[Simultaneous determination of maltol and seventeen saponins in red and black ginseng by UPLC-PDA wavelength switching method].

This study developed a UPLC-PDA wavelength switching method to simultaneously determine the content of maltol and seventeen saponins in red and black ginseng and compared the quality differences of two different processed products of red and black ginseng. A Waters HSS T3 column(2. 1 mm×100 mm, 1. 8 µm) at 30 ℃ was adopted, with the mobile phase of acetonitrile(A) and water containing 0. 1% phosphoric acid(B) under gradient elution, the flow rate of 0. 3 m L·min~(-1), and the injection volume of 2 µL.The wavelength switching was set at 273 nm within 0-11 min and 203 nm within 11-60 min. The content results of multiple batches of red and black ginseng samples were analyzed by the hierarchical cluster analysis(HCA) and principal component analysis(PCA) to evaluate the quality difference. The results showed that the 18 constituents exhibited good linear relationships within certain concentration ranges, with the correlation coefficients(r) greater than 0. 999 1. The relative standard deviations(RSDs) of precision,repeatability, and stability were all less than 5. 0%. The average recoveries ranged from 95. 93% to 104. 2%, with an RSD of 1. 8%-4. 2%. The content determination results showed that the quality of red and black ginseng samples was different, and the two types of processed products were intuitively distinguished by HCA and PCA. The method is accurate, reliable, and reproducible. It can be used to determine the content of maltol and seventeen saponins in red and black ginseng and provide basic information for the quality evaluation and comprehensive utilization of red and black ginseng.

Multifunctional osthole liposomes and brain targeting functionality with potential applications in a mouse model of Alzheimer's disease.

Osthole (Ost) is a coumarin compound and a potential drug for Alzheimer's disease (AD). However, the effectiveness of Ost is limited by solubility, bioavailability, and low permeability of the blood-brain barrier. In this study, we constructed Ost liposomes with modified CXCR4 on the surface (CXCR4-Ost-Lips), and investigated the intracellular distribution of liposomes in APP-SH-SY5Y cells. In addition, the neuroprotective effect of CXCR4-Ost-Lips was examined in vitro and in vivo. The results showed that CXCR4-Ost-Lips increased intracellular uptake by APP-SH-SY5Y cells and exerted a cytoprotective effect in vitro. The results of Ost brain distribution showed that CXCR4-Ost-Lips prolonged the cycle time of mice and increased the accumulation of Ost in the brain. In addition, CXCR4-Ost-Lips enhanced the effect of Ost in relieving AD-related pathologies. These results indicate that CXCR4-modified liposomes are a potential Ost carrier to treat AD.

A Coenzyme-Free Biocatalyst for the Value-Added Utilization of Lignin-Derived Aromatics.

Value-added utilization of lignin waste streams is vital to fully sustainable and economically viable biorefineries. However, deriving substantial value from its main constituents is seriously hindered by the constant requirement for expensive coenzymes. Herein, we devised a coenzyme-free biocatalyst that could transform lignin-derived aromatics into various attractive pharmaceutical and polymer building blocks. At the center of our strategy is the integrated use of new mining phenolic acid decarboxylase and aromatic dioxygenase with extremely high catalytic efficiency, which realizes the value-added utilization of lignin in a coenzyme-independent manner. Notably, a new temperature/pH-directed strategy was proposed to eliminate the highly redundant activities of endogenous alcohol dehydrogenases. The major components of lignin were simultaneously converted to vanillin and 4-vinylphenol. Since the versatile biocatalyst could efficiently convert many other renewable lignin-related aromatics to valuable chemicals, this green route paves the way for enhancing the entire efficiency of biorefineries.

Remodeling of the Photosynthetic Chain Promotes Direct CO2 Conversion into Valuable Aromatic Compounds.

