The tuberous root of
(Thunb.) Ker-Gawl. is a well-known Chinese medicine also called Maidong (MD) in Chinese. It could be divided into "Chuanmaidong" (CMD) and "Zhemaidong" (ZMD), according to the ...geographic origins. Meanwhile, the root of
(Thunb.) Lour. var.
Y. T. Ma (SMD) is occasionally used as a substitute for MD in the market. In this study, a reliable pressurized liquid extraction and HPLC-DAD-ELSD method was developed for the simultaneous determination of nine chemical components, including four steroidal saponins (ophiopojaponin C, ophiopogonin D, liriopesides B and ophiopogonin D'), four homoisoflavonoids (methylophiopogonone A, methylophiopogonone B, methylophiopogonanone A and methylophiopogonanone B) and one sapogenin (ruscogenin) in CMD, ZMD and SMD. The method was validated in terms of linearity, sensitivity, precision, repeatability and accuracy, and then applied to the real samples from different origins. The results indicated that there were significant differences in the contents of the investigated compounds in CMD, ZMD and SMD. Ruscogenin was not detected in all the samples, and liriopesides B was only found in SMD samples. CMD contained higher ophiopogonin D and ophiopogonin D', while the other compounds were more abundant in ZMD. Moreover, the anticancer effects of the herbal extracts and selected components against A2780 human ovarian cancer cells were also compared. CMD and ZMD showed similar cytotoxic effects, which were stronger than those of SMD. The effects of MD may be due to the significant anticancer potential of ophiopognin D' and homoisoflavonoids. These results suggested that there were great differences in the chemical composition and pharmacological activity among CMD, ZMD and SMD; thus, their origins should be carefully considered in clinical application.
Metasurfaces trigger great interests due to their potential ability to manipulate the propagation of electromagnetic (EM) waves. Plenty of fascinating EM phenomena have been generated using ...metasurface. However, two defects are hindering their development. The first one is that most metasurfaces only perform a specific functionality once designed, which means they do not possess tunable properties. The second defect is that most of them work in either reflection mode or transmission mode, leaving half of the EM space completely unexplored. Therefore, it is challenging to design metasurface with tunability and entire-space working modes simultaneously. Here, a tunable metasuface is presented to solve these problems. The proposed metasurface element is a multilayer structure which can manipulate EM waves in the entire space. Concurrently, p-i-n switches are loaded on each element which can dynamically control transmission and reflection phases. Thus, some intriguing EM modulation functions in the entire space are realized, such as beam forming, anomalous reflection, and diffusion. The simulated and experimental results prove the tunable metasurface. The proposed metasurface offers a feasible strategy to design tunable metadevices and for other related practical applications.
Among the various treatments, induction of synoviocyte apoptosis by natural products during a rheumatoid arthritis (RA) pathological condition can be considered to have vast potential. However, it is ...unclear that liquiritin, a kind of natural flavonoid extracted from the roots of Glycyrrhiza uralensis, induced the apoptosis of the synovial membrane and its molecular mechanism. In this study, interleukin-1β (IL-1β)-RA-FLS cells were incubated with different concentrations of liquiritin. An MTT assay, Hoechst 33342 staining, JC-1 staining, and Western blot were used to check the viability, cell apoptosis, mitochondrial membrane potential changes, and the expression of related proteins, respectively. In vivo, a TUNEL assay and HE staining of tissue were used for histopathological evaluation. Our results showed that liquiritin significantly inhibited the proliferation of IL-1β-induced-RA-FLS, promoted nuclear DNA fragmentation, and changed the mitochondrial membrane potential to accelerate cell apoptosis. Liquiritin downregulated the ratio of Bcl-2/Bax and inhibited the VEGF expression and phosphorylation of JNK and P38. Moreover, liquiritin improved the clinical score of rheumatism, inflammatory infiltration, and angiogenesis and induced apoptosis of the synovial tissue in vivo. Hence, liquiritin ameliorates RA by reducing inflammation, blocking MAPK signaling, and restraining angiogenesis.
Background
Acquired perforating dermatosis (APD) is a rare skin condition characterized by degenerated materials eliminated from the dermis. Several retrospective studies on APD have been reported; ...however, few data are available on Chinese APD and their features on dermoscopy and reflective confocal microscope (RCM) assays.
Objective
The aim of this study was to retrospectively evaluate the clinical and histopathologic data of 37 acquired perforating dermatosis cases, and assess their features on dermoscopy and RCM.
Methods
Thirty‐seven APD patients were retrospectively enrolled in our study. We characterized the clinical histopathological features, concomitant diseases, treatment responses, and the dermoscopy and RCM findings.
Results
Pruritus was the most common symptom, with the lower extremities as the most predilection sites (86.5%, n = 32; 91.9%, n = 34, respectively). Concomitant diseases were found in 34 patients (92.6%), among which diabetes mellitus was the most common, followed by thyroid nodules, allergic dermatosis, and chronic renal insufficiency. Dermoscopy and RCM assays were performed in 11 patients. The typical RCM images were hyperreflective cord‐like structures from the epidermis to dermis. Dermoscopy features of fully developed lesions showed central ulceration with peripheral hairpin‐like or loop‐like capillaries with characteristic garland arrangements.
