A terpenoids database with the chemical content as a novel agronomic trait.

Natural products play a pivotal role in drug discovery, and the richness of natural products, albeit significantly influenced by various environmental factors, is predominantly determined by intrinsic genetics of a series of enzymatic reactions and produced as secondary metabolites of organisms. Heretofore, few natural product-related databases take the chemical content into consideration as a prominent property. To gain unique insights into the quantitative diversity of natural products, we have developed the first TerPenoids database embedded with Content information (TPCN) with features such as compound browsing, structural search, scaffold analysis, similarity analysis and data download. This database can be accessed through a web-based computational toolkit available at http://www.tpcn.pro/. By conducting meticulous manual searches and analyzing over 10 000 reference papers, the TPCN database has successfully integrated 6383 terpenoids obtained from 1254 distinct plant species. The database encompasses exhaustive details including isolation parts, comprehensive molecule structures, chemical abstracts service registry number (CAS number) and 7508 content descriptions. The TPCN database accentuates both the qualitative and quantitative dimensions as invaluable phenotypic characteristics of natural products that have undergone genetic evolution. By acting as an indispensable criterion, the TPCN database facilitates the discovery of drug alternatives with high content and the selection of high-yield medicinal plant species or phylogenetic alternatives, thereby fostering sustainable, cost-effective and environmentally friendly drug discovery in pharmaceutical farming. Database URL: http://www.tpcn.pro/.

Oxymatrine induces apoptosis in non-small cell lung cancer cells by downregulating TRIM46.

Sophora flavescens Aiton, a traditional Chinese medicine that was supposed to predominantly play an anti-inflammatory role, has been used to treat multiple diseases, including cancer, for over two thousand years. Recently, it has attracted increasing attention due to the anti-tumor properties of Oxymatrine, one of the most active alkaloids extracted from S. flavescens. This study aims to explore it's anti-tumor effects in non-small cell lung cancer (NSCLC) and the underlying mechanisms. We first investigated the effects of oxymatrine on cell apoptosis in lung cancer cell lines A549 and PC9 as well as explored related genes in regulating the apoptosis by transcriptome analysis. Subsequently, to further study the role of TRIM46, we constructed two types of TRIM46 over-expression cells (A549TRIM46+ and PC9TRIM46+ cells) and then investigated the effect of TRIM46 on oxymatrine-induced apoptosis. Moreover, we explored the effect of TRIM46 on downstream signaling pathways. Transcriptome analysis suggested that shared differentially expressed genes (DEGs) in A549 and PC9 cells treated with oxymatrine were CACNA1I, PADI2, and TRIM46. According to TCGA database analysis, the abundance of TRIM46 expression was higher than CACNA1I, and PADI2 in lung cancer tissues, then was selected as the final DEG for subsequent studies. We observed that oxymatrine resulted in down-expression of TRIM46 as well as induced the apoptosis of the cancer cells in a dose- and time-dependent manner. Meanwhile, we found that apoptosis induced by oxymatrine was inhibited by over-expressing TRIM46. Furthermore, our study indicated that the NF-κB signaling pathway was involved in apoptosis suppressed by TRIM46. We conclude that TRIM46 is the direct target of oxymatrine to induce anti-tumor apoptosis and may activate the downstream NF-κB signaling pathway.

In Situ Growth Reaction on Photoelectrodes of Single-Atom Fe Incorporated Bi4O5I2: A General Photoelectrochemical Immunoassay Toward Sensitive Protein Analysis.