Directing CO2 conversion using photosynthetic microorganisms offers a promising route to couple CO2 sequestration with petrochemical replacement. However, the low-flux shikimate pathway remains largely unexploited for the synthesis of valuable aromatics. In addition, it is unclear how an enhanced low-flux pathway would influence the photosynthetic chain. We created a powerful metabolic sink by introducing the 2-phenylethanol pathway and an artificial feedback-inhibition-resistant cassette to Synechococcus elongatus. More than 30 % of the fixed carbon was redirected to the shikimate pathway for aromatic synthesis, and carbon fixation and O2 evolution increased significantly. A "self-remodeling" mechanism of the photosynthetic chain was discovered, which accelerates electron transport and reduces energy waste. This study represents a significant step toward the industrial viability of CO2 conversion into aromatic compounds and provides design guidance for improving photosynthetic efficiency.

Causal association between 731 immunocyte phenotypes and liver cirrhosis: A bidirectional two-sample mendelian randomization analysis.

BACKGROUND: Liver cirrhosis is a progressive hepatic disease whose immunological basis has attracted increasing attention. However, it remains unclear whether a concrete causal association exists between immunocyte phenotypes and liver cirrhosis. AIM: To explore the concrete causal relationships between immunocyte phenotypes and liver cirrhosis through a mendelian randomization (MR) study. METHODS: Data on 731 immunocyte phenotypes were obtained from genome-wide association studies. Liver cirrhosis data were derived from the Finn Gen dataset, which included 214403 individuals of European ancestry. We used inverse variable weighting as the primary analysis method to assess the causal relationship. Sensitivity analyses were conducted to evaluate heterogeneity and horizontal pleiotropy. RESULTS: The MR analysis demonstrated that 11 immune cell phenotypes have a positive association with liver cirrhosis [P < 0.05, odds ratio (OR) > 1] and that 9 immunocyte phenotypes were negatively correlated with liver cirrhosis (P < 0.05, OR < 1). Liver cirrhosis was positively linked to 9 immune cell phenotypes (P < 0.05, OR > 1) and negatively linked to 10 immune cell phenotypes (P < 0.05; OR < 1). None of these associations showed heterogeneity or horizontally pleiotropy (P > 0.05). CONCLUSION: This bidirectional two-sample MR study demonstrated a concrete causal association between immunocyte phenotypes and liver cirrhosis. These findings offer new directions for the treatment of liver cirrhosis.

Identification of diagnostic biomarkers of rheumatoid arthritis based on machine learning-assisted comprehensive bioinformatics and its correlation with immune cells.

Background: Rheumatoid arthritis (RA) is a chronic systemic autoimmune disease characterized by inflammatory cell infiltration, which can lead to chronic disability, joint destruction and loss of function. At present, the pathogenesis of RA is still unclear. The purpose of this study is to explore the potential biomarkers and immune molecular mechanisms of rheumatoid arthritis through machine learning-assisted bioinformatics analysis, in order to provide reference for the early diagnosis and treatment of RA disease. Methods: RA gene chips were screened from the public gene GEO database, and batch correction of different groups of RA gene chips was performed using Strawberry Perl. DEGs were obtained using the limma package of R software, and functional enrichment analysis such as gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), disease ontology (DO), and gene set (GSEA) were performed. Three machine learning methods, least absolute shrinkage and selection operator regression (LASSO), support vector machine recursive feature elimination (SVM-RFE) and random forest tree (Random Forest), were used to identify potential biomarkers of RA. The validation group data set was used to verify and further confirm its expression and diagnostic value. In addition, CIBERSORT algorithm was used to evaluate the infiltration of immune cells in RA and control samples, and the correlation between confirmed RA diagnostic biomarkers and immune cells was analyzed. Results: Through feature screening, 79 key DEGs were obtained, mainly involving virus response, Parkinson's pathway, dermatitis and cell junction components. A total of 29 hub genes were screened by LASSO regression, 34 hub genes were screened by SVM-RFE, and 39 hub genes were screened by Random Forest. Combined with the three algorithms, a total of 12 hub genes were obtained. Through the expression and diagnostic value verification in the validation group data set, 7 genes that can be used as diagnostic biomarkers for RA were preliminarily confirmed. At the same time, the correlation analysis of immune cells found that γδT cells, CD4+ memory activated T cells, activated dendritic cells and other immune cells were positively correlated with multiple RA diagnostic biomarkers, CD4+ naive T cells, regulatory T cells and other immune cells were negatively correlated with multiple RA diagnostic biomarkers. Conclusions: The results of novel characteristic gene analysis of RA showed that KYNU, EVI2A, CD52, C1QB, BATF, AIM2 and NDC80 had good diagnostic and clinical value for the diagnosis of RA, and were closely related to immune cells. Therefore, these seven DEGs may become new diagnostic markers and immunotherapy markers for RA.

