Design of 2.45 GHz High-Efficiency Rectifying Circuit for Wireless RF Energy Collection System.

A 2.45 GHz high-efficiency rectifying circuit for a wireless radiofrequency (RF) energy collection system is proposed. The RF energy collection system is composed of a transmitting antenna, a receiving antenna, a rectifying circuit and a load. The designed receiving antenna is a kind of dual-polarised cross-dipole antenna; its bandwidth is 2.3-2.5 GHz and gain is 7.97 dBi. The proposed rectifying circuit adopts the technology of an output matching network, which can suppress the high-harmonic components. When the input power at 2.45 GHz is 13 dBm and the load is 2 kΩ, the highest conversion efficiency of RF-DC is 74.8%, and the corresponding maximum DC output voltage is 4.92 V. The experiment results are in good agreement with the simulation results, which shows a good application prospect.

Grafting seedling rootstock strengthens tolerance to drought stress in polyploid mulberry (Morus alba L.).

The economically adaptable mulberry (Morus alba L.) has a long history of grafting in China, yet the physiological mechanisms and advantages in drought tolerance remain unexplored. In our study, we investigated the responses of self-rooted 2X (diploid), 3X (triploid), and 4X (tetraploid) plants, as well as polyploid plants grafted onto diploid seedling rootstocks (2X/2X, 3X/2X, and 4X/2X) under drought stress. We found that self-rooted diploid plants exhibited the most severe phenotypic damage, lowest water retention, photosynthetic capacity, and the least effective osmotic stress adjustment compared to tetraploid and triploid plants. However, grafted diploid and triploid plants showed effective mitigation of drought-induced damage, with higher relative water content and improved soil water retention. Grafted plants also improved the photosystem response to drought stress through elevated photosynthetic potential, closed stomatal aperture, and faster recovery of chlorophyll biosynthesis in the leaves. Additionally, grafted plants altered osmotic protective compound levels, including starch, soluble sugar, and proline content, thereby enhancing drought resistance. Absolute quantification PCR indicated that the expression levels of proline synthesis-related genes in grafted plants were not influenced after drought stress, whereas they were significantly increased in self-rooted plants. Consequently, our findings support that self-rooted triploid and tetraploid mulberries exhibited superior drought resistance compared to diploid plants. Moreover, grafting onto seedling rootstocks enhanced tolerance against drought stress in diploid and triploid mulberry, but not in tetraploid. Our study provides valuable insights for a comprehensive analysis of physiological effects in response to drought stress between stem-roots and seedling rootstocks.

Liver metabolomics reveals potential mechanism of Jieduan-Niwan formula against acute-on-chronic liver failure (ACLF) by improving mitochondrial damage and TCA cycle.

BACKGROUND: Acute-on-chronic liver failure (ACLF) is a refractory disease with high mortality, which is characterized by a pathophysiological process of inflammation-related dysfunction of energy metabolism. Jieduan-Niwan formula (JDNWF) is a eutherapeutic Chinese medicine formula for ACLF. However, the intrinsic mechanism of its anti-ACLF effect still need to be studied systematically. PURPOSE: This study aimed to investigate the mechanism of JDNWF against ACLF based on altered substance metabolic profile in ACLF the expression levels of related molecules. MATERIALS AND METHODS: The chemical characteristics of JDNWF were characterized using ultra performance liquid chromatography (UPLC) coupled with triple quadrupole mass spectrometry. Wistar rats subjected to a long-term CCL4 stimulation followed by a combination of an acute attack with LPS/D-GalN were used to establish the ACLF model. Liver metabolites were analyzed by LC-MS/MS and multivariate analysis. Liver function, coagulation function, histopathology, mitochondrial metabolic enzyme activity and mitochondrial damage markers were evaluated. The protein expression of mitochondrial quality control (MQC) was investigated by western blot. RESULTS: Liver function, coagulation function, inflammation, oxidative stress and mitochondrial enzyme activity were significantly improved by JDNWF. 108 metabolites are considered as biomarkers of JDNWF in treating ACLF, which were closely related to TCA cycle. It was further suggested that JDNWF alleviated mitochondrial damage and MQC may be potential mechanism of JDNWF improving mitochondrial function. CONCLUSIONS: Metabolomics revealed that TCA cycle was impaired in ACLF rats, and JDNWF had a regulatory effect on it. The potential mechanism may be improving the mitochondrial function through MQC pathway, thus restoring energy metabolism.