As one of the interesting signaling mechanisms, the in situ growth reaction on a photoelectrode has proven its powerful potential in photoelectrochemical (PEC) bioanalysis. However, the specific interaction between the signaling species with the photoactive materials limits the general application of the signal mechanism. Herein, on the basis of an in situ growth reaction on a photoelectrode of single-atom-based photoactive material, a general PEC immunoassay was developed in a split-type mode consisting of the immunoreaction and PEC detection procedure. Specifically, a single-atom photoactive material that incorporates Fe atoms into layered Bi4O5I2 (Bi4O5I2-Fe SAs) was used as a photoelectrode for PEC detection. The sandwich immunoreaction was performed in a well of a 96-well plate using Ag nanoparticles (Ag NPs) as signal tracers. In the PEC detection procedure, the Ag+ converted from Ag NPs were transferred onto the surface of the Bi4O5I2-Fe SAs photoelectrode and thereafter AgI was generated on the Bi4O5I2-Fe SAs in situ to form a heterojunction through the reaction of Ag+ with Bi4O5I2-Fe SAs. The formation of heterojunction greatly promoted the electro-hole separation, boosting the photocurrent response. Exemplified by myoglobin (Myo) as the analyte, the immunosensor achieved a wide linear range from 1.0 × 10-11 to 5.0 × 10-8 g mL-1 with a detection limit of 3.5 × 10-12 g mL-1. This strategy provides a general PEC immunoassay for disease-related proteins, as well as extends the application scope of in situ growth reaction in PEC analysis.

Two new compounds from biotransformation of glycyrrhetinic acid.

Glycyrrhetinic acid may undergo biotransformation to obtain derivatives with stronger pharmacological activity and fewer side effects. This study used 19 fungi to biotransform glycyrrhetinic acid and yielded two compounds namely bicyclo(14.15.27)glycyrrhetinic acid (1) and 2-ene-glycyrrhetinic acid (2) from the glycyrrhetinic acid metabolites of two fungi, Botrytis cinerea B05.10 ATCC 11542 and Aspergillus ochraceopetaliformis ATCC 12066. Compound 1 inhibited HMEC-1 cell proliferation in a concentration-dependent manner (IC50=239.1 µ M), but showed no significant cytotoxicity to A549 cells.

[Genome-wide identification and expression analysis of TCP gene family of Andrographis paniculata under abiotic stress].

Andrographis paniculata is an important medicinal plant in the Lingnan region of China, which has the functions of clearing heat, removing toxins, and resisting bacteria and inflammation. The TCP gene family is a class of transcription factors that regulate plant growth, development, and stress response. In order to analysis the role of the TCP gene family under abiotic stress in A. paniculata, this study identified the TCP gene family of A. paniculata at the genome-wide level and analyzed its expression pattern in response to abiotic stress. The results showed that the A. paniculata TCP gene family had 23 members, with length of amino acid ranging from 136 to 508, the relative molecular mass between 14 854.71 and 55 944.90 kDa, and the isoelectric point between 5.67 and 10.39. All members were located in the nucleus and unevenly distributed on 13 chromosomes. Phylogenetic analysis classified them into three subfamilies: PCF, CIN and CYC/TB1. Gene structure and conserved motif analysis showed that most members of the TCP gene family contained motif 1, motif 2, motif 3 in the same order and 1-3 CDS. The analysis of promoter cis-acting elements showed that the transcriptional expression of the TCP gene family in A. paniculata might be induced by light, hormones, and adversity stress. In light of the expression pattern analysis and qRT-PCR verification, the expression of ApTCP4, ApTCP5, ApTCP6, and ApTCP11 involved in response by various abiotic stresses such as drought, high temperature, and MeJA. This study lays the foundation for in-depth exploration of the functions of A. paniculata TCP genes in response to abiotic stress.

The interaction of anti-inflammatory and anti-tumor components in the traditional Chinese medicine Solanum lyratum Thunb.

Solanum lyratum Thunb is a traditional Chinese medicinal with a significant clinical outcome for tumor treatment; however, chemicals or fractions separated from the herb did not exhibit strong and comparable efficacy. To investigate the potential synergy or antagonism among chemicals in the extract, we obtained the compounds solavetivone (SO), tigogenin (TI) and friedelin (FR) from the herb. The anti-tumor effects of these three monomer compounds alone or in combination with the anti-inflammatory compound DRG were also tested in this study. SO, FR and TI used alone did not inhibit the proliferation of A549 and HepG2 cells, but the combination of the three achieved 40% inhibition. In vitro anti-inflammatory analysis showed that DRG had a stronger anti-inflammatory effect than TS at the same concentration, and the combination of DRG with SO, FR or TI inhibited the anti-tumor effect of DRG. This is the first study that documented the synergistic and antagonistic interactions between different compounds in a single herb.

