MiR-22-3p facilitates bone marrow mesenchymal stem cell osteogenesis and fracture healing through the SOSTDC1-PI3K/AKT pathway.

Bone fractures are the most common form of musculoskeletal trauma worldwide. Numerous microRNAs (miRNAs) have been suggested to be participants in regulating bone-related diseases. Recent studies revealed the regulatory role of miR-22-3p in osteogenic differentiation, but its role in fracture healing has not been investigated previously. Here, a rat femoral fracture model was established, Bone marrow mesenchymal stem cells (BMSCs) were isolated to detect the specific function and underlying mechanisms of miR-22-3p. MiR-22-3p and sclerostin domain-containing 1 (SOSTDC1) expression was determined by RT-qPCR and immunohistochemistry staining. The levels of proteins associated with osteogenic differentiation were assessed by western blotting. Flow cytometry was conducted to identify the isolated rat BMSCs. Alizarin red staining, alkaline phosphatase staining and Oil Red O staining were used to evaluate the osteogenic and adipogenic differentiation of rat BMSCs. The interaction between miR-22-3p and SOSTDC1 was verified using a luciferase reporter assay. Haematoxylin and Eosin (H&E) staining of the bone tissues was performed to analyse the effect of miR-22-3p on histopathological changes in vivo. MiR-22-3p was downregulated in the callus tissues of rat femoral fracture, while the expression of SOSTDC1 was upregulated. The isolated rat BMSCs had the capacity for both osteogenic and adipogenic differentiation. The differentiation capacity of BMSCs into osteoblasts was increased by miR-22-3p overexpression. MiR-22-3p activated the PI3K/AKT pathway by targeting SOSTDC1. SOSTDC1 overexpression and PI3K/AKT signalling inhibitor LY294002 abolished the enhancing effect of miR-22-3p overexpression on the osteogenesis of BMSCs. Thus MiR-22-3p facilitated the femoral fracture healing in rats. MiR-22-3p overexpression promoted fracture healing via the activation of PI3K/AKT pathway by targeting SOSTDC1.

Coding RNA expression profile and transcription factor analysis of H.pylori-associated chronic atrophic gastritis.

PURPOSE: Atrophic gastritis, one of the processes leading to gastric cancer (GC), is closely related to Helicobacter pylori (HP) infection. This study aimed to understand how HP causes chronic inflammation that leads to ulcers and stomach problems. METHODS: Twenty-eight CAG patients were included in the study (9 HP-infected and 19 HP-uninfected). Endoscopy, histopathology, and high-throughput mRNA sequencing were performed. Differentially expressed genes (DEGs) were validated via qRT-PCR. RESULTS: Principal component analysis (PCA) results showed that more than 88.9 â€‹% of the samples were classified into the HP (+) group. A total of 157 DEGs were identified, of which 38 were up-regulated and 119 were down-regulated. The DEGs were mainly enriched in the biological process (BP) terms associated with immune system process, adaptive immune response, G protein-coupled receptor signaling pathway, as well as point to numerous key pathways, including fat digestion and absorption, retinol metabolism, steroid hormone biosynthesis, ascorbate and aldarate metabolism, and chemical carcinogenesis. APOA1, APOA4, FOXP3, NR1H4, ABCG5, ACTA1, CCL19, CCR7, CYP3A4, and PDCD had the highest degrees in protein-protein interaction network as the hub genes; they were also included into the transcription factor (TF)-target network except for PDCD. APOA1 and CYP3A4 were extremely significantly up-regulated in HP (+) CAG patients compared with the HP (-) CAG patients, while FOXP3, CCR7 and CCL19 were significantly down-regulated. CONCLUSION: The expression of APOA1, CYP3A4, FOXP3, CCR7, and CCL19 are the potential indicators for CAG to GC development, being the biomarkers to predict progression of CAG and poor prognosis of GC.

The Association Between Mild Cognitive Impairment and Medication Non-adherence Among Elderly Patients With Chronic Diseases.

