Study on the dynamic metabolic characteristic of main active ingredients in Danggui Buxue Decoction by liquid chromatography-tandem mass spectrometry based on in situ sequential metabolism strategy.

Danggui Buxue Decoction is a classic formula for replenishing qi and nourishing blood. Despite its widespread use, its dynamic metabolism involved remains unclear. Based on the sequential metabolism strategy, blood samples from different metabolic sites were obtained via in situ closed intestine ring integrated with a jugular venous continuous blood supply technique. An ultra-high-performance liquid chromatography-linear triple quadruple-Orbitrap-tandem mass spectrometry method was developed for the identification of prototypes and metabolites in rat plasma. The dynamic absorption and metabolic landscape of flavonoids, saponins, and phthalides were characterized. Flavonoids could be deglycosylated, deacetylated, demethylated, dehydroxylated, and glucuronicated in the gut and then absorbed for further metabolism. Jejunum is an important metabolic site for saponins biotransformation. Saponins that are substituted by Acetyl groups tend to lose their acetyl groups and convert to Astragaloside IV in the jejunum. Phthalides could be hydroxylated and glucuronidated in the gut and then absorbed for further metabolism. Seven components serve as crucial joints in the metabolic network and are potential candidates for the quality control of Danggui Buxue Decoction. The sequential metabolism strategy described in this study could be useful for characterizing the metabolic pathways of Chinese medicine and natural products in the digestive system.

Pathological Study of Light Cupula Syndrome on a Visual Bionic Semicircular Canal.

A type of persistent direction-changing positional nystagmus with a null point during head position deflection is known as light cupula syndrome (LCS) in the clinic. To date, the pathogenesis and biomechanical response of human semicircular canals with light cupula syndrome (LCS) (HSCs-LCS) are still unclear. In this study, based on the anatomical structure and size of the one-dimensional human semicircular canal (HSC) and imitating the pathological changes of the endolymph in HSC with LCS, a visual bionic semicircular canal (BSC) with LCS was fabricated using three-dimensional printing technology, hydrogel modification, and target tracking technology. Through theoretical derivation, mathematical models of the HSC-LCS perception process were established. By conducting in vitro experiments on the bionic model, the biomechanical response process of HSC-LCS was studied, and the mathematical models were validated. The results of pulse acceleration stimulation showed that the pathological changes in the density and viscosity of the endolymph could reduce the deformation of the cupula of the BSC-LCS and increase the time constant. The results of the sinusoidal acceleration stimulation showed that the amplitude-frequency gain of the BSC-LCS decreased and the phase difference increased. The BSC-LCS can be used as a tool for pathological research of the HSC-LCS. The results of this study can provide a theoretical basis for clinical diagnosis.

Design of an In Vitro Semicircular Canal Model and Its Use for the Study of Canalithiasis.

Canalithiasis is a common vestibular system disorder, which may lead to a specific form of vertigo known as BPPV or top-shelf vertigo. In this paper, based on the actual geometric parameters of the human semicircular canal, we designed a four-fold in vitro one-dimensional semicircular canal model using technologies such as three-dimensional printing, image processing, and target tracking. We investigated the essential characteristics of the semicircular canal, such as the time constant of the cupula and the relationship between the number, density, and size of the canalith and the cupular deformation during canalith settlement. The results showed a linear relationship between the number and size of the canalith and the amount of cupular deformation. We also found that when the number of canaliths reached a particular scale, the interaction between the canaliths exerted an additional disturbance on the cupular deformation ("Z" twist). In addition, we explored the latency time of the cupula during canalith settlement. Finally, we verified that the canaliths had little effect on the frequency characteristics of the semicircular canal by a sinusoidal swing experiment. All the results validate the reliability of our 4-fold in vitro one-dimensional semicircular canal model.

Two-dimensional correlation infrared spectroscopy elucidated the volatilization process of the microemulsion composed of peppermint essential oil and composite herbal extract.

