Rash caused by lurasidone in old chinese patient with bipolar disorder: case-based review.

BACKGROUND: Rash is one of common adverse drug reaction and which have been reported in typical and atypical antipsychotics. Reports of lurasidone induced skin reactions are sparse. In this study, we report a case of rash caused by lurasidone. CASE PRESENTATION: A 63-year-old man with bipolar disorder (BD) who is treated by lurasidone. However, the patient presents a rash all over after lurasidone dose increasing from 40 mg/day to 60 mg/day. With the diagnosis of drug induced rash, lurasidone was discontinued, and the rash complete disappears within 2 weeks. In addition, all case reports about antipsychotics associated rash were reviewed by searching English and Chinese database including Pubmed, Embase, Cochrane Library, CNKI and Wanfang database. A total of 139 articles contained 172 patients were included in our study. The literature review and our case suggest that the cutaneous adverse events caused by antipsychotic drugs should not be ignored, particularly for the patient who was first use or at dose increasing of antipsychotic. CONCLUSIONS: In conclusion, we report a case of lurasidone related rash and review rash caused by antipsychotics. Psychiatrists should be alert to the possibility of the rash caused by antipsychotics, especially the patient was first use of antipsychotics or the antipsychotic dose was increasing.

Upconversion Luminescence-Initiated and GSH-Responsive Self-Driven DNA Motor for Automatic Operation in Living Cells and In Vivo.

In light of the worthy design flexibility and the good signal amplification capacity, the recently developed DNA motor (especially the DNA walker)-based fluorescent biosensors can offer an admirable choice for realizing bioimaging. However, this attractive biosensing strategy not only has the disadvantage of uncontrollable initiation but also usually demands the supplement of exogenous driving forces. To handle the above obstacles, some rewarding solutions are proposed here. First, on the surface of an 808 nm near-infrared light-excited low-heat upconversion nanoparticle, a special ultraviolet upconversion luminescence-initiated three-dimensional (3D) walking behavior is performed by embedding a photocleavage linker into the sensing elements, and such light-controlled target recognition can perfectly overcome the pre-triggering of the biosensor during the biological delivery to significantly boost the sensing precision. After that, a peculiar self-driven walking pattern is constructed by employing MnO2 nanosheets as an additional nanovector to physically absorb the sensing frame, for which the reduction of the widespread glutathione in the biological medium can bring about sufficient self-supplied Mn2+ to guarantee the walking efficiency. By selecting an underlying next-generation broad-spectrum cancer biomarker (survivin messenger RNA) as the model target, we obtain that the newly formed autonomous 3D DNA motor shows a commendable sensitivity (where the limit of detection is down to 0.51 pM) and even an outstanding specificity for distinguishing single-base mismatching. Beyond this sound assay performance, our sensing approach is capable of working as a powerful imaging platform for accurately operating in various living specimens such as cells and bodies, showing a favorable diagnostic ability for cancer care.

Biomimetic Chip Enhanced Time-Gated Luminescent CRISPR-Cas12a Biosensors under Functional DNA Regulation.

Despite that the currently discovered CRISPR-Cas12a system is beneficial for improving the detection accuracy and design flexibility of luminescent biosensors, there are still challenges to extend target species and strengthen adaptability in complicated biological media. To conquer these obstacles, we present here some useful strategies. For the former, the limitation to nucleic acids assay is broken through by introducing a simple functional DNA regulation pathway to activate the unique trans-cleavage effect of this CRISPR system, under which the expected biosensors are capable of effectively transducing a protein (employing dual aptamers) and a metal ion (employing DNAzyme). For the latter, a time-gated luminescence resonance energy transfer imaging manner using a long-persistent nanophosphor as the energy donor is performed to completely eliminate the background interference and a nature-inspired biomimetic periodic chip constructed by photonic crystals is further combined to enhance the persistent luminescence. In line with the above efforts, the improved CRISPR-Cas12a luminescent biosensor not only exhibits a sound analysis performance toward the model targets (carcinoembryonic antigen and Na+) but also owns a strong anti-interference feature to actualize accurate sensing in human plasma samples, offering a new and applicative analytical tool for laboratory medicine.