A Case of Giant Perianal Condylomata Acuminata with IgA Nephropathy Treated Successfully by a Topical Chinese Medicine Preparation Paiteling.

Giant condylomata acuminata (a sexually transmitted disease caused by HPV infection) currently is treated in many methods. Surgery, the mainstay treatment of giant condylomata acuminata, may cause a high cost or scar formation. It is important to explore effective and safe treatment options. Although the external treatment of traditional Chinese medicine treatment of condyloma acuminatum has not been widely used, in our case, the use of traditional Chinese medicine successfully treated a perianal giant condyloma acuminatum patient who also suffered from mixed hemorrhoid and IgA nephropathy meanwhile. The treatment process was simple and the effect obvious. There was no recurrence more than 10 months after treatment finished, and the patients felt safe, comfortable and highly coordinated. The outcome of this case suggests that the traditional Chinese medicine might be considered as a mild and effective option for the treatment of giant condyloma acuminatum.

[Source Apportionment of Ambient VOCs in Qingdao Based on Photochemical Loss Correction].

Ozone was one of the major pollutants affecting the environmental air quality in China. The accurate apportionment of key sources and their contributions of ambient ozone and its precursor VOCs played an important role in the effective prevention and control of ozone pollution. Therefore, this study utilized the photochemical-age-based parameterization method to estimate the initial concentrations of ambient VOCs data collected from January 1 to February 28, 2021 in Jiaozhou, Qingdao and corrected the photochemical losses of ambient VOC species. The positive matrix factorization(PMF) and ozone formation potential(OFP) models were used to conduct source apportionment of ambient VOCs and their OFPs so as to provide data support for the prevention and control of ozone pollution in Qingdao. The results showed that the average values of ambient ρ(TVOCs) and OFP in Qingdao during the study period were 65.9 µg·m-3 and 176.7 µg·m-3, respectively. Propane had the highest concentration(12.4 µg·m-3) and percentage(18.9%), whereas m/p-xylene had the highest OFP(24.6 µg·m-3) and percentage(13.9%). The mean initial concentration of TVOCs during the study was 153.1 µg·m-3, and its photochemical loss rate reached 63.8%. Alkenes were the VOC species with the highest photochemical loss rate(92.1%), and the photochemical loss rate of isoprene reached 98.6%, which was substantially higher than that of other VOC species. According to the source apportionment results of initial concentrations(IC-PMF), liquefied petroleum gas(24.2%), solvent use(17.8%), natural gas and petrochemical-related enterprises(16.6%), gasoline volatilization(13.2%), combustion and gasoline vehicle emissions(12.2%), biogenic emissions(8.6%), and diesel vehicle emissions(7.4%) were the main contributing sources of the ambient VOCs in Jiaozhou. Compared with the apportioned results of IC-PMF, the contribution of biogenic emissions was underestimated by 38.9% in the apportioned results based on observed concentrations(OC-PMF), and the contribution of natural gas and petrochemical-related enterprises was underestimated by 28.5%, and the underestimations of their contributions were substantially higher than those of other sources. Compared with that before the Spring Festival, the contribution of gasoline volatilization to ambient VOCs increased markedly during the Spring Festival, whereas the contributions of solvent use, combustion, and gasoline vehicle emissions to ambient VOCs increased most significantly after the Spring Festival. The main contributing sources of ambient ozone during the study period were solvent use(31.3%), natural gas and petrochemical-related enterprises(16.1%), biogenic emissions(14.5%), and combustion and gasoline vehicle emissions(13.2%). The primary contributors of ambient ozone in different Spring Festival periods showed substantial differences. Before the Spring Festival, solvent use had the highest contribution(71.1 µg·m-3), and gasoline volatilization was the highest contributor during the Spring Festival(34.4 µg·m-3), whereas biogenic emissions after the Spring Festival were the highest contributor(39.1 µg·m-3).

