Central and peripheral analgesic active components of triterpenoid saponins from Stauntonia chinensis and their action mechanism.

Triterpenoid saponins from Stauntonia chinensis have been proven to be a potential candidate for inflammatory pain relief. Our pharmacological studies confirmed that the analgesic role of triterpenoid saponins from S. chinensis occurred via a particular increase in the inhibitory synaptic response in the cortex at resting state and the modulation of the capsaicin receptor. However, its analgesic active components and whether its analgesic mechanism are limited to this are not clear. In order to further determine its active components and analgesic mechanism, we used the patch clamp technique to screen the chemical components that can increase inhibitory synaptic response and antagonize transient receptor potential vanilloid 1, and then used in vivo animal experiments to evaluate the analgesic effect of the selected chemical components. Finally, we used the patch clamp technique and molecular biology technology to study the analgesic mechanism of the selected chemical components. The results showed that triterpenoid saponins from S. chinensis could enhance the inhibitory synaptic effect and antagonize the transient receptor potential vanilloid 1 through different chemical components, and produce central and peripheral analgesic effects. The above results fully reflect that "traditional Chinese medicine has multi-component, multi-target, and multi-channel synergistic regulation".

Hosimosines A-E, structurally diverse cytisine derivatives from the seeds of Ormosia hosiei Hemsl. et Wils.

Ormosia hosiei Hemsl. et Wils (Fabaceae family) is an arbor species endemic to China. The seeds of O. hosiei have been used as traditional Chinese medicine to treat hernia, abdominal pain, blood stasis and amenorrhea. Cytisine-like and angustifoline type alkaloids were main components identified from this plant. In our research on the bioactive alkaloids from the promising Chinese medicinal plants, four new angustifoline type alkaloids (1-4) and a new cytisine-like alkaloid (5), named hosimosine A-E, together with 13 known analogues (6-18) were isolated from the seeds of O. hosiei. Their structures were elucidated by the extensive spectroscopic methods, especially the interpretation of NMR spectra and specific rotations, along with the methods of NMR and ECD calculation. Compounds 1-4 were identified as two pairs of epimers, whose relative configurations were deduced from density functional theory (DFT) calculations of NMR chemical shifts and DP4+ analysis, and absolute configurations were determined by comparison of their experimental and theoretical ECD spectra. Compound 5 displayed two sets of NMR data caused by the existence of tautomeric forms. Compounds 14, 17 and 18 were determined to be enantiomers of literature compounds. Some of the isolates exhibited moderate cytotoxic effects against HepG2, A2780 and MCF-7 cells.

Endofungal Bacterial Microbiota Promotes the Absorption of Chelated Inorganic Phosphorus by Host Pine through the Ectomycorrhizal System.

Ectomycorrhizal fungi play an irreplaceable role in phosphorus cycling. However, ectomycorrhizal fungi have a limited ability to dissolve chelated inorganic phosphorus, which is the main component of soil phosphorus. Endofungal bacteria in ectomycorrhizal fruiting bodies are always closely related to the ecological function of ectomycorrhizal fungi. In this study, we explore endofungal bacteria in the fruiting body of Tylopilus neofelleus and their function during the absorption of chelated inorganic phosphorus by host pine through the ectomycorrhizal system. The results showed that the endofungal bacterial microbiota in the fruiting body of T. neofelleus might be related to the dissolution of chelated inorganic phosphorus in soil. The soluble phosphorus content in the combined system of T. neofelleus and endofungal bacteria Bacillus sp. strain B5 was five times higher than the sum of T. neofelleus-only treatment and Bacillus sp. strain B5-only treatment in the dissolution experiment of chelated inorganic phosphorus. The results showed that T. neofelleus not only promoted the proliferation of Bacillus sp. strain B5 in the combined system but also improved the expression of genes related to organic acid metabolism, as assesed by transcriptomic analysis. Lactic acid content was five times higher in the combined system than the sum of T. neofelleus-only treatment and Bacillus sp. strain B5-only treatment. Two essential genes related to lactate metabolism of Bacillus sp. strain B5, gapA and pckA, were significantly upregulated. Finally, in a pot experiment, we verified that T. neofelleus and Bacillus sp. strain B5 could synergistically promote the absorption of chelated inorganic phosphorus by Pinus sylvestris in a ternary symbiotic system. IMPORTANCE Ectomycorrhizal fungi (ECMF) have a limited ability to dissolve chelated inorganic phosphorus, which is the main component of soil phosphorus. In the natural environment, the extraradical hyphae of ECMF alone may not satisfy the phosphorus demand of the plant ectomycorrhizal system. In this study, our results innovatively show that the ectomycorrhizal system might be a ternary symbiont in which ectomycorrhizal fungi might recruit endofungal bacteria that could synergistically promote the mineralization of chelated inorganic phosphorus, which ultimately promotes plant phosphorus absorption by the ectomycorrhizal system.

