Understanding asymmetric switching times in accumulation mode organic electrochemical transistors.

Understanding the factors underpinning device switching times is crucial for the implementation of organic electrochemical transistors in neuromorphic computing, bioelectronics and real-time sensing applications. Existing models of device operation cannot explain the experimental observations that turn-off times are generally much faster than turn-on times in accumulation mode organic electrochemical transistors. Here, using operando optical microscopy, we image the local doping level of the transistor channel and show that turn-on occurs in two stages-propagation of a doping front, followed by uniform doping-while turn-off occurs in one stage. We attribute the faster turn-off to a combination of engineering as well as physical and chemical factors including channel geometry, differences in doping and dedoping kinetics and the phenomena of carrier-density-dependent mobility. We show that ion transport limits the operation speed in our devices. Our study provides insights into the kinetics of organic electrochemical transistors and guidelines for engineering faster organic electrochemical transistors.

Chain Length Dependence of Electron Transport in an n-Type Conjugated Polymer with a Rigid-Rod Chain Topology.

Most currently known n-type conjugated polymers have a semiflexible chain topology, and their charge carrier mobilities are known to peak at modest chain lengths of below 40-60 repeat units. Herein, we show that the field-effect electron mobility of a model n-type conjugated polymer that has a rigid-rod chain topology grows continuously without saturation, even at a chain length exceeding 250 repeat units. We found the mechanism underlying the novel chain length-dependent electron transport to originate from the reduced structural disorder and energetic disorder with the increasing degree of polymerization inherent to the rigid-rod chain topology. Furthermore, we demonstrate a unique chain length-dependent decay of threshold voltage, which is rationalized by decreased trap densities and trap depths with respect to the degree of polymerization. Our findings provide new insights into the role of polymer chain topology in electron transport and demonstrate the promise of rigid-rod chain architectures for the design of future high-mobility conjugated polymers.

Synthesis of 3-sulfonylisoindolin-1-ones from olefinic amides and sodium sulfinates via electrooxidative tandem cyclization.

Sulfonyl groups are motifs that are widely found in biologically active compounds and drug molecules, many isolated natural products as well as pharmaceuticals contain sulfonyl groups. Herein, we present the synthesis of sulfonyl-substituted isoindolones by a electrochemical oxidative radical cascade cycloaddition reaction of olefinic amides with sodium sulfite under oxidant- and catalyst-free conditions. Various olefinic amides and sodium sulfinates were compatible and gave the desired products in yields up to 99%.

Human periodontal ligament stem cell sheets activated by graphene oxide quantum dots repair periodontal bone defects by promoting mitochondrial dynamics dependent osteogenic differentiation.

BACKGROUND: Bone defects in the maxillofacial region restrict the integrity of dental function, posing challenges in clinical treatment. Bone tissue engineering (BTE) with stem cell implants is an effective method. Nanobiomaterials can effectively enhance the resistance of implanted stem cells to the harsh microenvironment of bone defect areas by promoting cell differentiation. Graphene oxide quantum dots (GOQDs) are zero-dimensional nanoscale derivatives of graphene oxide with excellent biological activity. In the present study, we aimed to explore the effects of GOQDs prepared by two methods (Y-GOQDs and B-GOQDs) on the osteogenic differentiation of human periodontal ligament stem cells (hPDLSCs), as well as the effect of gelatin methacryloyl (GelMA)-encapsulated GOQD-induced hPDLSC sheets on the repair of mandibular periodontal defects in rats. We also explored the molecular biological mechanism through which GOQD promotes bone differentiation. RESULTS: There were significant differences in oxygen-containing functional groups, particle size and morphology between Y-GOQDs and B-GOQDs. Y-GOQDs promoted the osteogenic differentiation of hPDLSCs more effectively than did B-GOQDs. In addition, GelMA hydrogel-encapsulated Y-GOQD-induced hPDLSC cell sheet fragments not only exhibited good growth and osteogenic differentiation in vitro but also promoted the repair of mandibular periodontal bone defects in vivo. Furthermore, the greater effectiveness of Y-GOQDs than B-GOQDs in promoting osteogenic differentiation is due to the regulation of hPDLSC mitochondrial dynamics, namely, the promotion of fusion and inhibition of fission. CONCLUSIONS: Overall, Y-GOQDs are more effective than B-GOQDs at promoting the osteogenic differentiation of hPDLSCs by regulating mitochondrial dynamics, which ultimately contributes to bone regeneration via the aid of the GelMA hydrogels in vivo.