The gastrodin biosynthetic pathway in Pholidota chinensis Lindl. revealed by transcriptome and metabolome profiling.

Pholidota chinensis Lindl. is an epiphytic or lithophytic perennial herb of Orchidaceae family used as a garden flower or medicinal plant to treat high blood pressure, dizziness and headache in traditional Chinese medicine. Gastrodin (GAS) is considered as a main bioactive ingredient of this herb but the biosynthetic pathway remains unclear in P. chinensis. To elucidate the GAS biosynthesis and identify the related genes in P. chinensis, a comprehensive analysis of transcriptome and metabolome of roots, rhizomes, pseudobulbs and leaves were performed by using PacBio SMART, Illumina Hiseq and Ultra Performance Liquid Chromatography Tandem Mass Spectrometry (UPLC-MS/MS). A total of 1,156 metabolites were identified by UPLC-MS/MS, of which 345 differential metabolites were mainly enriched in phenylpropanoid/phenylalanine, flavone and flavonol biosynthesis. The pseudobulbs make up nearly half of the fresh weight of the whole plant, and the GAS content in the pseudobulbs was also the highest in four tissues. Up to 23,105 Unigenes were obtained and 22,029 transcripts were annotated in the transcriptome analysis. Compared to roots, 7,787, 8,376 and 9,146 differentially expressed genes (DEGs) were identified in rhizomes, pseudobulbs and leaves, respectively. And in total, 80 Unigenes encoding eight key enzymes for GAS biosynthesis, were identified. Particularly, glycosyltransferase, the key enzyme of the last step in the GAS biosynthetic pathway had 39 Unigenes candidates, of which, transcript28360/f2p0/1592, was putatively identified as the most likely candidate based on analysis of co-expression, phylogenetic analysis, and homologous searching. The metabolomics and transcriptomics of pseudobulbs versus roots showed that 8,376 DEGs and 345 DEMs had a substantial association based on the Pearson's correlation. This study notably enriched the metabolomic and transcriptomic data of P. chinensis, and it provides valuable information for GAS biosynthesis in the plant.

The current status of old traditional medicine introduced from Persia to China.

Traditional Chinese medicine (TCM) includes over ten thousand herbal medicines, some of which were introduced from outside countries and territories. The Silk Road enabled the exchange of merchandise such as teas, silks, carpets, and medicines between the East and West of the Eurasia continent. During this time, the 'Compendium of Materia Medica' (CMM) was composed by a traditional medicine practitioner, Shizhen Li (1,518-1,593) of the Ming Dynasty. This epoch-making masterpiece collected knowledge of traditional medical materials and treatments in China from the 16th century and before in utmost detail, including the origin where a material was obtained. Of 1892 medical materials from the CMM, 46 came from Persia (now Iran). In this study, the basic information of these 46 materials, including the time of introduction, the medicinal value in TCM theory, together with the current status of these medicines in China and Iran, are summarized. It is found that 20 herbs and four stones out of the 46 materials are registered as medicinal materials in the latest China Pharmacopoeia. Now most of these herbs and stones are distributed in China or replacements are available but saffron, ferula, myrrh, and olibanum are still highly dependent on imports. This study may contribute to the further development, exchange, and internationalization of traditional medicine of various backgrounds in the world, given the barriers of transportation and language are largely eased in nowadays.

The Deterioration of Agronomical Traits of the Continuous Cropping of Stevia Is Associated With the Dynamics of Soil Bacterial Community.