Human skin-on-a-chip for mpox pathogenesis studies and preclinical drug evaluation.

Timely intervention of preventative and therapeutic measures abated a 2022 mpox global outbreak. However, the high transmissibility and unique pathological characteristics of mpox demand further investigation. Here, we discuss the potentials of human skin-on-a-chip as a valuable model for mpox disease evaluation, to achieve in-depth physiological understanding and desirable therapeutic predictive capabilities.

[Effect of "Tiaoshen Tongluo" acupuncture on nerve function injury, muscle tension and neurotransmitters through Nrf2/ROS pathway in spastic rats after stroke].

OBJECTIVE: To observe the effect of "Tiaoshen Tongluo" acupuncture (TTA) at "Dingzhongxian" (MS5) and right "Dingpangxian" (MS8) on neurological injury, muscle tension and neurotransmitters through nuclear transcription factor E2 related factor 2 (Nrf2)/reactive oxygen species (ROS) signaling pathway in spastic rats after stroke, so as to explore its mechanisms underlying relief of post-stroke spasm (PSS). METHODS: A total of 90 male SD rats were randomly divided into 6 groups, i.e. sham operation, PSS model, medication, non-acupoint acupuncture, TTA, TTA+ML385 groups, with 15 rats in each group. The PSS model was established by middle cerebral artery occlusion. After modeling, rats of the medication group were treated by gavage of baclofen (0.4 mg/kg), once daily for 7 days. For rats of the non-acupoint acupuncture group, the spot about 10 mm above the iliac crest and below the armpit of the affected side was needled, and for those of the TTA group and TTA+ML385 group, EA stimulation (1 mA, 2 Hz/15 Hz) was applied to MS5 and right MS8 for 10 min, once daily for 7 consecutive days. Intraperitoneal injection of ML385 ［ a specific nuclear factor erythroid 2-related factor 2 (Nrf2) inhibitor, 30 mg/kg］ was given to rats of the TTA+ML385 group before TTA was performed. The rats' neurological deficit score (0-4 points) was evaluated by referring to Zea Longa's methods and the muscular spasm degree of the quadriceps femoris of the left hindlimb (0-4 points) assessed by using Ashworth scale (MAS). The muscular tension of the left quadriceps femoris was measured by using a tension sensor, and Hoffman (H)-reflex response and M and H waves of electromyogram of the muscle between the metatarsals of the left foot were measured using an electrophysiological recorder. The cerebral infarction volume was measured after 2,3,5-triphenyltetrazolium chloride (TTC) staining. The contents of γ-aminobutyric acid (GABA), glycine (Gly), glutamic acid (Glu) and aspartic acid (Asp) of the right cortical infarct area were detected by using high performance capillary electrophoresis, and the contents of 5-hydroxytryptamine (5-HT), dopamine (DA) and norepinephrine (NE) were detected by fluorescence spectrophoto-metry, as well as the level of ROS in the right cerebral cortical infarction tissues was detected by dihydroethidium staining. The expression levels of Nrf2 and heme oxygenase-1 (HO-1) proteins in the infarcted cerebral area were detected using Western blot. RESULTS: Compared with the sham operation group, the neurological deficit score, MAS score, percentage of cerebral infarction volume, Hmax/Mmax ratio, contents of Glu and Asp and ROS level were significantly increased (P<0.001), whereas the muscle tone, stimulation threshold for inducing H-reflex, GABA, Gly, 5-HT, DA and NE contents, cerebral Nrf2 and HO-1 protein expression levels were apparently decreased (P<0.001) in the model group. In comparison with the model group, the neurological deficit score, MAS score, percentage of cerebral infarction volume, Hmax/Mmax ratio, contents of Glu, Asp and ROS levels were decreased (P<0.001), and the muscle tone, stimulation threshold for inducing H-reflex, GABA, Gly, 5-HT, DA and NE contents, Nrf2 and HO-1 protein expressions were increased (P<0.001, P<0.01) in both the medication and TTA groups. No significant differences were found between the non-acupoint group and model group, and between the medication and TTA groups in all the indexes mentioned above (P>0.05). After administration of ML385, the effects of TTA in reducing neurological deficit score, MAS score, Hmax/Mmax, percentage of cerebral infarct volume, Glu, Asp, ROS, and up-regulating H-reflex threshold, GABA, Gly, 5-HT, DA, NE, Nrf2 and HO-1 levels were eliminated (P<0.001，P<0.05,P<0.01). CONCLUSION: TTA can improve neurological behavior and muscle spasm in rats with PSS, which may be associated with its functions in regulating the levels of neurotransmitters in the cortical infarcted area by activating the Nrf2/ROS signaling pathway.