[Evaluation of proficiency test with low number of participants:a case study on the testing of lead and nitrite in water].

OBJECTIVE: The gross error of the assigned value-classical statistical method was developed that all participants in proficiency testing activities could obtain unbiased evaluation in case of a low number of participants(& lt; 17). METHODS: This developed method was employed to evaluate the testing result of nitrite-N and lead in water from participants along the "Belt and Road", which was organized by CNCA in 2019. RESULTS: Use the specified value gross error-classical statistical method to evaluate the feedback result of 29(15+14) participants with non-normal distribution, 4 out of 15 participants in "Lead in Water" get a "unsatisfied", 5 out of the 14 participants in "Nitrite in Water(as Nitrogen)"get a "unsatisfactory". CONCLUSION: When the robust statistics and classical statistical method are unable to make objective evaluations respectively, this method could mildly remove outliers and avoid the extreme evaluation of "all satisfied"or "all dissatisfied", which truly reflected the real ability of each participant and could be applied to the proficiency testing activity with low number of participants.

Real-Time Monitoring of Temperature Variations around a Gold Nanobipyramid Targeted Cancer Cell under Photothermal Heating by Actively Manipulating an Optically Trapped Luminescent Upconversion Microparticle.

We demonstrate an effective approach to realize active and real-time temperature monitoring around the gold nanobipyramids (AuNBPs)-labeled cancer cell under 808 nm laser irradiation by combining optical tweezers and temperature-sensitive upconversion microparticles (UCMPs). On the one hand, the aptamer-modified AuNBPs that absorb laser at 808 nm not only act as an excellent photothermal reagent but also accurately and specifically bind the target cancer cells. On the other hand, the single optically trapped NaYF4:Yb3+, Er3+ UCMPs with a 980 nm laser exhibit temperature-dependent luminescence properties, where the intensity ratio of emission 525 and 547 nm varies with the ambient temperature. Therefore, real-time temperature variation monitoring is performed by 3D manipulation of the trapped single UCMP to control its distance from the AuNBPs-labeled cancer cell while being photothermally killed. The results show distance-related thermal propagation because the temperature increase reaches as high as 10 °C at a distance of 5 µm from the cell, whereas the temperature difference drops rapidly to 5 °C when this distance increases to 15 µm. This approach shows that the photothermal conversion from AuNBPs is sufficient to kill the cancer cells, and the temperature increase can be controlled within the micrometer level at a certain period of time. Overall, we present a micrometer-size thermometer platform and provide an innovative strategy to measure temperature at the micrometer level during photothermal killing of cancer cells.

Improving Flow Bead Assay: Combination of Near-Infrared Optical Tweezers Stabilizing and Upconversion Luminescence Encoding.

To enhance signal acquisition stability and diminish background interference for conventional flow bead-based fluorescence detection methods, we demonstrate here an exceptional microfluidic chip assisted platform by integrating near-infrared optical tweezers with upconversion luminescence encoding. For the former, a single 980 nm laser is employed to perform optical trapping and concurrently excite upconversion luminescence, avoiding the fluctuation of the signals and the complexity of the apparatus. By virtue of the favorable optical properties of upconversion nanoparticles (UCNPs), the latter is carried out by employing two-color UCNPs (Er-UCNPs and Tm-UCNPs) with negligible spectral overlaps. With the assistance of the double key techniques, we fabricated complex microbeads referred to a UCNPs-miRNAs-microbead sandwich construct by a one-step nucleic acid hybridization process and then obtained uniform terrace peaks for the automatic and simultaneous quantitative determination of miRNA-205 and miRNA-21 sequences with a detection limit of pM level on the basis of a special home-built flow bead platform. Furthermore, the technique was successfully applied for analyzing complex biological samples such as cell lysates and human tissue lysates, holding certain potential for disease diagnosis. In addition, it is expected that the flow platform can be utilized to investigate many other biomolecules of single cells and to allow analysis of particle heterogeneity in biological fluid by means of optical tweezers.

