Herbal medicines (HMs) are much appreciated for their significant contribution to human survival and reproduction by remedial and prophylactic management of diseases. Defining the scientific basis of ...HMs will substantiate their value and promote their modernization. Ever‐increasing evidence suggests that gut microbiota plays a crucial role in HM therapy by complicated interplay with HM components. This interplay includes such activities as: gut microbiota biotransforming HM chemicals into metabolites that harbor different bioavailability and bioactivity/toxicity from their precursors; HM chemicals improving the composition of gut microbiota, consequently ameliorating its dysfunction as well as associated pathological conditions; and gut microbiota mediating the interactions (synergistic and antagonistic) between the multiple chemicals in HMs. More advanced experimental designs are recommended for future study, such as overall chemical characterization of gut microbiota‐metabolized HMs, direct microbial analysis of HM‐targeted gut microbiota, and precise gut microbiota research model development. The outcomes of such research can further elucidate the interactions between HMs and gut microbiota, thereby opening a new window for defining the scientific basis of HMs and for guiding HM‐based drug discovery.
•New shear test method for RC beams.•Effect of span-to-depth ratio on shear strength components.•Variation of shear strength components.•Evaluation of existing shear strength models.
The additive ...model of shear strength of reinforced concrete (RC) members, i.e. shear strength (V) is equal to the sum of the contribution from concrete (Vc) and that from transverse reinforcement (Vs), has been widely accepted in the literature and engineering practice. Shear span-to-depth ratio (a/d) is known to be a significant factor affecting V of RC members. However, very few quantitative studies on the influence of a/d on Vc and Vs have been reported in the literature. Another issue is related to the controversial relationship between the shear force at first diagonal cracking (Vcr) and Vc, for which different guidelines are given in ACI, AASHTO LRFD and CSA codes. Through direct measurement of Vc and Vs from 11 RC beam tests, this work provides experimental evidence for these issues. The experimental results show that Vc can be very different from Vcr. At small shear span-to-depth ratio (a/d), Vc is much larger than Vcr, while it is the opposite for beams with a large a/d value. Not all stirrups crossing the critical shear crack yield at ultimate shear strength, and Vc as well as Vs are not constant under increasing member deformation. Although design codes give a conservative prediction of V, they predict an un-conservative value of Vc at large a/d.
Photoreceptor apoptosis is recognized as one key pathogenesis of retinal degeneration, the counteraction of which represents a promising approach to safeguard visual function. Recently, mesenchymal ...stem cell transplantation (MSCT) has demonstrated immense potential to treat ocular disorders, in which extracellular vesicles (EVs), particularly exosomes, have emerged as effective ophthalmological therapeutics. However, whether and how MSCT protects photoreceptors against apoptotic injuries remains largely unknown. Here, we discovered that intravitreal MSCT counteracted photoreceptor apoptosis and alleviated retinal morphological and functional degeneration in a mouse model of photoreceptor loss induced by N-methyl-N-nitrosourea (MNU). Interestingly, effects of MSCT were inhibited after blockade of exosomal generation by GW4869 preconditioning. Furthermore, MSC-derived exosomal transplantation (EXOT) effectively suppressed MNU-provoked photoreceptor injury. Notably, therapeutic efficacy of MSCT and EXOT on MNU-induced retinal degeneration was long-lasting as photoreceptor preservance and retinal maintenance were detected even after 1-2 months post to injection for only once. More importantly, using a natural occurring retinal degeneration model caused by a nonsense mutation of Phosphodiesterase 6b gene (Pde6b
), we confirmed that MSCT and EXOT prevented photoreceptor loss and protected long-term retinal function. In deciphering therapeutic mechanisms regarding potential exosome-mediated communications, we identified that miR-21 critically maintained photoreceptor viability against MNU injury by targeting programmed cell death 4 (Pdcd4) and was transferred from MSC-derived exosomes in vivo for functional regulation. Moreover, miR-21 deficiency aggravated MNU-driven retinal injury and was restrained by EXOT. Further experiments revealed that miR-21 mediated therapeutic effects of EXOT on MNU-induced photoreceptor apoptosis and retinal dysfunction. These findings uncovered the efficacy and mechanism of MSCT-based photoreceptor protection, indicating exosomal miR-21 as a therapeutic for retinal degeneration.
Cluster materials have attracted much attention because of their unique chemical and physical properties, hitherto unseen in bulk materials. Inspired by the lipid self‐assembly principle, a series of ...heterocluster Janus molecules (HCJMs) with atomic precision have been rationally designed and synthesized by connecting different clusters via covalent bonds for the construction of nanomaterials and nano‐objects. Due to their amphiphilicity, HCJMs self‐assemble into cluster‐containing nanomaterials or nano‐objects with versatile ordered structures beyond those observed in conventional crystals. Their hybrid composition and nanoscale size are also greatly advantageous in the study of their fine structure by electron microscopy techniques, and enable their formation mechanisms to be unraveled. Finally, the influence of the characteristics of the HCJMs on the structure and properties of the self‐assembled nano‐objects are explored comprehensively. This synthesis strategy will promote further development of cluster materials with advanced functions via rational molecular design toward the construction of hierarchical nanostructures via molecular self‐assembly.