New Monoterpenoid Indole Hybrids from Gelsemium elegans with Anti-Inflammatory and Osteoclast Inhibitory Activities.

Gelsegansymines A (1) and B (2), two new indole alkaloids along with six known analogues (3-8) were isolated from the aerial parts of Gelsemium elegans. Their structures were elucidated by means of spectroscopic techniques. Structurally, compounds 1 and 2 possessed the rare cage-like gelsedine skeleton hybrid with bicyclic monoterpenoid. The anti-inflammatory activities of isolated compounds (1-3) were tested on LPS induced RAW264.7 cells. Under the treated concentration without toxicity for cells, the cytokines levels of nitric oxide (NO), tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) were evaluated by Griess method and enzyme-linked immunosorbent assay (ELISA). The results showed that compounds 1-3 exhibited anti-inflammatory activities with dose-dependent manner range from 12.5 to 50 µmol/L. Furthermore, the inhibitory activities of compounds 1 and 2 on receptor activator of NF-κB ligand (RANKL) induced osteoclast formation were tested in vitro. Compounds 1 and 2 at 5 µmol/L exhibited the significant inhibitory effect on the osteoclastogenesis induced by RANKL. This work reported the anti-inflammatory and osteoclast inhibitory activities of new monoterpenoid indole hybrids, which may inspire the further light on the related traditional application research of G. elegans.

Genus Gelsemium and its Endophytic Fungi - Comprehensive Review of their Traditional Uses, Phytochemistry, Pharmacology, and Toxicology.

BACKGROUND: The use of ethnic medicinal plants has revitalized wide popularity in Africa, Asia, and most of the world because of the energy consumption barriers increase of synthetic drugs. Gelsemium is a traditional genus of plants with famous cultural and medicinal significance in Southeast Asia and North America. Three species are reported from the genus Gelsemium, including Gelsemium elegans (Gardn. & Camp.) Benth., Gelsemium sempervirens (L.) J.St.-Hil., and Gelsemium rankinii Small. Among them, G. elegans is well known for its toxicity and is used as a traditional remedy for skin problems, neuralgia, fractures, and cancer. The first record of the toxic medicine G. elegans is the Chinese herbal medicine classically known as Shen-Nong Ben-Cao Jing. In the legend, the Shennong emperor was poisoned by G. elegans, hence, it is also wellknown as Duan Chang Cao in China. In addition, G. sempervirens tincture is also used in the treatment of inflammation of the spinalcolumn, and diminishes blood to the cerebrospinal centers. INTRODUCTION: This review aims to provide up-to-date information on Gelsemium and its endophytic fungi on their traditional uses, phytochemistry, pharmacology, and toxicology. Mechanism studies regarding the detoxification profile of Gelsemium are also reviewed. METHODS: For this updated review, the literature survey and search were performed on the scientific databases PubMed, ScienceDirect, Wiley, China CNKI, Web of Science, SciFinder, and Google Scholar using the relevant keywords. RESULTS: The plants of the genus Gelsemium are all reported as rich sources of monoterpene indole alkaloids. Previous phytochemical studies published more than 200 alkaloids from Gelsemium and its endophytic fungi, which have attracted considerable attention from pharmaceutists and phytochemists due to their diverse and complex structures. The bioactivities of Gelsemium phytoconstituents studied using various chemical methods are summarized and described herein. Considering the huge influence of Gelsemium regarding its traditional applications, the activities of isolated compounds were focused on the anti-tumor, anti-inflammatory, analgesic and antianxiety, immunostimulatory, and immunosuppressive properties, which provide evidence supporting the ethnopharmacological effectiveness of the genus Gelsemium. Unlike all previous reviews of genus Gelsemium, to the best of our knowledge, the recently reported natural products from its endophytic fungi are first time summarized in this review. CONCLUSION: It is clearly suggested from the literature information that the structures and biological activities of Gelsemium have a wide range of attraction from folk to the community of scholars. However, as a highly toxic genus, the work on the detoxification mechanism and toxicology of Gelsemium is urgently needed before entering clinical research. It is noteworthy that the discussion about the relationship between structural and biological activities are a valuable topic of expectation, while the structural modification for active or toxic components may shed light on toxicological breakthrough. Besides the compounds from the plants of genus Gelsemium, the recently reported natural products from its endophytic fungi may provide a supplement for its ethnomedicinal uses and ethnological validity.