Transcriptome profiling of Fagopyrum tataricum leaves in response to lead stress.

BACKGROUND: Lead (Pb) pollution is a widespread environmental problem that is harmful to living organisms. Tartary buckwheat (Fagopyrum tataricum), a member of the family Polygonaceae, exhibits short growth cycles and abundant biomass production, could be an ideal plant for phytoremediation due to its high Pb tolerance. Here, we aimed to explore the molecular basis underlying the responses of this plant to Pb stress. RESULTS: In our study, ultrastructural localization assays revealed that Pb ions primarily accumulate in leaf vacuoles. RNA deep sequencing (RNA-Seq) of tartary buckwheat leaves was performed on two Pb-treated samples, named Pb1 (2000 mg/kg Pb (NO3)2) and Pb2 (10,000 mg/kg Pb (NO3)2), and a control (CK). A total of 88,977 assembled unigenes with 125,203,555 bases were obtained. In total, 2400 up-regulated and 3413 down-regulated differentially expressed genes (DEGs) were identified between CK and Pb1, and 2948 up-regulated DEGs and 3834 down-regulated DEGs were generated between CK and Pb2, respectively. Gene Ontology (GO) and pathway enrichment analyses showed that these DEGs were primarily associated with 'cell wall', 'binding', 'transport', and 'lipid and energy' metabolism. The results of quantitative real-time PCR (qRT-PCR) analyses of 15 randomly selected candidate DEGs and 6 regulated genes were consistent with the results of the transcriptome analysis. Heterologous expression assays in the yeast strain Δycf1 indicated that overexpressing CCCH-type zinc finger protein 14 (ZFP14) enhanced sensitivity to Pb2+, while 5 other genes, namely, metal transporter protein C2 (MTPC2), phytochelatin synthetase-like family protein (PCSL), vacuolar cation/proton exchanger 1a (VCE1a), natural resistance-associated macrophage protein 3 (Nramp3), and phytochelatin synthetase (PCS), enhanced the Pb tolerance of the mutant strain. CONCLUSION: Combining our findings with those of previous studies, we generated a schematic model that shows the metabolic processes of tartary buckwheat under Pb stress. This study provides important data for further genomic analyses of the biological and molecular mechanisms of Pb tolerance and accumulation in tartary buckwheat.

A Meta-Analysis of Abnormal Glucose Metabolism in First-Episode Drug-Naive Schizophrenia.

BACKGROUND: Patients with schizophrenia exhibit a higher mortality rate compared with the general population. This mortality has been attributed predominantly by the high risk of type 2 diabetes mellitus in the patients. We aimed to assess the inherent risk of glucose metabolism abnormalities in first-episode drug-naive schizophrenia. SUBJECTS AND METHODS: We searched English database (PubMed, EMBASE, MEDLINE, Cochrane Library databases) and Chinese database (Wan Fang Data, CBM disc, VIP, and CNKI) from their inception until Jul 2018 for case-control studies examining glucose metabolism abnormalities. Measurements, such as fasting plasma glucose levels, fasting plasma insulin levels, insulin resistance and HbA1c levels in first-episode antipsychotic-naive patients were used to test for prediabetes. Standardized/weighted mean differences and 95% confidence intervals were calculated and analyzed. RESULTS: 19 studies (13 in English and 6 in Chinese) consisting of 1065 patients and 873 controls were included. Fasting plasma glucose levels (95% CI; 0.02 to 0.29; P=0.03), 2 h plasma glucose levels after an OGTT (95% CI; 0.63 to 1.2; P<0.00001), fasting plasma insulin levels (95% CI; 0.33 to 0.73; P<0.00001), insulin resistance (95% CI; 0.29 to 0.6; P<0.00001) in patients with first-episode schizophrenia were significant elevated. There was no significant difference in HbA1c level (95% CI; -0.34 to 0.18; P=0.54) in patients with first-episode schizophrenia compared with controls. CONCLUSIONS: This meta-analysis showed that glucose metabolism was impaired in patients with first-episode schizophrenia. Higher quality studies with larger samples are warranted to confirm these findings.