The ATF4-regulated LncRNA MALAT1 promotes odontoblastic differentiation of human dental pulp stem cells via histone demethylase JMJD3: An in vitro study.

AIM: This study aimed to investigate the upstream regulators and specific mechanisms of metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) in the odontoblastic differentiation of human dental pulp stem cells (hDPSCs). METHODOLOGY: Human dental pulp stem cells were isolated and cultured, followed by conducting loss- or gain-of-function experiments on ATF4 and loss experiments on MALAT1 to elucidate their respective biological functions in odontoblastic differentiation. Chromatin immunoprecipitation assays and RNA immunoprecipitation were performed to uncover the interaction between ATF4-MALAT1 and MALAT1-JMJD3, respectively. The odontoblastic differentiation was estimated by the mRNA and protein of DSPP and DMP1, as well as alkaline phosphatase staining. RESULTS: Expression of MALAT1 was upregulated in the hDPSCs cultured in an odontoblastic medium, and MALAT1 downregulation suppressed the odontoblastic differentiation of the hDPSCs. Subsequent experiments confirmed that ATF4 promoted odontoblastic differentiation and induced MALAT1 expression by binding to the MALAT1 promoter region. Further experiments revealed that nuclear MALAT1 interacted with JMJD3. MALAT1 knockdown decreased the JMJD3 protein level and demethylase activity, and it enhanced H3K27me3 occupancy of the promoter region of DSPP and DMP1, resulting in the inhibition of DSPP and DMP1 transcription. Importantly, JMJD3 overexpression significantly attenuated the inhibition of odontoblastic differentiation induced by MALAT1 knockdown. CONCLUSIONS: ATF4-regulated MALAT1 plays a positive regulatory role in odontoblastic differentiation of hDPSCs through JMJD3-mediated H3K27me3 modifications of the DSPP and DMP1 promoters.

Hydration of a Side-Chain-Free n-Type Semiconducting Ladder Polymer Driven by Electrochemical Doping.

We study the organic electrochemical transistor (OECT) performance of the ladder polymer poly(benzimidazobenzophenanthroline) (BBL) in an attempt to better understand how an apparently hydrophobic side-chain-free polymer is able to operate as an OECT with favorable redox kinetics in an aqueous environment. We examine two BBLs of different molecular masses from different sources. Regardless of molecular mass, both BBLs show significant film swelling during the initial reduction step. By combining electrochemical quartz crystal microbalance gravimetry, in-operando atomic force microscopy, and both ex-situ and in-operando grazing incidence wide-angle X-ray scattering (GIWAXS), we provide a detailed structural picture of the electrochemical charge injection process in BBL in the absence of any hydrophilic side-chains. Compared with ex-situ measurements, in-operando GIWAXS shows both more swelling upon electrochemical doping than has previously been recognized and less contraction upon dedoping. The data show that BBL films undergo an irreversible hydration driven by the initial electrochemical doping cycle with significant water retention and lamellar expansion that persists across subsequent oxidation/reduction cycles. This swelling creates a hydrophilic environment that facilitates the subsequent fast hydrated ion transport in the absence of the hydrophilic side-chains used in many other polymer systems. Due to its rigid ladder backbone and absence of hydrophilic side-chains, the primary BBL water uptake does not significantly degrade the crystalline order, and the original dehydrated, unswelled state can be recovered after drying. The combination of doping induced hydrophilicity and robust crystalline order leads to efficient ionic transport and good stability.

Detecting Bell Correlations in Multipartite Non-Gaussian Spin States.

We expand the toolbox for studying Bell correlations in multipartite systems by introducing permutationally invariant Bell inequalities (PIBIs) involving few-body correlators. First, we present around twenty families of PIBIs with up to three- or four-body correlators, that are valid for an arbitrary number of particles. Compared to known inequalities, these show higher noise robustness, or the capability to detect Bell correlations in highly non-Gaussian spin states. We then focus on finding PIBIs that are of practical experimental implementation, in the sense that the associated operators require collective spin measurements along only a few directions. To this end, we formulate this search problem as a semidefinite program that embeds the constraints required to look for PIBIs of the desired form.

Osteoblast Jmjd3 regulates osteoclastogenesis via EphB4 and RANKL signalling.