Microemulsion is usually a transparent and isotropic liquid mixture composed of oil phase, water phase, surfactant and cosurfactant. The surfactant-framed nanoscale droplets in the microemulsion can penetrate into the skin surface to reduce its barrier function. This makes microemulsion an ideal preparation for the transdermal drug delivery. The permeability of microemulsion may be further enhanced when botanical essential oils that can dissolve the stratum corneum are used as the oil phase. However, the volatility of essential oils is possible to shorten the retention time of the microemulsion on the skin surface. Therefore, analytical methods are required to understand the volatilization process of the microemulsion composed of essential oils to develop the reasonable topical drug carrier system. In this research, Fourier transform infrared (FTIR) spectroscopy with an attenuated total reflection (ATR) accessory cooperated with two-dimensional correlation spectroscopy (2DCOS) to elucidate the volatilization processes of some microemulsions composed of peppermint essential oil. Principal component analysis (PCA) and moving-window two-dimensional correlation spectroscopy (MW2DCOS) revealed the multiple stages of the volatilization processes of the microemulsions. Synchronous 2D correlation infrared spectra indicated the compositional changes during each stage. It was found that the successive volatilizations of ethanol, water and menthone were the major events during the volatilization process of the microemulsion composed of peppermint essential oil. Ethanol can accelerate the volatilization of water, while the composite herbal extract seemed to not influence the volatilization of the other ingredients. After a 20-min-long volatilization process, the remaining microemulsion still contained considerable peppermint essential oil to affect the skin. The above results showed the feasibility of developing the microemulsion composed of peppermint essential oil for the transdermal drug delivery of composite herbal extract. This research also proved that the combination of ATR-FTIR spectroscopy and 2DCOS was valuable to study the volatilization process of the microemulsion.

Interventional effect of processing temperature on anti-angiogenesis of Coptis chinensis and screening of active components by UPLC-MS/MS on quail chick chorioallantoic membrane model.

ETHNOPHARMACOLOGICAL RELEVANCE: Coptis chinensis Franch. (CC), as a commonly used heat-clearing and toxin-resolving traditional Chinese herbal medicine, has gained increased attention for its anti-tumor activity. However, little is known about the anti-tumor angiogenesis effect of CC and its possible bioactive components. Also, it has been shown that temperature affects the quality of CC, albeit whether and how it affects the anti-angiogenic activity of CC is currently unknown. AIM OF THE STUDY: To determine the processing temperatures (40, 60, 80, 120, 140, 150, 160 and 200 °C) at which CC has the strongest anti-angiogenic effect and speculate the possible bioactive components. MATERIALS AND METHODS: The q-CAM model was constructed to explore the anti-angiogenesis agents of CC. The angiogenesis inhibition effects of CC samples at different processing temperatures and its seven alkaloids were determined based on morphological observation and vascular area proportion analysis. UPLC-MS/MS was employed to screen the potent active components of CC on anti-angiogenesis. RESULTS: All the intervention by CC at different processing temperatures and its seven alkaloids could inhibit angiogenesis on q-CAM vessels, as evidenced by a poor vasular development in morphological observation and a low vascular area proportion in vascular quantitative analysis, most evident in CC processed at 40 °C and palmatine. LC-MS revealed that palmatine displayed strongest inhibitory effect on q-CAM vessels with a high absorption due to its stable structure. And the maternal nucleus transformation phenomenon of CC alkaloids was found in the quail embryo metabolism. CONCLUSIONS: The q-CAM models in conjunction with the UPLC-MS/MS technique could be a useful tool for assessing tumor angiogenesis and screening tumor-targeted medicines. Processing temperature can affect the anti-angiogenesis effect of CC because of its function on the content of alkaloids, and palmatine can be considered as a prospective anti-angiogenic drug.

A low-frequency acceleration sensor inspired by saccule in human vestibule.

A human vestibular system is a group of devices in the inner ear that govern the balancing movement of the head, in which the saccule is responsible for sensing gravity accelerations. Imitating the sensing principle and structure of the Sensory Hair (SH) cell in the saccule, a Bionic Sensory Hair (BSH) was developed, and 9 BSH arrays were arranged in the bionic macular at the bottom of the spherical shell to prepare a Bionic Saccule (BS). Based on the piezoelectric equation, the electromechanical theoretical models of the BSH cantilever and BS were deduced. They were subjected to impact oscillations using an exciter, and their output charges were analyzed to check their sensing ability. The results showed that BSH could sense its bending deflection, and the BS could sense its position change in the sagittal plane and in space. They exhibited a sensitivity of 1.6104 Pc s2/m and a fast response and similar sensing principles and low resonance frequency to those of the human saccule. The BS is expected to be used in the field of robotics and clinical disease diagnosis as a part of the artificial vestibular system in the future.

