Vibro-tactile stimulation of the neck reduces pain in people with cervical dystonia: a proof-of-concept study.

BACKGROUND: Pain is a common non-motor symptom in patients with cervical dystonia (CD), severely impacting their quality of life. The pathophysiology of CD is incompletely understood but it involves altered processing of proprioceptive and pain signals. OBJECTIVES: The purpose of this proof-of-concept study was to determine if vibro-tactile stimulation (VTS)-a non-invasive form of neuromodulation targeting the somatosensory system-can modulate neck pain in people with CD. METHODS: In a multi-center study, 44 CD patients received VTS to sternocleidomastoid and/or trapezius muscles for up to 45 min under 9 different stimulation conditions that either targeted a single or a pair of muscles. The primary outcome measure was a perceived pain score (PPS) rated by participants on a 100-point analogue scale. RESULTS: During VTS, 29/44 (66%) of participants experienced a reduction in PPS of at least 10% with 17/44 (39%) reporting a reduction in pain of 50% or higher. After VTS cessation, 57% of participants still reported a 10% or higher reduction in PPS. Effects were significant at the group level and persisted for up to 20 min post-treatment. No distinct optimal stimulation profiles were identified for specific CD phenotypes. Clinical markers of disease severity or duration did not predict the degree of VTS-induced pain reduction. CONCLUSION: This proof-of-concept study demonstrates the potential of VTS as a new non-invasive therapeutic option for treating neck pain associated with CD. Further research needs to delineate optimal dosage and long-term effects.

PIK3CA somatic mutations as potential biomarker for immunotherapy in elder or TP53 mutated gastric cancer patients.

Immune checkpoint inhibitors (ICIs) improve overall survival in patients with advanced gastric cancer (GC). However, the molecular characterization of GC in ICIs responders is unclear. A total of 288 advanced GC patients were included in this study. Next-generation sequencing analysis was performed on tumor tissue and paired blood to screen for somatic mutants in 639 tumor-associated genes. We demonstrated that ARID1A, HER2/3/4, KMT2C/2D, LRP1B, PIK3CA, SPTA1, and TP53 mutations were significantly correlated with high tumor mutation burden (TMB) score, as well as HER2 amplification. For HER2 and PIK3CA mutations types, this relationship was statistically significant with age and TP53 mutation status, which was also found in the CDH1 gene. These results were confirmed by sequencing 873 GC cases in the cBioPortal database. PIK3CA mutations appear to be associated with longer survival in elderly population and TP53 mutant subtypes. For the first time, we found that GC patients ≥60 years old or with TP53 mutated type and PIK3CA mutations were associated with higher TMB and better ICI response. Building upon the age and TP53 mutation status, this study suggested a novel stratification approach to GC patients and explored the correlations between genetic somatic mutations and TMB score.

Tumor- and metastasis-promoting roles of miR-488 inhibition via HULC enhancement and EZH2-mediated p53 repression in gastric cancer.

Dysregulation of microRNAs (miRNAs or miRs) is implicated in the development of gastric cancer (GC), which is possibly related to their roles in targeting tumor-suppressive or tumor-promoting genes. Herein, the current study was intended to ascertain the function of miR-488 and its modulatory mechanism in GC. Initially, human GC cells were assayed for their in vitro malignancy after miRNA gain- or loss-of-function and RNA interference or overexpression. Also, tumorigenesis and liver metastasis were evaluated in nude mouse models. Results demonstrated that miR-488 elevation suppressed GC (MKN-45 and OCUM-1) cell proliferation, migration, and invasiveness in vitro and reduced their tumorigenesis and liver metastasis in vivo. The luciferase assay identified that miR-488 bound to HULC and inhibited its expression. Furthermore, HULC could enhance EZH2-H3K27me3 enrichment at the p53 promoter region and epigenetically repress the p53 expression based on the data from RIP- and ChIP-qPCR assay. Additionally, HULC was validated to enhance GC growth and metastasis in vitro and in vivo. Overall, HULC re-expression elicited by miR-488 inhibition can enhance EZH2-H3K27me3 enrichment in the p53 promoter and repress the p53 expression, thus promoting the growth and metastasis of GC.