BACKGROUND: Medication adherence is essential for optimizing treatment outcomes in elderly patients who frequently contend with multiple chronic diseases requiring pharmacological interventions. Mild cognitive impairment (MCI) is a prevalent cognitive disorder among the elderly population, but its impact on medication adherence among elderly patients is still uncertain. This cross-sectional study aimed to investigate the impact of MCI on medication adherence among elderly patients. METHODS: A cross-sectional study of 436 elderly patients with common chronic diseases aged 60 years and above was conducted. Medication adherence was measured using the Morisky Medication Adherence Scale-8 (MMAS-8). MCI was screened, and cognitive status was assessed using the Mini-Mental State Examination (MMSE) questionnaire. Multivariate logistic regression analysis was performed to identify independent risk factors of medication non-adherence. RESULTS: Among these elderly patients, 212 (48.6%) had poor medication compliance, and 181 (41.5%) had MCI. Preliminary analyses showed a significant association between MCI and medication non-adherence among elderly patients (odds ratio (OR)=3.95, 95% confidence interval (95%CI)=2.63-5.92, P<0.001). Multivariate logistic regression analysis showed that MCI was independently associated with the risk of medication non-adherence among elderly patients (adjusted OR=2.64, 95%CI=1.64-4.24, P<0.001). Additionally, adverse drug reaction and poor evaluation of medication effects were also independently associated with medication non-adherence in elderly patients (P<0.05). CONCLUSION: Findings from this cross-sectional study proved the substantial adverse impact of MCI on medication adherence among elderly patients, and MCI was an independently influential factor of medication non-adherence. Identifying the MCI status early and providing interventions to enhance medication adherence are undoubtedly essential for optimizing healthcare outcomes in elderly patients.

Hesperidin Anti-Osteoporosis by Regulating Estrogen Signaling Pathways.

Osteoporosis (OP) is distinguished by a reduction in bone mass and degradation of bone micro-structure, frequently resulting in fractures. As the geriatric demographic expands, the incidence of affected individuals progressively rises, thereby exerting a significant impact on the quality of life experienced by individuals. The flavonoid compound hesperidin has been subject to investigation regarding its effects on skeletal health, albeit the precise mechanisms through which it operates remain ambiguous. This study utilized network pharmacology to predict the core targets and signaling pathways implicated in the anti-OP properties of hesperidin. Molecular docking and molecular dynamics simulations were employed to confirm the stability of the interaction between hesperidin and the core targets. The effects of hesperidin on osteoblastic cells MC3T3-E1 were assessed using MTT, ELISA, alkaline phosphatase assay, and RT-qPCR techniques. Furthermore, in vivo experiments were conducted to determine the potential protective effects of hesperidin on zebrafish bone formation and oxidative stress response. The results demonstrate that network pharmacology has identified 10 key target points, significantly enriched in the estrogen signaling pathway. Hesperidin exhibits notable promotion of MC3T3-E1 cell proliferation and significantly enhances ALP activity. ELISA measurements indicate an elevation in NO levels and a reduction in IL-6 and TNF-α. Moreover, RT-qPCR analysis consistently reveals that hesperidin significantly modulates the mRNA levels of ESR1, SRC, AKT1, and NOS3 in MC3T3-E1 cells. Hesperidin promotes osteogenesis and reduces oxidative stress in zebrafish. Additionally, we validate the stable and tight binding of hesperidin with ESR1, SRC, AKT1, and NOS3 through molecular dynamics simulations. In conclusion, our comprehensive analysis provides evidence that hesperidin may exert its effects on alleviating OP through the activation of the estrogen signaling pathway via ESR1. This activation leads to the upregulation of SRC, AKT, and eNOS, resulting in an increase in NO levels. Furthermore, hesperidin promotes osteoblast-mediated bone formation and inhibits pro-inflammatory cytokines, thereby alleviating oxidative stress associated with OP.

Identification of quality markers for Cyanotis arachnoidea and analysis of its physiological mechanism based on chemical pattern recognition, network pharmacology, and experimental validation.