BACKGROUND: Osteoblasts suppress osteoclastogenesis during the reversal phase of bone remodelling and the mechanism needs to be further investigated. Here, we investigated the role of histone demethylase Jumonji domain-containing 3 (Jmjd3) in osteoblasts on regulating osteoclastogenesis. METHODS: Jmjd3 expression was silenced in osteoblasts. Osteoblasts and osteoclasts were co-cultured in direct or indirect contact ways, and osteoclastogenesis was determined by tartrate-resistant acid phosphatase (TRAP) staining and Western blotting. Additionally, Ephrin receptor B4 (EphB4) and receptor activator of nuclear factor-kappa Β ligand (RANKL) expression were quantified in osteoblasts via real-time PCR, Western blotting, and enzyme-linked immunosorbent assay. Subsequently, EphB4 was overexpressed in osteoblasts and RANKL expression and osteoclastogenesis was quantified. RESULTS: Osteoclastogenesis and marker protein expression levels was promoted when osteoclasts were co-cultured with Jmjd3-silenced osteoblasts. Silencing of Jmjd3 expression in osteoblasts decreased EphB4 expression, owing to suppression of demethylation of H3K27me3 on the promoter region of EphB4. Whereas RANKL expression was upregulated in Jmjd3-silenced osteoblasts. Overexpression of EphB4 in osteoblasts inhibited osteoclastogenesis and RANKL expression. CONCLUSION: Jmjd3 in osteoblasts is a crucial regulator of osteoblast-to-osteoclast communication through EphB4-EphrinB2, RANKL-RANK and EphB4-RANKL signalling axes, suggesting the pivotal role of Jmjd3 in bone remodelling process in bone destruction disease such as chronic apical periodontitis.

Deep learning in automatic detection of dysphonia: Comparing acoustic features and developing a generalizable framework.

BACKGROUND: Auditory-perceptual assessment of voice is a subjective procedure. Artificial intelligence with deep learning (DL) may improve the consistency and accessibility of this task. It is unclear how a DL model performs on different acoustic features. AIMS: To develop a generalizable DL framework for identifying dysphonia using a multidimensional acoustic feature. METHODS & PROCEDURES: Recordings of sustained phonations of /a/ and /i/ were retrospectively collected from a clinical database. Subjects contained 238 dysphonic and 223 vocally healthy speakers of Chinese Mandarin. All audio clips were split into multiple 1.5-s segments and normalized to the same loudness level. Mel frequency cepstral coefficients and mel-spectrogram were extracted from these standardized segments. Each set of features was used in a convolutional neural network (CNN) to perform a binary classification task. The best feature was obtained through a five-fold cross-validation on a random selection of 80% data. The resultant DL framework was tested on the remaining 20% data and a public German voice database. The performance of the DL framework was compared with those of two baseline machine-learning models. OUTCOMES & RESULTS: The mel-spectrogram yielded the best model performance, with a mean area under the receiver operating characteristic curve of 0.972 and an accuracy of 92% in classifying audio segments. The resultant DL framework significantly outperformed both baseline models in detecting dysphonic subjects on both test sets. The best outcomes were achieved when classifications were made based on all segments of both vowels, with 95% accuracy, 92% recall, 98% precision and 98% specificity on the Chinese test set, and 92%, 95%, 90% and 89%, respectively, on the German set. CONCLUSIONS & IMPLICATIONS: This study demonstrates the feasibility of DL for automatic detection of dysphonia. The mel-spectrogram is a preferred acoustic feature for the task. This framework may be used for vocal health screening and facilitate automatic perceptual evaluation of voice in the era of big data. WHAT THIS PAPER ADDS: What is already known on this subject Auditory-perceptual assessment is the current gold standard in clinical evaluation of voice quality, but its value may be limited by the rater's reliability and accessibility. DL is a new method of artificial intelligence that can overcome these disadvantages and promote automatic voice assessment. This study explored the feasibility of a DL approach for automatic detection of dysphonia, along with a quantitative comparison of two common sets of acoustic features. What this study adds to existing knowledge A CNN model is excellent at decoding multidimensional acoustic features, outperforming the baseline parameter-based models in identifying dysphonic voices. The first 13 mel-frequency cepstral coefficients (MFCCs) are sufficient for this task. The mel-spectrogram results in greater performance, indicating the acoustic features are presented in a more favourable way than the MFCCs to the CNN model. What are the potential or actual clinical implications of this work? DL is a feasible method for the detection of dysphonia. The current DL framework may be used for remote vocal health screening or documenting voice recovery after treatment. In future, DL models may potentially be used to perform auditory-perceptual tasks in an automatic, efficient, reliable and low-cost manner.