UBE3C promotes proliferation and inhibits apoptosis by activating the ß-catenin signaling via degradation of AXIN1 in gastric cancer.

Gastric cancer (GC) remains one of the most frequent cancers worldwide. Previous studies have shown that E3 ubiquitin ligase E3C (UBE3C) promotes the progression of multiple types of cancer. However, little is known about the expression and molecular mechanism of UBE3C in GC. In this study, UBE3C is upregulated in clinical GC samples and RNA-seq data from The Cancer Genome Atlas, and the UBE3C upregulation is correlated with poor clinical outcomes in patients with GC. In vitro, knockdown of UBE3C suppresses proliferation and enhances apoptosis in GC cells by inhibiting ß-catenin signaling pathway. In contrast, in vitro overexpression of UBE3C promotes GC cell proliferation and inhibits apoptosis through the upregulation of ß-catenin signaling by promoting ubiquitination of AXIN1. In vivo, knockdown of UBE3C inhibits tumor growth in a nude mouse model. Concurrently, the UBE3C knockdown resulted in an increase of AXIN1 and a reduction of ß-catenin in the nucleus and cytoplasm in the xenograft tumor tissues. Our results demonstrate that UBE3C promotes GC progression through activating the ß-catenin signaling via degradation of AXIN1. Our data suggest that UBE3C exerts oncogenic effects in GC and thus provides a promising prognostic biomarker and a potential therapeutic target for GC therapy.

TRIM32 promotes cell proliferation and invasion by activating ß-catenin signalling in gastric cancer.

The tripartite motif (TRIM) family comprises more than 70 members involved in the regulation of many cellular pathways. TRIM32 acts as an E3 ubiquitin ligase and has been reported to participate in many human cancers. Here, we aimed to investigate the role of TRIM32 in gastric cancer (GC) and the clinical implications. High expression of TRIM32 was observed in GC tissues and cell lines, and was significantly associated with poor prognosis. Knockdown TRIM32 expression remarkably suppressed the proliferation, migration, and invasion of GC cells in vitro and tumour growth in vivo, whereas overexpression of TRIM32 yielded the opposite results. Western blotting and quantitative reverse-transcription PCR (qRT-PCR) analyses revealed that up-regulation of TRIM32 significantly enhanced expression of ß-catenin protein and of its downstream targets TCF1, cyclin D1, Axin2 and MMP7 mRNAs. Moreover, we found that the mechanism behind the TRIM32-promoted GC progression was related to the ß-catenin signalling pathway. Collectively, these data suggest that TRIM32 promotes GC cell proliferation, migration, and invasion by activating the ß-catenin signalling pathway.

Curcumin regulates proliferation, autophagy, and apoptosis in gastric cancer cells by affecting PI3K and P53 signaling.

In this study, we aimed to investigate the effects of curcumin on cell activities of gastric cancer (GC), and the connection between curcumin and P53, as well as, PI3K signaling. This study was conducted with two cell lines SGC-7901 and BGC-823, both were exposed to curcumin at the concentrations of 0, 10, 20, and 40 µm. MTT assay, flow cytometry (FCM) assay, transmission electron microscopy (TEM) were used to study the underlying mechanisms of curcumin in respective of proliferation, apoptosis, and autophagy. Western blot assay was also employed to detect impacts of curcumin on tophosphatidylinositol-3 kinase (PI3K) and P53 signaling pathways-related proteins. MTT assay displayed that curcumin inhibited GC cell proliferation. FCM results indicated that curcumin induced the apoptosis of GC cells. TEM revealed that curcumin induced autophagy in GC cells. Western blot results showed that curcumin activated P53 signaling pathway and inhibited PI3K signaling pathway. Curcumin may inhibit proliferation and induce the autophagy and apoptosis in GC cells. Additionally, curcumin activated the P53 signaling pathway by up-regulating P53 and P21, which also inhibited PI3K pathway through down-regulating PI3K, p-Akt, and p-mTOR.