Cyanotis arachnoidea C. B. Clarke is a traditional Chinese medicinal herb that has a limited clinical use in the treatment of diabetes mellitus (DM) in minority areas of Guizhou in China. However, few prior reports are available on the quality control of Cyanotis arachnoidea, and its quality markers and hypoglycemic mechanism are still unclear. The purpose of this study is to explore the quality markers (Q-markers) of Cyanotis arachnoidea and predict its hypoglycemic mechanism. In this study, ultra-high-performance liquid chromatography (UHPLC) fingerprint combined with chemical pattern recognition were performed, and four differential components were screened out as quality markers, including 20-Hydroxyecdysone, 3-O-acetyl-20-hydroxyecdysone, Ajugasterone C, and 2-O-acetyl-20-hydroxyecdysone. Network pharmacology analysis revealed 107 therapeutic target genes of Cyanotis arachnoidea in DM treatment, and the key targets were Akt1, TNF, IL-6, MAPK3, and JUN. The hypoglycemic mode of action of Cyanotis arachnoidea may be mediated by tumor necrosis factor (TNF) signaling, cancer, insulin resistance, and JAK-STAT pathways. Molecular docking analysis disclosed that the foregoing quality markers effectively bound their key target genes. An in vitro experiment conducted on pancreatic islet ß-cells indicated that the forenamed active components of Cyanotis arachnoidea had hypoglycemic efficacy by promoting PI3K/Akt and inhibiting MAPK signaling. UHPLC also accurately quantified the quality markers. The identification and analysis of quality markers for Cyanotis arachnoidea is expected to provide references for the establishment of a quality control evaluation system and clarify the material basis and hypoglycemic mechanisms of this traditional Chinese medicine (TCM).

MIMU Optimal Redundant Structure and Signal Fusion Algorithm Based on a Non-Orthogonal MEMS Inertial Sensor Array.

A micro-inertial measurement unit (MIMU) is usually used to sense the angular rate and acceleration of the flight carrier. In this study, multiple MEMS gyroscopes were used to form a spatial non-orthogonal array to construct a redundant MIMU system, and an optimal Kalman filter (KF) algorithm was established by a steady-state KF gain to combine array signals to improve the MIMU's accuracy. The noise correlation was used to optimize the geometric layout of the non-orthogonal array and reveal the mechanisms of influence of correlation and geometric layout on MIMU's performance improvement. Additionally, two different conical configuration structures of a non-orthogonal array for 4,5,6,8-gyro were designed and analyzed. Finally, a redundant 4-MIMU system was designed to verify the proposed structure and KF algorithm. The results demonstrate that the input signal rate can be accurately estimated and that the gyro's error can also be effectively reduced through fusion of non-orthogonal array. The results for the 4-MIMU system illustrate that the gyro's ARW and RRW noise can be decreased by factors of about 3.5 and 2.5, respectively. In particular, the estimated errors (1σ) on the axes of Xb, Yb and Zb were 4.9, 4.6 and 2.9 times lower than that of the single gyroscope.

[Effect of Liangfang Wenjing Decoction on expression of key glycolytic enzymes in uterus and ovaries of rats with coagulating cold and blood stasis syndrome].

