The anti-hyperlipidemia effect of Atractylodes macrocephala Rhizome increased HDL via reverse cholesterol transfer.

Aim: Atractylodes macrocephala Rhizome (AM) has been used to treat hyperlipidemia for centuries, but its functional components and mechanisms are not clear. This research aimed to investigate the active components in AM and the mechanisms that underlie its anti-hyperlipidemia effect. Methods: SD rats were fed a high-sucrose high-fat diet in conjunction with alcohol (HSHFDAC) along with different AM extracts (AMW, AMO, AME, and AMP) for 4 weeks. AM's active components were analyzed using multiple databases, and their mechanisms were explored through network pharmacology. The relationship between AM's effect of enhancing serum HDL-c and regulating the expression of reverse cholesterol transport (RCT)-related proteins (Apo-A1, LCAT, and SR-BI) was further validated in the HSHFDAC-induced hyperlipidemic rats. The kidney and liver functions of the rats were measured to evaluate the safety of AM. Results: AMO, mainly comprised of volatile and liposoluble components, contributed the most significant anti-hyperlipidemia effect among the four extracts obtained from AM, significantly improving the blood lipid profile. Network pharmacology analysis also suggested that volatile and liposoluble components, comprise AM's main active components and they might act on signaling pathways associated with elevated HDL-c. Validation experiments found that AMO substantially and dose-dependently increased HDL-c levels, upregulated the expression of Apo-A1, SR-BI, and LCAT, improved the pathological changes in the kidney and liver, and significantly reduced the serum creatinine levels in rats with hyperlipidemia. Conclusion: The main anti-hyperlipidemia active components of AM are its volatile and liposoluble components, which may enhance serum HDL-c by increasing the expression of the RCT-related proteins Apo-A1, LCAT, and SR-BI.

Bioinformatics and LC-QTOF-MS based discovery of pharmacodynamic and Q-markers of Pitongshu against functional dyspepsia.

ETHNOPHARMACOLOGICAL RELEVANCE: Pitongshu (PTS) is a clinically effective empirical formula for the treatment of FD. The efficacy and safety of PTS have been demonstrated in randomized, controlled, double-blind trials, but there is a lack of understanding of the systematic evaluation of the efficacy of PTS and its material basis. OBJECTIVE: To investigate the efficacy of PTS in Functional dyspepsia (FD) mice and possible Q-markers. METHOD: In this study, we used "irregular feeding + chronic unpredictable chronic stimulation" to establish a mice model of FD with hepatogastric disharmony. The efficacy of PTS was assessed from hair condition, behavioral, pain, gastrointestinal function, and serum 5-HT, GAS, MTL levels in mice by instillation of different doses of PTS. In addition, the composition of drugs in blood was analyzed by LC-QTOF-MS and potential Q-markers were selected by combining network pharmacology, molecular docking and actual content. RESULT: Our study showed that different doses of PTS increased pain threshold and writhing latency, decreased the number of writhings, increased gastric emptying rate and small intestinal propulsion rate, decreased total acidity of gastric contents and gastric acid secretion, and increased serum levels of 5-HT, GAS, and MTL in mice to different degrees. Enrichment analysis showed that PTS may be anti-FD through multiple pathways such as Serotonergic synapse, thyroid hormone signaling pathway, cholinergic synapse, and dopaminergic synapse. In addition, potential active ingredient substances were explored by LC-QTOF-MS combined with bioinformatics. Combined with the actual contentselected six constituents, hesperidin, neohesperidin, naringin, paeoniflorin, magnolol and honokiol, possible as Q-markers. CONCLUSION: PTS may exert its anti-FD effects through multi-component, multi-target and multi-pathway". Constituents, hesperidin, neohesperidin, naringin, paeoniflorin, magnolol and honokiol may be the Q-markers of its anti-FD effects.

Integrated bioinformatics and network pharmacology to explore the therapeutic target and molecular mechanisms of Bailing capsule on polycystic ovary syndrome.