Integrin ß1 promotes gemcitabine resistance in pancreatic cancer through Cdc42 activation of PI3K p110ß signaling.

Pancreatic ductal adenocarcinoma (PDAC) is one of the most common malignancies with very poor prognosis due to its broad resistance to chemotherapy. Our previous study showed that integrin ß1 expression is upregulated in PDAC and confers gemcitabine resistance in PDAC cells via the signaling pathway including Cdc42 and AKT activation. But the accurate signal transductions are not clear. Here, we aimed to illuminate the signal transductions of integrin ß1 in the acquisition of gemcitabine resistance in PDAC. Drug-resistance (DR) cells from AsPC-1 parent cell line (PCL) were selected. Integrin ß1 expression was determined using western blot assay. Changes in drug response and the activity of phosphatidylinositol 3-kinase (PI3K) signaling after knockdown of integrin ß1, Cdc42 or p110ß were evaluated using MTT, cleaved caspase-3 immunofluorescence and western blot assay. Western blot assays also detected the variations in Cdc42 activity and p110ß expression after integrin ß1 knockdown. The interaction between Cdc42 and p110ß was determined by Glutathione S-transferase (GST) pull-down assay. The results showed that integrin ß1 expression was upregulated in DR-AsPC-1 cells, and integrin ß1 knockdown significantly decreased the activity of Cdc42, a target molecule of integrin ß1, and p110ß expression. Knockdown of anyone of integrin ß1, Cdc42 and p110ß inhibited the activity of PI3K signaling, and sensitized DR-AsPC-1 cells to gemcitabine. GST pull-down assay showed that GTP-Cdc42 interacted with p110ß. Collectively, these data indicated that integrin ß1 promoted gemcitabine resistance in PDAC through Cdc42 activation of PI3K p110ß signaling. In vivo experiments also confirmed this conclusion. These findings contribute to a better understanding the molecular mechanism of chemoresistance and facilitate the development of more targeted and effective treatment strategy for PDAC.

[Development of Abdominal Vacuum Extractor Characterized by Portability and Constant Negative Pressure Which Applying to Battlefield].

There are some problems such as difficulty of pressure control, inconvenience of use and carry, congested easily and dredged hardly in clinical application of vacuum extractor in common use. For solving the above problems, researchers have designed a new portable and pressure stabilized abdominal drainage system which was composed of integral double spherical aspirator and separated double cannula. The new apparatus has achieved good effects in drainage which is suitable for not only rescuing of abdominal trauma and war wound, but also abdominal surgery that manifested as sucking safe and effective, using easily and convenient, that was verified by testing.

Integrinß1 modulates tumour resistance to gemcitabine and serves as an independent prognostic factor in pancreatic adenocarcinomas.

Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal malignancies because of its broad resistance to chemotherapy. Numerous evidence indicates that integrinß1 is upregulated in some human cancers, and it is correlated with resistance to various therapies. However, the role of integrinß1 in chemotherapy is not clear in pancreatic cancer. The present study evaluates the potential of integrinß1 to predict chemoresistance and prognosis in patients and to modulate resistance to gemcitabine in PDAC cells. Primary drug-resistance (DR) cancer cells were isolated, and DR cells from MiaPaCa-2 and AsPC-1 parent cell lines (PCL) were selected. Integrinß1 expression was determined using immunohistochemistry (IHC), quantitative real-time PCR (qRT-PCR) and Western blotting. Changes in drug response after knockdown of integrinß1 via RNA interference (RNAi) were evaluated using the viability of cancer cells as colon formation, proliferation using Western blot of Ki-67 and apoptosis using cleaved caspase-3 immunofluorescence. qRT-PCR and Western blot also detected variations in the activities of cdc42 and AKT after integrinß1 suppression. Patient survival and relative factors were assessed using Kaplan-Meier and Cox regression analyses. Integrinß1 expression was upregulated in PDAC, which was significantly associated with intrinsic and acquired gemcitabine resistance and worse outcomes. The downregulation of integrinß1 attenuated PDAC chemoresistance, and this attenuation partially correlated with reduced Cdc42 and AKT activity, which are target molecules of integrinß1 in some human cancers. These findings identified integrinß1 as a special marker of drug resistance and a serious prognosis, and they furthermore support the use of integrinß1 as a novel potential therapeutic target to overcome chemotherapy resistance. The results also suggest a possible drug-resistant signalling pathway of integrinß1 in PDAC.