4-octyl itaconate ameliorates alveolar macrophage pyroptosis against ARDS via rescuing mitochondrial dysfunction and suppressing the cGAS/STING pathway.

Acute respiratory distress syndrome (ARDS) is a high-mortality pulmonary disorder characterized by an intense inflammatory response and a cytokine storm. As of yet, there is no proven effective therapy for ARDS. Itaconate, an immunomodulatory derivative accumulated during inflammatory macrophage activation, has attracted widespread attention for its potent anti-inflammatory and anti-oxidative properties. This study pointed to explore the protective impacts of 4-octyl itaconate (4-OI) on ARDS. The results showed that lung injury was attenuated markedly after 4-OI pre-treatment, as represented by decreased pulmonary edema, inflammatory cell infiltration, and production of inflammatory factors. LPS stimulation induced NLRP3-mediated pyroptosis in vitro and in vivo, as represented by the cleavage of gasdermin D (GSDMD), IL-18 and IL-1ß release, and these changes could be prevented by 4-OI pretreatment. Mechanistically, 4-OI eliminated mitochondrial reactive oxygen species (mtROS) and mtDNA escaping to the cytosol through the opening mitochondrial permeability transition pore (mPTP) in alveolar macrophages (AMs) under oxidative stress. In addition, 4-OI pretreatment markedly downregulated cyclic GMP-AMP synthase (cGAS), stimulator of interferon genes (STING) expression, and interferon regulatory factor 3 (IRF3) phosphorylation in vitro and in vivo. Meanwhile, inhibition of STING/IRF3 pathway alleviated NLRP3-mediated pyroptosis induced by LPS in vitro. Taken together, this study indicated that 4-OI ameliorated ARDS by rescuing mitochondrial dysfunction and inhibiting NLRP3-mediated macrophage pyroptosis in a STING/IRF3-dependent manner, which further revealed the potential mechanism of itaconate in preventing inflammatory diseases.

Dynamic analysis of rabies transmission and elimination in mainland China.

Rabies is an acute zoonotic infectious disease caused by rabies virus. In 2015, the World Health Organization proposed the goal of eliminating dog-induced human rabies by 2030. In response to this goal positively, China has been dedicated to the control and elimination of rabies mainly caused by dogs, for nearly 10 years. By applying infectious disease dynamics, in this paper, we establish a dog-human rabies transmission model to forecast future epidemic trends of rabies, assess whether the goal of eliminating dog-induced human rabies cases in China can be achieved in 2030, and further evaluate and suggest the follow-up sustained preventive measures after the elimination of human rabies. By analyzing and simulating above dynamic model, it is concluded that rabies has been well controlled in China in recent years, but dog-induced human rabies cannot be eliminated by 2030 according to current situation. In addition, we propose to improve rabies control efforts by increasing the immunization coverage rate of rural domestic dogs, controlling the number of stray dogs and preventing the import of rabies virus in wild animals. Immunization coverage rate of rural domestic dogs which is currently less than 10% is far from requirement, and it needs to reach 50%-60% to meet the goal of 2030. Since it is difficult to immunize stray dogs, we suggest to control the number of stray dogs below 15.27 million to achieve the goal. If the goal of eliminating human rabies is reached in 2030, the essential immunization coverage needs to be maintained for 18 years to reduce the number of canine rabies cases to zero. Lastly, to prevent transmission of rabies virus from wild animals to dogs, the thresholds of the number of dogs and the immunization coverage rate of dogs after eliminating canine rabies cases are also discussed.

Physical exercise attenuates age-related muscle atrophy and exhibits anti-ageing effects via the adiponectin receptor 1 signalling.