Conclusion
APD is an uncommon skin disorder associated with various systemic conditions in Chinese individuals. Thyroid disorders are an overlooked complication and may play an important role in the development of APD. The results of this study indicate that noninvasive dermoscopy and RCM examination are helpful in the rapid diagnosis and early intervention of APD.
Resistance to temozolomide (TMZ), the frontline chemotherapeutic agent for glioblastoma (GBM), has emerged as a formidable obstacle, underscoring the imperative to identify alternative therapeutic ...strategies to improve patient outcomes. In this study, we comprehensively evaluated a novel agent, O6-methyl-2'-deoxyguanosine-5'-triphosphate (O6-methyl-dGTP) for its anti-GBM activity both in vitro and in vivo. Notably, O6-methyl-dGTP exhibited pronounced cytotoxicity against GBM cells, including those resistant to TMZ and overexpressing O6-methylguanine-DNA methyltransferase (MGMT). Mechanistic investigations revealed that O6-methyl-dGTP could be incorporated into genomic DNA, disrupting nucleotide pools balance, and inducing replication stress, resulting in S-phase arrest and DNA damage. The compound exerted its anti-tumor properties through the activation of AIF-mediated apoptosis and the parthanatos pathway. In vivo studies using U251 and Ln229 cell xenografts supported the robust tumor-inhibitory capacity of O6-methyl-dGTP. In an orthotopic transplantation model with U87MG cells, O6-methyl-dGTP showcased marginally superior tumor-suppressive activity compared to TMZ. In summary, our research, for the first time, underscores the potential of O6-methyl-dGTP as an effective candidate against GBM, laying a robust scientific groundwork for its potential clinical adoption in GBM treatment regimens.
We systematically analyzed, designed, fabricated, and measured a three-layer perfect metamaterial-inspired absorber based on the double split-serration-rings (DSSRs) structure in this communication. ...The equivalent circuit model was presented to demonstrate the absorbing mechanism. The characters of polarized-insensitivity, wideband, and multiband absorption for the absorber were illuminated by the angular absorptions and surface current distributions. Transformation from wideband absorption with a relative bandwidth of 93.5% from 5.34 to 14.72 GHz, of which the absorptivity was larger than 90%, to multiband absorption was obtained by rotating DSSR-II of 90°. Two absorber prototypes with a thickness of 3.6 mm had been easily implemented using the common printed circuit board fabrication techniques and measured in a microwave anechoic chamber. Simulated and experimental results indicated that the perfect metamaterial-inspired absorber performed wideband and multiband absorption when DSSRs were perpendicular and parallel to each other, respectively.
Objectives
Cholestasis is a critical risk factor for severe hepatic disease or cirrhosis. The anti‐inflammatory effect of Paeonia lactiflora Pall. (PLP), named Chishao in traditional Chinese medicine ...(TCM), on alpha‐naphthylisothiocyanate (ANIT)‐induced cholestasis model was tried to be elucidated in this research.
Methods
Therapeutic effect indices on hepatic function, including ALT, AST, TBIL, DBIL, ALP, TBA and γ‐GT, were measured. To further investigate the protective mechanism of PLP, the mRNA and protein expression levels of NF‐κB‐NLRP3 inflammasome pathway were detected.
Results
Our results showed that compared with the model group, PLP could significantly reduce the increased serum indices such as ALT, AST, TBIL, DBIL, ALP, TBA and γ‐GT induced by ANIT in a dose‐dependent way. Moreover, we found that PLP downregulated the mRNA expression levels including IKK, p65, NLRP3, caspase‐1 and IL‐1β, especially at the large dose. Furthermore, PLP also significantly inhibited NF‐κB‐NLRP3 inflammasome pathway by decreasing the protein levels of p65, p‐p65, p‐IKK, NLRP3, caspase‐1 and IL‐1β.
Conclusions
The results indicated that PLP could ameliorate ANIT‐induced cholestasis in rats and the anti‐inflammatory effect of PLP might be related to regulating NF‐κB‐NLRP3 inflammasome pathway. This study will provide scientific evidence for PLP as a potential drug candidate for cholestasis.
•Roadside vegetation barriers are investigated as a passive control method within urban street canyons.•Both field measurements and CFD simulations are used to investigate the impacts of vegetation ...barriers on roadside air quality.•Roadside vegetation barriers demonstrate a potential to improve air quality over the slow lanes of street canyons.•The optimal vegetation barrier heights in a specific street canyon can be determined by CFD simulations.