[Differential transcription of mating-type genes during sexual reproduction of natural Cordyceps sinensis].

Natural Cordyceps sinensis as an insect-fungal complex, which is developed after Ophiocordyceps sinensis infects a larva of Hepialidae family. Seventeen genotypes of O. sinensis have been identified in natural C. sinensis. This paper summarized the literature reports and GenBank database regarding occurrence and transcription of the mating-type genes of MAT1-1 and MAT1-2 idiomorphs in natural C. sinensis, in Hirsutella sinensis(GC-biased Genotype #1 of O. sinensis), to infer the mating pattern of O. sinensis in the lifecycle of natural C. sinensis. The mating-type genes and transcripts of MAT1-1 and MAT1-2 idiomorphs were identified in the metagenomes and metatranscriptomes of natural C. sinensis. However, their fungal sources are unclear because of co-colonization of several genotypes of O. sinensis and multiple fungal species in natural C. sinensis. The mating-type genes of MAT1-1 and MAT1-2 idiomorphs were differentially present in 237 H. sinensis strains, constituting the genetic control of the O. sinensis reproduction. Transcriptional control of the O. sinensis reproduction includes: differential transcription or silencing of the mating-type genes of MAT1-1 and MAT1-2 idiomorphs, and the MAT1-2-1 transcript with unspliced intron I that contains 3 stop codons. Research on the H. sinensis transcriptome demonstrated differential and complementary transcriptions of the mating-type genes of MAT1-1 and MAT1-2 idiomorphs in Strains L0106 and 1229, which may become mating partners to accomplish physiological heterothallism. The differential occurrence and transcription of the mating-type genes in H. sinensis are inconsistent with the self-fertilization hypothesis under homothallism or pseudohomothallism, but instead indicate the need of mating partners of the same H. sinensis species, either monoecious or dioecious, for physiological heterothallism, or heterospecific species for hybridization. Multiple GC-and AT-biased genotypes of O. sinensis were identified in the stroma, stromal fertile portion(densely covered with numerous ascocarps) and ascospores of natural C. sinensis. It needs to be further explored if the genome-independent O. sinensis genotypes could become mating partners to accomplish sexual reproduction. S. hepiali Strain FENG experienced differential transcription of the mating-type genes with a pattern complementary to that of H. sinensis Strain L0106. Additional evidence is needed to explore a hybridization possibility between S. hepiali and H. sinensis, whether they are able to break the interspecific reproductive isolation. Genotypes #13～14 of O. sinensis feature large DNA segment reciprocal substitutions and genetic material recombination between 2 heterospecific parental fungi, H. sinensis and an AB067719-type fungus, indicating a possibility of hybridization or parasexuality. Our analysis provides important information at the genetic and transcriptional levels regarding the mating-type gene expression and reproduction physiology of O. sinensis in the sexual life of natural C. sinensis and offers crucial reproductive physiology evidence, to assist in the design of the artificial cultivation of C. sinensis to supplement the increasing scarcity of natural resource.

Anti-tumour effect of Huangqin Decoction on colorectal cancer mice through microbial butyrate mediated PI3K/Akt pathway suppression.

Introduction. Huangqin Decoction (HQD), a Chinese herbal formula, is widely used for various diseases, including colorectal cancer (CRC).Hypothesis/Gap Statement. We proposed that microbial butyrate mediated PI3K/Akt pathway suppression might involve the anti-cancer effect of HQD.Aim. This study aimed to evaluate the potential mechanism of HQD against CRC.Methodology. An azoxymethane plus dextran sulphate sodium induced CRC mouse model was used, and the intestinal flora and faecal short-chain fatty acid changes were detected, respectively, after HQD administration with 16S rRNA sequencing and gas chromatography coupled with mass spectrometry. Disease activity index, colon length and levels of inflammatory cytokines were measured to evaluate the effect of HQD on intestinal inflammation. Tumour size, number and histopathology were assessed to reflect the impact of HQD on tumour burden. Apoptosis and PI3K/Akt pathway activity were measured by TUNEL staining and Western-blotting. In vitro, the effects of sodium butyrate (NaB) on the viability of CRC cell lines were detected by the Cell-counting Kit-8. The apoptotic cells were determined by TUNEL staining. Cell migration and invasion were assessed by wound healing assay and Transwell assay, respectively. Western-blotting and immunofluorescent staining were used to test the activity of PI3K/Akt pathway.Results. Animal study showed that HQD could improve the gut dysbiosis, increase the abundance of Clostridium and the level of faecal butyric acid. Then, we found that HQD could attenuate colitis, reduce tumour burden, promote cell apoptosis and suppress PI3K/Akt pathway activity in CRC mice. In vitro experiment revealed that NaB treatment could inhibit cell growth, migration and invasion in CRC cell lines. Additionally, NaB enhanced cellular apoptosis, and reduced phosphorylated PI3K and Akt expressions. Interestingly, addition of 740Y-P, an agonist of PI3K, reversed the NaB effects on CRC cells.Conclusion. Overall, in this study, we revealed that HQD could induce apoptosis through microbial butyrate mediated PI3K/Akt inhibition and perform anti-CRC activity.

