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Background: Erzhi formula (EZF) is a traditional Chinese medicine prescription, which has been widely used in the treatment of osteoporosis and premature ovarian failure. Objective: To enhance curative effects, the other two herbal medicines, including Spatholobi Caulis (SC) and Achyranthes bidentata Blume (ABB), were added into the original EZF formula to obtain two new Jiawei-EZF (JW-EZF) preparations. To clarify the effect of the compatibility of herbs for original formulas, the chemical constituents and bioactive compounds in vivo were detected. Methods: An efficient and sensitive targeted and untargeted UHPLC/ESI-Q-Orbitrap MS method, together with mass defect filter and precursor ion list, was established firstly for the profiling of different EZF formulas. Furthermore, eleven absorbed compounds (apigenin, luteoloside, luteolin, oleuropein, wedelolactone, acteoside, specnuezhenide, 11-methyloleoside, ecliptasaponin A, formononetin, and β-ecdysone) were simultaneously quantified in rat plasma. Results: A total of 124, 162, and 177 compounds were identified or tentatively identified in EZF, JW-3-EZF (EZF+SC) and JW-4-EZF (EZF+SC+ABB), respectively. 110 compounds were found to be common constituents in the three formulas. Moreover, 66 prototypes were unambiguously identified in the rats' plasma after oral administration of the three formulas using the same strategy. 11 out of the 66 absorbed components were simultaneously quantitated in the pharmacokinetic (PK) study. Compared to the original EZF, the plasma AUC(0-24h) and AUC(0-∞) of apigenin, 11-methyloleoside, luteolin, luteoloside, wedelolactone, and acteoside were found to be significantly increased after oral administration of JW-3-EZF, and plasma AUC(0-24h) and AUC(0-∞) of apigenin, wedelolactone, and acteoside, were also found to be significantly increased after JW-4-EZF administration. Conclusion: The combined qualitative and quantitative methods were used to provide a potential approach to the characterization and quality control of the Traditional Chinese Medicine (TCM) and its preparations.

With the development of science and technology, nanotechnology gradually becomes the growing energy shortage of new energy technology, and gains more and more scientists’ attention. Friction nanogenerator (TENG) is a nanogenerator with efficient energy conversion. Nanotextile (TEF-F) is a kind of friction material suitable for human skin, because nanotextiles have antibacterial function, radiation prevention, antistatic resistance, flame retardant, and other functions, and they can act on the outer layer of the skin and play a very good protective role. This article aims at studying a flexible friction nanogenerator and sensor as a safety monitoring equipment for sports. In this article, PTFE and nylon are proposed as friction nanomaterials of a flexible friction nanogenerator. A model of power generation by friction between insole and athlete is designed and tested. The experimental results show that the output voltage of PTFE friction nanomaterials with 50% water tightness can reach 200 V. Under the same conditions, compared with the output voltage of different textile fibers, the output voltage of nylon is up to 180 V. The output voltage of thin PTFE can reach 200 V, while that of nylon can reach 180 V. The output voltage of PTFE with medium thickness is 65 V, while that of nylon is 84 V. For thicker PTFE, the output voltage is only 58 V, while that of nylon is only 67 V. Therefore, for cotton, polyester, and nylon under the same conditions, the output voltage of nylon is significantly higher than that of different textile fibers. Moreover, for PTFE and nylon friction nanomaterials, the thinner their thickness, the higher their output voltage is.

Radian Sophorae flavescentis is a traditional Chinese medicine commonly used to treat cancer in China. However, its active components and underlying mechanism remain ambiguous. In this study, we have screened the pharmacokinetic parameters of the main chemical constituents of Radian Sophorae flavescentis by Traditional Chinese Medicine Systems Pharmacology (TCMSP) Database and Analysis Platform and have found that Sophoridine is one of the best antitumor active ingredients. We have found that MAPKAPK2 is a potential target for Sophoridine by the PharmMapper and KEGG databXase analysis. Moreover, we have found that Sophoridine selectively inactivates phospho-MAPKAPK2 (Thr222) and directly binds into the ATP site of MAPKAPK2 by molecular docking. Furthermore, we have found out a direct binding between MAPKAPK2 and Sophoridine by cellular thermal shift assay and drug affinity responsive targets stability assay. The inhibition effects are further confirmed by Western blot: Sophoridine significantly decreases phospho-MAPKAPK2 (Thr222) in a time-dependent manner, but there is no obvious change in its total expression in colorectal cancer cells. Clinical studies have shown that a higher level of MAPKAPK2 is associated with a poorer percent survival rate (prognosis). Furthermore, a higher level of MAPKAPK2 is positively associated with the enrichment of downregulation of apoptosis and autophagy by gene set enrichment analysis, as well as upregulation of proliferation and cell-cycle arrest. Taken together, our results suggest that the MAPKAPK2 plays a key role in Sophoridine-inhibited growth and invasion in colorectal cancers.Implications:These studies show that Sophoridine may be a promising therapeutic strategy that blocks tumorigenesis in colorectal cancers.