Development of Bionic Semicircular Canals and the Sensation of Angular Acceleration.

To study the sensing process of the human semicircular canals (HSCs) during head rotation, which is difficult to directly measure due to physiological reasons. A 1-BSC (one-dimensional bionic semicircular canal) and 3-BSC were prepared with soft SMPFs (symmetric electrode metal core polyvinylidene difluoride fibers), which could sense deformations similar to human sensory cells. Based on these models, experiments were carried out to study the principle of the HSCs. Deformations of the bionic ampulla (BA) depended on the angular acceleration. Gravity had a strong influence on the deformation of the BA in the vertical plane. When the 3-BSC was subjected to angular acceleration around one of its centerlines, the three BAs all deformed. The deformation of the BAs was linearly related to the angular acceleration. The deformation of the BA in the main semicircular canal was exactly three times that of the other two BAs.

Study the biomechanical performance of the membranous semicircular canal based on bionic models.

A BA (bionic ampulla) was designed and fabricated using an SMPF (Symmetric electrodes Metal core PVDF Fiber) sensor, which could imitate the sensory hair cells to sense the deformation of the cupula of the BA. Based on the BA, a bionic semicircular canal with membrane semicircular canal (MBSC) and a bionic semicircular canal without membrane semicircular canal (NBSC) were designed and fabricated. The biomechanical models of the MBSC and NBSC were established. The biomechanical models were verified through the perception experiments of the MBSC and the NBSC. The results showed that the SMPF could sense the deformation of the cupula. The MBSC and NBSC could sense the angular velocity and accelerations. What's more, it was speculated that in a human body, the endolymph probably had a function of liquid mass while the membranous semicircular canal and the cupula had a function similar to a spring in the human semicircular canal.

Outcomes of the bionic semicircular canals support the "density hypothesis" and "circular hypothesis".

To date, there are three main hypotheses explaining why the human semicircular canals (HSCCs) cannot sense linear accelerations. To further study this issue, we designed a bionic ampulla (BA) instrumented with a symmetrical metal core polyvinylidene fluoride fiber as a bionic sensor, which imitates the structure and function of the human ampulla. The BA was confirmed to have a good sensing ability in experiments with a straight tube. Additionally, we designed a bionic semicircular canal model, a blocking model, and a square model. We compared the perception performance of these three models to test the "density hypothesis," the "closed loop hypothesis," and the "circular hypothesis." The outcomes of these experiments verified the "density hypothesis" and "circular hypothesis," but did not support the "closed loop hypothesis," shedding light on why the HSCC is sensitive to angular acceleration, but not to linear acceleration.

Study on the Perception Mechanism of Utricles Based on Bionic Models.

BACKGROUND: The relationship between utricle diseases and structural lesions is not very clear in the clinic due to the complexity and delicacy of the utricle structure. Therefore, it is necessary to study the perception mechanism of the utricle. METHODS: Imitating the sensory cells in the macula of the utricle, a symmetrical metal core PVDF fiber (SMPF) was designed as a bionic hair sensor to fabricate a bionic macula (BM), a bionic macula with sand (BMS) and a bionic utricle (BU). Then experiments were carried out on them. RESULTS: This indicated the SMPF sensor can sense its bending deformation, which was similar to the sensory cell. The amplitude of the output charges of the SMPF in BMS and BU were significantly improved. The SMPF, whose electrode boundary was perpendicular to the impact direction, exhibited the largest output charges. CONCLUSION: The presence of otoliths and endolymph can improve the sensing ability of the utricle. The human brain can judge the direction of head linear accelerations based on the location of the sensory cell in the macula that produces the largest nerve signals. This provides a possibility of studying utricle abnormal functions in vitro in the future.

Design and fabrication of an E-whisker using a PVDF ring.