Structural Elucidation and Cytotoxic Activity of New Monoterpenoid Indoles from Gelsemium elegans.

Two new monoterpenoid indole alkaloids, gelselegandines F (1) and G (2), were isolated from the aerial parts of Gelsemium elegans. Their structures were elucidated by means of spectroscopic techniques and quantum chemical calculations. The ECD calculations were conducted at the B3LYP/6-311G(d,p) level and NMR calculations were carried out using the Gauge-Including Atomic Orbitals (GIAO) method. Structurally, the two new compounds possessed rare, cage-like, monoterpenoid indole skeletons. All isolated compounds and the total alkaloids extract were tested for cytotoxicity against four different tumor cell lines. The total alkaloids extract of G. elegans exhibited significant antitumor activity with IC50 values ranging from 32.63 to 82.24 ug/mL. In order to discover anticancer leads from the active extraction, both new indole compounds (1-2) were then screened for cytotoxicity. Interestingly, compound 2 showed moderate cytotoxicity against K562 leukemia cells with an IC50 value of 57.02 uM.

Biological Activities and Secondary Metabolites from Sophora tonkinensis and Its Endophytic Fungi.

The roots of Sophora tonkinensis Gagnep., a traditional Chinese medicine, is known as Shan Dou Gen in the Miao ethnopharmacy. A large number of previous studies have suggested the usage of S. tonkinensis in the folk treatment of lung, stomach, and throat diseases, and the roots of S. tonkinensis have been produced as Chinese patent medicines to treat related diseases. Existing phytochemical works reported more than 300 compounds from different parts and the endophytic fungi of S. tonkinensis. Some of the isolated extracts and monomer compounds from S. tonkinensis have been proved to exhibit diverse biological activities, including anti-tumor, anti-inflammatory, antibacterial, antiviral, and so on. The research progress on the phytochemistry and pharmacological activities of S. tonkinensis have been systematically summarized, which may be useful for its further research.

Bioinformatics analyses of potential ACLF biological mechanisms and identification of immune-related hub genes and vital miRNAs.

Acute-on-chronic liver failure (ACLF) is a critical and refractory disease and a hepatic disorder accompanied by immune dysfunction. Thus, it is essential to explore key immune-related genes of ACLF and investigate its mechanisms. We used two public datasets (GSE142255 and GSE168048) to perform various bioinformatics analyses, including WGCNA, CIBERSORT, and GSEA. We also constructed an ACLF immune-related protein-protein interaction (PPI) network to obtain hub differentially expressed genes (DEGs) and predict corresponding miRNAs. Finally, an ACLF rat model was established to verify the results. A total of 388 DEGs were identified in ACLF, including 162 upregulated and 226 downregulated genes. The enrichment analyses revealed that these DEGs were mainly involved in inflammatory-immune responses and biosynthetic metabolic pathways. Twenty-eight gene modules were obtained using WGCNA and the coral1 and darkseagreen4 modules were highly correlated with M1 macrophage polarization. As a result, 10 hub genes and 2 miRNAs were identified to be significantly altered in ACLF. The bioinformatics analyses of the two datasets presented valuable insights into the pathogenesis and screening of hub genes of ACLF. These results might contribute to a better understanding of the potential molecular mechanisms of ACLF. Finally, further studies are required to validate our current findings.

