Understanding the mechanisms influencing patterns and processes of biological diversity is critical to protecting biodiversity, particularly in species-rich ecosystems such as mountains. Even so, ...there is limited knowledge of biodiversity patterns and processes in the mountains of eastern China, especially about small mammals. In this study, we examined the taxonomic, functional, and phylogenetic diversity of small mammal distribution and community structure along the elevational gradient of Qingliang Mountain, eastern China. We then evaluated how they are influenced by space (area and mid-domain effect (MDE)), environment (temperature, precipitation, and normalized difference vegetation index (NDVI)), and human disturbance. The results showed hump-shaped patterns of taxonomic and phylogenetic diversity along elevation gradients, peaking at 1000 m, unlike functional diversity, which peaked at lower elevations (600 m). The mean pairwise distance and mean nearest taxon distance of functional and phylogenetic variance (MFD and MPD, respectively) were also incongruent. The MFD and MPD showed hump-shaped patterns along elevations; however, unlike MFD, which peaked at lower elevations (600 m), MPD peaked at higher elevations (1200 m). The mean nearest functional taxon distance (MNFD) decreased, while the mean nearest phylogenetic taxon distance (MNTD) increased along the elevation gradient. The higher elevations were functionally more clustered, while the lower elevations were phylogenetically more clustered, suggesting that environmental filtering for traits was stronger at higher elevations. In comparison, phylogenetic conservatism of ecological niches had a stronger influence at lower elevations. The diversity and community structure indices were inconsistently explained, with human disturbance and MDE accounting for the biggest proportions of the model-explained variances. Overall, the results confirm that environmental filtering and human disturbance significantly influence small mammals’ diversity and community structure. These findings also emphasize the need for increased conservation efforts in the middle and lower elevation regions of Qingliang Mountain.
Background:
Dianbaizhu (
Gaultheria leucocarpa
var.
yunnanensis
), a traditional Chinese/ethnic medicine (TC/EM), has been used to treat rheumatoid arthritis (RA) for a long time. The anti–rheumatic ...arthritis fraction (ARF) of
G
.
yunnanensis
has significant anti-inflammatory and analgesic activities and is mainly composed of methyl salicylate glycosides, flavonoids, organic acids, and others. The effective ingredients and rudimentary mechanism of ARF remedying RA have not been elucidated to date.
Purpose:
The aim of the present study is to give an insight into the effective components and mechanisms of Dianbaizhu in ameliorating RA, based on the estimation of the absorption, distribution, metabolism, and excretion (ADME) properties, analysis of network pharmacology, and
in vivo
and
in vitro
validations
.
Study design and methods:
The IL-1β–induced human fibroblast-like synoviocytes of RA (HFLS-RA) model and adjuvant-induced arthritis in the rat model were adopted to assess the anti-RA effect of ARF. The components in ARF were identified by using UHPLC-LTQ-Orbitrap-MS
n
. The quantitative structure–activity relationship (QSAR) models were developed by using five machine learning algorithms, alone or in combination with genetic algorithms for predicting the ADME properties of ARF. The molecular networks and pathways presumably referring to the therapy of ARF on RA were yielded by using common databases and visible software, and the experimental validations of the key targets conducted
in vitro
.
Results:
ARF effectively relieved RA
in vivo
and
in vitro
. The five optimized QSAR models that were developed showed robustness and predictive ability. The characterized 48 components in ARF had good biological potency. Four key signaling pathways were obtained, which were related to both cytokine signaling and cell immune response. ARF suppressed IL-1β–induced expression of EGFR, MMP 9, IL2, MAPK14, and KDR in the HFLS-RA .
Conclusions
: ARF has good druggability and high exploitation potential. Methyl salicylate glycosides and flavonoids play essential roles in attuning RA. ARF may partially attenuate RA by regulating the expression of multi-targets in the inflammation–immune system. These provide valuable information to rationalize ARF and other TC/EMs in the treatment of RA.
For quality control improvement of medicine and food homology (MFH) health food, the concept of functional quality control and rapid screening strategy of functional compounds were proposed based on ...the dual identity characteristics. Taking Wuweisanqi Capsule as the research object, firstly, a modified method “syndrome correlation-network analysis” based on network pharmacology was used for analysis. Functions related targets were collected from common medical databases, while the clustering algorithm was used to extract the information of clinical records related to daily health care from traditional Chinese medicine (TCM) database to obtain the targets. The bioactive compounds and related targets were retrieved from the TCM Systems Pharmacology Database and Analysis Platform around the five materials included in formula. Protein-protein interaction (PPI) network and pathway enrichment analysis were performed on the intersection targets. According to the constructed formula material-compound-target-pathway network, the potential functional compounds were preliminarily identified. Secondly, key targets and compounds were analyzed by molecular docking to further screen functional compounds. Finally, combined with references, the screening and establishing determination methods of functional compounds containing total saponins, astragaloside IV, puerarin and schisandrin were finished. The rapid screening strategy adequately utilizes the advantage of TCM background for MFH health food and the effective extracting ability of massive data by the algorithm. It links three aspects of health food functions, formula materials and functional compounds, providing an efficient solution for the realization of function-formula-component integrated functional quality control, which has great application potential in health food industry.