BACKGROUND: Polycystic ovary syndrome (PCOS) is a complex endocrine and metabolic disorder that is common in women of reproductive age. The clinical features of PCOS include hyperandrogenemia and polycystic ovarian changes. Bailing capsule (BL), a proprietary Chinese medicine that contains fermented Cordyceps sinensis powder, has been applied to treat PCOS. However, the specific active ingredients of BL and its mechanisms of action are yet to be elucidated. METHODS: Initially, the effectiveness of BL on PCOS model mice was evaluated. Subsequently, the active ingredients of BL were searched in the TCMSP and TCM Systems Pharmacology databases, and their targets were predicted using Swiss Target Prediction and SEA databases. Furthermore, the GEO gene database was used to screen for differentially expressed genes (DEGs) related to PCOS. Data from Gene Card, OMIM, DDT, and Drugbank databases were then combined to establish a PCOS disease gene library. Cross targets were imported into the STRING database to construct a protein-protein interaction network. In addition, GO and KEGG pathway enrichment analyses were performed using Metascape and DAVID databases and visualized using Cytoscape software and R 4.2.3. The core targets were docked with SYBYL-X software, and their expressions in PCOS mice were further verified using qPCR. RESULTS: The core active ingredients of BL were identified to be linoleyl acetate, cholesteryl palmitate, arachidonic acid, among others. Microarray data sets from four groups containing disease and normal samples were obtained from the GEO database. A total of 491 DEGs and 106 drug-disease cross genes were selected. Estrous cycle and ovarian lesions were found to be improved in PCOS model mice following BL treatment. While the levels of testosterone, progesterone, and prolactin decreased, that of estradiol increased. qPCR findings indicated that the expressions of JAK2, PPARG, PI3K, and AKT1 were upregulated, whereas those of ESR1 and IRS1 were downregulated in PCOS model mice. After the administration of BL, the expressions of associated genes were regulated. This study demonstrated that BL exerted anti-PCOS effects via PIK3CA, ESR1, AKT, PPARG, and IRS1 targets affecting PI3K-Akt signaling pathways. DISCUSSION: This research clarified the multicomponent, multitarget, and multichannel action of BL and provided a theoretical reference for further investigations on its pharmacological basis and molecular mechanisms against PCOS.

Highly stable, substrate-free, and flexible broadband halide perovskite paper photodetectors.

In this work, we aim to fabricate a highly stable and flexible perovskite paper photodetector based on a Zn-doped MA0.6FA0.4PbI3 perovskite and CNC. The paper photodetector has been successfully synthesized by the vacuum filtration method and deposited with interdigitated electrodes. The paper photodetector exhibits a significant photoresponse with a responsivity of 0.23 A W-1 under 650 nm light irradiation when operated at 5 V. The stability of the paper photodetector has also been tested and it shows high photoresponse after 30 days under ambient conditions. Therefore, this paper photodetector holds promise for developing efficient, stable, and flexible optoelectronic devices in the future.

Effects of a Macroporous Resin Extract of Dendrobium officinale Leaves in Rats with Hyperuricemia Induced by Anthropomorphic Unhealthy Lifestyle.

Aim: Hyperuricemia (HUA) has received increased attention in the last few decades due to its global prevalence. Our previous study found that administration of a macroporous resin extract of Dendrobium officinale leaves (DoMRE) to rats with HUA that was induced by exposure to potassium oxazine combined with fructose and a high-purine diet led to a significant reduction in serum uric acid (SUA) levels. The aim of this study was to explore the effects of DoMRE on hyperuricemia induced by anthropomorphic unhealthy lifestyle and to elucidate its possible mechanisms of action. Methods: Dosages (5.0 and 10.0 g/kg/day) of DoMRE were administered to rats daily after induction of HUA by anthropomorphic unhealthy lifestyle for 12 weeks. The levels of UA in the serum, urine, and feces; the levels of creatinine (Cr) in the serum and urine; and the levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) in serum were all measured using an automatic biochemical analyzer. The activities of xanthine oxidase (XOD) and adenosine deaminase (ADA) in the serum, liver, and intestine tissue supernatant were measured using appropriate kits for each biological target. The expressions levels of UA transporters (ABCG2 and GLUT9), tight junction (TJ) proteins (ZO-1 and occludin), and inflammatory factors (IL-6, IL-8, and TNF-α) in the intestine were assayed by immunohistochemical (IHC) staining. Hematoxylin and eosin (H&E) staining was used to assess histological changes in the renal and intestinal tissues. Results: DoMRE treatment significantly reduced SUA levels and concomitantly increased fecal UA (FUA) levels and the fractional excretion of UA (FEUA) in HUA rats. Furthermore, DoMRE significantly reduced both the XOD activity in the serum, liver, and intestine and the ADA activity in the liver and intestine. DoMRE also effectively regulated the expression of GLUT9 and ABCG2 in the intestine, and it significantly upregulated the expression of the intestinal TJ proteins ZO-1 and occludin. Therefore, DoMRE reduced the damage to the intestinal barrier function caused by the increased production of inflammatory factors due to HUA to ensure normal intestinal UA excretion. Conclusion: DoMRE demonstrated anti-HUA effects in the HUA rat model induced by an anthropomorphic unhealthy lifestyle, and the molecular mechanism appeared to involve the regulation of urate transport-related transporters (ABCG2 and GLUT9) in the intestine, protection of the intestinal barrier function to promote UA excretion, and inhibition of XOD and ADA activity in the liver and intestine to inhibit UA production in the HUA-induced rats.