Jieduan-Niwan Formula Ameliorates Oxidative Stress and Apoptosis in Acute-on-Chronic Liver Failure by Suppressing HMGB1/TLR-4/NF-κB Signaling Pathway: A Study In Vivo and In Vitro.

Jieduan-Niwan (JDNW) formula is a traditional Chinese medicine compound created by the famous Chinese medicine expert Professor Qian Ying, and has been used clinically for decades to treat acute-on-chronic liver failure (ACLF) and exhibits remarkable efficacy. However, the exact mechanism remains to be discovered. As an important hepatocyte damage-associated molecular patterns (DAMP) factor, high mobility group box 1 (HMGB1) is a potential therapeutic target as an accelerator of ACLF in the pathogenesis. Therefore, the present study investigated whether JDNW inhibits the overexpression and cytoplasmic translocation of HMGB1 in ACLF liver tissue and alleviates its mediated oxidative stress and apoptosis. In vivo, an immune-induced ACLF rat model was established, and then treated with JDNW for 5, 10, and 15 d. The results showed that a large number of cytoplasmic translocations of HMGB1 occurred in the ACLF group. And there was an increase in the expression of HMGB1 in the M-5 d group. After the intervention of JDNW, the overexpression and translocation of HMGB1 were inhibited. In vitro, D-GaLN caused an increase in the expression and translocation of HMGB1 in L02 cells. Similar to the inhibitor of HMGB1, JDNW serum alleviated this kind of increase. Further tests showed that JDNW attenuated ACLF-related oxidative stress and apoptosis, and the inhibition was associated with the regulation of TLR-4/NF-κB signaling pathway. In conclusion, our present findings suggest that the therapeutic effect of JDNW on ACLF was associated with the inhibition of high expression and cytoplasmic translocation of HMGB1 during the acute injury phase, thus, attenuating oxidative stress injury and apoptosis induced by HMGB1/TLR-4/NF-κB pathway.

The Beneficial Effects of Combining Anti-Aß Antibody NP106 and Curcumin Analog TML-6 on the Treatment of Alzheimer's Disease in APP/PS1 Mice.

Alzheimer's disease (AD) is a progressive neurodegenerative disease with a multifactorial etiology. A multitarget treatment that modulates multifaceted biological functions might be more effective than a single-target approach. Here, the therapeutic efficacy of combination treatment using anti-Aß antibody NP106 and curcumin analog TML-6 versus monotherapy was investigated in an APP/PS1 mouse model of AD. Our data demonstrate that both combination treatment and monotherapy attenuated brain Aß and improved the nesting behavioral deficit to varying degrees. Importantly, the combination treatment group had the lowest Aß levels, and insoluble forms of Aß were reduced most effectively. The nesting performance of APP/PS1 mice receiving combination treatment was better than that of other APP/PS1 groups. Further findings indicate that enhanced microglial Aß phagocytosis and lower levels of proinflammatory cytokines were concurrent with the aforementioned effects of NP106 in combination with TML-6. Intriguingly, combination treatment also normalized the gut microbiota of APP/PS1 mice to levels resembling the wild-type control. Taken together, combination treatment outperformed NP106 or TML-6 monotherapy in ameliorating Aß pathology and the nesting behavioral deficit in APP/PS1 mice. The superior effect might result from a more potent modulation of microglial function, cerebral inflammation, and the gut microbiota. This innovative treatment paradigm confers a new avenue to develop more efficacious AD treatments.

Quercetin Reduces Oxidative Stress and Apoptosis by Inhibiting HMGB1 and Its Translocation, Thereby Alleviating Liver Injury in ACLF Rats.