Objective:
Curcumae Rhizoma
–
Sparganii Rhizoma
(CR-SR) is a traditional botanical drug pair that can promote blood circulation, remove blood stasis, and treat tumors in clinics. The aim of the ...present study was to investigate the therapeutic material basis and potential mechanisms of CR-SR, CR, and SR for the treatment of liver cancer.
Method:
The chemical profile analyses of CR-SR, CR, and SR were performed by molecular networking and UPLC-LTQ-Orbitrap MS
n
. The anti-liver cancer activities of CR-SR, CR, and SR were assessed by using a zebrafish xenograft model
in vivo
for the first time and detected by the HepG2 cell model
in vitro
. Combining the network analysis and molecular docking, real-time quantitative polymerase chain reaction (RT-qPCR) experiments were undertaken to further explore the mechanisms of CR-SR, CR, and SR for the treatment of liver cancer.
Results:
In total, 65 components were identified in CR-SR, CR, and SR. Based on the clusters of molecular networking, a total of 12 novel diarylheptanoids were identified from CR-SR and CR. By combining our results with information from the literature, 32 sesquiterpenoids and 21 cyclic dipeptides were identified from CR-SR, CR, and SR. The anti-liver cancer activities were observed in both the drug pair and the single botanical drugs
in vitro
and
in vivo
, and the order of activity was CR-SR > CR > SR. They could downregulate the expression of proto-oncogene tyrosine-protein kinase Src (SRC), epidermal growth factor receptor (EGFR), estrogen receptor-α (ESR1), prostaglandin endoperoxide synthase 2 (PTGS2), and amyloid precursor protein (APP).
Conclusion:
Taken together, the present study provided an experimental basis for the therapeutic material basis and potential molecular mechanisms of CR-SR, CR, and SR. This study provided a novel insight for objective clinical treatment of liver cancer.
Recently, rapid advances in flexible strain sensors have broadened their application scenario in monitoring of various mechanophysiological signals. Among various strain sensors, the crack-based ...strain sensors have drawn increasing attention in monitoring subtle mechanical deformation due to their high sensitivity. However, early generation and rapid propagation of cracks in the conductive sensing layer result in a narrow working range, limiting their application in monitoring large biomechanical signals. Herein, we developed a stress-deconcentrated ultrasensitive strain (SDUS) sensor with ultrahigh sensitivity (gauge factor up to 2.3 × 10
6
) and a wide working range (0%–50%)
via
incorporating notch-insensitive elastic substrate and micro-crack-tunable conductive layer. Furthermore, the highly elastic amine-based polymer-modified polydimethylsiloxane substrate without obvious hysteresis endows our SDUS sensor with a rapid response time (2.33 ms) to external stimuli. The accurate detection of the radial pulse, joint motion, and vocal cord vibration proves the capability of SDUS sensor for healthcare monitoring and human-machine communications.
Clinical xenotransplantations have been hampered by human preformed antibody-mediated damage of the xenografts. To overcome biological incompatibility between pigs and humans, one strategy is to ...remove the major antigens Gal, Neu5Gc, and Sd(a) present on pig cells and tissues. Triple gene (GGTA1, CMAH, and β 4GalNT2) knockout (TKO) pigs were produced in our laboratory by CRISPR-Cas9 targeting. To investigate the antigenicity reduction in the TKO pigs, the expression levels of these three xenoantigens in the cornea, heart, liver, spleen, lung, kidney, and pancreas tissues were examined. The level of human IgG/IgM binding to those tissues was also investigated, with wildtype pig tissues as control. The results showed that αGal, Neu5Gc, and Sd(a) were markedly positive in all the examined tissues in wildtype pigs but barely detected in TKO pigs. Compared to wildtype pigs, the liver, spleen, and pancreas of TKO pigs showed comparable levels of human IgG and IgM binding, whereas corneas, heart, lung, and kidney of TKO pigs exhibited significantly reduced human IgG and IgM binding. These results indicate that the antigenicity of TKO pig is significantly reduced and the remaining xenoantigens on porcine tissues can be eliminated via a gene targeting approach.
Abstract Conventional wound closure methods, including sutures and tissue adhesives, present significant challenges for self‐care treatment, particularly in the context of bleeding wounds. Existing ...stimuli‐responsive contractile materials designed for autonomous wound closure frequently lack sufficient output work density to generate the force needed to bring the wound edges into proximity or necessitate stimuli that are not compatible with the human body. Here, semi‐transparent, flexible, and water‐responsive shrinkable films, composed of poly(ethylene oxide) and α‐cyclodextrin, are reported. These films exhibit remarkable stability under ambient conditions and demonstrate significant contraction (≈50%) within 6 s upon exposure to water, generating substantial contractile stress (up to 6 MPa) and output work density (≈1028 kJ m −3 ), which is 100 times larger than that of conventional hydrogel and 25 times larger than that of skeletal muscles. Remarkably, upon hydration, these films are capable of lifting objects 10 000 times their own weight. Leveraging this technology, water‐shrink tapes, which, upon contact with water, effectively constrict human skin and autonomously close bleeding wounds in animal models within 10 seconds, are developed further. This work offers a novel approach to skin wound management, showing significant potential for emergency and self‐care scenarios.