Vestigial-Like 3 Plays an Important Role in Osteoblast Differentiation by Regulating the Expression of Osteogenic Transcription Factors and BMP Signaling.

Our previous gene profiling analysis showed that the transcription cofactor vestigial-like 3 (VGLL3) gene expression was upregulated by mechanical tension in the mouse cranial suture, coinciding with accelerated osteoblast differentiation. Therefore, we hypothesized that VGLL3 plays a significant role in osteogenic differentiation. To clarify the function of VGLL3 in osteoblasts, we examined its expression characteristics in mouse bone tissue and the osteoblastic cell line MC3T3-E1. We further examined the effects of Vgll3 knockdown on osteoblast differentiation and bone morphogenetic protein (BMP) signaling. In the mouse cranial suture, where membranous ossification occurs, VGLL3 was immunohistochemically detected mostly in the nucleus of osteoblasts, preosteoblasts, and fibroblastic cells. VGLL3 expression in MC3T3-E1 cells was transient and peaked at a relatively early stage of differentiation. RNA sequencing revealed that downregulated genes in Vgll3-knockdown cells were enriched in gene ontology terms associated with osteoblast differentiation. Interestingly, most of the upregulated genes were related to cell division. Targeted Vgll3 knockdown markedly suppressed the expression of major osteogenic transcription factors (Runx2, Sp7/osterix, and Dlx5) and osteoblast differentiation. It also attenuated BMP signaling; moreover, exogenous BMP2 partially restore osteogenic transcription factors' expression in Vgll3-knockdown cells. Furthermore, overexpression of Vgll3 increased the expression of osteogenic transcription factors. These results suggest that VGLL3 plays a critical role in promoting osteoblast differentiation and that part of the process is mediated by BMP signaling. Further elucidation of VGLL3 function will increase our understanding of osteogenesis and skeletal disease etiology.

Deep-learning-enabled inverse engineering of multi-wavelength invisibility-to-superscattering switching with phase-change materials.

Inverse design of nanoparticles for desired scattering spectra and dynamic switching between the two opposite scattering anomalies, i.e. superscattering and invisibility, is important in realizing cloaking, sensing and functional devices. However, traditionally the design process is quite complicated, which involves complex structures with many choices of synthetic constituents and dispersions. Here, we demonstrate that a well-trained deep-learning neural network can handle these issues efficiently, which can not only forwardly predict scattering spectra of multilayer nanoparticles with high precision, but also inversely design the required structural and material parameters efficiently. Moreover, we show that the neural network is capable of finding out multi-wavelength invisibility-to-superscattering switching points at the desired wavelengths in multilayer nanoparticles composed of metals and phase-change materials. Our work provides a useful solution of deep learning for inverse design of nanoparticles with dynamic scattering spectra by using phase-change materials.

Resveratrol Suppresses Matrix Metalloproteinase-2 Activation Induced by Lipopolysaccharide in Mouse Osteoblasts via Interactions with AMP-Activated Protein Kinase and Suppressor of Cytokine Signaling 1.

Porphyromonas endodontalis (P. endodontalis) lipopolysaccharide (LPS) is associated with the progression of bone resorption in periodontal and periapical diseases. Matrix metalloproteinase-2 (MMP-2) expression and activity are elevated in apical periodontitis and have been suggested to participate in bone resorption. Therefore, inhibiting MMP-2 activation may be considered a therapeutic strategy for treating apical periodontitis. Resveratrol is a natural non-flavonoid polyphenol that has been reported to have antioxidant, anti-cancer, and anti-inflammatory properties. However, the capacity of resveratrol to protect osteoblast cells from P. endodontalis LPS insults and the mechanism of its inhibitory effects on MMP-2 activation is poorly understood. Here, we demonstrate that cell viability is unchanged when 10 mg L-1P. endodontalis LPS is used, and MMP-2 expression is drastically induced by P. endodontalis LPS in a concentration- and time-dependent manner. Twenty micromolar resveratrol did not reduce MC3T3-E1 cell viability. Resveratrol increased AMP-activated protein kinase (AMPK) phosphorylation, and Compound C, a specific AMPK inhibitor, partially abolished the resveratrol-mediated phosphorylation of AMPK. In addition, AMPK inhibition blocked the effects of resveratrol on MMP-2 expression and activity in LPS-induced MC3T3-E1 cells. Treatment with resveratrol also induced suppressor of cytokine signaling 1 (SOCS1) expression in MC3T3-E1 cells. SOCS1 siRNA negated the inhibitory effects of resveratrol on LPS-induced MMP-2 production. Additionally, resveratrol-induced SOCS1 upregulation was reduced by treatment with compound C. These results demonstrate that AMPK and SOCS1 activation are important signaling events during resveratrol-mediated inhibition of MMP-2 production in response to LPS in MC3T3-E1 cells, and there is crosstalk between AMPK and SOCS1 signaling.