Breaking Through Bead-Supported Assay: Integration of Optical Tweezers Assisted Fluorescence Imaging and Luminescence Confined Upconversion Nanoparticles Triggered Luminescent Resonance Energy Transfer (LRET).

Herein, a conceptual approach for significantly enhancing a bead-supported assay is proposed. For the fluorescence imaging technology, optical tweezers are introduced to overcome the fluid viscosity interference and immobilize a single tested bead at the laser focus to guarantee a fairly precise imaging condition. For the selection of fluorescent materials and the signal acquisition means, a type of innovative luminescence confined upconversion nanoparticle with a unique sandwich structure is specially designed to act as an efficient energy donor to trigger the luminescent resonance energy transfer (LRET) process. By further combining the double breakthrough with a molecular beacon model, the newly developed detection strategy allows for achieving a pretty high LRET ratio (≈ 88%) to FAM molecules and offering sound assay performance toward miRNA analysis with a detection limit as low as the sub-fM level, and is capable of well identifying single-base mismatching. Besides, this approach not only is able to accurately qualify the low-abundance targets from as few as 30 cancer cells but also can be employed as a valid cancer early warning tool for performing liquid biopsy.

Combining Holographic Optical Tweezers with Upconversion Luminescence Encoding: Imaging-Based Stable Suspension Array for Sensitive Responding of Dual Cancer Biomarkers.

Establishment of a stable analytical methodology with high-quality results is an urgent need for screening cancer biomarkers in early diagnosis of cancer. In this study, we incorporate holographic optical tweezers with upconversion luminescence encoding to design an imageable suspension array and apply it to conduct the detection of two liver cancer related biomarkers, carcinoembryonic antigen and alpha fetal protein. This bead-based assay is actualized by forming a bead array with holographic optical tweezers and synchronously exciting the upconversion luminescence of corresponding trapped complex beads fabricated with a simple one-step sandwich immunological recognition. Owing to the fact that these flowing beads are stably trapped in the focal plane of the objective lens which tightly converges the array of the laser beams by splitting a 980 nm beam using a diffraction optical element, a fairly stable excitation condition is achieved to provide reliable assay results. By further taking advantage of the eminent encoding capability of upconversion nanoparticles and the extremely low background signals of anti-Stokes luminescence, the two targets are well-identified and simultaneously detected with quite sound sensitivity and specificity. Moreover, the potential on-demand clinical application is presented by employing this approach to respond the targets toward complex matrices such as serum and tissue samples, offering a new alternative for cancer diagnosis technology.

The radiotherapy-sensitization effect of cantharidin: Mechanisms involving cell cycle regulation, enhanced DNA damage, and inhibited DNA damage repair.