Main index of routine blood test of Sophoridine

Main serum biochemical index of Sophoridine

Supplementary Figure 1. The pharmacokinetics and cytotoxic effects of Sophoridine. Supplementary Figure 2. Sophoridine inhibited MAPKAPK2 activity and the docking interaction of p38-MAPKAPK2. Supplementary Figure 3. Sophoridine promotes the apoptotic and autophagic capacities and cell cycle arrest via MAPKAPK2 inactivation. Supplementary Figure 4. Full scans of western-blot data shown in Figure 1. Supplementary Figure 5. Full scans of western-blot data shown in Figure 2. Supplementary Figure 6. Full scans of western-blot data shown in Figure 4. Supplementary Figure 7. Full scans of western-blot data shown in Figure 5.

Cancer-associated genes were retrieved from the disGeNET database

Main pharmacokinetic parameters of Sophoridine after injection of caudal vein in rats

Primers for q-PCR

Pharmacophore candidates identified by pharmMapper

The cyclic GMP–AMP synthase (cGAS)–stimulator of interferon genes (STING) signaling exert essential regulatory function in microbial-and onco-immunology through the induction of cytokines, primarily type I interferons. Recently, the aberrant and deranged signaling of the cGAS–STING axis is closely implicated in multiple sterile inflammatory diseases, including heart failure, myocardial infarction, cardiac hypertrophy, nonalcoholic fatty liver diseases, aortic aneurysm and dissection, obesity, etc. This is because of the massive loads of damage-associated molecular patterns (mitochondrial DNA, DNA in extracellular vesicles) liberated from recurrent injury to metabolic cellular organelles and tissues, which are sensed by the pathway. Also, the cGAS–STING pathway crosstalk with essential intracellular homeostasis processes like apoptosis, autophagy, and regulate cellular metabolism. Targeting derailed STING signaling has become necessary for chronic inflammatory diseases. Meanwhile, excessive type I interferons signaling impact on cardiovascular and metabolic health remain entirely elusive. In this review, we summarize the intimate connection between the cGAS–STING pathway and cardiovascular and metabolic disorders. We also discuss some potential small molecule inhibitors for the pathway. This review provides insight to stimulate interest in and support future research into understanding this signaling axis in cardiovascular and metabolic tissues and diseases., Graphical abstract The review summarizes the current impact of hyperactivation of the cGAS–STING signaling, with emphasis on the link with cardiovascular and metabolic diseases and the emerged pathway's inhibitors for therapeutic prospects.Image 1

A novel dual-port phase antenna is proposed to realize 2-D scanning. The antenna consists of two monopoles on both sides and a fishbone structure in the middle. By changing the phase difference ${\Delta \varphi }$ between two monopoles, energy is coupled to the proposed structure, exciting different degrees of superposition of even and odd modes. The continuous switching from the broadside lobe to the end-fire lobe is realized, and it has the characteristic of 2-D scanning. Furthermore, to provide an in-depth insight into the 2-D scanning mechanism, two linear arrays (Array 2 and Array 3) based on the proposed antenna element and a generalized principle of pattern multiplication (GPPM) are developed. The fabricated Array 2 can offer scanning angles of 0°–73° along the $\theta $ -direction with the gain of 6.5–10.4 dBi and 90°–140° along the $\Phi $ -direction with the gain of 6.1–11.7 dBi. Its scanning coverage of 3 dB beamwidth is $0^{\circ } , $0^{\circ } . The manufactured Array 3 can scan 0°–90° along $\theta $ -direction with the gain of 8.2–11.1 dBi and 50°–90° along the $\Phi $ -direction with the gain of 6–9.36 dBi, and its 3 dB coverage of the main beam scanning is $0^{\circ } , $0^{\circ } . Consequently, the proposed antenna and GPPM can be readily extended to wide-angle scanning phased arrays.