The impact of environmental regulation and economic expectations on crop-livestock integration among hog farmers: a field study from China.

Decoupling of crop-livestock systems increases the risks of pollution, waste of nutrient resources, and biodiversity loss. Crop-livestock integration (CLI) is an effective solution to these problems, and motivating farmers to adopt CLI is the key. Many countries have implemented environmental regulations (ER) aiming to influence farmers' CLI adoption decisions. Based on a field study of 316 hog farmers from Shaanxi Province of China, this paper applies the triple-hurdle model to empirically examine the impacts of economic expectations (EE) and ER on CLI adoption decisions. It also verifies the income effect of CLI. The results are as follows: 90.5% of farmers are willing to adopt CLI, but the adoption rate is only 40.8% and the average integration degree is only 0.236; CLI not been widely popularized. EE and ER promote farmers' CLI adoption significantly, while the impact of interaction between EE and ER on CLI adoption differs. IER weakens the positive impact of EE on farmers' CLI integration degree, which has a "crowding out effect." GER negatively moderates the impact of EE on farmers' adoption willingness of CLI. CER strengthens the positive effect of EE on farmers' adoption behavior and CLI integration degree. CLI increases the farmers' income. These results contribute to our understanding of the mechanisms of CLI adoption decisions and sustainable policy optimization for green agricultural development.

Ammonium sulfate denatures transport medium less dependent on guanidinium isothiocyanate and enables SARS-CoV-2 RNA and antigen detection compatibility.

Introduction: Rapid identification of infected individuals through viral RNA or antigen detection followed by effective personal isolation is usually the most effective way to prevent the spread of a newly emerging virus. Large-scale detection involves mass specimen collection and transportation. For biosafety reasons, denaturing viral transport medium has been extensively used during the SARS-CoV-2 pandemic. However, the high concentrations of guanidinium isothiocyanate (GITC) in such media have raised issues around sufficient GITC supply and laboratory safety. Moreover, there is a lack of denaturing transport media compatible with SARS-CoV-2 RNA and antigen detection. Methods: Here, we tested whether supplementing media containing low concentrations of GITC with ammonium sulfate (AS) would affect the throat-swab detection of SARS-CoV-2 or a viral inactivation assay targeting coronavirus and other enveloped and non-enveloped viruses. The effect of adding AS to the media on RNA stability and its compatibility with SARS-CoV-2 antigen detection were also tested. Results and discussion: We found that adding AS to the denaturing transport media reduced the need for high levels of GITC, improved SARS-COV-2 RNA detection without compromising virus inactivation, and enabled the denaturing transport media compatible with SARS-CoV-2 antigen detection.

Typical Development of Finger Position Sense From Late Childhood to Adolescence.

Finger position sense is a proprioceptive modality highly important for fine motor control. Its developmental time course is largely unknown. This cross-sectional study examined its typical development in 138 children (8-17 years) and a group of 14 healthy young adults using a fast and novel psychophysical test that yielded objective measures of position sense acuity. Participants placed their hands underneath a computer tablet and judged the perceived position of their unseen index finger relative to two visible areas displayed on a tablet following a two-forced-choice paradigm. Responses were fitted to a psychometric acuity function from which the difference between the point-of-subjective-equality and the veridical finger position (ΔPSE) was derived as a measure of position sense bias, and the uncertainty area (UA) as a measure of precision. The main results are: First, children under 12 exhibited a significantly greater UA than adults while adolescent children (13-17 years) exhibited no significant differences when compared to adults. Second, no significant age-related differences in ΔPSE were found across the age range of 8-17 years. This implies that the typical development of finger position sense from late childhood to adulthood is characterized as an age-dependent increase in proprioceptive precision and not as a decrease in bias.

From pilots to demonstrations: the green economic development effect of low-carbon city pilot policies.