Pitongshu Alleviates the Adverse Symptoms in Rats with Functional Dyspepsia Through Regulating Visceral Hypersensitivity Caused by 5-HT Overexpression.

AIM: The aim of the study was to explore the efficacy as well as the mechanism of action of Pitongshu (PTS) on rats with functional dyspepsia (FD) induced by iodoacetamide gavage and tail clamping. METHODS: The bioactive components of PTS were obtained from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP), whereas the potential targets of PTS were obtained from the Similarity Ensemble Approach (SEA), TCMSP, and Swiss Target Prediction Database. The disease targets were obtained from the DisGeNET database, whereas Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed using the R Software. The method of iodoacetamide gavage combined with tail clamping was used to establish the FD rat model in this study. Body weight, food intake, gastrointestinal motility, gastric acidity and secretion, and the mechanical pain threshold of rats were measured. The open-field test was also performed. The stomach and duodenum were histologically observed. The levels of serotonin (5-HT), Calcitonin Gene-Related Peptide (CGRP), Motilin (MTL), and Gastrin (GAS) in gastric tissues were detected by ELISA. RESULTS: A total of 139 bioactive components and 17 potential targets of PTS were identified through a network pharmacology approach. The results of GO and KEGG enrichment analyses indicated that PTS could reduce the 5-HT secretion of gastric tissues through the serotonergic synaptic pathway and alleviate the symptoms of FD, indicating that PTS plays a therapeutic role. The results of animal experiments showed that PTS could increase body weight and food intake, improve autonomous activity, and decrease gastric acidity and secretion in FD rats. Furthermore, gastric sensitivity increased in FD rats, and PTS treatment could significantly decrease it. The results of ELISA showed that the overexpression of 5-HT and CGRP was decreased after PTS treatment in FD rats. Lastly, PTS could significantly improve gastrointestinal motility, as well as the levels of GAS and MTL in FD rats. CONCLUSION: PTS may reduce 5-HT secretion by regulating the serotonergic synaptic pathway, thereby reducing visceral sensitivity and alleviating the symptoms of FD.

Polysaccharide, the Active Component of Dendrobium officinale, Ameliorates Metabolic Hypertension in Rats via Regulating Intestinal Flora-SCFAs-Vascular Axis.

Metabolic hypertension (MH) is the most common type of hypertension worldwide because of unhealthy lifestyles, such as excessive alcohol intake and high-sugar/high-fat diets (ACHSFDs), adopted by humans. Poor diets lead to a decrease in the synthesis of short-chain fatty acids (SCFAs), which are produced by intestinal flora and transferred by G protein-coupled receptors (GPCRs), resulting in impaired gastrointestinal function, disrupted metabolic processes, increased blood pressure (BP), and ultimately, MH. It is not clear whether Dendrobium officinale polysaccharide (DOPS) can mediate its effects by triggering the SCFAs-GPCR43/41 pathway. In this study, DOPS, with a content of 54.45 ± 4.23% and composition of mannose, glucose, and galacturonic acid at mass percentages of 61.28, 31.87, and 2.53%, was isolated from Dendrobium officinale. It was observed that DOPS, given to rats by intragastric administration after dissolution, could lower the BP and improve the abnormal lipid metabolic processes in ACHSFD-induced MH rats. Moreover, DOPS was found to increase the production, transportation, and utilization of SCFAs, while improving the intestinal flora and strengthening the intestinal barrier, as well as increasing the intestinal levels of SCFAs and the expression of GPCR43/41. Furthermore, DOPS improved vascular endothelial function by increasing the expression of GPCR41 and endothelial nitric oxide synthase in the aorta and the nitric oxide level in the serum. However, these effects were all reversed by antibiotic use. These findings indicate that DOPS is the active component of Dendrobium officinale, and it can reverse MH in rats by activating the intestinal SCFAs-GPCR43/41 pathway.