BACKGROUND: Although the adiponectin signalling exerts exercise-mimicking effects, whether this pathway contributes to the anti-ageing benefits of physical exercise has not been established yet. METHODS: Swim exercise training and wheel running were used to measure lifespan in the nematode Caenorhabditis elegans and skeletal muscle quality in mice, respectively. Muscle weight, muscle fibre cross-sectional area (CSA) and myonuclei number were used to evaluate muscle mass. RNA sequencing (RNA-Seq) analysis of skeletal muscle in exercised mice was used to study the underlying mechanisms. Western blot and immunofluorescence were performed to explore autophagy- and senescence-related markers. RESULTS: The C. elegans adiponectin receptor PAQR-1/AdipoR1, but not PAQR-2/AdipoR2, was activated (3.55-fold and 3.48-fold increases in p-AMPK on Days 1 and 6, respectively, P < 0.001), which was involved in lifespan extension in exercised worms. Exercise training increased skeletal muscle mass index (1.29-fold, P < 0.01), muscle weight (1.75-fold, P < 0.001), myonuclei number (1.33-fold, P < 0.05), muscle fibre CSA (1.39-fold, P < 0.05) and capillary abundance (2.19-fold, P < 0.001 for capillary density; 1.58-fold, P < 0.01 for capillary number) in aged mice. Physical exercise reduced protein (2.94-fold, P < 0.001) and mRNA levels (1.70-fold, P < 0.001) of p16INK4a , a marker for cellular senescence, in skeletal muscle of aged mice. These beneficial effects of exercise on skeletal muscle of mice were dependent on AdipoR1. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis for differentially expressed genes in skeletal muscle between exercised mice with and without AdipoR1 knockdown by RNA-Seq analysis revealed that several KEGG pathways, such as 'AMPK signalling pathway' (P < 0.001), 'FOXO signalling pathway' (P < 0.001) and 'autophagy' (P < 0.001) were overrepresented. Knockdown of FoxO3a inhibited exercise-mediated beneficial effects on skeletal muscle quality of mice by inhibiting autophagy/mitophagy (3.81-fold reduction in LC3-II protein, P < 0.001; 1.53-fold reduction in BNIP3 protein, P < 0.05). Knockdown of daf-16, the FoxO homologue in C. elegans, reduced autophagy (2.77-fold and 2.06-fold reduction in GFP::LGG-1 puncta in seam cells and the intestine, respectively, P < 0.05) and blocked lifespan extension by exercise in worms. CONCLUSIONS: Our findings provide insights into how the AdipoR1 pathway has an impact on the anti-ageing benefits of exercise and implicate that activation of the AdipoR1 signalling may represent a potential therapeutic strategy for reducing age-related loss of skeletal muscle.

Effects of Olfactory Stimulation with Aroma Oils on Psychophysiological Responses of Female Adults.

This study investigated the effects of olfactory stimulation with aroma oils on the psychophysiological responses in women. Ten aromatic oils (lavender, rosemary, rose, eucalyptus, jasmine, geranium, chamomile, clary sage, thyme, and peppermint) were used on 23 women aged between 20 and 60 years. They inhaled the scent for 90 s through a glass funnel attached to their lab apron, 10 cm below their nose, while the pump was activated. Electroencephalography, blood pressure, and pulse rate were measured before and during inhalation of the aroma oils. The relative alpha (RA) power spectrums indicating relaxation and resting state of the brain significantly increased when lavender, rosemary, eucalyptus, jasmine, chamomile, clary sage, and thyme oils were inhaled compared to those of before olfactory stimulation. The ratio of alpha to high beta (RAHB), an indicator of brain stability and relaxation, significantly increased when rosemary, jasmine, clary sage, and peppermint oils were inhaled. The relative low beta (RLB) power spectrum, an indicator of brain activity in the absence of stress, significantly increased when stimulated with lavender, rosemary, rose, and geranium scents. Further, systolic blood pressure significantly decreased after introduction of all 10 types of aromatic oils, which indicates stress reduction. Thus, olfactory stimulation with aroma oil had a stabilizing effect on the prefrontal cortex and brain activity and decreased systolic blood pressure.

Psychophysiological Responses of Cut Flower Fragrances as an Olfactory Stimulation by Measurement of Electroencephalogram in Adults.