This study aimed to investigate the relationship between coagulating cold and blood stasis syndrome and glycolysis, and observe the intervention effect of Liangfang Wenjing Decoction(LFWJD) on the expression of key glycolytic enzymes in the uterus and ovaries of rats with coagulating cold and blood stasis. The rat model of coagulating cold and blood stasis syndrome was established by ice-water bath. After modeling, the quantitative scoring of symptoms were performed, and according to the scoring results, the rats were randomly divided into a model group and LFWJD low-, medium-and high-dose groups(4.7, 9.4, 18.8 g·kg~(-1)·d~(-1)), with 10 in each group. Another 10 rats were selected as the blank group. After 4 weeks of continuous administration by gavage, the quantitative scoring of symptoms was repeated. Laser speckle flowgraphy was used to detect the changes of microcirculation in the ears and uterus of rats in each group. Hematoxylin-eosin(HE) staining was used to observe the pathological morphology of uterus and ovaries of rats in each group. The mRNA and protein expressions of pyruvate dehydrogenase kinase 1(PDK1), hexokinase 2(HK2) and lactate dehydrogenase A(LDHA) in the uterus and ovaries of rats were examined by real-time quantitative polymerase chain reaction(RT-qPCR) and Western blot, respectively. The rats in the model group showed signs of coagulating cold and blood stasis syndrome, such as curl-up, less movement, thickened veins under the tongue, and reduced blood perfusion in the microcirculation of the ears and uterus, and HE staining revealed a thinning of the endometrium with disorganized arrangement of epithelial cells and a decrease in the number of ovarian follicles. Compared with the model group, the treatment groups had alleviated coagulating cold and blood stasis, which was manifested as red tongue, reduced nail swelling, no blood stasis at the tail end as well as increased blood perfusion of the microcirculation in the ears and uterus(P<0.05 or P<0.01). Among the groups, the LFWJD medium-and high-dose groups had the most significant improvement in coagulating cold and blood stasis, with neatly arranged columnar epithelial cells in uterus, and the number of ovarian follicles was higher than that in the model group, especially mature follicles. The mRNA and protein expressions of PDK1, HK2, LDHA in uterus and ovaries were up-regulated in the model group(P<0.05 or P<0.01), while down-regulated in LFWJD medium-and high-dose groups(P<0.05 or P<0.01). The LFWJD low-dose group presented a decrease in the mRNA expressions of PDK1, HK2 and LDHA in uterus and ovaries as well as in the protein expressions of HK2 and LDHA in uterus and HK2 and PDK1 in ovaries(P<0.05 or P<0.01). The therapeutic mechanism of LFWJD against coagulating cold and blood stasis syndrome is related to the down-regulation of key glycolytic enzymes PDK1, HK2 and LDHA, and the inhibition of glycolytic activities in uterus and ovaries.

Social support and cognitive function in Chinese older adults who experienced depressive symptoms: is there an age difference?

Objective: This study examined the moderating effect of overall social support and the different types of social support on cognitive functioning in depressed older adults. We also investigated whether the moderating effect varied according to age. Methods: A total of 2,500 older adults (≥60 years old) from Shanghai, China were enrolled using a multistage cluster sampling method. Weighted linear regression and multiple linear regression was utilized to analyze the moderating effect of social support on the relationship between depressive symptoms and cognitive function and to explore its differences in those aged 60-69, 70-79, and 80 years and above. Results: After adjusting for covariates, the results indicated that overall social support (ß = 0.091, p = 0.043) and support utilization (ß = 0.213, p < 0.001) moderated the relationship between depressive symptoms and cognitive function. Support utilization reduced the possibility of the cognitive decline in depressed older adults aged 60-69 years (ß = 0.310, p < 0.001) and 80 years and above (ß = 0.199, p < 0.001), while objective support increased the possibility of cognitive decline in depressed older people aged 70-79 years (ß = -0.189, p < 0.001). Conclusion: Our findings highlight the buffering effects of support utilization on cognitive decline in depressed older adults. We suggest that age-specific measures should be taken when providing social support to depressed older adults in order to reduce the deterioration of cognitive function.

Adjuvant effects of Chinese medicinal tonics on gastric, liver, and colorectal cancers-OMICs-based contributions to understanding their mechanism of action.

Gastric, liver, and colorectal cancers belong to gastrointestinal (GI) cancers, one of the most threatening diseases in the world. The tonics class in Chinese medicines plays a critical role in antigastrointestinal cancer as adjuvants. However, it is a challenge to study the effects and underlying mechanisms of tonics due to their multiple components and multiple targets; OMICs were introduced to facilitate the investigation of the complex mixture of tonics. In this review, the online databases PubMed, ProQuest, Web of Knowledge, China National Knowledge Infrastructure (CNKI), Chongqing VIP, and Wanfang were retrieved from 1 January 2011 to 31 May 2022, in an aim to summarize and discuss the research progress of the effects and, especially, the underlying mechanisms of tonics for antigastrointestinal cancers via OMICs. The results showed that through the combination of OMICs and other technologies, tonics have been used for gastrointestinal cancer by targeting cancer hallmarks, enhancing body resistance to carcinogenesis, enhancing therapeutic effects, and/or decreasing side effects. In conclusion, tonics may play a promising role in gastric, liver, and colorectal cancers as adjuvants and can be well investigated via the combination of OMICs and other technologies, which deserves further study.