A Facile, Fabric Compatible, and Flexible Borophene Nanocomposites for Self-Powered Smart Assistive and Wound Healing Applications.

Smart fabrics that can harvest ambient energy and provide diverse sensing functionality via triboelectric effects have evoked great interest for next-generation healthcare electronics. Herein, a novel borophene/ecoflex nanocomposite is developed as a promising triboelectric material with tailorability, durability, mechanical stability, and flexibility. The addition of borophene nanosheets enables the borophene/ecoflex nanocomposite to exhibit tunable surface triboelectricity investigated by Kelvin probe force microscopy. The borophene/ecoflex nanocomposite is further fabricated into a fabric-based triboelectric nanogenerator (B-TENG) for mechanical energy harvesting, medical assistive system, and wound healing applications. The durability of B-TENG provides consistent output performance even after severe deformation treatments, such as folding, stretching, twisting, and washing procedures. Moreover, the B-TENG is integrated into a smart keyboard configuration combined with a robotic system to perform an upper-limb medical assistive interface. Furthermore, the B-TENG is also applied as an active gait phase sensing system for instantaneous lower-limb gait phase visualization. Most importantly, the B-TENG can be regarded as a self-powered in vitro electrical stimulation device to conduct continuous wound monitoring and therapy. The as-designed B-TENG not only demonstrates great potential for multifunctional self-powered healthcare sensors, but also for the promising advancements toward wearable medical assistive and therapeutic systems.

The Mechanism of Dendrobium officinale as a Treatment for Hyperlipidemia Based on Network Pharmacology and Experimental Validation.

Materials and Methods: The active compounds in DO, their targets, and targets associated with hyperlipidemia were screened across various databases, and the hidden targets of DO in treating hyperlipidemia were forecast. The compound-target (C-T), protein-protein interaction (PPI), and compound-target-pathway (C-T-P) networks of DO were set up with Cytoscape software. The hub genes and core clusters of DO predicted to be active against hyperlipidemia were calculated by Cytoscape. The DAVID database was adopted for Gene Ontology (GO) analysis and KEGG pathway enrichment analysis. Next, we used the high-sucrose-fat diet and alcohol (HFDA)-induced hyperlipidemia rats to evaluate the hypolipidemic effect of DO. Results: In this study, we obtained 264 compounds from DO, revealed 11 bioactive compounds, and predicted 89 potential targets of DO. The network analysis uncovered that naringenin, isorhamnetin, and taxifolin might be the compounds in DO that are mainly in charge of its roles in hyperlipidemia and might play a role by modulating the targets (including PPARG, ADIPOQ, AKT1, TNF, and APOB). The pathway analysis showed that DO might affect diverse signaling pathways related to the pathogenesis of hyperlipidemia, including PPAR signaling pathway, insulin resistance, AMPK signaling pathway, and non-alcoholic fatty liver disease simultaneously. Meanwhile, in the HFDA-induced hyperlipidemia rat model, DO could significantly decrease the level of TC, TG, LDL-c, and ALT in serum, and increase HDL-c as well. The liver pathological section indicated that DO could ease liver damage and lipid cumulation. Conclusion: In summary, the biological targets of the main bioactive compounds in DO were found to distribute across multiple metabolic pathways. These findings suggest that a mutual regulatory system consisting of multiple components, targets, and pathways is a likely mechanism through which DO may improve hyperlipidemia. Validation experiments indicated that DO may treat hyperlipidemia by affecting NAFLD-related signaling pathways.

Metal-Free Perovskite Piezoelectric Nanogenerators for Human-Machine Interfaces and Self-Powered Electrical Stimulation Applications.

Single crystal metal-free halide perovskites have received great attention in recent years owing to their excellent piezoelectric and ferroelectric properties. However, the nanotoxicity and piezoelectricity within the nanoscale of such materials have yet been reported for the demonstration of practical applications. In this work, the observation of intrinsic piezoelectricity in metal-free perovskite (MDABCO-NH4 I3 ) films using piezoresponse force microscopy (PFM) is reported. A cytotoxicity test is also performed on MDABCO-NH4 I3 to evaluate its low-toxic nature. The as-synthesized MDABCO-NH4 I3 is further integrated into a piezoelectric nanogenerator (PENG). The MDABCO-NH4 I3 -based PENG (MN-PENG) exhibits optimal output voltage and current of 15.9 V and 54.5 nA, respectively. In addition, the MN-PENG can serve as a self-powered strain sensor for human-machine interface applications or be adopted in in vitro electrical stimulation devices. This work demonstrates a path of perovskite-based PENG with high performance, low toxicity, and multifunctionality for future advanced wearable sensors and portable therapeutic systems.