Horticultural therapy (HT) is green care that can help improve and recover the health of modern people living in cities through natural experiences. Many studies have been conducted to determine HT's therapeutic effects and underlying mechanisms, but investigation for developing readily applicable clinical techniques is insufficient. We aimed to investigate adults' brain activity and emotional state during flower arrangement (FA) with different flowers in an HT program. We recruited thirty adults and used a randomized cross-over study method to set them to participate in five FA tasks at 90-s intervals. While performing FA tasks, the participants' prefrontal cortex brain waves were measured by a wireless electroencephalography device and their emotional states between FA tasks were measured by questionnaires. Results showed that each FA task resulted in a different attention level of the participants. The participants showed the highest attention level during FA with stocks and carnations, while FA with lilies showed the lowest attention level among the five FA tasks. Instead, the participants showed the highest arousal, tension, and anxiety for emotional states during FA with lilies. Therefore, this study confirmed the differences in attention level and emotional changes according to flower types for using clinical techniques of HT for various clients.

Active constituent of Polygala tenuifolia attenuates cognitive deficits by rescuing hippocampal neurogenesis in APP/PS1 transgenic mice.

BACKGROUND: Alzheimer's disease (AD) is the most common dementia worldwide, and there is still no satisfactory drug or therapeutic strategy. Polygala tenuifolia is a traditional Chinese medicine with multiple neuroprotective effects. In present study, we investigated the effects of three active constituents [3,6'-disinapoyl sucrose (DISS), onjisaponin B (OB) and tenuifolin (TEN)] of Polygala tenuifolia (PT) on the proliferation and differentiation of neural stem cells (NSCs) to identify the potential active constituent of PT promoting hippocampal neurogenesis. METHODS: NSCs were isolated from hippocampi of newborn C57BL/6 mice, and transfected with mutant amyloid precursor protein (APP) gene to establish an AD cell model (APP-NSCs). 3-(4,5- Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and lactate dehydrogenase (LDH) assays were performed, and the proliferation and differentiation of NSCs were assessed by neurosphere formation assay, 5-bromo-2'-deoxyuridine (BrdU) incorporation assay and immunofluorescence (IF) staining analysis. APP/PS1 transgenic mice were administrated with the potential active constituent DISS for 4 weeks. Morris water maze (MWM), Nissl staining assay and IF staining assays were carried out to evaluate the cognitive function, neural damages and hippocampal neurogenesis, respectively. RESULTS: DISS exerted the optimal ability to strengthen APP-NSCs proliferation and neuronal differentiation, followed by OB and TEN. Furthermore, DISS treatment for 4 weeks strikingly rescued the cognitive deficits, neuronal injures, and neurogenesis disorder in adult APP/PS1 transgenic mice. CONCLUSIONS: Our findings demonstrated that DISS is the constituent of PT that triggers the most potent increase of hippocampal neurogenesis in our mouse model of AD.

Structural and functional characterization of multiple myeloma associated cytoplasmic poly(A) polymerase FAM46C.

BACKGROUND: Multiple myeloma (MM) is a hematologic malignancy characterized by the accumulation of aberrant plasma cells within the bone marrow. The high frequent mutation of family with sequence similarity 46, member C (FAM46C) is closely related with the occurrence and progression of MM. Recently, FAM46C has been identified as a non-canonical poly(A) polymerase (PAP) that functions as a tumor suppressor in MM. This study aimed to elucidate the structural features of this novel non-canonical PAP and how MM-related mutations affect the structural and biochemical properties of FAM46C, eventually advancing our understandings towards FAM46C mutation-related MM occurrence. METHODS: We purified and crystallized a mammalian FAM46C construct, and solved its structure. Next, we characterized the property of FAM46C as a PAP through a combination of structural analysis, site-directed mutagenesis and biochemical assays, and by comparison with its homolog FAM46B. Finally, we structurally analyzed MM-related FAM46C mutations and tested the enzymatic activity of corresponding mutants. RESULTS: We determined the crystal structure of a mammalian FAM46C protein at 2.35 Å, and confirmed that FAM46C preferentially consumed adenosine triphosphate (ATP) and extended A-rich RNA substrates. FAM46C showed a weaker PAP activity than its homolog FAM46B, and this difference was largely dependent on the residue variance at particular sites. Of them, residues at positions 77, 290, and 298 of mouse FAM46C were most important for the divergence in enzymatic activity. Among the MM-associated FAM46C mutants, those residing at the catalytic site (D90G and D90H) or putative RNA-binding site (I155L, S156F, D182Y, F184L, Y247V, and M270V) showed abolished or compromised PAP activity of FAM46C, while N72A and S248A did not severely affect the PAP activity. FAM46C mutants D90G, D90H, I155L, S156F, F184L, Y247V, and M270V had significantly lower inhibitory effect on apoptosis of RPMI-8226 cells as compared to wild-type FAM46C. CONCLUSIONS: FAM46C is a prokaryotic-like PAP with preference for A-rich RNA substrates, and showed distinct enzymatic efficiency with its homolog FAM46B. The MM-related missense mutations of FAM46C lead to various structural and biochemical outcomes to the protein.