Accurately assessing the impact of low-carbon urban construction on green economic development has great significance for achieving economic development with environmental protection, and for building an ecological civilization and a beautiful China. Based on panel data for 271 cities in China from 2004 to 2019, multi-period and spatial difference-in-difference econometric models were used to comprehensively investigate the impact of three batches of low-carbon city pilot policies on green economic development, finding the following: The contribution of low-carbon urban construction on urban green economic development is significant and positive, and still holds under a series of robustness tests. Parallel trend tests also show a lag in the policy effect, and the effect is strengthened over policy implementation time. Green orientation of technological progress, green transformation of industry, and green upgrade of consumption are important channels for the effect of the policies. The promotion effect of low-carbon city construction is stronger in the central and northern cities, and in cities with high green economic development, than in western and southern cities, and those with low green economic development. Construction of low-carbon pilot cities not only promotes their own green economic development, but also that in neighboring cities, exerting a demonstration effect. This effect is greater in urban areas. This study provides empirical support for policy planning to promote low-carbon urban construction across the country.

Atypical Activation of Laryngeal Somatosensory-Motor Cortex During Vocalization in People With Unexplained Chronic Cough.

Importance: Unexplained chronic cough is common and has substantial negative quality-of-life implications, yet its causes are not well understood. A better understanding of how peripheral and central neural processes contribute to chronic cough is essential for treatment design. Objective: To determine if people with chronic cough exhibit signs of abnormal neural processing over laryngeal sensorimotor cortex during voluntary laryngeal motor activity such as vocalization. Design, Setting, and Participants: This was a cross-sectional study of a convenience sample of participants with chronic cough and healthy participants. Testing was performed in an acoustically and electromagnetically shielded chamber. In a single visit, electroencephalographic (EEG) signals were recorded from participants with chronic cough and healthy participants during voice production. The chronic cough group participants presented with unexplained cough of 8 weeks or longer duration with prior medical evaluation including negative results of chest imaging. None of the participants had a history of any neurologic disease known to impair vocalization or swallowing. Data collection for the healthy control group occurred from February 2 to June 28, 2018, and for the chronic cough group, from November 22, 2021, to June 21, 2022. Data analysis was performed from May 1 to October 30, 2022. Exposure: Participants with or without chronic cough. Main Outcome Measures: Event-related spectral perturbation over the laryngeal area of somatosensory-motor cortex from 0 to 30 Hz (ie, θ, α, and ß bands) and event-related coherence as a measure of synchronous activity between somatosensory and motor cortical regions. Results: The chronic cough group comprised 13 participants with chronic cough (mean [SD] age, 63.5 [7.8] years; 9 women and 4 men) and the control group, 10 healthy age-matched individuals (mean [SD] age, 60.3 [13.9] years; 6 women and 4 men). In the chronic cough group, the typical movement-related desynchronization over somatosensory-motor cortex during vocalization was significantly reduced across θ, α, and ß frequency bands when compared with the control group. Conclusions and Relevance: This cross-sectional study found that the typical movement-related suppression of brain oscillatory activity during vocalization is weak or absent in people with chronic cough. Thus, chronic cough affects sensorimotor cortical activity during the asymptomatic voluntary activation of laryngeal muscles.

Comprehensive chemical profiling and quantitative analysis of ethnicYi medicine Miao-Fu-Zhi-Tong granules using UHPLC-MS/MS.

Developing analytical methods for the chemical components of natural medicines remains a challenge due to its diversity and complexity. Miao-Fu-Zhi-Tong (MFZT) granules, an ethnic Yi herbal prescription, comprises 10 herbs and has been clinically applied for gouty arthritis (GA) therapy. Herein, a series of chemical profiling strategies including in-house library matching, molecular networking and MS/MS fragmentation behavior validation based on ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) were developed for qualitative analysis of MFZT granules. A total of 207 compounds were identified or characterized in which several rare guanidines were discovered and profiled into alkyl substituted or cyclic subtypes. Moreover, network pharmacology analysis indicated that MFZT's anti-gout mechanism was mostly associated with the nuclear factor kappa-B (NF-κB) signaling, nucleotide oligomerization domain (NOD)-like signaling and rheumatoid arthritis pathways, along with the synergistic effect of 84 potential active compounds. In addition, a quantitative analytical method was developed to simultaneously determine the 29 potential effective components. Among them, berberine, pellodendrine, 3-feruloylquinic acid, neoastilbin, isoacteoside and chlorogenic acid derivatives at higher concentrations were considered as the chemical markers for quality control. These findings provide a holistic chemical basis for MFZT granules and will support the development of effective analytical methods for the herbal formulas of natural medicines.