BACKGROUND: Cantharidin is an inhibitor of protein phosphatase 2 A (PP2A), and has been frequently used in clinical practice. In our previous study, we proved that cantharidin could arrest cell cycle in G2/M phase. Since cells at G2/M phase are sensitive to radiotherapy, in the present study, we investigated the radiotherapy-sesitization effect of cantharidin and the potential mechanisms involved. METHODS: Cell growth was determined by MTT assay. Cell cycle was evaluated by flow cytometry. DNA damage was visualized by phospho-Histone H2A.X staining. Expression of mRNA was tested by microarray assay and real-time PCR. Clinical information and RNA-Seq expression data were derived from The Cancer Genome Atlas (TCGA) pancreatic cancer cohort. Survival analysis was obtained by Kaplan-Meier estimates. RESULTS: Cantharidin strengthened the growth inhibition effect of irradiation. Cantharidin drove pancreatic cancer cells out of quiescent G0/G1 phase and arrested cell cycle in G2/M phase. As a result, cantharidin strengthened DNA damage which was induced by irradiation. Moreover, cantharidin repressed expressions of several genes participating in DNA damage repair, including UBE2T, RPA1, GTF2HH5, LIG1, POLD3, RMI2, XRCC1, PRKDC, FANC1, FAAP100, RAD50, RAD51D, RAD51B and DMC1, through JNK, ERK, PKC, p38 and/or NF-κB pathway dependent manners. Among these genes, worse overall survival for pancreatic cancer patients were associated with high mRNA expressions of POLD3, RMI2, PRKDC, FANC1, RAD50 and RAD51B, all of which could be down-regulated by cantharidin. CONCLUSION: Cantharidin can sensitize pancreatic cancer cells to radiotherapy. Multiple mechanisms, including cell cycle regulation, enhanced DNA damage, and inhibited DNA damage repair, may be involved.

High-throughput sequencing and degradome analysis reveal altered expression of miRNAs and their targets in a male-sterile cybrid pummelo (Citrus grandis).

BACKGROUND: G1 + HBP is a male sterile cybrid line with nuclear genome from Hirado Buntan pummelo (C. grandis Osbeck) (HBP) and mitochondrial genome from "Guoqing No.1" (G1, Satsuma mandarin), which provides a good opportunity to study male sterility and nuclear-cytoplasmic cross talk in citrus. High-throughput sRNA and degradome sequencing were applied to identify miRNAs and their targets in G1 + HBP and its fertile type HBP during reproductive development. RESULTS: A total of 184 known miRNAs, 22 novel miRNAs and 86 target genes were identified. Some of the targets are transcription factors involved in floral development, such as auxin response factors (ARFs), SQUAMOSA promoter binding protein box (SBP-box), MYB, basic region-leucine zipper (bZIP), APETALA2 (AP2) and transport inhibitor response 1 (TIR1). Eight target genes were confirmed to be sliced by corresponding miRNAs using 5' RACE technology. Based on the sequencing abundance, 42 differentially expressed miRNAs between sterile line G1 + HBP and fertile line HBP were identified. Differential expression of miRNAs and their target genes between two lines was validated by quantitative RT-PCR, and reciprocal expression patterns between some miRNAs and their targets were demonstrated. The regulatory mechanism of miR167a was investigated by yeast one-hybrid and dual-luciferase assays that one dehydrate responsive element binding (DREB) transcription factor binds to miR167a promoter and transcriptionally repress miR167 expression. CONCLUSION: Our study reveals the altered expression of miRNAs and their target genes in a male sterile line of pummelo and highlights that miRNA regulatory network may be involved in floral bud development and cytoplasmic male sterility in citrus.

Electroacupuncture Relieves Nerve Injury-Induced Pain Hypersensitivity via the Inhibition of Spinal P2X7 Receptor-Positive Microglia.