Prospects of Metal-Free Perovskites for Piezoelectric Applications.

Metal-halide perovskites have emerged as versatile materials for various electronic and optoelectronic devices such as diodes, solar cells, photodetectors, and sensors due to their interesting properties of high absorption coefficient in the visible regime, tunable bandgap, and high power conversion efficiency. Recently, metal-free organic perovskites have also emerged as a particular class of perovskites materials for piezoelectric applications. This broadens the chemical variety of perovskite structures with good mechanical adaptability, light-weight, and low-cost processability. Despite these achievements, the fundamental understanding of the underlying phenomenon of piezoelectricity in metal-free perovskites is still lacking. Therefore, this perspective emphasizes the overview of piezoelectric properties of metal-halide, metal-free perovskites, and their recent progress which may encourage material designs to enhance their applicability towards practical applications. Finally, challenges and outlooks of piezoelectric metal-free perovskites are highlighted for their future developments.

The growth mechanism and intriguing optical and electronic properties of few-layered HfS2.

Due to electronic properties superior to group VIB (Mo and W) transition metal dichalcogenides (TMDs), group IVB (Hf and Zr) TMDs have become intriguing materials in next-generation nanoelectronics. Therefore, the growth of few-layered hafnium disulfide (HfS2) on c-plane sapphire as well as on a SiO2/Si substrate has been demonstrated using chemical vapour deposition (CVD). The structural properties of HfS2 were investigated by recording X-ray diffraction patterns and Raman spectra. The XRD results reveal that the layers are well oriented along the (0001) direction and exhibit the high crystalline quality of HfS2. The Raman spectra confirm the in-plane and out-plane vibration of Hf and S atoms. Moreover, the HfS2 layers exhibit strong absorption in the UV to visible region. The HfS2 layer-based photodetector shows a photoresponsivity of ∼1.6, ∼0.38, and ∼0.21 µA W-1 corresponding to 9, 38, and 68 mW cm-2, respectively under green light illumination and is attributed to the generation of a large number of electron-hole pairs in the active region of the device. Besides, it also exhibits the highly crystalline structure of HfS2 at high deposition temperature. The PL spectrum shows a single peak at ∼1.8 eV and is consistent with the pristine indirect bandgap of HfS2 (∼2 eV). Furthermore, a few layered HfS2 back gate field-effect transistor (FET) is fabricated based on directly grown HfS2 on SiO2/Si, and the device exhibits p-type behaviour. Thus, the controllable and easy growth method opens the latest pathway to synthesize few layered HfS2 on different substrates for various electronic and optoelectronic devices.

High-stability inorganic perovskite quantum dot-cellulose nanocrystal hybrid films.

Inorganic perovskite quantum dots (IPQDs) such as cesium lead halide (CsPbX3, X = Cl, Br and I) quantum dots have attracted much attention for developing cadmium-free quantum light-emitting displays (QLEDs) based on outstanding light emission properties including narrow full width at half maximum (FWHM), tunable bandgap and ultrahigh (>90%) photoluminescence quantum yield (PLQY). Nevertheless, their poor stability under ambient conditions, at high temperature or under continuous light irradiation is the main problem for practical applications. In this study, a new method is proposed to effectively stabilize CsPbBr3 IPQDs by synthesizing them with sulfate-functionalized cellulose nanocrystals (CNCs) at room temperature without using traditional quantum dot stabilizers such as oleylamine (OLA) and oleic acid (OA). The as-prepared CsPbBr3 IPQD/CNC hybrid paper-like films are highly stable and the relative photoluminescence (PL) intensity can be maintained at 92% under continuous UV light (306 nm, 15 W) illumination for 130 h, >99% at high temperature (100 °C) for 130 h, and >99% in ambient conditions for 15 d. Additionally, the PLQY and FWHM of IPQD/CNC are 45.69% and 22 nm, respectively. The ultrahigh stability and narrow FWHM characteristics proposed here for IPQD/CNC hybrid films can provide new possibilities for practical applications in the future development of IPQD-related devices.