[Research progress in targeting autophagy of traditional Chinese medicine and natural compounds to regulate atherosclerosis].

Atherosclerosis(AS) is the common pathological basis of many ischemic cardiovascular diseases, and its formation process involves various aspects such as vascular endothelial injury and platelet activation. Vascular endothelial injury is the initiating factor of AS plaque. Monocytes are recruited to differentiate into macrophages at the damaged endothelial cells, which absorb oxidized low-density lipoprotein(ox-LDL) and slowly transform into foam cells. Smooth muscle cells(SMCs) proliferate and migrate continuously. As the only cell producing interstitial collagen fibers in the fibrous cap, SMCs largely determine whether the plaque ruptured or not. The amplifying inflammatory response during the formation of AS recruits platelets to adhere to the damaged area of vascular endothelium and stimulates excessive platelet aggregation. Autophagy activity is associated with vascular lesions and abnormal platelet activation, and excessive autophagy is considered to be a negative factor for plaque stability. Therefore, precise regulation of different types of vascular autophagy and platelet autophagy to treat AS may provide a new therapeutic perspective for the prevention and treatment of atherosclerotic ischemic cardiovascular disease. Currently, treatment strategies for AS still focus on lowering lipid levels with high-intensity statins, which often cause significant side effects. Therefore, the development of safer and more effective drugs and treatment modes is the focus of current research. Traditional Chinese medicine and natural compounds have the potential to treat AS by targeted autophagy, and have been playing an increasingly important role in the prevention and treatment of cardiovascular diseases in China. This paper summarizes the experimental studies on different vascular cell types and platelet autophagy in AS, and sums up the published research results on targeted autophagy of traditional Chinese medicine and natural plant compounds to regulate AS, providing new ideas for further research.

Acupuncture for gastrointestinal diseases.

Acupuncture, an important component of traditional Chinese medicine, has gained growing attention around the world in the past decades. Both manual and electroacupuncture are commonly used in clinical practice, especially by patients with gastrointestinal disorders seeking symptoms control due to disease signs recurrence and/or lack of effective treatments. Currently, patients with functional gastrointestinal disorders, constipation, gastroesophageal reflux disease, inflammatory bowel disease, ileus, acute pancreatitis, and gastroparesis may benefit from acupuncture treatment, as clinically evident, and the most frequently used acupoints are chosen from the large intestine, stomach, bladder, and spleen meridian. The underlying mechanisms of acupuncture involve the neuromodulation, adjustment of gastrointestinal motility and visceral hypersensitivity, anti-inflammation, repairment of gut microbiota, and intestinal barrier. As methodology advanced, cumulative number of well-designed clinical trials has been established, which might help elevating clinicians and gastroenterologists' awareness and perception toward application of acupuncture for gastrointestinal diseases management.

Slicing specifications in general rule of processing in Chinese Pharmacopoeia from slicing development of Chinese materia medica processed product and thinking and suggestion on slicing techniques / 中国中药杂志

Slicing is critical in the processing of Chinese materia medica(CMM) processed product and the specification(thickness) is closely related to the quality of the decoction. On the basis of clarifying the concept and evolution of slicing of CMM processed product by reviewing the Chinese herbal classics of the past dynasties and general rules of local processing standards, this study discussed the development history of slicing specifications in general rules of Chinese Pharmacopoeia(2020 edition), analyzed the current situation and key problems, and proposed the thinking and suggestion on promoting the sound development of slicing of CMM processed product. Since 2000, the slicing thickness of CMM processed product in the general rules of local CMM processed product processing specifications newly revised and issued by 27 provinces, autonomous regions, and municipalities has been consistent with that in the general rules of the Chinese Pharmacopoeia(2020 edition). The standard that the thickness of extremely thin pieces is less than 0.5 mm is rarely retained, and the pieces in 0.5-1 mm thickness have not been found on the market, which is consistent with the provisions of the general rules of the Chinese Pharmacopoeia. This study can provide a historical and modern basis for the rationality of slicing of CMM processed product.