An integrative analysis to predict the active compounds and explore polypharmacological mechanisms of Orthosiphon stamineus Benth.

BACKGROUND: Orthosiphon stamineus Benth is a dietary supplement and traditional Chinese herb with widespread clinical applications, but a comprehensive understanding of its active compounds and polypharmacological mechanisms is lacking. This study aimed to systematically investigate the natural compounds and molecular mechanisms of O. stamineus via network pharmacology. METHODS: Information on compounds from O. stamineus was collected via literature retrieval, while physicochemical properties and drug-likeness were evaluated using SwissADME. Protein targets were screened using SwissTargetPrediction, while the compound-target networks were constructed and analyzed via Cytoscape with CytoHubba for seed compounds and core targets. Enrichment analysis and disease ontology analysis were then carried out, generating target-function and compound-target-disease networks to intuitively explore potential pharmacological mechanisms. Lastly, the relationship between active compounds and targets was confirmed via molecular docking and dynamics simulation. RESULTS: A total of 22 key active compounds and 65 targets were identified and the main polypharmacological mechanisms of O. stamineus were addressed. The molecular docking results suggested that nearly all core compounds and their targets possess good binding affinity. In addition, the separation of receptor and ligands was not observed in all dynamics simulation processes, whereas complexes of orthosiphol Z-AR and Y-AR performed best in simulations of molecular dynamics. CONCLUSION: This study successfully identified the polypharmacological mechanisms of the main compounds in O. stamineus, and predicted five seed compounds along with 10 core targets. Moreover, orthosiphol Z, orthosiphol Y, and their derivatives can be utilized as lead compounds for further research and development. The findings here provide improved guidance for subsequent experiments, and we identified potential active compounds for drug discovery or health promotion.

The Antitumor Effect of TPD52L2 Silencing on Oxaliplatin-Resistant Gastric Carcinoma Is Related to Endoplasmic Reticulum Stress In Vitro.

Tumor protein D52-like 2 or simply TPD52L2 belongs to the TPD52 family which has been implicated in a variety of human carcinomas. However, the TPD52L2 function in the gastric carcinoma oxaliplatin (OXA) resistance remains elusive. The main objective of this study is to evaluate the TPD52L2 effect in OXA-resistant gastric carcinoma cells in vitro. Oxaliplatin-resistant gastric carcinoma cells were generated in MGC-803 and SGC-7901 cells. siRNA-mediated knockdown of TPD52L2 was investigated in OXA-resistant MGC-803-OXA and SGC-7901-OXA cells. qRT-PCR was performed to assess the expression level of TPD52L2 mRNA. TPD52L2 protein expression level, apoptosis, and endoplasmic reticulum (ER) stress-associated proteins were identified via immunoblotting analysis. MTT assay was conducted for the evaluation of cell viability, while colony-forming activity was carried out via crystal violet staining. SGC-7901-OXA and MGC-803-OXA cells were found to be more resistant to OXA, as compared to the parental cell lines. The expression of TPD52L2 was found to be upregulated in OXA-resistant cells. Knockdown of TPD52L2 suppressed cell colony-forming potency, cell growth, and development in OXA-resistant cells. TPD52L2 knockdown also enhanced the PARP and caspase-3 cleavage. ER-associated proteins such as PERK, GRP78, CHOP, and IRE1α were found to be elevated in TPD52L2 knockdown cells. ER stress might be involved in TPD52L2 knockdown-induced apoptosis in OXA-resistant gastric carcinoma cells.