BACKGROUND: Acute on chronic liver failure (ACLF) is a syndrome of acute liver failure that occurs on the basis of chronic liver disease, which is characterized by a rapid deterioration in a short period and high mortality. High mobility group box 1 (HMGB1) may be involved in the pathological process of ACLF; its specific role remains to be further elucidated. Our previous studies have shown that quercetin (Que) exerts anti-oxidant and anti-apoptotic effects by inhibiting HMGB1 in vitro. The present study aimed to investigate the effect of Que on liver injury in ACLF rats. METHODS: The contents of ALT, AST, TBiL, and PT time of rats in each group were observed. HE staining was used to detect liver pathology. The levels of oxidative stress indicators such as MDA, GSH, and 4-HNE in the rat liver were detected. TUNEL assay was used to detect apoptosis in rat hepatocytes. Immunofluorescence and western blot analysis were performed to explore the protective effect of Que on ACLF rats and the underlying mechanism. RESULTS: The results showed that Que could reduce the increase of serum biochemical indices, improve liver pathology, and reduce liver damage in ACLF rats. Further results confirmed that Que reduced the occurrence of oxidative stress and apoptosis of hepatocytes, and these reactions may aggravate the progress of ACLF. Meanwhile, the results of immunofluorescence and western blotting also confirmed that the expression of HMGB1 and extranuclear translocation in ACLF rat hepatocytes were significantly increased, which was alleviated by the treatment of Que. In addition, when cotreated with glycyrrhizin (Gly), an inhibitor of HMGB1, the inhibition of Que on HMGB1 and its translocation, apoptosis and oxidative stress, and the related proteins of HMGB1-mediated cellular pathway have been significantly enhanced. CONCLUSION: Thus, Que alleviates liver injury in ACLF rats, and its mechanism may be related to oxidative stress and apoptosis caused by HMGB1 and its translocation.

New Monoterpenoid Indoles with Osteoclast Activities from Gelsemium elegans.

The well-known toxic medicine Gelsemium elegans is widely and historically used to treat bone fracture and skin ulcers by the folk people of China. Two new monoterpenoid indole alkaloids, gelselegandines D and E, together with the known analogue gelegamine A were isolated from G. elegans. Their structures were elucidated by means of spectroscopic techniques and quantum chemical calculations. All isolated compounds were tested for the effects on RANKL-induced osteoclast formation. Interestingly, gelselegandine E and gelegamine A, respectively, showed significant promoting and inhibitory activities on osteoclastogenesis, while gelselegandine D had no activity under the same concentration. This work suggested the different configurations for the carbons near the C-19/20 oxygen rings of the isolated compounds may be the key active groups on osteoclast formation and provided the evidence for the rationality as the traditional treatment for bone-related diseases of G. elegans.

Exploring the Potential Mechanism of Tang-Shen-Ning Decoction against Diabetic Nephropathy Based on the Combination of Network Pharmacology and Experimental Validation.

BACKGROUND: Diabetic nephropathy (DN) has become one of the leading causes of the end-stage renal disease (ESRD). Tang-Shen-Ning (TSN) decoction, an effective Traditional Chinese formula for DN, can improve the renal function and inhibit renal fibrosis in DN. However, its potential mechanism is still unexplored. METHODS: A network pharmacology approach was employed in this study, including screening for differential expressed genes of DN (DN-DEGs), protein-protein interaction (PPI) network analysis, and GO and KEGG enrichment analysis. Besides, a rat model was established to verify the potential effect of TSN in DN. RESULTS: Twenty-three TSN-related DN-DEGs targets were identified. These genes were associated with decreased glomerular filtration rate (GFR) DN. The enrichment analysis suggested that the inhibition of renal fibrosis and inflammation through growth factors and chemokines is the potential mechanism through which TSN improves DN. TSN reduced renal fibrosis and improved pathological damage in the kidney in vivo through the regulation of GJA1, CTGF, MMP7, and CCL5, which are genes associated with ECM deposition. CONCLUSION: This study revealed that TSN improves DN through a multicomponent, multitarget, and multipathway synergy. We provide a scientific basis for potential targets for TSN use to treat DN, yet further experimental validation is needed to investigate these targets and mechanisms.

Network Pharmacology-Based Analysis on the Potential Biological Mechanisms of Sinisan Against Non-Alcoholic Fatty Liver Disease.