Stevia rebaudiana Bertoni is grown worldwide as an important, natural sweetener resource plant. The yield of steviol glycosides (SVglys) is greatly influenced by continuous cropping. In this study, we collected the roots, rhizosphere soils, and bulk soils from 2 years of continuous cropping (Y2) and 8 years of continuous cropping (Y8). A high-throughput sequencing technology based on Illumina Hiseq 2500 platform was used to study the structure and diversity of bacterial communities in the roots and soils of stevia with different years of continuous cropping. The results demonstrated that although the content of a group of SVglys was significantly increased in stevia of long-term continuous cropping, it inhibited the growth of plants and lowered the leaf dry weight; as a result, the total amount of SVglys was significantly decreased. Meanwhile, continuous cropping changed the physicochemical properties and the bacterial composition communities of soil. The different sampling sources of the root, rhizosphere soil, and bulk soil had no impact on the richness of bacterial communities, while it exhibited obvious effects on the diversity of bacterial communities. Continuous cropping had a stronger effect on the bacterial community composition in rhizosphere soil than in root and bulk soil. Based on linear discriminant analysis effect size (LEfSe), in the rhizosphere soil of Y8, the relative abundance of some beneficial bacterial genera of Sphingomonas, Devosia, Streptomyces, and Flavobacterium decreased significantly, while the relative abundance of Polycyclovorans, Haliangium, and Nitrospira greatly increased. Moreover, the soil pH and nutrient content, especially the soil organic matter, were correlated with the relative abundance of predominant bacteria at the genus level. This study provides a theoretical basis for uncovering the mechanism of obstacles in continuous stevia cropping and provides guidance for the sustainable development of stevia.

Ultrasensitive fluorescence detection of microRNA through DNA-induced assembly of carbon dots on gold nanoparticles with no signal amplification strategy.

An ultrasensitive fluorescence assay strategy on the basis of carbon dots (CDs) and cDNA-modified gold nanoparticles (AuNP-cDNA) was developed for the determination of microRNA-21 (miRNA-21) via internal filtering effect (IFE). Positively charged CDs (PEI-CDs), the fluorophores in IFE, were synthesized via a hydrothermal method using polyethyleneimine (PEI) as surface ligand. The maximum emission wavelength is located at 500 nm under the excitation of 410 nm. AuNPs, the absorbers, were modified with single-stranded DNA (cDNA), which is completely complementary to miRNA-21. The fluorescence of PEI-CDs is quenched due to the assembly of PEI-CDs and AuNPs-cDNA. In the presence of miRNA-21, the hybridization between miRNA-21 and cDNA causes the release of PEI-CDs and the recovery of fluorescence intensity.The fluorescence recovery degree is linearly correlated with the logarithm of miRNA-21 concentration in the range of 1-1000 fM. This method can be applied to determine miRNA-21 in real serum samples, and the detection results are in well agreement with those of qRT-PCR. The determination of miRNA-21 spiked into diluted human serum samples displays satisfactory recovery within the range 88.44-112.7%, which confirmed the reliability for miRNAs detection in real samples.

An Optimized Two-Herb Chinese Food as Medicine Formula Reduces Cisplatin-Induced Nephrotoxicity in the Treatment of Lung Cancer in Mice.

Chemotherapy is considered a most effective way to treat cancer. However, it is very common that chemotherapy causes unbearable mental and physical side effects to cancer patients, which ultimately reduces the patients' confidence of overcoming diseases and compromises the treatment of chemotherapy. Cisplatin (DDP), a widely used anticancer agent for various types of cancers, also damages nontumor cells and tissues, which are mostly related to the activation of the inflammation pathway. Previously, we have discovered a few rational formulas of food as medicine materials that reduced systemic inflammation in in vitro and in vivo models. Hence, this study reports the ability of an optimized traditional Chinese anti-inflammatory formulation capable of synergizing the antitumor effect of DDP in vitro and in vivo. More significantly, by formulation of two anti-inflammatory herbal medicine, the Chrysanthemum × morifolium (Ramat.) Hemsl [Asteraceae] and Lonicera japonica Thunb [Caprifoliaceae] with a mediator Glycyrrhiza uralensis Fisch. ex DC [Fabaceae], a best formula relieved the kidney damage imposed by DDP. Treatments of various combinations of major chemical components of the three herbs also exhibited a similar trend for lowering the DDP-induced nephrotoxicity; however, contrary to that of the formula of herbal extracts, all chemical formulas could not recover the body weight and food intake of the tumor-bearing mice treated by DDP. Our findings suggested that the therapeutic index of DDP-based chemotherapy was able to be improved by minimizing toxicities from the two-herb formula to inhibit the inflammation in mouse tumor models and DDP-induced acute kidney injury mouse models.