Inspired by lipid self‐assembly and nanocluster functionalities, the design and subsequent creation of a series of heterocluster Janus molecules (HCJMs) are pioneered. Owing to efficient shape control, HCJMs self‐assemble into nanostructures that can go beyond those of predicated nanoaggregates of traditional amphiphiles. Thus, an efficient strategy for bridging the gap between clusters and cluster materials is established.
•A key ion filter (KIF) strategy was developed to process untargeted LC/MS data.•The strategy was realized by using UHPLC/orbitrap-MS to analyze S. baicalensis.•High-resolution MS and MS/MS data were ...collected automatically.•Diagnostic ions from MS/MS spectra were extracted to recognize key substructures.•A total of 132 compounds were identified from S. baicalensis in a 20-min run.
Structural identification of natural products by tandem mass spectrometry requires laborious spectral analysis. Herein, we report a targeted post-acquisition data processing strategy, key ion filtering (KIF), to analyze untargeted mass spectral data. This strategy includes four steps: (1) untargeted data acquisition by ultra-high performance liquid chromatography coupled with hybrid quadrupole orbitrap mass spectrometry (UHPLC/orbitrap-MS); (2) construction of a key ion database according to diagnostic MS/MS fragmentations and conservative substructures of natural compounds; (3) high-resolution key ion filtering of the acquired data to recognize substructures; and (4) structural identification of target compounds by analyzing their MS/MS spectra. The herbal medicine Huang-Qin (Scutellaria baicalensis Georgi) was used to illustrate this strategy. Its extract was separated within 20min on a C18 column (1.8μm, 2.1×150mm) eluted with acetonitrile, methanol, and water containing 0.1% formic acid. The compounds were detected in the (−)-ESI mode, and their MS/MS spectra were recorded in the untargeted manner. Key ions were then filtered from the LC/MS data to recognize flavones, flavanones, O-/C-glycosides, and phenylethanoid glycosides. Finally, a total of 132 compounds were identified from Huang-Qin, and 59 of them were reported for the first time. This study provides an efficient data processing strategy to rapidly profile the chemical constituents of complicated herbal extracts.
Sieb. et Zucc. is part of the genus
of the family
. Ripening and dry fruits (
) are recognized as an essential herb medicine in the traditional Chinese medicine (TCM) and have been widely used for ...over 2000 years. This review provides a comprehensive summary of
(CF), including the botany, phytochemistry, traditional use, and current pharmacological activities. According to the basic theory of TCM, CF usually participates in various Chinese medicinal formulae to exert the essential roles in replenishing liver and kidney, arresting seminal emission and sweat. Based on modern pharmacological studies, about 90 compounds have been isolated and identified from CF. In vivo and in vitro experimental studies indicate that CF exhibits extensive pharmacological activities including hypoglycemic, antioxidant, anti-inflammatory, anticancer, neuroprotective, hepatoprotective, and nephroprotective activities. However, only about 18% of chemical constituents in CF were tested. It means the potential pharmacological activities and clinical values of CF need to be further investigated.
•New test method for shear resistance of RC beams.•Distribution of strain in shear reinforcement.•Principal compression strain and correlation with principal compression stress.•Variation of shear ...strength components.
This paper presents an experimental work and analysis of test results on diagonal cracking behavior of reinforced concrete (RC) beams that failed in shear. The strain distributions of transverse reinforcement, obtained by closely spaced strain gauges mounted inside transverse reinforcement without disturbing bond, are presented in a form of contour lines at different load levels. The diagonal crack width, average principal and shear strain fields of the shear span were obtained by using the digital image correlation (DIC). Based on the strains of transverse reinforcement along the path of the critical diagonal crack, the shear strength contribution of the transverse reinforcement (Vs) is isolated from the shear strength contribution of concrete (Vc). The value of Vs calculated in this way is generally larger than that obtained from the strains measured at mid-height of stirrups in the case of strong bond, while the difference is insignificant in the case of weak bond. With the full and detailed pictures of internal and external strain fields of the beams, important shear characteristics such as inclination of the principal compression strain and its correlation with principal compression stress, variation of Vc and Vs with respect to crack width and member deflection, relationships between crack width, shear force, principal tensile strain of concrete, and strain of transverse reinforcement, etc. are studied in this work. These relationships shed light on further study of the shear behavior of RC beams.
Oolong tea (OT) is a traditional Chinese tea (Camellia sinensis) and is especially popular in south China. This review is to comprehensively summarize the miscellaneous research that has been done ...towards to the processing, phytochemistry, health benefit, and risk of OT. These literatures were carried out not only from different electronic databases but also from text books written in English, Japanese, and Chinese, including those traditional records tracing back to the Tang Dynasty (A.D. 618-907). The full process OT producing is depicted below in this review. The phytochemistry of OT has been comprehensively investigated. More than 100 chemical compositions have been isolated and identified. In health benefit, OT performs outstandingly in reducing obesity and controlling diabetes explained by modern pharmacological studies. (−)-Epigallocatechin-3-gallate (6) in OT prevention of cancerous cells developing. OT can also improve and reduce on heart and vascular disease, protect teeth and bone, function as anti-oxidative and antibacterial agents. This review also mentioned the risk, summarized briefly on various forms of toxicity and harmful associated with OT. In short, this review can provided a natural product library of OT, gave inspirations for further new garden systems, designed idea on quality, bioactivity-oriented screening. In addition, it is suggested more scientists and education is necessary to guarantee the stability and safety of drinking OT.