Genome-Wide Analysis of the RNase T2 Family and Identification of Interacting Proteins of Four ClS-RNase Genes in 'XiangShui' Lemon.

S-RNase plays vital roles in the process of self-incompatibility (SI) in Rutaceae plants. Data have shown that the rejection phenomenon during self-pollination is due to the degradation of pollen tube RNA by S-RNase. The cytoskeleton microfilaments of pollen tubes are destroyed, and other components cannot extend downwards from the stigma and, ultimately, cannot reach the ovary to complete fertilisation. In this study, four S-RNase gene sequences were identified from the 'XiangShui' lemon genome and ubiquitome. Sequence analysis revealed that the conserved RNase T2 domains within S-RNases in 'XiangShui' lemon are the same as those within other species. Expression pattern analysis revealed that S3-RNase and S4-RNase are specifically expressed in the pistils, and spatiotemporal expression analysis showed that the S3-RNase expression levels in the stigmas, styles and ovaries were significantly higher after self-pollination than after cross-pollination. Subcellular localisation analysis showed that the S1-RNase, S2-RNase, S3-RNase and S4-RNase were found to be expressed in the nucleus according to laser confocal microscopy. In addition, yeast two-hybrid (Y2H) assays showed that S3-RNase interacted with F-box, Bifunctional fucokinase/fucose pyrophosphorylase (FKGP), aspartic proteinase A1, RRP46, pectinesterase/pectinesterase inhibitor 51 (PME51), phospholipid:diacylglycerol acyltransferase 1 (PDAT1), gibberellin receptor GID1B, GDT1-like protein 4, putative invertase inhibitor, tRNA ligase, PAP15, PAE8, TIM14-2, PGIP1 and p24beta2. Moreover, S3-RNase interacted with TOPP4. Therefore, S3-RNase may play an important role in the SI of 'XiangShui' lemon.

Total Flavonoids of Drynariae Rhizoma Improve Glucocorticoid-Induced Osteoporosis of Rats: UHPLC-MS-Based Qualitative Analysis, Network Pharmacology Strategy and Pharmacodynamic Validation.

Background: Glucocorticoid-induced osteoporosis (GIOP) is a common form of secondary osteoporosis caused by the protracted or a large dosage of glucocorticoids (GCs). Total flavonoids of Drynariae rhizoma (TFDR) have been widely used in treating postmenopausal osteoporosis (POP). However, their therapeutic effects and potential mechanism against GIOP have not been fully elucidated. Methods: Ultra-high-performance liquid chromatography coupled with electrospray ionization quadrupole time-of-flight mass spectrometry (UHPLC-ESIQ-TOF-MS) experiments were performed for qualitative analysis. We performed hematoxylin-eosin (HE) staining and microcomputed tomography (micro-CT) analysis to detect the changes in bone microstructure. The changes in biochemical parameters in the serum samples were determined by performing an enzyme-linked immunosorbent assay (ELISA). The prediction results of network pharmacology were verified via quantitative real-time polymerase chain reaction (qRT-PCR) to elucidate the potential mechanism of TFDR against GIOP. Results: A total of 191 ingredients were identified in vitro and 48 ingredients in vivo. In the in-vivo experiment, the levels of the serum total cholesterol (TC), the serum triglyceride (TG), Leptin (LEP), osteocalcin (OC), osteoprotegerin (OPG), bone morphogenetic protein-2 (BMP-2), propeptide of type I procollagen (PINP), tartrate-resistant acid phosphatase (TRACP) and type-I collagen carboxy-terminal peptide (CTX-1) in the TFDR group significantly changed compared with those in the GIOP group. Moreover, the TFDR group showed an improvement in bone mineral density and bone microstructure. Based on the results of network pharmacology analysis, 67 core targets were selected to construct the network and perform PPI analysis as well as biological enrichment analysis. Five of the targets with high "degree value" had differential gene expression between groups using qRT-PCR. Conclusion: TFDR, which may play a crucial role between adipose metabolism and bone metabolism, may be a novel remedy for the prevention and clinical treatment of GIOP.

Potential mechanism of oral baicalin treating psoriasis via suppressing Wnt signaling pathway and inhibiting Th17/IL-17 axis by activating PPARγ.