Context Tangwang Mingmu granule (TWMM), a traditional Chinese medicine, has been widely used in the treatment of diabetic retinopathy (DR), the most common microvascular complication in diabetes mellitus. Objective To establish a method to select target compounds from herbs for a pharmacokinetic study using network pharmacology, which could be applied in clinical settings. Materials and methods First, UPLC/Q Exactive Q-Orbitrap and GCMS 2010 were used to determine the non-volatile and volatile ingredients of TWMM. Based on the identified compounds, network pharmacology was used to screen the key compounds and targets of TWMM in the treatment of DR. Based on the compound-target-pathway network and identification of components emigrant into blood, the potential compound markers in vivo were chosen. Then, Sprague-Dawley (SD) rats were administrated of TWMM at a 9.6 g/kg dose to investigating pharmacokinetic parameters using the UPLC-QQQ-MS. Results Ninety and forty-five compounds were identified by UPLC-MS and GC-MS, respectively. Based on the network pharmacology, nine compounds with a degree value above 15 were screened and implied that these compounds are the most active in DR treatment. Moreover, criteria of degree value greater than 7 were applied, and PTGS2, NOS2, AKT1, ESR1, TNF, and MAPK14 were inferred as the core targets in treating DR. After identification of components absorbed into blood, luteolin and formononetin were selected and used to investigate the pharmacokinetic parameters of TWMM after its oral administration. Conclusions The reported strategy provides a method that combines ingredient profiling, network pharmacology, and pharmacokinetics to determine luteolin and formononetin as the pharmacokinetic markers of TWMM. This strategy provides a clinically relevant methodology that allows for the screening of pharmacokinetic markers in Chinese medicines.

The generalized principle of pattern multiplication (GPPM) and its application to wide-angle scanning array are investigated. It includes the generalized element factor (GEF), generalized array factor (GAF), and their beam match condition. The GEF model based on the phase mode currents in an aperture is given. A phase-mode antenna (PMA) with dual ports is designed to realize GEF function in the unit aperture. The prototype of the PMA exhibits a main lobe scanning range of -43.9° to 43.9° at 2.4 GHz. A 1-D four-element phased array using the PMA with element spacing 0.7λ based on the GEF and the GPPM is designed to verify GPPM. The array can scan maximum to ±78° in the operating band. Furthermore, an improved compacted phase-mode antenna (ICPMA) is designed, which is capable of lobe steering too. And the linear array with elements spacing 0.4λ using ICPMA is constructed, which can scan maximum to ±76° with the 1st SLL -13.7 dB in experiment. The proposed phased array based on PMA, ICPMA verify the advantages of GPPM, and presents attractive features in future wireless communication and radar system.

For the attainment of a sharp cube-textured tape, the influence of deformation degree and rolling regime on deformation and recrystallization texture was studied. Low Curie temperature ternary alloy of Ni-7.9at.%Cr-1.8at.%Mo ingot was prepared by using cold crucible induction levitation melting, and a final thickness of 80-μm textured tape was obtained after forging, hot rolling, cold rolling and recrystallization annealing. The results showed that with an increase in rolling reduction from 50 to 99.5%, S + C-type textures were enhanced and B + G-type textures were reduced, and the volume fraction of cube texture in recrystallized tape was increased; a two-stage rolling obviously refines the initial microstructure for the second large reduction cold rolling and thus slightly lowers the volume fraction of B texture component in the deformed matrix, leading to a high percentage of cube texture after recrystallization. The intermediate annealing in a two-stage rolling process reduces the grain size and mitigates the inhomogeneity of the microstructure.