Identification of Subtype-Specific Metastasis-Related Genetic Signatures in Sarcoma.

Background: Sarcomas are heterogeneous rare malignancies constituting approximately 1% of all solid cancers in adults and including more than 70 histological and molecular subtypes with different pathological and clinical development characteristics. Method: We identified prognostic biomarkers of sarcomas by integrating clinical information and RNA-seq data from TCGA and GEO databases. In addition, results obtained from cell cycle, cell migration, and invasion assays were used to assess the capacity for Tanespimycin to inhibit the proliferation and metastasis of sarcoma. Results: Sarcoma samples (N = 536) were divided into four pathological subtypes including DL (dedifferentiated liposarcoma), LMS (leiomyosarcoma), UPS (undifferentiated pleomorphic sarcomas), and MFS (myxofibrosarcoma). RNA-seq expression profile data from the TCGA dataset were used to analyze differentially expressed genes (DEGs) within metastatic and non-metastatic samples of these four sarcoma pathological subtypes with DEGs defined as metastatic-related signatures (MRS). Prognostic analysis of MRS identified a group of genes significantly associated with prognosis in three pathological subtypes: DL, LMS, and UPS. ISG15, NUP50, PTTG1, SERPINE1, and TSR1 were found to be more likely associated with adverse prognosis. We also identified Tanespimycin as a drug exerting inhibitory effects on metastatic LMS subtype and therefore can serve a potential treatment for this type of sarcoma. Conclusions: These results provide new insights into the pathogenesis, diagnosis, treatment, and prognosis of sarcomas and provide new directions for further study of sarcoma.

Transferrin-Modified Osthole PEGylated Liposomes Travel the Blood-Brain Barrier and Mitigate Alzheimer's Disease-Related Pathology in APP/PS-1 Mice.

INTRODUCTION: Osthole (Ost) is a coumarin compound that strengthens hippocampal neurons and neural stem cells against Aß oligomer-induced neurotoxicity in mice, and is a potential drug for the treatment of Alzheimer's disease (AD). However, the effectiveness of the drug is limited by its solubility and bioavailability, as well as by the low permeability of the blood-brain barrier (BBB). In this study, a kind of transferrin-modified Ost liposomes (Tf-Ost-Lip) was constructed, which could improve the bioavailability and enhance brain targeting. METHODS: Tf-Ost-Lip was prepared by thin-film hydration method. The ability of liposomal formulations to translocate across BBB was investigated using in vitro BBB model. And the protective effect of Tf-Ost-Lip was evaluated in APP-SH-SY5Y cells. In addition, we performed pharmacokinetics study and brain tissue distribution analysis of liposomal formulations in vivo. We also observed the neuroprotective effect of the varying formulations in APP/PS-1 mice. RESULTS: In vitro studies reveal that Tf-Ost-Lip could increase the intracellular uptake of hCMEC/D3 cells and APP-SH-SY5Y cells, and increase the drug concentration across the BBB. Additionally, Tf-Ost-Lip was found to exert a protective effect on APP-SH-SY5Y cells. In vivo studies of pharmacokinetics and the Ost distribution in brain tissue indicate that Tf-Ost-Lip prolonged the cycle time in mice and increased the accumulation of Ost in the brain. Furthermore, Tf-Ost-Lip was also found to enhance the effect of Ost on the alleviation of Alzheimer's disease-related pathology. CONCLUSION: Transferrin-modified liposomes for delivery of Ost has great potential for AD treatment.

