoubiquitination and degradation of cIAP1 and cIAP2, which further induces the decrease of the ubiquitination of RIP1 to inhibit the activation of pro-survival signaling pathways and accelerate the necrosis of MDA-MB-231 cells. The disclosed mechanisms of SKO induced necrosis and apoptosis in our study is firstly reported, and it is believed that SKO could be considered as a potential candidate and further developed for the treatment of triple negative breast cancer.

Multifunctional ginsenoside Rg3-based liposomes for glioma targeting therapy.

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.

Tracking evidences of Coptis chinensis for the treatment of inflammatory bowel disease from pharmacological, pharmacokinetic to clinical studies.

ETHNOPHARMACOLOGICAL RELEVANCE: Coptis chinensis (C. chinensis, Huanglian in Chinese), a famous traditional herbal medicine used for clearing heat and detoxification since thousands of years ago, is widely and traditionally used for clinical treatment of stomach inflammation, duodenum and digestive tract ulcers alone or through combing with other herbs in compound formulations. AIM OF THE REVIEW: Through literature reviews of C. chinensis and berberine (one of the most important bioactive compounds derived from this plant) for the treatment of inflammatory bowel disease (IBD), this review aims to provide beneficial information for further exploration of the potent bioactive constituents from C. chinensis, deep investigation on the molecular mechanisms for the treatment of IBD, as well as further research and development of brand new products from C. chinensis for clinical therapy of IBD. METHODS: "C. chinensis" and "IBD" were selected as the main keywords, and various online search engines, such as Google Scholar, PubMed, Web of Science, China National Knowledge Infrastructure database (CNKI) and other publication resources, were used for searching literatures. RESULTS: To present, C. chinensis together with other herbs are involved in plenty of Chinese herbal prescriptions for the treatment of IBD, but little research focused on the single therapeutic effects of C. chinensis or extracts from this herb for the treatment of this disease. Berberine, one of important and representative bioactive compound isolated from C. chinensis, was reported to treat IBD effectively at a big arising speed in recent years. However, systematically and comprehensively reviews on the research of C. chinensis and berberine for the treatment of IBD from the aspects of chemical constituents, pharmacological effects, pharmacokinetics as well as clinical studies are seldom accomplished by researchers. Bioactive components from C. chinensis exert therapeutic effects for the treatment of IBD mainly through the inhibition of oxidative stress, antinociception, protection of intestinal mucosal epithelial barrier, regulation of T helper cells, as well as antibacterial activity. Although numerous studies on bioactive compounds from C. chinense have been performed by clinical investigators in recent years, most of them should be performed in a more strict and standard way to ensure the safety and efficacy of these compounds. CONCLUSIONS: Berberine is considered as the representative and effective component from C. chinensis, but many other chemical components isolated from C. chinensis also have therapeutic effects for the treatment of IBD, which need deep research and further exploration. To accelerate research and development of C. chinensis and its bioactive components for the treatment of IBD, clinical trials are needed to clarify the effectiveness and safety of these chemical components from C. chinensis, as well as their molecular mechanisms for IBD treatment in vitro and in vivo. It is believed that continuous research and exploration on C. chinensis together with its bioactive compounds will bring great hope to the treatment of IBD.

Bilirubin Nanomedicines for the Treatment of Reactive Oxygen Species (ROS)-Mediated Diseases.

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.

Astragali Radix (Huangqi): A promising edible immunomodulatory herbal medicine.

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.

Lattice vibration characteristics in layered InSe films and the electronic behavior of field-effect transistors.

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

Naturally occurring anti-cancer compounds: shining from Chinese herbal medicine.

Numerous natural products originated from Chinese herbal medicine exhibit anti-cancer activities, including anti-proliferative, pro-apoptotic, anti-metastatic, anti-angiogenic effects, as well as regulate autophagy, reverse multidrug resistance, balance immunity, and enhance chemotherapy in vitro and in vivo. To provide new insights into the critical path ahead, we systemically reviewed the most recent advances (reported since 2011) on the key compounds with anti-cancer effects derived from Chinese herbal medicine (curcumin, epigallocatechin gallate, berberine, artemisinin, ginsenoside Rg3, ursolic acid, silibinin, emodin, triptolide, cucurbitacin B, tanshinone I, oridonin, shikonin, gambogic acid, artesunate, wogonin, ß-elemene, and cepharanthine) in scientific databases (PubMed, Web of Science, Medline, Scopus, and Clinical Trials). With a broader perspective, we focused on their recently discovered and/or investigated pharmacological effects, novel mechanism of action, relevant clinical studies, and their innovative applications in combined therapy and immunomodulation. In addition, the present review has extended to describe other promising compounds including dihydroartemisinin, ginsenoside Rh2, compound K, cucurbitacins D, E, I, tanshinone IIA and cryptotanshinone in view of their potentials in cancer therapy. Up to now, the evidence about the immunomodulatory effects and clinical trials of natural anti-cancer compounds from Chinese herbal medicine is very limited, and further research is needed to monitor their immunoregulatory effects and explore their mechanisms of action as modulators of immune checkpoints.

Menthol-modified casein nanoparticles loading 10-hydroxycamptothecin for glioma targeting therapy.

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.

Novel drug delivery systems of Chinese medicine for the treatment of inflammatory bowel disease.

Inflammatory bowel disease (IBD) is an idiopathic intestinal inflammatory disease that comprises ulcerative colitis (UC) and Crohn's disease (CD). IBD involves the ileum, rectum, and colon, and common clinical manifestations of IBD are diarrhea, abdominal pain, and even bloody stools. Currently, non-steroidal anti-inflammatory drugs, glucocorticoids, and immunosuppressive agents are used for the treatment of IBD, while their clinical application is severely limited due to unwanted side effects. Chinese medicine (CM) is appealing more and more attention and investigation for the treatment of IBD owing to the potent anti-inflammation pharmacological efficacy and high acceptance by patients. In recent years, novel drug delivery systems are introduced apace to encapsulate CM and many CM-derived active constituents in order to improve solubility, stability and targeting ability. In this review, advanced drug delivery systems developed in the past and present to deliver CM for the treatment of IBD are summarized and future directions are discussed.