Quality evaluation of the classical prescription, Danggui Jianzhong decoction, using ultra-high-performance liquid chromatography fingerprint, chemical pattern recognition, and network pharmacology.

Danggui Jianzhong decoction is a classical prescription that has been widely used for thousands of years. However, the quality of this formula is difficult to control owing to its complex chemical component system. In this study, a simple and efficient method comprising ultra-high-performance liquid chromatography fingerprint, chemical pattern recognition, and network pharmacology was established to evaluate the quality of this decoction. A total of 20 common peaks were obtained by fingerprint analysis and 19 chemicals were identified. The fingerprint similarity of 15 batch samples ranged from 0.963 to 0.991. Chemical pattern recognition analysis could clearly classify 15 batches of Danggui Jianzhong decoction into three groups. Further, seven chemical markers were screened out. A herbs-active components-targets-disease network was constructed and enrichment analyses were performed, which indicated that these 19 chemical components are the medicinal substances of Danggui Jianzhong decoction. Further, the mechanism employed by this formula to treat primary dysmenorrhea may be related to the regulation of inflammatory response. In conclusion, this combination approach enables accurate evaluation and prediction of the quality of Danggui Jianzhong decoction, and lays the foundation for studies on the material basis and exploration of the mechanism of Danggui Jianzhong decoction in the treatment of primary dysmenorrhea.

CHCHD2 Regulates Mitochondrial Function and Apoptosis of Ectopic Endometrial Stromal Cells in the Pathogenesis of Endometriosis.

Endometriosis is a disease that involves dysfunction of mitochondria, imbalance of proliferation, and apoptosis. Coiled-coil-helix-coiled-coil-helix domain containing 2 (CHCHD2) is a major mitochondrial protein which could regulate the mitochondrial function and apoptosis in various tumor cells, promote migration and then lead to tumor progression. This study aimed to explore the role of CHCHD2 on endometriosis. We investigated the expression of CHCHD2 in ectopic and eutopic endometrium tissues of patients with endometriosis and normal endometrium tissues. Furthermore, CHCHD2 was downregulated to explore the corresponding change of mitochondrial function and morphology, mitochondrial-mediated apoptosis pathway, and proliferation and migration of ectopic endometrial stromal cells. Our results demonstrated that the mRNA and protein expression levels of CHCHD2 were significantly increased in eutopic and ectopic endometrium tissues compared with the normal endometrium tissues. The knockdown of CHCHD2 could cause mitochondrial dysfunction, including the opening of mitochondrial permeability transition pore, loss of mitochondrial membrane potential and the release of cytochrome c, and morphological damage. In addition, CHCHD2 down-expression could also lead to inhibition of cell proliferation, decrease of migration ability, and aggravation of mitochondrial-mediated apoptosis. Together, these findings suggest that increased expression of CHCHD2 in endometriotic tissues may contribute to the pathogenesis of endometriosis via regulating mitochondrial function and apoptosis, and CHCHD2 may be a potential target for interrupting the development of endometriosis.

Intravitreal conbercept for diabetic macular oedema: 2-year results from a randomised controlled trial and open-label extension study.

BACKGROUND: To demonstrate the efficacy and safety of intravitreal injections of conbercept versus laser photocoagulation in the treatment of diabetic macular oedema (DME). METHODS: A 12-month multicentre, randomised, double-masked, double-sham, parallel controlled, phase III trial (Sailing Study), followed by a 12-month open-label extension study. Patients with centre-involved DME were randomly assigned to receive either laser photocoagulation followed by pro re nata (PRN) sham intravitreal injections (laser/sham) or sham laser photocoagulation followed by PRN 0.5 mg conbercept intravitreal injections (sham/conbercept). Patients who entered the extension study received PRN conbercept treatment. The primary endpoint was the changes in best-corrected visual acuity (BCVA) from baseline. RESULTS: A total of 248 eyes were included in the full analysis set and 157 eyes continued in the extension study. Significant improvement in mean change in BCVA from baseline to month 12 was observed in the sham/conbercept group (8.2±9.5 letters), whereas no improvement was observed in the laser/sham group (0.3±12.0 letters). Patients in the laser/sham group showed a marked improvement in BCVA after the switch to conbercept in the extension study, and there was no difference in BCVA between the two groups at the end of the extension study. CONCLUSION: The use of a conbercept PRN intravitreal injection regimen improved the BCVA of patients with DME, and its efficacy was better than that of laser photocoagulations, and the same efficacy was observed when the eyes treated with laser alone were switched to conbercept. TRIAL REGISTRATION NUMBER: NCT02194634.