The anticancer properties of Salvia miltiorrhiza Bunge (Danshen): a systematic review.

Salvia miltiorrhiza Bunge (Danshen in Chinese) is a classical Huoxue Huayu (a traditional Chinese medical term means promoting blood circulation and removing blood stasis) herb with 1000 years of clinical application. It mainly contains two groups of ingredients: the hydrophilic phenolic acids and the lipophilic tanshinones. Both groups have demonstrated multiple bioactivities, such as antioxidative stress, antiplatelet aggregation, anti-inflammation, among others. Recent data have demonstrated that its lipophilic compounds, especially the tanshinones, show potent anticancer activities both in vitro and in vivo. The anticancer effects of the hydrophilic phenolic acids have also been reported. Furthermore, tanshinones provide structural skeletons for chemical modifications, allowing for a series of derivatives of interests. This review provides a systematic summary of the anticancer profile and the underlying mechanisms of the bioactive compounds isolated from Danshen with special emphasis on tanshinones, aiming to bring new insights for further research and development of this ancient herb.

High-density, highly sensitive sensor array of spiky carbon nanospheres for strain field mapping.

While accurate mapping of strain distribution is crucial for assessing stress concentration and estimating fatigue life in engineering applications, conventional strain sensor arrays face a great challenge in balancing sensitivity and sensing density for effective strain mapping. In this study, we present a Fowler-Nordheim tunneling effect of monodispersed spiky carbon nanosphere array on polydimethylsiloxane as strain sensor arrays to achieve a sensitivity up to 70,000, a sensing density of 100 pixel cm-2, and logarithmic linearity over 99% within a wide strain range of 0% to 60%. The highly ordered assembly of spiky carbon nanospheres in each unit also ensures high inter-unit consistency (standard deviation ≤3.82%). Furthermore, this sensor array can conformally cover diverse surfaces, enabling accurate acquisition of strain distributions. The sensing array offers a convenient approach for mapping strain fields in various applications such as flexible electronics, soft robotics, biomechanics, and structure health monitoring.

The complete chloroplast genome of Geum longifolium (Maxim.) Smedmark 2006 (Rosaceae: Colurieae) and its phylogenomic implications.

Geum longifolium (Maxim.) Smedmark 2006 belongs to the family Rosaceae, subfamily Rosoideae, tribe Colurieae. Geum longifolium is endemic to China and its whole herb is used in Chinese medicine. Here, the first complete chloroplast (cp) genome of G. longifolium was assembled and annotated based on genome skimming, and its phylogenetic position was investigated using phylogenomic evidence. The cp genome size of G. longifolium was 155,884 bp with the total GC content of 36.7%. Its cp genome presented a typical tetrad structure, composed of a large single copy (LSC) region (85,338 bp), a small single copy (SSC) region (18,358 bp), and a pair of inverted repeat (IR) regions (26,094 bp). The cp genome encoded 129 genes, including 84 protein-coding genes, 37 tRNA genes, and eight rRNA genes. Phylogenetic analysis indicated that G. longifolium was sister to G. elatum Wall. ex G.Don 1832 in current taxa sampling. This study can enrich the chloroplast genomic resource of Geum and lay the foundation for future phylogenetic studies on Geum.

Flexible Capacitive Sensing and Ultrasound Calibration for Skeletal Muscle Deformations.

Skeletal muscles are critical to human-limb motion dynamics and energetics, where their mechanical states are seldom explored in vitro due to practical limitations of sensing technologies. This article aims to capture mechanical deformations of muscle contraction using wearable flexible sensors, which is justified with model calibration and experimental validation. The capacitive sensor is designed with the composite of conductive fabric electrodes and the porous dielectric layer to increase the pressure sensitivity and prevent lateral expansions. In this way, the compressive displacement of muscle deformation is captured in the muscle-sensor coupling model in terms of sensor deformation and parameters of pretension, material, and shape properties. The sensing model is calibrated in a linear form using ultrasound medical imaging. The sensor is capable of measuring muscle strain of 70% with an error of <3.6% and temperature disturbance of <5.6%. After 10K cycles of compression, the drift is only 3.3%. Immediate application of the proposed method is illustrated by gait pattern identification, where the K-nearest neighbor prediction accuracy of squats, level walking, stair ascent/descent, and ramp ascent is over 97% with a standard deviation below 2.6% compared to that of 94.61 ± 4.24% for ramp descent, and the response time is 14.37 ± 0.52 ms. The wearable sensing method is valid for muscle deformation monitoring and gait pattern identification, and it provides an alternative approach to capture mechanical motions of muscles, which is anticipated to contribute to understand locomotion biomechanics in terms of muscle forces and metabolic landscapes.