Thymus quinquecostatus Celak., a member of thymus genus in Lamiaceae family, has been used as a folk medicine for relieving exterior syndrome and alleviating pain in China. The polyphenol-rich ...fraction (PRF) derived from Thymus quinquecostatus Celak. had been validated that it can protect cerebral ischemia-reperfusion injury (CIRI) by activating Keap1/Nrf2/HO-1 signaling pathway.
Aim of this study: To explore effective components and their pharmacokinetic and pharmacodynamic characteristics as well as possible mechanisms of PRF in treating CIRI.
Normal treated group (NTG) and tMCAO model treated group (MTG) rats were administrated PRF intragastrically. The prototype components and metabolites of PRF in plasma and brain were analyzed by the UPLC-Q-Exactive Orbitrap MSn method. Subsequently, the pharmacokinetics properties of indicative components were performed based on HPLC-QQQ-MS/MS. SOD and LDH activities were determined to study the pharmacodynamic (PD) properties of PRF. The PK-PD relationship of PRF was constructed. In addition, the effect of PRF on endogenous metabolites in plasma and brain was investigated using metabolomic method.
Salvianic acid A, caffeic acid, rosmarinic acid, scutellarin, and apigenin-7-O-glucuronide were selected as indicative components based on metabolic analysis. The non-compartmental parameters were calculated for indicative components in plasma and brain of NTG and MTG rats. Furthermore, single-component and multi-component PK-PD modeling involved Emax, Imax PD models for effect indexes were fitted as well as ANN models were established, which indicated that these components can work together to regulate SOD and LDH activities in plasma and SOD activity in brain tissue to improve CIRI. Additionally, PRF may ameliorate CIRI by regulating the disorder of endogenous metabolites in lipid metabolism, amino acid metabolism, and purine metabolism pathways in vivo, among which lipid metabolism and purine metabolism are closely related to oxidative stress.
The PK-PD properties of effect substances and mechanisms of PRF anti-CIRI were further elaborated. The findings provide a convincing foundation for the application of T. quinquecostatus Celak. in the maintenance of human health disorders.
Display omitted
•The prototype components and metabolites of PRF in plasma and brain were analyzed.•The ADMET properties of PRF were explored by pharmacokinetic study.•The single-component and multi-component integrated as well as ANN PK-PD modelings were established and clarified the effective components of PRF anti-CIRI.•PRF improved CIRI mainly by regulating the disorder of amino acid metabolism, lipid metabolism, and purine metabolism.
Mesenchymal stem cell (MSC)-based cardiac patches are envisioned to be a promising treatment option for patients with myocardial infarction. However, their therapeutic efficacy and duration are ...hampered due to their limited retention on the epicardium. We engineered a scaffold-free MSC sheet with an inherent ability to migrate into the infarcted myocardium, a strategy enabled by actively establishing a sustained intracellular hypoxic environment through the endocytosis of our FDA-approved ferumoxytol. This iron oxide nanoparticle stabilized hypoxia-induced factor-1α, triggering upregulation of the CXC chemokine receptor and subsequent MSC chemotaxis. Thus, MSCs integrated into 2/3 depth of the left ventricular anterior wall in a rat model of acute myocardial infarction and persisted for at least 28 days. This led to spatiotemporal delivery of paracrine factors by MSCs, enhancing cardiac regeneration and function. Ferumoxytol also facilitated the noninvasive MRI tracking of implanted MSCs. Our approach introduces a strategy for mobilizing MSC migration, holding promise for rapid clinical translation in myocardial infarction treatment.
A tactile sensor needs to perceive static pressures and dynamic forces in real-time with high accuracy for early diagnosis of diseases and development of intelligent medical prosthetics. However, ...biomechanical and external mechanical signals are always aliased (including variable physiological and pathological events and motion artifacts), bringing great challenges to precise identification of the signals of interest (SOI). Although the existing signal segmentation methods can extract SOI and remove artifacts by blind source separation and/or additional filters, they may restrict the recognizable patterns of the device, and even cause signal distortion. Herein, an in-memory tactile sensor (IMT) with a dynamically adjustable steep-slope region (SSR) and nanocavity-induced nonvolatility (retention time >1000 s) is proposed on the basis of a machano-gated transistor, which directly transduces the tactile stimuli to various dope states of the channel. The programmable SSR endows the sensor with a critical window of responsiveness, realizing the perception of signals on demand. Owing to the nonvolatility of the sensor, the mapping of mechanical cues with high spatiotemporal accuracy and associative learning between two physical inputs are realized, contributing to the accurate assessment of the tissue health status and ultralow-power (about 25.1 μW) identification of an occasionally occurring tremor.
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