Culture and in situ H2O2-mediated electrochemical study of cancer cells using three-dimensional scaffold based on graphene foam coated with Fe3O4 nanozyme.

For real-time evaluation of the cell behavior and function under in vivo-like 3D environment, the 3D functionalized scaffolds simultaneously integrate the function of 3D cell culture, and electrochemical sensing is a convincing candidate. Herein, Fe3O4 nanoparticles as the nanozyme (peroxide oxidase mimics) were modified on graphene foam scaffold to construct a 3D integrated platform. The platform displayed a wide linear range of 100 nM to 20 µM and a high sensitivity of 53.2 nA µM-1 toward detection of hydrogen peroxide (H2O2) under the working potential of + 0.6 V (vs. Ag/AgCl). The obtained 3D scaffold also displayed satisfactory selectivity toward the possible interferents that appeared in the cell culture environment. Furthermore, the cells still maintained high cell viability (almost 100%) after their growth and proliferation on the scaffold for 7 days. With the superior performance on cell culture and electrochemical monitoring, the functions on the 3D culture of MCF-7 or HeLa cells and in situ monitoring of cell-released H2O2 was easily achieved on this 3D platform, which show its great application prospects on further cancer-related disease diagnosis or drug screening. A nanozyme-based three-dimensional graphene scaffold was successfully constructed for cell culture and identification of cancer cells through in situ electrochemical monitoring of the cell-released H2O2.

Yeast Surface Display for In Vitro Biosynthetic Pathway Reconstruction.

The enzymes immobilized through yeast surface display (YSD) can be used in in vitro metabolic pathway reconstruction as alternatives to the enzymes isolated or purified through conventional biochemistry methods. They can be easily prepared by growing and collecting yeast cells harboring display constructs. This may provide an economical method for enriching certain enzymes for biochemistry characterization and application. Herein, we took the advantage of one-pot cascade reactions catalyzed by YSD-immobilized enzymes in the mevalonate pathway to produce geraniol in vitro. YSD-immobilized enzymes of 10 cascade reactions for geraniol production, together with optimization of catalytic components, cofactor regeneration, and byproduct removal, achieved a final yield of 7.55 mg L-1 after seven cycles. This study demonstrated that it is feasible to reconstitute a complex multi-enzymatic system for the chemical biosynthesis in vitro by exploiting YSD-immobilized cascade enzymes.

Addition of Vegetable Oil to Improve Triterpenoids Production in Liquid Fermentation of Medicinal Fungus Antrodia cinnamomea.

The liquid fermentation of Antrodia cinnamomea is a promising alternative source for fungus production compared to the wildly grown fruiting body. Elicitation is a strong tool to enhance the productivity in microbial cells to obtain more compounds of interest. In this study, in order to improve the fungus growth and its terpenoids production, various vegetable oils were added in the fermentation broth of A. cinnamomea. It was found that corn oil from a group of vegetable oils exhibited the best effect on the biomass and triterpenoid content. After optimization, the initial addition of 1% (v/v) corn oil plus the inoculation of 10% (v/v) mycelia led to a maximum triterpenoid yield (532.3 mg L-1), which was increased as much as fourfold compared to the blank control. Differential transcriptome analysis demonstrated that corn oil significantly enriched several metabolic pathways including glycolysis/gluconeogenesis, propanoate metabolism and transmembrane hydrophobins. The enriched pathways interacted with deferentially expressed genes (DEGs) induced by corn oil treatment. Our research provides a potential strategy for the large production of triterpenoids by the improved fermentation of A. cinnamomea.

Genomic and Transcriptomic Insight of Giant Sclerotium Formation of Wood-Decay Fungi.