BACKGROUND: Electroacupuncture (EA) has therapeutic effects on neuropathic pain induced by nerve injury; however, the underlying mechanisms remain unclear. In this study, we examined whether EA treatment relieves pain hypersensitivity via the down-regulation of spinal P2X7 receptor-positive (P2X7R⁺) microglia-mediated overexpression of interleukin (IL)-1ß and/or IL-18. METHODS: Male Sprague-Dawley rats underwent chronic constriction injury (CCI) or 3'-O-(4-benzoylbenzoyl) adenosine 5'-triphosphate (BzATP) intrathecal injection. Von Frey and Hargreaves tests were performed to evaluate the effect of EA on pain hypersensitivity. The spinal P2X7R, IL-1ß, and IL-18 expression levels were determined by real-time polymerase chain reaction, Western blot analysis, immunofluorescence staining, and enzyme-linked immunosorbent assay. The selective P2X7R antagonist A-438079 was used to examine the P2X7R⁺ microglia-dependent release of IL-1ß and IL-18. Primary cultures were subsequently used to assess the P2X7R⁺ microglia-induced IL-1ß and IL-18 release. RESULTS: EA treatment significantly improved the pain thresholds and inhibited spinal P2X7R⁺ microglia activation induced by CCI or BzATP administration, which was accompanied by the suppression of spinal IL-1ß and IL-18 overexpression. Moreover, A-438079 also improved pain thresholds and suppressed overexpression of IL-1ß in the CCI- and BzATP-injected rats. The analysis of cultured microglia further demonstrated that A-438079 markedly decreased BzATP-induced IL-1ß release. CONCLUSIONS: EA treatment relieves nerve injury-induced tactile allodynia and thermal hyperalgesia via the inhibition of P2X7R⁺ microglia-mediated IL-1ß overexpression.

Protein profiles of cardiomyocyte differentiation in murine embryonic stem cells exposed to perfluorooctane sulfonate.

Perfluorooctane sulfonate (PFOS) is a persistent organic contaminant that may affect diverse systems in animals and humans, including the cardiovascular system. However, little is known about the mechanism by which it affects the biological systems. Herein, we used embryonic stem cell test procedure as a tool to assess the developmental cardiotoxicity of PFOS. The differentially expressed proteins were identified by quantitative proteomics that combines the stable isotope labeling of amino acids with high-performance liquid chromatography-electrospray ionization tandem mass spectrometry. Results of the embryonic stem cell test procedure suggested that PFOS was a weak embryotoxic chemical. Nevertheless, a few marker proteins related to cardiovascular development (Brachyury, GATA4, MEF2C, α-actinin) were significantly reduced by exposure to PFOS. In total, 176 differential proteins were identified by proteomics analysis, of which 67 were upregulated and 109 were downregulated. Gene ontology annotation classified these proteins into 13 groups by molecular functions, 12 groups by cellular locations and 10 groups by biological processes. Most proteins were mainly relevant to either catalytic activity (25.6%), nucleus localization (28.9%) or to cellular component organization (19.8%). Pathway analysis revealed that 32 signaling pathways were affected, particularly these involved in metabolism. Changes in five proteins, including L-threonine dehydrogenase, X-ray repair cross-complementing 5, superoxide dismutase 2, and DNA methyltransferase 3b and 3a were confirmed by Western blotting, suggesting the reliability of the technique. These results revealed potential new targets of PFOS on the developmental cardiovascular system.

[Optimization on Preparation of Total Saponins of Aralia taibaiensis Phospholipid Complex by Central Composite Design-Response Surface Method].

Objective: To optimize the preparation of total saponins of Aralia taibaiensis phospholipid complex( TSAT-PC) by the central composite design-response surface method. Methods: Total saponins of Aralia taibaiensis phospholipid complex was prepared by using solvent evaporation method, five factors including reaction solvent, reaction time, reaction temperature, ratio of reactants on this reaction, and the concentration of the drug were investigated, then to optimize the preparation of TSAT-PC by the central composite design response surface method, and to study its physicochemical properties. Results: The optimal process conditions were as follows, the reaction time was 1 h, the reaction temperature was 45 ℃,the ratio of soya lecithine ( SL) and TSAT was 3∶ 1, the reaction concentration was16 mg / m L, the complexing rate was 97. 23%,it was less than 5% with the predicted deviation; IR analysis proved the formation of TSAT-PC, and the solubility in the octyl alcohol was higher than the original drug. Conclusion: TSAT-PC was successfully developed by the optimized process, enhance the solubility in octyl alcohol, which provide the reference for the further development and utilization of Chinese materia medica preparation.