[Three dimensional study on change ratios of hard and soft tissue after orthognathic surgery].

PURPOSE: To investigate the change ratios of soft and hard tissue after orthognathic surgery three-dimensionally in osseous Class Ⅲ patients, in order to predict postoperative soft tissue three-dimensionally. METHODS: Twenty adult patients were selected as the experimental group, craniofacial spiral CT and three-dimensional (3D) stereophotogrammetry were conducted 2 weeks before surgery and 3 months after surgery. Dolphin imaging software was used to establish 3D image digitizing model and 3D measurement coordinate system. Nineteen soft and hard tissue land marks were selected and matched into 12 pairs. 3D coordinate value of these landmarks were read both before and after surgery and were used for statistical analysis with SPSS 22.0 software package. RESULTS: There was a linear relationship only in Pn/A, Gn'/Gn and Me'/Me in X axis, in Gn'/Gn in Y axis and all pairs of landmarks had a close correlation except UL'/UI and UL/SPr in Z axis. Additionally, the change ratio between soft and hard tissue landmarks of mandible was greater than maxilla. CONCLUSIONS: The changes of soft and hard tissue after orthognathic surgery only lie in Z axis(forward and backward), each pair of matched landmarks exhibits a linear relationship, and the change ratio of mandible is greater than the maxilla.

Irreversible electroporation-mediated shRNA knockdown of the HPV18 E6 gene suppresses cervical cancer growth in vitro and in vivo.

Irreversible electroporation (IRE) is a physical, non-thermal cancer therapy, which leads to cell death via permanent membrane permeability. This differs from reversible electroporation (RE), which is used to transfer macromolecules into target cells via transient membrane permeability. Given the electrical impedance of the electric field, RE co-exists outside the central zone of IRE ablation. In the present study, the feasibility of using IRE at a therapeutic dose to mediate short hairpin RNA (shRNA) knockdown of human papillomavirus (HPV)18 E6 in HeLa cervical cancer cells in vitro and in vivo was investigated. Experimental results indicated that the HeLa cells survived the combined treatment with IRE and shRNA plasmid transfection. Additionally, residual tumor tissue in a nude mouse model demonstrated green fluorescence. Subsequent studies showed that the combined treatment inhibited the growth of HeLa cells and tumors. Western blotting analysis showed marked changes in the growth-associated proteins between the combined treatment group and the control. It was concluded that a therapeutic dose of IRE was able to mediate the transfection of HPV18 E6 shRNA into HeLa cervical cancer cells in vitro and in vivo. This combined treatment strategy has promising implications in cancer treatment for the ablation of tumors, and in eliminating microscopic residual tumor tissue.

Diagnosis and microecological characteristics of aerobic vaginitis in outpatients based on preformed enzymes.

OBJECTIVE: Aerobic vaginitis (AV) is a recently proposed term for genital tract infection in women. The diagnosis of AV is mainly based on descriptive diagnostic criteria proposed by Donders and co-workers. The objective of this study is to report AV prevalence in southwest China using an objective assay kit based on preformed enzymes and also to determine its characteristics. MATERIALS AND METHODS: A total of 1948 outpatients were enrolled and tested by a commercial diagnostic kit to investigate the AV prevalence and characteristics in southwestern China. The study mainly examined the vaginal ecosystem, age distribution, Lactobacillus amount, and changes in pH. Differences within groups were analyzed by Wilcoxon two-sample test. RESULTS: The AV detection rate is 15.40%. The AV patients were usually seen in the sexually active age group of 20-30 years, followed by those in the age group of 30-40 years. The vaginal ecosystems of all the patients studied were absolutely abnormal, and diagnosed to have a combined infection [aerobic vaginitis (AV) + bacterial vaginitis (BV) 61.33%; 184/300]. Aerobic bacteria, especially Staphylococcus aureus and Escherichia coli, were predominantly found in the vaginal samples of these women. CONCLUSION: AV is a common type of genital infection in southwestern China and is characterized by sexually active age and combined infection predominated by the AV and BV type.