Illegal additives can bring the economic benefit, resulting in the continuous irregularities in the use of illegal additives. In this study, a method for rapid, sensitive, and simultaneous detection of multiple illegal additives including enrofloxacin, malachite green, nitrofurazone, and Sudan Ⅰ in feed and food samples by surface-enhanced Raman spectroscopy (SERS) with Cu

Fiber reinforced composites can meet the needs of lightweight, heavy load, long-span, high strength, and modern structures and work under strict conditions. Therefore, it is widely used in various fields. Sports equipment generally cannot meet the requirements of high-strength use, so there is an urgent need for new fiber materials to make these instruments. Aiming at improving the efficiency of measurement and the reliability of measurement results, this paper studies the quantitative characterization method of the microstructure of short fiber reinforced composites. The swept-frequency OCT system is a newly developed high-resolution biomedical imaging system. The method of this paper is to study the performance parameters of swept frequency OCT system, deduce the application of image processing technology in fiber material detection, and then study the detection of residual strength and residual stiffness of composites, so as to obtain a composite material detection method that can be popularized. On this basis, image processing and performance analysis of the composites were carried out, and the composites were tested. And the prospect of application in this field has been analyzed. The experimental results show that better fiber length can be obtained by this method, and the maximum relative error is only 4.5%, thus ensuring the accurate determination of fiber length. Calculations were carried out using the experimental data, and the results showed that the performance of the sports product increased from 15.4% to 48.6% with the graphite-rubber composite. Using this material can improve the comprehensive performance of sports equipment by 2.1%∼4.5%.

Radian Sophorae flavescentis is a traditional Chinese medicine commonly used to treat cancer in China. However, its active components and underlying mechanism remain ambiguous. In this study, we have screened the pharmacokinetic parameters of the main chemical constituents of Radian Sophorae flavescentis by Traditional Chinese Medicine Systems Pharmacology (TCMSP) Database and Analysis Platform and have found that Sophoridine is one of the best antitumor active ingredients. We have found that MAPKAPK2 is a potential target for Sophoridine by the PharmMapper and KEGG databXase analysis. Moreover, we have found that Sophoridine selectively inactivates phospho-MAPKAPK2 (Thr222) and directly binds into the ATP site of MAPKAPK2 by molecular docking. Furthermore, we have found out a direct binding between MAPKAPK2 and Sophoridine by cellular thermal shift assay and drug affinity responsive targets stability assay. The inhibition effects are further confirmed by Western blot: Sophoridine significantly decreases phospho-MAPKAPK2 (Thr222) in a time-dependent manner, but there is no obvious change in its total expression in colorectal cancer cells. Clinical studies have shown that a higher level of MAPKAPK2 is associated with a poorer percent survival rate (prognosis). Furthermore, a higher level of MAPKAPK2 is positively associated with the enrichment of downregulation of apoptosis and autophagy by gene set enrichment analysis, as well as upregulation of proliferation and cell-cycle arrest. Taken together, our results suggest that the MAPKAPK2 plays a key role in Sophoridine-inhibited growth and invasion in colorectal cancers. Implications: These studies show that Sophoridine may be a promising therapeutic strategy that blocks tumorigenesis in colorectal cancers.

Benign prostatic hyperplasia (BPH) is a urinary system disease with high prevalence among the middle and elder men. In BPH, proliferation of prostate cells and the imbanlance between androgen and estrogen are both important inducers. Previous studies have demonstrated that compounds from Ligustri Lucidi Fructus (LLF) and Ecliptae Herba (EH) are of phytoestrogenic or phytoandrogenic activities. The combination of LLF with EH at the ratio of 1:1 on crude drugs quantity is called Erzhi formula (EZF), which is used for in vivo research of our study.This study aimed to investigate potential mechanisms of EZF and its active pharmaceutical ingredients on BPH in vitro and in vivo.Therapeutic effects of EZF was evaluated in EEZF treatment significantly attenuated rat prostate enlargement, alleviated BPH pathological features, and decreased the expression of PCNA. The up-regulation of AR, ERα, SRD5A1/2 expressions, and down-regulation of ERβ expression at prostate of rat BPH model were significantly blocked by EZF administration. The expression levels of testosterone, DHT, EEZF, ligustrosidic acid from LLF and echinocystic acid from EH showed inhibitive effects on BPH via down-regulating prostatic AR, ERα, SRD5A1/2 expressions and up-regulating ERβ expression.