Non-alcoholic fatty liver disease (NAFLD) has become the most prevalent liver disease in China. Sinisan (SNS) is a traditional Chinese medicine formula that has been widely used in treating chronic liver diseases, including NAFLD. However, its underlying biological mechanisms are still unclear. In this study, we employed a network pharmacology approach consisting of overlapped terms- (genes or pathway terms-) based analysis, protein-protein interaction (PPI) network-based analysis, and PPI clusters identification. Unlike the previous network pharmacology study, we used the shortest path length-based network proximity algorithm to evaluate the efficacy of SNS against NAFLD. And we also used random walk with restart (RWR) algorithm and Community Cluster (Glay) algorithm to identify important targets and clusters. The screening results showed that the mean shortest path length between genes of SNS and NAFLD was significantly smaller than degree-matched random ones. Six PPI clusters were identified and ten hub targets were obtained, including STAT3, CTNNB1, MAPK1, MAPK3, AGT, NQO1, TOP2A, FDFT1, ALDH4A1, and KCNH2. The experimental study indicated that SNS reduced hyperlipidemia, liver steatosis, and inflammation. Most importantly, JAK2/STAT3 signal was inhibited by SNS treatment and was recognized as the most important signal considering the network pharmacology part. This study provides a systems perspective to study the relationship between Chinese medicines and diseases and helps to discover potential mechanisms by which SNS ameliorates NAFLD.

A Gravity-Triggered Liquid Metal Patch Antenna with Reconfigurable Frequency.

In this paper, a gravity-triggered liquid metal microstrip patch antenna with reconfigurable frequency is proposed with experimental verification. In this work, the substrate of the antenna is quickly obtained through three-dimensional (3D) printing technology. Non-toxic EGaIn alloy is filled into the resin substrate as a radiation patch, and the NaOH solution is used to remove the oxide film of EGaIn. In this configuration, the liquid metal inside the antenna can be flexibly flowed and deformed with different rotation angles due to the gravity to realize different working states. To validate the conception, the reflection coefficients and radiation patterns of the prototyped antenna are then measured, from which it can be observed that the measured results closely follow the simulations. The antenna can obtain a wide operating bandwidth of 3.69-4.95 GHz, which coverage over a range of frequencies suitable for various channels of the 5th generation (5G) mobile networks. The principle of gravitational driving can be applied to the design of reconfigurable antennas for other types of liquid metals.

HMGB1-Induced Hepatocyte Pyroptosis Expanding Inflammatory Responses Contributes to the Pathogenesis of Acute-on-Chronic Liver Failure (ACLF).

BACKGROUND: Acute-on-chronic liver failure (ACLF) is a critical disease with a high fatality rate. Immune dysfunction and inflammatory responses are key risk factors in ACLF. Pyroptosis is a form of programmed cell death characterized by the release of inflammatory cytokines, which causes the strong inflammatory responses. High mobility group box-1 (HMGB1) could induce pyroptosis and is closely related to ACLF. However, the role of HMGB1-induced hepatocyte pyroptosis in ACLF has never been proposed; whether HMGB1-induced hepatocyte pyroptosis participates in the development of ACLF and the mechanisms involved are barely understood. PURPOSE: This study aimed to clarify the roles of HMGB1-induced hepatocyte pyroptosis in ACLF and the molecular mechanisms involved. METHODS: Wistar rats were randomly divided into five groups, viz.: Normal, ACLF model, HMGB1 inhibitor, Caspase-1 inhibitor, and HMGB1 inhibitor+Caspase-1 inhibitor groups. The ACLF rat model was established using 40% carbon tetrachloride-induced liver fibrosis, followed by D-galactosamine and lipopolysaccharide joint acute attacks. The liver function, coagulation function and pathological damage of rats in each group were evaluated. The biological mechanisms of HMGB1-induced pyroptosis and the release of inflammatory cytokines were investigated using Western blot, quantitative real-time PCR (RT-qPCR), immunofluorescence, enzyme-linked immunosorbent assay (ELISA), and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay. RESULTS: The liver function and coagulation function of ACLF rats were seriously impaired; liver tissue showed massive or submassive necrosis, accompanied by inflammatory cell infiltration; the percentage of pyroptotic hepatocytes significantly increased, and a large number of inflammatory cytokines were released. The expression levels of pyroptosis-related genes and proteins in liver tissues and serum significantly increased. But these phenomenons were improved by the inhibition of HMGB1, and the dual inhibition of HMGB1 and Caspase-1 showed a stronger effect. CONCLUSION: The findings indicate, for the first time, that pyroptosis is a crucial pathophysiological event of ACLF involved in its pathogenesis, and HMGB1-induced hepatocyte pyroptosis expands inflammatory responses to aggravate ACLF, suggesting that it may be a potential therapeutic target for ACLF treatment.