Laparoscopic versus open colorectal surgery within enhanced recovery after surgery programs: a systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Laparoscopic surgery and enhanced recovery after surgery (ERAS) programs were two major improvements for the management of colorectal diseases. The purpose of this systemic review was to examine whether laparoscopic colorectal surgery still improved short-term postoperative outcomes in comparison with open surgery when both groups of patients received ERAS programs. METHODS: PubMed, Embase, the Cochrane Central Register of Controlled Trials, and reference lists of the identified studies were searched to identify randomized clinical trials that compared laparoscopic with open surgery in patients undergoing colorectal resection in the context of ERAS programs. The outcome measures were analyzed, and the quality of evidence for each outcome was assessed using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system. RESULTS: Five randomized clinical trials encompassing 598 patients were included in the final analysis. Two of them were multicenter trials. The ERAS programs implemented in the five included trials cannot be classified as optimal ERAS programs, but suboptimal ERAS programs. Laparoscopic colorectal surgery significantly reduced total hospital stay (weighted mean difference (WMD) -1.92 days; 95 % confidence interval (CI) -2.61--1.23 days; P < 0.00001) and number of complications (relative risk (RR) 0.78; 95 % CI 0.66-0.94; P = 0.007) compared with open surgery in the setting of ERAS programs. No significant differences were found between groups for primary hospital stay, number of patients with complications, readmission rates, and mortality. The quality of evidence for all outcomes was low-to-moderate on the GRADE scale, and none had high quality. CONCLUSIONS: Laparoscopic colorectal resection significantly reduced total hospital stay and number of complications when compared with open surgery in the setting of suboptimal ERAS programs, but the benefits of laparoscopic colorectal resection remain to be proved within optimal ERAS programs.

iTRAQ-based quantitative proteomics analysis revealed alterations of carbohydrate metabolism pathways and mitochondrial proteins in a male sterile cybrid pummelo.

Comprehensive and quantitative proteomic information on citrus floral bud is significant for understanding male sterility of the cybrid pummelo (G1+HBP) with nuclear genome of HBP and foreign mitochondrial genome of G1. Scanning electron microscopy and transmission electron microscopy analyses of the anthers showed that the development of pollen wall in G1+HBP was severely defective with a lack of exine and sporopollenin formation. Proteomic analysis was used to identify the differentially expressed proteins between male sterile G1+HBP and fertile type (HBP) with the aim to clarify their potential roles in anther development and male sterility. On the basis of iTRAQ quantitative proteomics, we identified 2235 high-confidence protein groups, 666 of which showed differentially expressed profiles in one or more stages. Proteins up- or down-regulated in G1+HBP were mainly involved in carbohydrate and energy metabolism (e.g., pyruvate dehydrogenase, isocitrate dehydrogenase, ATP synthase, and malate dehydrogenase), nucleotide binding (RNA-binding proteins), protein synthesis and degradation (e.g., ribosome proteins and proteasome subunits). Additionally, the proteins located in mitochondria also showed changed expression patterns. These findings provide a valuable inventory of proteins involved in floral bud development and contribute to elucidate the mechanism of cytoplasmic male sterility in the cybrid pummelo.

Streptomyces lopnurensis sp. nov., an actinomycete isolated from soil.

A novel actinomycete, designated strain TRM 49590(T), was isolated from a soil sample from Lop Nur in Xinjiang Province, China. Strain TRM 49590(T) was aerobic, Gram-staining-positive, with an optimum NaCl concentration for growth of 1.5 % (w/v) and an optimum temperature for growth of 28-37 °C. The aerial mycelium was sparse, cylindrical and smooth-surfaced with irregular branches on ISP medium 4. The whole-cell sugars of strain TRM 49590(T) were ribose and glucose. The diagnostic diamino acid contained ll-diaminopimelic acid. The predominant menaquinones were MK-9(H6) and MK-9(H8), with MK-9(H4) and MK-10(H6) present in smaller amounts. The major fatty acids were iso-C16 : 0, anteiso-C15 : 0 and anteiso-C17 : 0. The G+C content of the genomic DNA was 62.2 mol%. The major polar lipids were diphosphatidylglycerol, phosphatidylethanolamine, phosphatidylcholine, phosphatidylinositol and phosphatidylinositol mannoside. Phylogenetic analysis based on 16S rRNA gene sequences showed that strain TRM 49590(T) belongs to the genus Streptomyces with a sequence similarity of 97.16 % with the most closely related species Streptomyces sodiiphilus. Based on these observations, strain TRM 49590(T) is proposed to represent a novel species of the genus Streptomyces for which the name Streptomyces lopnurensis sp. nov. is suggested. The type strain is TRM 49590(T) ( = CCTCC AA 2013018(T) = NRRL B59109(T)).