Many fungi form persistent and dormant sclerotia with compact hardened mycelia during unfavorable circumstances. While most of these sclerotia are small in size, Wolfiporia cocos, a wood-decay fungus, grows into giant sclerotia, which are mainly composed of polysaccharides of linear (1→3)-ß-D-glucans. To explore the underlying mechanism of converting sophisticated wood polysaccharides for biosynthesis of highly homogenized glucans in W. cocos, we sequenced and assembled the genome of a cultivated W. cocos strain (WCLT) in China. The 62-Mb haploid genome contains 44.2% repeat sequences, of which, 48.0% are transposable elements (TEs). Contrary to the genome of W. cocos from North America, WCLT has independently undergone a partial genome duplication (PGD) event. The large-scale TE insertion and PGD occurrence overlapped with an archeological Pleistocene stage of low oxygen and high temperature, and these stresses might have induced the differences in sclerotium due to geographical distribution. The wood decomposition enzymes, as well as sclerotium-regulator kinases, aquaporins, and highly expanded gene families such as NAD-related families, together with actively expressed 1,3-ß-glucan synthase for sclerotium polysaccharides, all have contributed to the sclerotium formation and expansion. This study shall inspire further exploration on how fungi convert wood into simple glucans in the sclerotium of W. cocos.

Creation of an Anti-Inflammatory, Leptin-Dependent Anti-Obesity Celastrol Mimic with Better Druggability.

Obesity is characterized by an excessive body mass, but is also closely associated with metabolic syndrome. And, so far, only limited pharmacological treatments are available for obesity management. Celastrol, a pentacyclic triterpenoid from a traditional Chinese medicine (Tripterygium wilfordii Hook.f.), has shown remarkable potency against obesity, inflammation and cancer, but its high toxicity, low natural abundance and tedious chemical synthesis hindered its translation into clinics. In the present work, a triterpenoid library was screened for compounds with both high natural abundance and structural similarity to celastrol; from this library, glycyrrhetinic acid (GA), a compound present in extremely high yields in Glycyrrhiza uralensis Fisch. ex DC., was selected as a possible scaffold for a celastrol mimic active against obesity. A simple chemical modification of GA resulted in GA-02, a derivative that suppressed 68% of food intake in diet-induced obesity mice and led to 26.4% weight loss in 2 weeks. GA-02 plays a role in obesity treatment by re-activating leptin signaling and reducing systemic and, more importantly, hypothalamic inflammation. GA-02 was readily bioavailable with unnoticeable in vitro and in vivo toxicities. The strategy of scaffold search and modification on the basis of bio-content and structural similarity has proved to be a green, economic, efficient and practical way of widening the medicinal applications of "imperfect" bioactive natural compounds.

Metabolomic and Pharmacologic Insights of Aerial and Underground Parts of Glycyrrhiza uralensis Fisch. ex DC. for Maximum Utilization of Medicinal Resources.

The roots of Glycyrrhiza spp. have been utilized in Traditional Chinese medicine (TCM) for thousands of years. Non-traditional (aerial) parts constitute a large portion of the biomass of Glycyrrhiza plants and are mostly discarded after harvesting the roots and rhizomes. Through comparative phytochemical and anti-inflammatory activity analyses, this study explored the potential benefits of the aerial parts of Glycyrrhiza uralensis Fisch. ex DC. as medicinal materials. First, a combined approach based on GC/MS and UHPLC-ESI-QTof MS analysis was adopted for the identification and quantitative examination of medicinally important compounds from G. uralensis. Additionally, a bioassay-guided fractioning of ethanolic extracts of G. uralensis leaf material was performed and its anti-inflammatory activity was tested. The aerial portion of G. uralensis was rich in medicinally important compounds. Two compounds (henicosane-1 and decahydroisoquinoline-2) were found to exert a significant anti-inflammatory effect, inhibiting the release of pro-inflammatory mediators (NO and PGE2) and cytokines (IL-1ß, IL6, and TNF-α), without exerting cytotoxic effects. Moreover, both compounds down-regulated iNOS and COX-2 mRNA expression. These results suggest that non-traditional parts of G. uralensis are suitable sources of bioactive metabolites that can be explored for medicinal purposes.

A Stretchable Scaffold with Electrochemical Sensing for 3D Culture, Mechanical Loading, and Real-Time Monitoring of Cells.