Psoriasis (PSO), an immune-mediated chronic inflammatory skin disease, has seriously affected the quality of patients' life. It is urgent to find effective medicines with lower costs and less side effects. Baicalin (HQG) is the main bioactive substance from Scutellaria baicalensis with effects of anti-inflammation and immunoregulation. Herein, we explored the effect of oral HQG treating PSO and its potential mechanism. Firstly, network pharmacology was used to predict that HQG may act on Estrogen, TNF-alpha (tumor necrosis factor, TNF), interleukin-17 (IL-17) signaling pathways and Th17 cell differentiation, especially the key targets including TNF, Proto-oncogene tyrosine-protein kinase Src, Peroxisome proliferator-activated receptor gamma and Matrix metalloproteinase-9. Imiquimod (IMQ)-induced mice were then used to study the effects of HQG treating PSO. HQG could significantly ameliorate the skin lesions, decrease the level of inflammatory factors and inhibit Th1/Th17 cell differentiation in IMQ-induced mice. Finally, transcriptome analysis of skin lesions integrated with the prediction of network pharmacology further demonstrated that the potential mechanism may be associated with suppressing Wnt signaling pathway and inhibiting Th17/IL-17 axis by activating PPARγ. In conclusion, this study suggested that HQG may be a promising agent for further studies in the search for therapeutic strategies to treat PSO in the future.

Potential shared therapeutic and hepatotoxic mechanisms of Tripterygium wilfordii polyglycosides treating three kinds of autoimmune skin diseases by regulating IL-17 signaling pathway and Th17 cell differentiation.

ETHNOPHARMACOLOGICAL RELEVANCE: Tripterygium wilfordii polyglycosides (TWP) are extracted from Tripterygium wilfordii Hook. f., which has the significant effects of anti-inflammation and immunosuppression and has been widely used to treat autoimmune diseases in traditional Chinese medicine. AIM OF STUDY: In Chinese clinical dermatology, TWP was generally used for the treatment of autoimmune skin diseases including psoriasis (PSO), systemic lupus erythematosus (SLE) and pemphigus (PEM). However, the potential hepatotoxicity (HPT) induced by TWP was also existing with the long-term use of TWP. This study aims to explore the potential shared therapeutic mechanism of TWP treating PSO, SLE, PEM and the possible hepatotoxic mechanism induced by TWP. MATERIALS AND METHODS: Network pharmacology was used to predict the potential targets and pathways in this study. The main bioactive compounds in TWP was screened according to TCMSP, PubChem, ChEMBL databases and Lipinski's Rule of Five. The potential targets of these chemical constituents were obtained from PharmMapper, SEA and SIB databases. The related targets of PSO, SLE, PEM and HPT were collected from GeneCards, DrugBank, DisGeNET and CTD databases. The target network construction was performed through STRING database and Cytoscape. GO enrichment, KEGG enrichment and molecular docking were then performed, respectively. In particular, imiquimod (IMQ)-induced PSO model was selected as the representative for the experimental verification of effects and shared therapeutic mechanisms of TWP. RESULTS: 41 targets were considered as the potential shared targets of TWP treating PSO, SLE and PEM. KEGG enrichment indicated that IL-17 signaling pathway and Th17 cell differentiation were significant in the potential shared therapeutic mechanism of TWP. The animal experimental verification demonstrated that TWP could notably ameliorate skin lesions (P˂0.001), decrease inflammatory response (P˂0.05, P˂0.01, P˂0.001) and inhibit the differentiation of Th1/Th17 cells (P˂0.05, P˂0.01) compared to PSO model group. The molecular docking and qPCR validation then showed that TWP could effectively act on MAPK14, IL-2, IL-6 and suppress Th17 cell differentiation and IL-17 signaling pathway. The possible hepatotoxic mechanism of TWP indicated that there were 145 hepatotoxic targets and it was also associated with IL-17 signaling pathway and Th17 cell differentiation, especially for the key role of ALB, CASP3 and HSP90AA1. Meanwhile, the potential correlations between efficacy and hepatotoxicity of TWP showed that 28 targets were shared by therapeutic and hepatotoxic mechanisms such as IL-6, IL-2, MAPK14, MMP9, ALB, CASP3 and HSP90AA1. These significant relevant targets were also involved in IL-17 signaling pathway and Th17 cell differentiation. CONCLUSIONS: There were shared disease targets in PSO, SLE and PEM, and TWP could treat them by potential shared therapeutic mechanisms of suppressing IL-17 signaling pathway and Th17 cell differentiation. The possible hepatotoxicity induced by TWP was also significantly associated with the regulation of IL-17 signaling pathway and Th17 cell differentiation. Meanwhile, the potential correlations between efficacy and hepatotoxicity of TWP also mainly focused on IL-17 signaling pathway and Th17 cell differentiation, which provided a potential direction for the study of the mechanism of "You Gu Wu Yun" theory of TWP treating autoimmune skin diseases in the future.