Effects of sevoflurane exposure on apoptosis and cell cycle of peripheral blood lymphocytes, and immunologic function.

BACKGROUND: Waste anesthetic gases (WAGs) leaked from new-type halogenated inhalational anesthetics such as sevoflurane have been were reported to pose a risk for the health of operating room personnel. The effects of WAGs on peripheral blood lymphocytes, however, remain yet controversial. The present study was undertaken to examine the effects of occupational sevoflurane exposure on the peripheral blood lymphocytes of medical personnel who work in the operating room. METHODS: A cohort of 56 medical residents were divided into exposed group (n = 28) and control group (non-exposed group) (n = 28). Gas chromatography was used to measure the concentration of sevoflurane in the medical resident's breathing zone during surgeries under inhalation anesthesia in the exposure group. The gas collection lasted an hour. Peripheral blood lymphocytes were isolated from venous blood, and then apoptosis and cell cycle were analyzed by flow cytometry. EDTA-anticoagulated whole blood was harvested to analyze the lymphocyte subsets by flow cytometry. Immunoglobulins (IgA, IgM, IgG) were quantified by immunoturbidimetry. RESULTS: The average concentration of sevoflurane in the exposed group was 1.03 ppm with a range from 0.03 ppm to 2.24 ppm. No significant effects were found on the apoptosis rates or cell cycles of peripheral blood lymphocytes in the exposed group relative to the control group (P > 0.05). Similarly, there were no significant differences in the lymphocyte subsets or the levels of immunoglobulins (IgA, IgM, IgG) between the two groups (P > 0.05). CONCLUSIONS: Occupational exposure to low-level sevoflurane has no significant effect on the peripheral blood lymphocytes of operating room staff, but this conclusion needs to be confirmed by multicenter and long-term follow-up studies with large samples. TRIAL REGISTRATION NUMBER AND DATE OF REGISTRATION: ChiCTR2000040772 , December 9, 2020 (Retrospective registration).

Phytochemical Analysis Using UPLC-MS/MS Combined with Network Pharmacology Methods to Explore the Biomarkers for the Quality Control of Lingguizhugan Decoction.

As a classic TCM prescription, LGZG has been widely used in clinical prevention and treatment of heart failure, nonalcoholic fatty liver, and hyperlipidemia. However, there are few studies on chemical components in recent years, and the basis of quality evaluation is not sufficient. This study was to find the active ingredients of the Lingguizhugan decoction using UPLC-MS/MS and network pharmacology. By comparing the retention time and MS dates of the reference and self-building database, the cleavage rules of chemical composition whose mass errors are less than 1 ppm(FL less than 3 ppm) are analyzed. On this basis, a network pharmacology method was used to find biomarkers for quantitative analysis. The results show that 149 compounds were preliminaries identified or inferred, including 63 flavonoids, 30 triterpenes, 22 phenylpropanoids, 13 organic acids, 6 lactones, 5 alkaloids, 4 anthraquinones, and 6 other compounds. According to the network pharmacology results, 20 chemical constituents were selected as the biomarkers, which were determined simultaneously for the first time, including poricoic acid A, poricoic acid B, glycyrrhizic acid, glycyrrhetinic acid, liquiritin, isoliquiritin, liquiritigenin, isoliquiritin apioside, cinnamic acid, caffeic acid, neochlorogenic acid, chlorogenic acid, cryptochlorogenic acid, isochlorogenic acid A, B, and C, atractylenolide I, II, and III, and coumarin. The methodological results show that the linearity, stability, precision, repeatability, and recovery of the method are satisfactory. Therefore, a comprehensive quality assessment system for LGZG was established on the basis of a systematic study of chemical substances and network pharmacology, which provided an important reference for the foundation of pharmacological action and its mechanics.