Astragalus membranaceus is a traditional Chinese medicine derived from the roots of Astragalus membranaceus (Fisch.) Bge., which has the same medicinal and edible uses in China. It is also widely ...used in daily food, and its pharmacological effects mainly include antioxidant effects, vascular softening effects, etc. Currently, it is increasingly widely used in the prevention of hypertension, cerebral ischemia, and stroke in China. Formononetin and its glucopyranoside (ononin) are both important components of Astragalus membranaceuss and may play important roles in the treatment of cardiovascular diseases (CVDs). This study conducted metabolic studies using formononectin and its glucopyranoside (ononin), including a combination of the in vitro metabolism of Formonetin using rat liver S9 and the in vivo metabolism of ononin administered orally to rats. Five metabolites (Sm2, 7, 9, 10, and 12) were obtained from the solution incubated with formononetin and rat hepatic S9 fraction using chromatographic methods. The structures of the five metabolites were elucidated as (Sm2)6,7,4′-trihydroxy-isoflavonoid; (Sm7)7,4′-dihydroxy-isoflavonoid; (Sm9)7,8,4′-trihydroxy-isoflavonoid; (Sm10)7,8,-dihydroxy-4′-methoxy-isoflavonoid; and (Sm12)6,7-dihydroxy-4′-methoxy- isoflavonoid on the basis of UV, NMR, and MS data. Totally, 14 metabolites were identified via HPLC-DAD-ESI-IT-TOF-MSn analysis, from which the formononetin was incubated with rat hepatic S9 fraction, and the main metabolic pathways were hydroxylation, demethylation, and glycosylation. Then, 21 metabolites were identified via HPLC-DAD-ESI-IT-TOF-MSn analysis from the urine samples from SD rats to which ononin was orally administered, and the main metabolic pathways were glucuronidation, hydroxylation, demethylation, and sulfonation. The main difference between the in vitro metabolism of formononetin and the in vivo metabolism of ononin is that ononin undergoes deglycemic transformation into Formonetin in the rat intestine, while Formonetin is absorbed into the bloodstream for metabolism, and the metabolic products also produce combined metabolites during in vivo metabolism. The six metabolites obtained from the aforementioned separation indicate the primary forms of formononetin metabolism, and due to their higher contents of similar isoflavone metabolites, they are considered the main active compounds that are responsible for pharmacological effects. To investigate the metabolites of the active ingredients of formononetin in the rat liver S9 system, network pharmacology was used to evaluate the cardiovascular disease (CVD) activities of the six primary metabolites that were structurally identified. Additionally, the macromolecular docking results of six main components and two core targets (HSP90AA1 and SRC) related to CVD showed that formononetin and its main metabolites, Sm10 and Sm12, may have roles in CVD treatment due to their strong binding activities with the HSP90AA1 receptor, while the Sm7 metabolite may have a role in CVD treatment due to its strong binding activity with the SRC receptor.
Herbs and dietary supplement-induced liver injury (HILI) is the leading cause of drug-induced liver injury in China. Among different hepatotoxic herbs, the pyrrolizidine alkaloid (PA)-producing herb ...Gynura japonica contributes significantly to HILI by inducing hepatic sinusoidal obstruction syndrome (HSOS), a liver disorder characterized by hepatomegaly, hyperbilirubinemia, and ascites. In China, G. japonica has been used as one of the plant species for Tu-San-Qi and is often misused with non-PA-producing Tu-San-Qi (Sedum aizoon) or even San-Qi (Panax notoginseng) for self-medication. It has been reported that over 50% of HSOS cases are caused by the intake of PA-producing G. japonica. In this review, we provide comprehensive information to distinguish these Tu-San-Qi-related herbal plant species in terms of plant/medicinal part morphologies, medicinal indications, and chemical profiles. Approximately 2156 Tu-San-Qi-associated HSOS cases reported in China from 1980 to 2019 are systematically reviewed in terms of their clinical manifestation, diagnostic workups, therapeutic interventions, and outcomes. In addition, based on the application of our developed mechanism-based biomarker of PA exposure, our clinical findings on the definitive diagnosis of 58 PA-producing Tu-San-Qi-induced HSOS patients are also elaborated. Therefore, this review article provides the first comprehensive report on 2214 PA-producing Tu-San-Qi (G. japonica)-induced HSOS cases in China, and the information presented will improve public awareness of the significant incidence of PA-producing Tu-San-Qi (G. japonica)-induced HSOS and facilitate future prevention and better clinical management of this severe HILI.
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