In the field of three-dimensional (3D) cell culture and tissue engineering, great advance focusing on functionalized materials and desirable culture systems has been made to mimic the natural environment of cells in vivo. Mechanical loading is one of the critical factors that affect cell/tissue behaviors and metabolic activities, but the reported models or detection methods offer little direct and real-time information about mechanically induced cell responses. Herein, for the first time, a stretchable and multifunctional platform integrating 3D cell culture, mechanical loading, and electrochemical sensing is developed by immobilization of biomimetic peptide linked gold nanotubes on porous and elastic polydimethylsiloxane. The 3D scaffold demonstrates very good compatibility, excellent stretchability, and stable electrochemical sensing performance. This allows mimicking the articular cartilage and investigating its mechanotransduction by 3D culture, mechanical stretching of chondrocytes, and synchronously real-time monitoring of stretch-induced signaling molecules. The results disclose a previously unclear mechanotransduction pathway in chondrocytes that mechanical loading can rapidly activate nitric oxide signaling within seconds. This indicates the promising potential of the stretchable 3D sensing in exploring the mechanotransduction in 3D cellular systems and engineered tissues.

Deciphering the Formulation Secret Underlying Chinese Huo-Clearing Herbal Drink.

Herbal teas or herbal drinks are traditional beverages that are prevalent in many cultures around the world. In Traditional Chinese Medicine, an herbal drink infused with different types of medicinal plants is believed to reduce the 'Shang Huo', or excessive body heat, a status of sub-optimal health. Although it is widely accepted and has a very large market, the underlying science for herbal drinks remains elusive. By studying a group of herbs for drinks, including 'Gan' (Glycyrrhiza uralensis Fisch. Ex DC.), 'Ju' (Dendranthema morifolium (Ramat.) Tzvelev), 'Bu' (Microcos paniculata L.), 'Jin' (Lonicera japonica Thunb.), 'Xia' (Prunella vulgaris L.), and 'Ji' (Plumeria rubra L.), the long-term jargon is connected with the inflammation of modern immunology through a few pro-inflammatory markers. In vitro studies have indicated that cellular inflammation is lowered by Ju and Jin either individually or synergistically with Gan. Among all herbs, only Gan detoxicated cellular toxicity of Bu in a dose dependent manner. The synergistic formulation of Ju and Gan, or Jin and Gan, in a reduction of Shang Huo, was tested in vivo. Both combinations exhibited a lower percentage of neutrophils, monocytes, and CD4+/CD8+ ratio in the blood, as well as inflammatory cytokines. Furthermore, body weight in the combinatory groups was more stable than treatments using single herbs. The combination of old traditional oriental methods with Western science logistics, has resulted in the formulation of different herbs into one concoction for the use of detoxification and synergism.

A Three-Dimensional Electrochemical Biosensor Integrated with Hydrogel Enables Real-Time Monitoring of Cells under Their In Vivo-like Microenvironment.

Three-dimensional (3D) cell culture can better reproduce the in vivo cell environment and has been extensively used in fields such as tissue engineering, drug screening, and pathological research. Despite the tremendous advancement of 3D cultures, an analysis technique that could collect real-time information of the biological processes therein is sorely lacking. Electrochemical sensing with fast response and high sensitivity has played a vital role in real-time monitoring of living cells, but most current sensors are based on planar electrodes and fail to perfectly match the 3D cell culture matrix. Herein, we developed a robust 3D electrochemical sensor based on functionalized graphene foam (GF), which could be integrated with hydrogels for the 3D culture and in situ monitoring of cells for the first time. Specifically, platinum nanoparticles (Pt NPs) electrodeposited on GF (GF/Pt NPs) conferred the prominent electrochemical sensing performance, and the anti-fouling coating of poly(3,4-ethylenedioxythiophene) (PEDOT) endowed the GF/Pt NPs electrode with greatly improved stability. As a proof of concept, collagen hydrogel with microglia seeded in was filled into the interspace of the 3D GF/Pt NPs/PEDOT sensor to establish an integrated platform, which allowed the successful real-time monitoring of reactive oxygen species released from microglia in the collagen matrix. Given the versatility, our proposed biosensor in conjunction with various 3D culture models will serve as an excellent tool to provide biochemical information of cells under their in vivo-like microenvironment.