Mammalian whiskers can perceive obstacles and airflows. In this study, an electronic whisker (E-whisker) sensor was designed and fabricated by setting a PVDF ring with symmetrical electrodes on the root of a fiber beam. Vibration displacements with different waveforms were applied at the free end of the E-whisker beam to study the relationship between the vibration displacements and the output signals. The E-whisker protrusion sensing ability was investigated by driving it to sweep through the surface of a base platform. A static E-whisker beam and a swinging E-whisker were then separately placed in a wind tunnel to detect the airflow perception of the sensor. The experimental results suggested that the E-whisker could sense the frequencies and amplitudes of displacements at its free end, the height and width of a platform or the heights of other irregular protrusions; the static E-whisker could sense the magnitude or direction of an impact airflow, while the swinging E-whisker could sense the magnitude of a constant airflow. Thus, this kind of E-whisker could perceive the environment and airflow through touch sensation and could be used as a physical model to study the principles and abilities of animal whiskers to perceive obstacles and airflows.

Valeriana jatamansi Jones ex Roxb. Against Post-Traumatic Stress Disorder, Network Pharmacological Analysis, and In Vivo Evaluation.

Zhi zhu xiang (ZZX) is the root and rhizome of Valeriana jatamansi Jones ex Roxb. Recent studies have shown that ZZX can exert antianxiety, antidepressant, and sedative effects. Because post-traumatic stress disorder (PTSD) is similar to depression and anxiety in terms of its etiology, pathogenesis, and clinical manifestations, it is possible that ZZX may also be useful for the prevention and treatment of PTSD. In this study, a mouse model of PTSD was established and used to study the pharmacological action of a 95% ethanol extract of ZZX on PTSD via a series of classic behavioral tests. We found that a 95% ethanol extract of ZZX was indeed effective for relieving the symptoms of PTSD in mice. Moreover, network pharmacology analysis was used to predict the potential active ingredients, targets, and possible pathways of ZZX in the treatment of PTSD. The neurotransmitter system, the hypothalamic-pituitary-adrenal (HPA) axis, and the endocannabinoid (eCB) system were identified to be the most likely pathways for anti-PTSD action in ZZX. Due to the lack of a falsification mechanism in network pharmacology, in vivo tests were carried out in mice, and the expression levels of neurotransmitters, hormones, and genes of key targets were detected by enzyme-linked immunosorbent assay and real-time PCR to further verify this inference. Analysis showed that the levels of norepinephrine, 5-hydroxytryptamine, and glutamic acid were increased in the hippocampus, prefrontal cortex, and amygdala of PTSD mice, while the levels of dopamine and γ-aminobutyric acid were decreased in these brain regions; furthermore, ZZX could restore the expression of these factors, at least to a certain extent. The levels of adrenocorticotropic hormone, corticosterone, and corticotropin-releasing hormone were increased in these different brain regions and the serum of PTSD mice; these effects could be reversed by ZZX to a certain extent. The expression levels of cannabinoid receptor 1 and diacylglycerol lipase α mRNA were decreased in PTSD mice, while the levels of fatty acid amide hydrolase and monoacylglycerol lipase mRNA were increased; these effects were restored by ZZX to a certain extent. In conclusion, our findings suggest that ZZX may provide new therapeutic pathways for treating PTSD by the regulation of neurotransmitters, the HPA, and expression levels of eCB-related genes in the brain.

MnO2 Nanosheet-Assembled Hollow Polyhedron Grown on Carbon Cloth for Flexible Aqueous Zinc-Ion Batteries.

Aqueous zinc-ion batteries (ZIBs) have been considered as prospective alternatives for lithium-ion batteries, which are able to serve as power sources for next-generation wearable and flexible devices, owing to the merits of abundant zinc resources and high safety of aqueous electrolyte. However, the lack of suitable cathode materials with flexibility for ZIBs hinders their further application. Herein, a novel cathode material [i.e., MnO2 nanosheet-assembled hollow polyhedron anchored on carbon cloth (MnO2 /CC)] was prepared through a rapid hydrothermal method by using ZIF-67 as self-sacrificing template. When tested in an aqueous ZIB, the MnO2 /CC delivered a high reversible capacity of 263.9 mAh g-1 at 1.0 A g-1 after 300 cycles, far exceeding those of the commercial MnO2 electrode. More importantly, benefiting from the unique structural advantages, a flexible ZIB assembled based on the MnO2 /CC displayed a stable output voltage of 1.53 V and a specific capacity of 91.7 mAh g-1 at 0.1 A g-1 after 30 cycles. It also successfully lit LED bulbs even under different bending angles, showing good flexibility. This research contributes to the development of MnO2 -based cathode materials for high-performance flexible ZIBs.