Integrated analysis of DNA methylation and gene expression profiles identified S100A9 as a potential biomarker in ulcerative colitis.

Ulcerative colitis (UC) is a prevalent relapsing-remitting inflammatory bowel disease whose pathogenetic mechanisms remain elusive. In the present study, colonic biopsies samples from three UC patients treated in the Traditional Chinese Medicine Hospital and three healthy controls were obtained. The genome-wide mRNA and lncRNA expression of the samples were profiled through Agilent gene expression microarray. Moreover, the genome-wide DNA methylation dataset of normal and UC colon tissues was also downloaded from GEO for a collaborative analysis. Differential expression of lncRNA (DELs) and mRNAs (DEMs) in UC samples compared with healthy samples were identified by using limma Bioconductor package. Differentially methylated promoters (DMPs) in UC samples compared with controls were obtained through comparing the average methylation level of CpGs located at promoters by using t-test. Functional enrichment analysis was performed by the DAVID. STRING database was applied to the construction of gene functional interaction network. As a result, 2090 DEMs and 1242 DELs were screened out in UC samples that were closely associated with processes related to complement and coagulation cascades, osteoclast differentiation vaccinia, and hemorrhagic diseases. A total of 90 DEMs and 72 DELs were retained for the construction of functional network for the promoters of their corresponding genes were identified as DMPs. S100A9, HECW2, SOD3 and HIX0114733 showed high interaction degrees in the functional network, and expression of S100A9 was confirmed to be significantly elevated in colon tissues of UC patients compared with that of controls by qRT-PCR that was consistent with gene microarray analysis. These indicate that S100A9 could potentially be used as predictive biomarkers in UC.

Efficient 3D silicon mode (de)multiplexer based on a sidewall-aligned vertical coupler.

An efficient three-dimensional (3D) quasi-TE0 and quasi-TE1 mode (de)multiplexer [(De)MUX] is proposed and optimized based on a dual-waveguide 3D-coupler, in which the sidewalls of a bottom silicon waveguide and an upper poly-silicon waveguide are aligned vertically. The full-vectorial finite element method and 3D full-vectorial finite difference time domain method are utilized to study the performances of the proposed 3D mode (De)MUX. The results indicate that the proposed mode (De)MUX can achieve a compact coupling length of 6.88 µm, a mode crosstalk of -30.04dB, an insertion loss of 0.02 dB, and an ultra-broad 1 dB bandwidth of 300 nm. The proposed 3D mode (De)MUX based on a sidewall-aligned vertical coupler has the potential to extend the functionality and to increase the integration of the mode division multiplexing (MDM) systems.

KRAS-retroviral fusion transcripts and gene amplification in arsenic-transformed, human prostate CAsE-PE cancer cells.

CAsE-PE cells are an arsenic-transformed, human prostate epithelial line containing oncogenic mutations in KRAS compared to immortalized, normal KRAS parent cells, RWPE-1. We previously reported increased copy number of mutated KRAS in CAsE-PE cells, suggesting gene amplification. Here, KRAS flanking genomic and transcriptomic regions were sequenced in CAsE-PE cells for insight into KRAS amplification. Comparison of DNA-Seq and RNA-Seq showed increased reads from background aligning to all KRAS exons in CAsE-PE cells, while a uniform DNA-Seq read distribution occurred in RWPE-1 cells with normal transcript expression. We searched for KRAS fusions in DNA and RNA sequencing data finding a portion of reads aligning to KRAS and viral sequence. After generation of cDNA from total RNA, short and long KRAS probes were generated to hybridize cDNA and KRAS enriched fragments were PacBio sequenced. More KRAS reads were captured from CAsE-PE cDNA versus RWPE-1 by each probe set. Only CAsE-PE cDNA showed KRAS viral fusion transcripts, primarily mapping to LTR and endogenous retrovirus sequences on either 5'- or 3'-ends of KRAS. Most KRAS viral fusion transcripts contained 4 to 6 exons but some PacBio sequences were in unusual orientations, suggesting viral insertions within the gene body. Additionally, conditioned media was extracted for potential retroviral particles. RNA-Seq of culture media isolates identified KRAS retroviral fusion transcripts in CAsE-PE media only. Truncated KRAS transcripts suggested multiple retroviral integration sites occurred within the KRAS gene producing KRAS retroviral fusions of various lengths. Findings suggest activation of endogenous retroviruses in arsenic carcinogenesis should be explored.