A new method for rapidly detecting of total chlorogenic acids (CGAs) in plants by surface-enhanced Raman spectroscopy (SERS) based on reusable Cu

Detection and identification of the in vivo metabolites of traditional Chinese medicine by untargeted profiling strategies are often confronted with severe interference from complex endogenous substances. Here we developed an integral approach, by combining untargeted data-dependent MS2 (dd-MS2) of Q-Orbitrap mass spectrometry and predictive multiple reaction monitoring-information dependent acquisition-enhanced product ion scan (pMRM-IDA-EPI) of triple quadrupole-linear ion trap (QTRAP) mass spectrometry, aiming to detect and identify more extensive metabolites in bio-samples. Ecliptae Herba (EH) is a widely consumed medicinal herb with the effects of nourishing liver/kidney, but its metabolites in vivo have not been fully elucidated. Firstly, after UHPLC separation on an HSS T3 column, chemical fingerprinting of 70% ethanolic extract of EH was performed by untargeted dd-MS2 in negative ion mode. We could characterize 41 compounds from EH, and 24 were detectable in the plasma of rats (prototypes) after oral administration of EH extract (1 g/kg). Secondly, using echinocystic acid (triterpene), wedelolactone (coumarin), and apigenin (flavonoid) as the different parent templates, an MRM list containing 150 predicted ion-pairs was established to enhance MS2 scan by pMRM-IDA-EPI, which enabled the primary identification of up to 200 metabolites. The biotransformations mainly involve oxidation, hydrogenation, methylation, glucuronidation, sulfonation etc. Thirdly, the rat plasma samples obtained after oral administration of three pure compounds (echinocystic acid, wedelolactone and apigenin) were analyzed to verify the reliability of metabolites identification, and 11, 4, and 10 metabolites were found individually. This is the first comprehensive research on the metabolism of EH in vivo.

Objective Monitoring the unbound drug concentration in blood in combination therapy is necessary, because its concentration determines the efficacy of drug therapy. This study was designed to explore the effect of Dan Hong Injection (DHI) on the unbound warfarin using two approaches including an in vivo pharmacokinetic and in vitro fluorescence studies. Methods The effect of DHI on the pharmacokinetic properties of the unbound warfarin was investigated by a microdialysis sampling method coupled with LC–MS/MS. The effect of DHI and salvianolic acid B (SaB) on warfarin binding with bovine serum albumin (BSA) was conducted by fluorescence spectrometry. Results The AUC0-tn of warfarin with DHI group was higher than that of warfarin alone group. The result showed that DHI could increase the concentration of unbound warfarin in rat blood, which may be due to the competition between warfarin and DHI as well as its components binding to serum albumin. The competition process was demonstrated by fluorescence study. Conclusion Combination therapy of DHI with warfarin could enhance the release profile of warfarin from serum protein.

Ethnopharmacological relevance Danggui Liuhuang Tang (DGLHT), first recorded in “Lan-Shi-Mi-Cang” (written in 1276 AD), is a famous classical formula. In 2018, it was listed in the Catalogue of Ancient Classic and Famous Prescriptions (First Batch) formulated by the National Administration of Traditional Chinese Medicine and the National Medical Products Administration. Perimenopausal syndrome (PMS) refers to a series of syndromes with autonomic nervous system dysfunction and neuropsychological symptoms. The treatment of PMS demands non-hormonal drugs. Natural products are considered to be effective substitutes for the treatment of PMS. It is reported that DGLHT has not only good therapeutic effects but also higher safety and fewer side effects in the treatment of PMS. However, the mechanism of DGLHT in treating PMS is not clear. Aim of the study To explore the chemical basis and the mechanism of DGLHT in treating PMS. Materials and methods Multivariate statistical analysis was used to analyze the difference of components in supernatant before and after compatibility of DGLHT based on LC-MS data. The qualitative analysis was performed on the precipitate formed in the decocting process using LC-MS while the quantitative analysis on the potential markers using LC-UV. Then, the potential markers were analyzed by network pharmacology. The regulatory effect of DGLHT on FSH, P and E2 were carried out in PMS rats. Results Five potential markers, epiberberine, coptisine, palmatine, berberine and baicalin, were screened from the analysis of compounds in the supernatant. Four complexes, composed of potential marker monomers, were identified in the sediment, including two that have not been reported. The key targets of potential markers include TNF, NOS3, EGFR, ESR1, PTGS2, AR, CDC42 and RPS6KB1. The top signaling pathways include the cGMP-PKG signaling pathway, PI3K-Akt signaling pathway and estrogen signaling pathway. DGLHT could call back the hormone levels of P and E2 in PMS rats. Conclusion DGLHT active ingredients, epiberberine, coptisine, palmatine, berberine and baicalin contribute a lot to the therapeutic effect. And DGLHT takes effect by regulating hormones secreted by the ovary.