Giant Extrinsic Spin Hall Effect in Platinum-Titanium Oxide Nanocomposite Films.

Although the spin Hall effect provides a pathway for efficient and fast current-induced manipulation of magnetization, application of spin-orbit torque magnetic random access memory with low power dissipation is still limited to spin Hall materials with low spin Hall angles or very high resistivities. This work reports a group of spin Hall materials, Pt1 -x (TiO2 )x nanocomposites, that combines a giant spin Hall effect with a low resistivity. The spin Hall angle of Pt1 -x (TiO2 )x in an yttrium iron garnet/Pt1 -x (TiO2 )x double-layer heterostructure is estimated from a combination of ferromagnetic resonance, spin pumping, and inverse spin Hall experiments. A giant spin Hall angle 1.607 ± 0.04 is obtained in a Pt0.94 (TiO2 )0.06 nanocomposite film, which is an increase by an order of magnitude compared with 0.051 ± 0.002 in pure Pt thin film under the same conditions. The great enhancement of spin Hall angle is attributed to strong side-jump induced by TiO2 impurities. These findings provide a new nanocomposite spin Hall material combining a giant spin Hall angle, low resistivity and excellent process compatibility with semiconductors for developing highly efficiency current-induced magnetization switching memory devices and logic devices.

Drug Repositioning for Hand, Foot, and Mouth Disease.

Hand, foot, and mouth disease (HFMD) is a highly contagious disease in children caused by a group of enteroviruses. HFMD currently presents a major threat to infants and young children because of a lack of antiviral drugs in clinical practice. Drug repositioning is an attractive drug discovery strategy aimed at identifying and developing new drugs for diseases. Notably, repositioning of well-characterized therapeutics, including either approved or investigational drugs, is becoming a potential strategy to identify new treatments for virus infections. Various types of drugs, including antibacterial, cardiovascular, and anticancer agents, have been studied in relation to their therapeutic potential to treat HFMD. In this review, we summarize the major outbreaks of HFMD and the progress in drug repositioning to treat this disease. We also discuss the structural features and mode of action of these repositioned drugs and highlight the opportunities and challenges of drug repositioning for HFMD.

Peroxisome proliferator-activated receptor gamma inhibits hepatic fibrosis in rats.

BACKGROUND: Hepatic fibrosis is a necessary step in the development of hepatic cirrhosis. In this study we used lentiviral vector-mediated transfection technology to evaluate the effect of peroxisome proliferator-activated receptor gamma (PPAR-gamma) on rat hepatic fibrosis. METHODS: Hepatic fibrosis in rats was induced by CCl4 for 2 weeks (early fibrosis) and 8 weeks (sustained fibrosis). The rats were randomly divided into four groups: normal control, fibrosis, blank vector, and PPAR-gamma. They were infected with the recombinant lentiviral expression vector carrying the rat PPAR-gamma gene by portal vein injection. The liver of the rats was examined histologically and hydroxyproline was assessed. In vitro primary hepatic stellate cells (HSCs) were infected with the recombinant lentiviral expression vector carrying the rat PPAR-gamma gene. The status of HSC proliferation was measured by the MTT assay. The protein levels of PPAR-gamma, alpha-smooth muscle actin (alpha-SMA) and type I collagen expression were evaluated by the Western blotting method. RESULTS: In vitro studies revealed that expression of PPAR-gamma inhibited expression of alpha-SMA and type I collagen in activated HSCs (P<0.01) as well as HSC proliferation (P<0.01). In vivo experiments indicated that in the early hepatic fibrosis group, the hydroxyproline content and the level of collagen I protein in the liver in the PPAR-gamma transfected group were not significantly different compared to the hepatic fibrosis group and the blank vector group; whereas the expressions of PPAR-gamma and alpha-SMA were different compared to the hepatic fibrosis group (P<0.01). In the sustained hepatic fibrosis group, there were significant differences in the hydroxyproline content and the expression of PPAR-gamma, alpha-SMA, and type I collagen between each group. CONCLUSION: PPAR-gamma can inhibit HSC proliferation and hepatic fibrosis, and suppress alpha-SMA and type I collagen expression.