Quercetin Attenuates d-GaLN-Induced L02 Cell Damage by Suppressing Oxidative Stress and Mitochondrial Apoptosis via Inhibition of HMGB1.

High mobility group box-1 (HMGB1) plays an important role in various liver injuries. In the case of acute liver injury, it leads to aseptic inflammation and other reactions, and also regulates specific cell death responses in chronic liver injury. HMGB1 has been demonstrated to be a good therapeutic target for treating liver failure. Quercetin (Que), as an antioxidant, is a potential phytochemical with hepatocyte protection and is also considered to be an inhibitor of HMGB1. However, the mechanism of its hepatoprotective effects remains to be characterized. The present study explored whether the hepatoprotective effect of Que antagonizes HMGB1, and subsequent molecular signaling events. Our results indicated that Que protects L02 cells from d-galactosamine (d-GaLN)-induced cellular damage by reducing intracellular reactive oxygen species (ROS) production and apoptotic responses in the mitochondrial pathway. Immunofluorescence and Western blot assays showed that HMGB1 was involved in d-GaLN-induced L02 cell damage. Further research showed that after transfection with HMGB1 short hairpin RNA (shRNA), cell viability was improved, and intracellular ROS production and apoptosis were suppressed. When co-treated with Que, the expression of HMGB1 was decreased significantly, the expression of proteins in the corresponding signal pathway were further reduced, and the production of ROS and apoptosis were further suppressed. Molecular docking also indicated the binding of Que and HMGB1. Taken together, these results indicate that Que significantly improves d-GaLN-induced cellular damage by inhibiting oxidative stress and mitochondrial apoptosis via inhibiting HMGB1.

Network Pharmacology Approach to Explore the Potential Mechanisms of Jieduan-Niwan Formula Treating Acute-on-Chronic Liver Failure.

BACKGROUND: Acute-on-chronic liver failure (ACLF) is a clinical syndrome with acute jaundice and coagulation dysfunction caused by various inducements on the basis of chronic liver disease. Western medical treatment is limited. Previous studies have confirmed that Jieduan-Niwan Formula (JDNW Formula), an empirical prescription for the treatment of ACLF, can inhibit inflammation and resist hepatocyte apoptosis. However, potential targets and mechanisms still need to be explored. METHODS: In this study, network pharmacological analysis was performed to investigate the key components and potential mechanisms of JDNW Formula treating ACLF. Firstly, we predicted the potential active ingredients of JDNW Formula and the corresponding potential targets through TCMSP, BATMAN-TCM platform, and literature supplement. Then, the ACLF targets database was built using OMIM, DisGeNET, and GeneCard database. Based on the matching targets between JDNW Formula and ACLF, the PPI network was constructed for MCODE analysis and common targets were enriched by Metascape. Furthermore, the ACLF rat model was used to verify the potential mechanism of JDNW Formula in treating ACLF. RESULTS: 132 potential bioactive components of JDNW Formula and 168 common targets were obtained in this study. The enrichment analysis shows that the AMPK signaling pathway was associated with the treating effects of JDNW Formula. Quercetin was hypothesized to be the key bioactive ingredient in JDNW Formula and has a good binding affinity to AMPK based on molecular docking verification. JDNW Formula and quercetin were verified to treat ACLF by regulating the AMPK/PGC-1α signaling pathway as a prediction. CONCLUSION: The study predicted potential mechanisms of JDNW Formula in the treatment of ACLF, involving downregulation of inflammatory factor expression, antioxidant stress, and inhibition of hepatocyte apoptosis. JDNW Formula may improve mitochondrial quality in ACLF via the AMPK signaling pathway, which serves as a guide for further study.