Flexible Electronic Skin for Monitoring of Grasping State During Robotic Manipulation.

Electronic skin for robotic tactile sensing has been studied extensively over the past years, yet practical applications of electronic skin for the grasping state monitoring during robotic manipulation are still limited. In this study, we present the fabrication and implementation of electronic skin sensor arrays for the detection of unstable grasping. The piezoresistive sensor arrays have the advantages of facile fabrication, fast response, and high reliability. With the tactile data from the sensor array, we propose two quantitative indicators, correlation coefficient and wavelet coefficient, to identify grasping with variable forces and slippage. Those two indicators reflect both time and frequency domain characteristics in the contact forces from the sensor array and can be obtained without large amount of calculation. We demonstrate the utility of this method under various conditions, the results indicate grasping with variable forces, and slippage can be distinguished by this method. The flexible sensor arrays are adopted for tactile sensing on a bionic hand, and the effectiveness of this method in detecting various grasping states has been verified. The electronic skin sensor array and the grasping state monitoring method are promising for applications in robotic dexterous manipulation.

Biological activities and potential molecular targets of cucurbitacins: a focus on cancer.

Cucurbitacin and its derivatives (cucurbitacins) are a class of highly oxidized tetracyclic triterpenoids. They are widely distributed in the plant kingdom, where they act as heterologous chemical pheromones that protect plants from external biological insults. Their bioactivities first attracted attention in the 1960s. Documented data demonstrate that cucurbitacins possess strong pharmacological properties, such as antitumor, anti-inflammatory, and hepatoprotective effects, etc. Several molecular targets for cucurbitacins have been discovered, such as fibrous-actin, signal transducer and activator of transcription 3, cyclooxygenase-2, etc. The present study summarizes the achievements of the 50 years of research on cucurbitacins. The aim was to systematically analyze their bioactivities with an emphasis on their anticancer effects. Research and development has shed new insight into the beneficial properties of these compounds.

Furanodiene induces endoplasmic reticulum stress and presents antiproliferative activities in lung cancer cells.

Furanodiene (FUR) is a natural terpenoid isolated from Curcumae Rhizoma, a well-known Chinese medicinal herb that presents antiproliferation activities in several cancer cell lines. In this study, we demonstrated that FUR concentration dependently inhibits the cell proliferation of A549, NIH-H1299, and 95-D lung cancer cells. ß-elemene, another terpenoid isolated from Curcumae Rhizoma, exhibited weaker antiproliferative effects in A549 and NIH-H1299 cells and activities similar to FUR in 95-D cells. FUR significantly inhibited colony formation in A549 and 95-D cells and upregulated both the mRNA and protein expression levels of binding immunoglobulin protein (BIP) and C/EBP homologous protein (CHOP), indicating that endoplasmic reticulum (ER) stress is induced. FUR treatment led to the accumulation of CHOP in the nucleus, which further confirms induction of ER stress. Furthermore, combined treatment of FUR with paclitaxel showed significant synergetic activities in NIH-H1299 and 95-D cells, suggesting its potential roles in combination therapy. These findings provide a basis for the further study of the anticancer effects in vivo and the internal mechanisms of FUR.

[Inspirations from natural products based drug research and development for Chinese medicine research--analysis of natural products recoded in TTD].

Natural product is an important source of new drug research and development (R&D). Traditional Chinese medicine (TCM) innovation is the key step for its modernization and internationalization. However, due to the complexity of TCM, there are many difficulties and confusions in this process. Target-based drug discovery is the mainstream model and method of R&D. TTD, short for therapeutic target database, is developed by National University of Singapore. Besides a large amount of information on drug targets, the database also contains considerable information related to natural products. This paper briefly introduces the TTD, analyzes the natural products derived drugs/compounds recorded in TTD, which we think might provide some inspiration for the innovation of TCM.