Adsorption Characteristics of Phosphate Based on Al-Doped Waste Ceramsite: Batch and Column Experiments.

Phosphorus widely existing in rainfall and wastewater impacts the water environment. In this study, sludge, cement block, and coal fly ash were employed as ceramsite material to synthesize Al-doped waste ceramsite (Al-ceramsite) for removing phosphate (PO43--P) from aqueous solutions. Batch static adsorption-desorption experiments were designed to investigate the effect of various parameters such as Al-ceramsite dosage, PO43--P concentration, temperature, initial pH, coexisting ions, and desorbents on the removal of PO43--P. Also, the fate of PO43--P removal efficiency in actual rainwater was studied through dynamic adsorption column experiments using Al-ceramsite. Results showed that Al-ceramsite could remove PO43--P efficiently under the optimum parameters as follows: Al-ceramsite dosage of 40 g/L, initial PO43--P concentration of 10 mg/L, temperature of 25 °C, and pH of 5. Besides that, the Al-ceramsite could completely remove PO43--P in actual rainwater, and the effluent PO43--P concentration was lower than the environmental quality standards for surface water Class Ⅰ (0.02 mg/L). The adsorption characteristics of Al-ceramsite on PO43--P by X-ray photoelectron spectroscopy (XPS) were further explained. As a result, ligand exchange and complexation were confirmed as the main PO43--P removal mechanism of Al-ceramsite. Thus, Al-ceramsite was prepared from industrial waste and has shown excellent potential for phosphorus removal in practical applications.

Save reservoirs of humid subtropical cities from eutrophication threat.

Reservoir water is the most important freshwater resource for many cities, especially in densely populated humid subtropical areas. Economic growth, population increase, and urbanization have been putting reservoir water of Shenzhen (China), a humid subtropical city, under severe threat of eutrophication and water supply shortage. In this study, we focused on an upstream reservoir of Shenzhen and established a 3-dimensional hydrodynamic-ecological model to investigate the water dynamics and nutrient budget. Tributaries to the reservoir were identified as the greatest contributors to nitrogen and phosphorus loads. Zones with weak flows and high nutrient concentration have high risks of causing blooms. Several mitigation measures were proposed, including improving flow by adding additional water exit locations in the reservoir, reducing nutrients in tributaries, and enhancing algal predation, and were evaluated with the established model. The strategies combining hydrodynamic improvement and phosphorus reduction were suggested to decision makers and government managers for short-term management. However, for future water safety, excessive nitrogen is a potential danger. This study provides a modeling framework that can be applied to anthropogenic-influenced reservoirs elsewhere.

Subambient daytime radiative cooling textile based on nanoprocessed silk.

Decreasing energy consumption is critical to sustainable development. Because temperature regulation for human comfort consumes vast amounts of energy, substantial research efforts are currently directed towards developing passive personal thermal management techniques that cool the human body without any energy consumption1-9. Although various cooling textile designs have been proposed previously, textile-based daytime radiative cooling to a temperature below ambient has not been realized6-13. Silk, a natural protein fabric produced by moth caterpillars, is famous for its shimmering appearance and its cooling and comforting sensation on skin14-17. It has been recently recognized that silk, with its optical properties derived from its hierarchical microstructure, may represent a promising starting point for exploring daytime radiative cooling18-21. However, the intrinsic absorption of protein in the ultraviolet region prevents natural silk from achieving net cooling under sunlight. Here we explore the nanoprocessing of silk through a molecular bonding design and scalable coupling reagent-assisted dip-coating method, and demonstrate that nanoprocessed silk can achieve subambient daytime radiative cooling. Under direct sunlight (peak solar irradiance >900 W m-2) we observed a temperature of ~3.5 °C below ambient (for an ambient temperature of ~35 °C) for stand-alone nanoprocessed silks. We also observed a temperature reduction of 8 °C for a simulated skin when coated with nanoprocessed silk, compared with natural silk. This subambient daytime radiative cooling of nanoprocessed silk was achieved without compromising its wearability and comfort. This strategy of tailoring natural fabrics through scalable nanoprocessing techniques opens up new pathways to realizing thermoregulatory materials and provides an innovative way to sustainable energy.

The interpretation of human body in traditional Chinese medicine and its influence on the characteristics of TCM theory.