3D printing algorithm of anisotropic biological scaffold with oxidized nanocellulose and gelatin.

Tissue scaffolds need to have anisotropic mechanical properties and a porous structure to meet the needs of different tissues and organs. This report presents results of a study on an especially-designed 3D printing method with oxidized nanocellulose and gelatin, analyzes the servo principle of pneumatic condensing extrusion 3D printer, and proposes a hexagonal algorithm. For the purpose of this study, a printing process file was written by G code, physical and mechanical performance of the 3D scaffolds was evaluated with Solidworks simulation, the porous structure and pressure-pull performance of the printed 3D scaffolds was observed by SEM, and experiments were conducted to measure their bio-compatibility. The study draws the conclusion that scaffolds thus printed have a highly porous structure and anisotropic mechanical properties.

3D printing process of oxidized nanocellulose and gelatin scaffold.

For tissue engineering applications tissue scaffolds need to have a porous structure to meet the needs of cell proliferation/differentiation, vascularisation and sufficient mechanical strength for the specific tissue. Here we report the results of a study of the 3D printing process for composite materials based on oxidized nanocellulose and gelatin, that was optimised through measuring rheological properties of different batches of materials after different crosslinking times, simulation of the pneumatic extrusion process and 3D scaffolds fabrication with Solidworks Flow Simulation, observation of its porous structure by SEM, measurement of pressure-pull performance, and experiments aimed at finding out the vitro cytotoxicity and cell morphology. The materials printed are highly porous scaffolds with good mechanical properties.

Preparation of cellulose nanocrystals from Humulus japonicus stem and the influence of high temperature pretreatment.

As one of the most abundant wild herbs in nature, the Humulus japonicus stem (HJS) is a new low-cost source of cellulosic material. In this work, cellulose nanocrystals (CNCs) were isolated from HJS using acid hydrolysis. The influence of high temperature pretreatment (HT pretreatment) on the properties and yields of these HT-HJS (HJS fibers after HT pretreatment at different temperatures) and HT-CNCs (CNCs prepared from the HT-HJS) was studied. The results showed that there was no variation of the chemical structure among the HT-HJS and HT-CNCs. The thermal stabilities and crystallinities of the HT-HJS were higher than bleached HJS. The average diameters of the HT-CNCs were significantly smaller while the average aspect ratios of them were obviously bigger than the CNCs, and the biggest average aspect ratio of HT140-CNCs (63.40) was almost twice of CNCs (32.00). Compared with the CNCs (70.05%, 212.8°C), the crystallinity and initial degradation temperature also showed increase for the HT-CNCs and increased up to maximum of 86.93% and 227.5°C for the HT160-CNCs.

Study of the Mechanism of Perceived Rotational Acceleration of a Bionic Semicircular Canal on the Basis of the "Circular Geometry Hypothesis".

Academia often uses the "circular geometry hypothesis" to explain the sensing principle of the human semicircular canal (SCC) system for angular acceleration, which is widely accepted as an important angular acceleration sensor in the human balance system. On the basis of this hypothesis and the anatomical structure of human SCCs, a series of physical SCC models with different geometries at 4× magnification were prepared via three-dimensional printing and modification of hydrogels. Theoretical models of the SCC perception mechanism were established. Then, impulse angular acceleration, sinusoidal rotation, and sinusoidal linear stimulation were applied to the models, and their responses were visually observed and analyzed in detail. As a result, the circular SCC model had a larger system gain and a smaller phase difference for angular acceleration stimulation but a smaller system gain and a larger phase difference for linear acceleration stimulation. These results verified that the circular semicircular canal was more sensitive to angular acceleration. Our bionic model is hoped to be used for demonstrating the human SCC working process, facilitating researchers in better understanding of the working mechanism of the human SCC, or as a manual model for medical staff to simulate the diagnosis and treatment of human SCC.