Vegetation barriers have been widely applied along urban streets to improve roadside air quality. For a deep investigation of their influences, field measurements and numerical simulations are performed in this study. Carbon monoxide (CO) is selected as a representative of gaseous traffic emissions for both field observations and numerical models. Computational Fluid Dynamics (CFD) models of the standard k-ε turbulent model and Eulerian approach for species transport are solved by FLUENT solver. Results obtained from numerical simulations show a good agreement with field observations on the distribution of roadside CO. In perpendicular wind conditions, both field observations and numerical simulations present a prominent CO reduction over the slow lanes (footpath and bikeway) when vegetation barriers exist. To effectively mitigate roadside air pollution, numerical simulations also provide the optimal heights for roadside vegetation barriers in the given street canyons. For street canyons with an aspect ratio (the ratio of building height to street width) ranging from 0.3 to 1.67, 1.1m can be used as an optimal height, and 2.0m could serve as an alternative if tall vegetation barriers are considered. For street canyons with an aspect ratio of lower than 0.3, 0.9m to 2.5m can be considered as the optimal heights for roadside vegetation barriers. According to sensitivity analysis, the optimal heights for vegetation barriers are largely insensitive to wind velocities in the given street canyons. In the more complicated urban street canyons and complex meteorological conditions, the optimal heights can be determined by specific numerical simulations. These findings are expected to provide important insights into alleviation of gaseous mobile emissions in terms of vegetation barrier design in urban streets.
Background
There are no effective pharmacological treatments for sarcopenia. We aim to identify potential therapeutic targets for sarcopenia by integrating various publicly available datasets.
...Methods
We integrated druggable genome data, cis‐eQTL/cis‐pQTL from human blood and skeletal muscle tissue, and GWAS summary data of sarcopenia‐related traits to analyse the potential causal relationships between drug target genes and sarcopenia using the Mendelian Randomization (MR) method. Sensitivity analyses and Bayesian colocalization were employed to validate the causal relationships. We also assessed the side effects or additional indications of the identified drug targets using a phenome‐wide MR (Phe‐MR) approach and investigated actionable drugs for target genes using available databases.
Results
MR analysis identified 17 druggable genes with potential causation to sarcopenia in human blood or skeletal muscle tissue. Six of them (HP, HLA‐DRA, MAP 3K3, MFGE8, COL15A1, and AURKA) were further confirmed by Bayesian colocalization (PPH4 > 90%). The up‐regulation of HP higher ALM (beta: 0.012, 95% CI: 0.007–0.018, P = 1.2*10−5) and higher grip strength (OR: 0.96, 95% CI: 0.94–0.98, P = 4.2*10−5), MAP 3K3 higher ALM (beta: 0.24, 95% CI: 0.21–0.26, P = 1.8*10−94), higher grip strength (OR: 0.82, 95% CI: 0.75–0.90, P = 2.1*10−5), and faster walking pace (beta: 0.03, 95% CI: 0.02–0.05, P = 8.5*10−6), and MFGE8 higher ALM (muscle eQTL, beta: 0.09, 95% CI: 0.06–0.11, P = 6.1*10−13; blood pQTL, beta: 0.05, 95% CI: 0.03–0.07, P = 3.8*10−09), as well as the down‐regulation of HLA‐DRA lower ALM (beta: ‐0.09, 95% CI: −0.11 to −0.08, P = 5.4*10−36) and lower grip strength (OR: 1.13, 95% CI: 1.07–1.20, P = 1.8*10−5) and COL15A1 higher ALM (muscle eQTL, beta: ‐0.07, 95% CI: −0.10 to −0.04, P = 3.4*10−07; blood pQTL, beta: ‐0.05, 95% CI: −0.06 to −0.03, P = 1.6*10−07), decreased the risk of sarcopenia. AURKA in blood (beta: ‐0.16, 95% CI: −0.22 to −0.09, P = 2.1*10−06) and skeletal muscle (beta: 0.03, 95% CI: 0.02 to 0.05, P = 5.3*10−05) tissues showed an inverse relationship with sarcopenia risk. The Phe‐MR indicated that the six potential therapeutic targets for sarcopenia had no significant adverse effects. Drug repurposing analysis supported zinc supplementation and collagenase clostridium histolyticum might be potential therapeutics for sarcopenia by activating HP and inhibiting COL15A1, respectively.
Conclusions
Our research indicated MAP 3K3, MFGE8, COL15A1, HP, and HLA‐DRA may serve as promising targets for sarcopenia, while the effectiveness of zinc supplementation and collagenase clostridium histolyticum for sarcopenia requires further validation.
In this article, a six-component self-sorting process that involves three types of crown ether macrocycle and three types of cation guest molecule was carefully and thoroughly investigated. The six ...components include three kinds of crown ether, namely bis(
-phenylene-34-crown-10) (BPP34C10), dibenzo-24-crown-8 (DB24C8) and benzo-21-crown-7 (B21C7), and their corresponding cation guest molecules, namely a 4,4'-bipyridine dication (BPY
) and dibenzylammonium (DBA) and benzylalkylammonium (BAA) ions, respectively. Based on this well-established highly selective six-component self-sorting process, a hetero6rotaxane bearing three different kinds of crown ether macrocycle was designed and successfully synthesized through a facile and efficient one-pot "click" stoppering strategy. Such work is proposed to be a significant advance in the construction of mechanically interlocked molecules with high structural complexity, as well as a good supplement in the areas of multi-component self-sorting and noncovalent self-assembly.