Traditional Chinese medicine (TCM) has a long history of serving the Chinese people's health since its birth, including playing an important role in treating and preventing COVID-19 in 2020. The fact that TCM has been used in China for thousands of years shows the value and reason why it must exist. Although TCM has been or is being questioned, there is no doubt about its importance in terms of efficacy. This article focuses on how TCM understands the human body in comparison with anatomy knowledge in western medicine and discusses the development and advances of TCM in terms of the body view and the theory innovation. The purpose is to let foreign scholars get better understanding of TCM from this perspective.

Comparative Efficacy of Seven Kinds of Chinese Medicine Injections in Acute Lung Injury and Acute Respiratory Distress Syndrome: A Network Meta-analysis of Randomized Controlled Trials.

Background: Chinese medicine injection is wildly used in Acute Lung Injury and Acute respiratory distress syndrome (ALI/ARDS) treatment. However, what kinds of CMIs are more effective in the ALI/ARDS treatment is uncertain. Objectives: Compare the efficacy of different CMIs to identify the optimal one for the therapy of ALI/ARDS patients. Data sources: We searched the data up to April 30, 2020 from MEDLINE, EMBASE, The Cochrane Library, Web of Science, the China Science Journal Citation Report (VIP database), WanFang and the China National Knowledge Infrastructure Study selection: Randomized Clinical Trials assessed at least one of the following outcomes: mortality, Oxygenation Index, length of ICU stay, mechanical ventilation duration, APACHEⅡ score, SOFA score and Murray score, for adult patients of ALI/ADRS. Eligible Studies should also use CMIs as complementary therapies in addition to the standard treatment. Data extraction and synthesis: Two reviewers independently assessed the data. Then, we used a Bayesian random-effects network meta-analysis for data synthesis. Results: Twenty-six studies were selected (involved 2073 participants). Seven kinds of CMIs were evaluated. Compared with standard treatment, Xuebijing is associated with lower mortality. Tanreqing and Xuebijing have the best effect on improving the Oxygenation Index. Huangqi, Danshen, Tanreqing and Xuebijing can significantly reduce the APACHE II score (Huangqi works better than Xuebijing). Huangqi and Xuebijing have the best effect on reducing mechanical ventilation duration and Murray score, while Xuebijing has the best effect on shortening the length of ICU stay. Conclusions: As adjuvant drugs, Xuebijing, Tanreqing and Huangqi show certain effects on treating ALI/ARDS in different aspects.

Influence of Methylenetetrahydrofolate Reductase C677T and A1298C Polymorphism on High-Dose Methotrexate-Related Toxicities in Pediatric Non-Hodgkin Lymphoma Patients.

PURPOSE: This retrospective study aimed to investigate the relationships between the methylenetetrahydrofolate reductase (MTHFR) C677T/A1298C and high-dose methotrexate (HD-MTX)-related toxicities in pediatric non-Hodgkin lymphoma (NHL) patients. PATIENTS AND METHODS: We reviewed the medical records of 93 NHL patients aged under 18 years who received HD-MTX therapy at the dose of 5 g/m2 with 24-h infusion at Sun Yat-sen University Cancer Center between 2014 and 2019. RESULTS: There were 61 males and 32 females, with a median age of 8.8 years (0.9-15.8 years). The tumor types included lymphoblastic lymphoma (n = 38), Burkitt's lymphoma (n = 31), anaplastic large cell lymphoma (n = 18), diffuse large B-cell lymphoma (n = 6). Overall, 355 courses of HD-MTX therapy were prescribed. All patients were rescued with calcium folinate 12 h after the end of MTX infusion. We found that plasma MTX levels > 0.2 µmol/L at 48 h post-infusion increased the risk of developing oral mucositis (2.4% VS. 9.5%, P = 0.018). Also, patients carrying the C677T and T677T genotypes had tendencies to be more susceptible to oral mucositis (P = 0.034). Patients harboring mutant 677T allele were more likely to develop leucopenia (38.5 vs. 50.3%, P = 0.025) and thrombocytopenia (22.0 vs. 32.4%, P = 0.028). For polymorphism A1298C, the mutant genotype played a protective role in vomiting (11.1 vs. 4.3%, P = 0.018) but increased the risk of anemia (23.8 vs. 41.7%, P < 0.001) and leucopenia (38.1 vs. 50.3%, P = 0.021). CONCLUSION: Childhood NHL patients harboring C677T genotype were more vulnerable to oral mucositis, leucopenia, and thrombocytopenia, while those with A1298C genotype were at a decreased risk of vomiting and more likely to develop anemia and leucopenia.