Screening and Identification of the Main Metabolites of Schisantherin a In Vivo and In Vitro by Using UHPLC-Q-TOF-MS/MS.

Schisantherin A is an active ingredient originating from Schisandra chinensis (Turcz.) which has hepatoprotective and anti-oxidation activities. In this study, in vitro metabolisms investigated on rat liver microsomes (RLMs) and in vivo metabolisms explored on male Sprague Dawley rats of Schisantherin A were tested, respectively. The metabolites of Schisantherin A were identified using ultra-high-performance liquid chromatography coupled with hybrid triple quadrupole time-of-flight mass spectrometry (UHPLC-Q-TOF-MS/MS). Based on the method, 60 metabolites were successfully identified and structurally characterized including 48 phase-I and 12 phase-II metabolites. Among the metabolites, 45 metabolites were reported for the first time. Moreover, 56 and eight metabolites were detected in urine and bile and 19 metabolites were identified in rats' plasma. It demonstrated that hepatic and extra-hepatic metabolic pathways were both involved in Schisantherin A biotransformation in rats. Five in vitro metabolites were structurally characterized for the first time. The results indicated that the metabolic pathways mainly include oxidation, reduction, methylation, and conjugation with glucuronide, taurine, glucose, and glutathione groups. This study provides a practical strategy for rapidly screening and identifying metabolites, and the results provide basic data for future pharmacological and toxicology studies of Schisantherin A and other lignin ingredients.

Data for "joint modeling of lithosphere and mantle dynamics: Sensitivity to viscosities within the lithosphere, asthenosphere, transition zone, and D" layers".

The article presents the data calculated from four different viscosity structures V1, V2 [1], SH08 [2], and GHW13 [3], as well as two tomography models S40RTS [4] and SAW642AN [5], using the joint modeling of lithosphere and mantle dynamics technique [3, 6-9]. Besides, the data contain the information on the viscosity variations of the lithosphere, asthenosphere, transition zone, and D″ layer based on the viscosity structure SH08.

Polyphyllin I suppresses proliferation and promotes apoptosis of gastric cancer cell by inhibiting stat3 phosphorylation.

BACKGROUND: Polyphyllin I, a bioactive phytochemical extracted from Rhizoma Paridis, has been reported to exhibit anticancer activity. However, little is known about the potential of Polyphyllin I in induction of gastric cancer (GC) cell apoptosis and its underlying mechanisms. METHODS: Dual-luciferase reporter assay was performed to test the bioactivity of Polyphyllin I on inhibiting JAK2/STAT3 signaling pathway. The anti-proliferation activity of Polyphyllin I was tested using cell clone formation assay. The effect of Polyphyllin I on cell cycle and apoptosis were confirmed by flow cytometry and TUNEL assay. Western blot was used to test the effect of Polyphyllin I on JAK/STAT3 pathway and apoptosis related proteins. The subcutaneous GC mouse model was established to examine whether polyphyllin I could inhibit GC growth in vivo. RESULTS: A dual-luciferase reporter assay showed that polyphyllin I could inhibit the activity of Bcl-2 which is downstream of JAK2/STA3. Polyphyllin I significantly inhibited GC cell proliferation and induced cell apoptosis in a dose-dependent manner. The western blot results indicated that polyphyllin I mainly inhibited the phosphorylation of STAT3 by the way which is different from AG490. It was inferred that polyphyllin I may inhibit the JAK2/STAT3 pathway and affect the expression level of apoptosis related genes. Finally, in the tumor xenograft experiment proved that polyphyllin I significantly inhibited the growth of GC in vivo. CONCLUSIONS: Polyphyllin I may play its anticancer activity by inhibiting phosphorylation of STAT3 in GC cells.