mGluR5 stimulating Homer-PIKE formation initiates icariin induced cardiomyogenesis of mouse embryonic stem cells by activating reactive oxygen species.

Icariin (ICA) has been reported to facilitate cardiac differentiation of mouse embryonic stem (ES) cells; however, the mechanism by which ICA induced cardiomyogenesis has not been fully elucidated yet. Here, an underlying signaling network including metabotropic glutamate receptor 5 (mGluR5), Homer, phosphatidylinositol 3-Kinase Enhancer (PIKE), phosphatidylinositol 3-Kinase (PI3K), reactive oxygen species (ROS) and nuclear factor-kappaB (NF-κB) was investigated in ICA induced cardiomyogenesis. Our results showed that the co-expression of mGluR5 together with α-actinin or Troponin T in embryoid bodies (EBs) treated with ICA was elevated to 10.86% and 9.62%, compared with the case in the control (4.04% and 3.45%, respectively). Exposure of EBs to ICA for 2 h remarkably increased the dimeric form of mGluR5, which was inhibited by small interfering RNA targeting mGluR5 (si-mGluR5). Moreover, the extracellular glutamate concentration in ICA treatment medium was elevated to 28.9±3.5 µM. Furthermore, the activation of mGluR5 by ICA triggered the formation of Homer-PIKE complex and activated PI3K, stimulating ROS generation and NF-κB nuclear translocation. Knockdown of mGluR5 or inhibition of PI3K by LY294002 blocked ICA induced cardiomyogenesis via repressing mGluR5 pathway, reducing ROS and NF-κB activation. These results revealed that the inducible mechanisms of ICA were related to activate mGluR5 pathway.

Telekin suppresses human hepatocellular carcinoma cells in vitro by inducing G2/M phase arrest via the p38 MAPK signaling pathway.

AIM: Telekin, isolated from the Chinese herb Carpesium divaricatum, has shown anti-proliferation effects against various cancer cells, including hepatocellular carcinoma cells. In this study, we investigated the anti-proliferation mechanisms of telekin in human hepatocellular carcinoma HepG2 cells in vitro. METHODS: HepG2 cells were treated with telekin. Cell viability was evaluated using MTT assay. Flow cytometry was used to measure cell cycle profiles, ROS level and apoptosis. The protein expression levels were analyzed with Western blotting. RESULTS: Telekin (3.75-30 µmol/L) dose-dependently inhibited the viability of HepG2 cells and induced l apoptosis. Furthermore, the treatment induced cell cycle arrest at G2/M phase, accompanied by significantly increased the phosphorylation of Cdc25A and Cdc2, and decreased Cyclin B1 level. Moreover, the treatment significantly stimulated ROS production, and increased the phosphorylation of p38 and MAPKAPK-2 in the cells. Pretreatment with the antioxidant NAC (2.5, 5, and 10 mmol/L), or the p38 MAPK inhibitor SB203580 (2.5 and 5 µmol/L) dose-dependently attenuated these telekin-induced effects in the cells. CONCLUSION: Telekin suppresses hepatocellular carcinoma cells in vitro by inducing G2/M phase arrest via activating the p38 MAPK pathway.