Soluble epoxide hydrolase modulates immune responses in activated astrocytes involving regulation of STAT3 activity.

BACKGROUND: Astrocyte activation is a common pathological feature in many brain diseases with neuroinflammation, and revealing the underlying mechanisms might shed light on the regulatory processes of the diseases. Recently, soluble epoxide hydrolase (sEH) has been proposed to affect neuroinflammation in brain injuries. However, the roles of astrocytic sEH in brains with neurodegeneration remain unclear. METHODS: The expression of astrocytic sEH in the brains of APPswe/PSEN1dE9 (APP/PS1) mice developing Alzheimer's disease (AD)-like pathology was evaluated by confocal imaging. LPS-activated primary astrocytes with mRNA silencing or overexpression of sEH were used to investigate its regulatory roles in astrocyte activation and the induction of pro-inflammatory markers. Primary astrocytes isolated from a sEH knockout (sEH-/-) background were also applied. RESULTS: The immunoreactivity of sEH was increased in activated astrocytes in parallel with the progression of AD in APP/PS1 mice. Our data from primary astrocyte cultures further demonstrate that the overexpression of sEH ameliorated, while the silencing of sEH mRNA enhanced, the lipopolysaccharides (LPS)-induced expression of pro-inflammatory markers, such as inducible nitric oxide, cyclooxygenase 2 (COX-2), and pro-inflammatory cytokines. These findings suggest that sEH negatively regulates astrocyte immune responses. Enhanced immune responses found in LPS-activated sEH-/- astrocytes also support the notion that the expression of sEH could suppress the immune responses during astrocyte activation. Similarly, sEH-/- mice that received intraperitoneal injection of LPS showed exacerbated astrocyte activation in the brain, as observed by the elevated expression of glial fibrillary acidic protein (GFAP) and pro-inflammatory markers. Moreover, our data show that the phosphorylation of the signal transducer and activator of transcription 3 (STAT3) was upregulated in activated astrocytes from sEH mouse brains, and the pharmacological blockade of STAT3 activity alleviated the pro-inflammatory effects of sEH deletion in LPS-activated primary astrocytes. CONCLUSIONS: Our results provide evidence, for the first time, showing that sEH negatively regulates astrocytic immune responses and GFAP expression, while the underlying mechanism at least partly involves the downregulation of STAT3 phosphorylation. The discovery of a novel function for sEH in the negative control of astrocytic immune responses involving STAT3 activation confers further insights into the regulatory machinery of astrocyte activation during the development of neurodegeneration.

MelanomaNet: An Effective Network for Melanoma Detection.

Melanoma is one of the most deadly skin lesion, which often uses the skin dermoscopy to detect it. However, the low interclass variations between melanoma images make manual dermoscopic detection time-consuming and laborious. Therefore, an automatic recognition algorithm of skin image is highly desirable. However, the traditional methods still have the limitations (e.g., weak robustness and generalization ability). To meet the challenge, we propose an effective architecture based on residual - squeeze - and - excitation -Inception-v4 network (MelanomaNet) to detect melanoma. Specifically, Inception-v4 structure is utilized to get the rich spatial features and increase feature diversity. We also consider the relationship between feature channels by adding residual-squeeze-and-excitation (RSE) blocks in Inception- v4 network using the feature recalibration strategies. Finally, we use the support vector machine (SVM) as the classifier for the skin lesion classification. We evaluate our proposed method on the public available ISIC skin lesion challenge datasets in 2018 for training and evaluation. The experimental results show that the proposed method has achieved better performance over the state-of-the-arts methods.