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Fermented bamboo shoots (FBS) is a region-specific food widely consumed in Southwestern China, with Lactobacillusas the predominant fermenting bacteria. However, the probiotic potential of Lactobacillusderived from FBS reminds largely unexplored, especially for diseases with a low prevalence in areas consuming FBS, namely, inflammatory bowel disease. In this study, Lactiplantibacillus pentosusYQ001 and Lentilactobacillus seniorisYQ005 were screening by in vitroprobiotic tests to further investigate the probiotic-like bioactivity in dextran sulfate sodium (DSS)-induced ulcerative colitis (UC) mouse. They exhibited more positive probiotic effects than Lactobacillus rhamnosusGG in preventing intestinal inflammatory response. The results revealed that both strains improved the abundance of deficient intestinal microbiota in UC mice, including Muribaculaceae and Akkermansia. In the serum metabolome, they modulated the DSS-disturbed levels of metabolites, with significant increment of cinnamic acid. Meanwhile, they reduced the expression levels of interleukin-1β (IL-1β), interleukin-6 (IL-6) inflammatory factors and increased zonula occludens-1 (ZO-1), Occludin, and cathelicidin-related antimicrobial peptide (CRAMP) in the colon. Consequently, these results demonstrated that Lactobacillusspp. isolates derived from FBS showed promising probiotic activity based on the gut microbiome homeostasis modulation, anti-inflammation and intestinal barrier protection in UC mice.

With the advancement of bioinformatics, the integration of genome mining with efficient separation technology enables the discovery of a greater number of novel bioactive compounds. The deletion of the key gene responsible for triterpene cyclase biosynthesis in the polar strain Eutypellasp. D-1 instigated metabolic shunting, resulting in the activation of dormant genes and the subsequent production of detectable, new compounds. Fifteen sesquiterpenes were isolated from the mutant strain, with eight being new compounds. The structural elucidation of these compounds was obtained through a combination of HRESIMS, NMR spectroscopy, and ECD calculations, revealing six distinct skeleton types. Compound 7possessed a unique skeleton of 5/10 macrocyclic ether structure. Based on the gene functions and newly acquired secondary metabolites, the metabolic shunting pathway in the mutant strain was inferred. Compounds 6, 8, 11, 14, and 15exhibited anti-inflammatory effects without cytotoxicity through the release of nitric oxide from lipopolysaccharide-stimulated RAW264.7 cells. Notably, acorane-type sesquiterpene 8inhibited nitric oxide production and modulated the MAPK and NLRP3/caspase-1 signaling pathways. Compound 8also alleviated the CuSO4-induced systemic neurological inflammation symptoms in a transgenic fluorescent zebrafish model.

Abstract: Vitamin D3(VD3) is the main form of vitamin D and an essential nutrient for maintaining human life. Currently, traditional methods for detecting 25-hydroxyvitamin D3(25(OH)D3) are complex and expensive. In this study, we constructed an accurate, sensitive, simple, and cost-effective label-free biosensor based on an aptamer for the detection of 25(OH)D3. The aptamer-modified sulfhydryl adopted self-assembly as a way to stably immobilize at the glassy carbon electrode (GCE) surface modified by gold nanoparticles (AuNPs). Upon 25(OH)D3binding to the aptamer, the complexes inhibit electron transfer at the electrode surface, leading to reduced [Fe(CN)6]3−/4−redox peak current. Consequently, the quantity of 25(OH)D3that interacts with the electrode-bound aptamer correlates with the observed electric current response values. The Aptamer/AuNPs/GCE aptasensor achieved direct and highly sensitive detection of 25(OH)D3over a wide concentration range (1.0–1000 nM), with a limit of detection of 1.0 nM. At the same time, other molecules with a similar structure, such as 25(OH)D2, Vitamin D3, and Vitamin D2, had lower response interference than 25(OH)D3. Therefore, this biosensor has great potential to become a portable diagnostic device for 25(OH)D3. Graphic abstract:

Presently, piezoelectric materials are gradually playing a significant role within composites to improve the damping and vibrational attenuation capacities of host composites. Previous studies paid attention to isolating the mechanical damping contribution and piezoelectric contribution of polymer-based piezoelectric composites (PPCs). However, reports detailing the piezoelectric damping of such materials have not paid sufficient attention to the technologies and methods to improve the piezoelectric damping of PPCs. In this study, we propose novel damping polyurethane (PU)-based piezoelectric composites with carbon-coated piezoelectric fillers (PZT@C/PU) with improved piezoelectric damping ability. The mechanical damping and piezoelectric damping of composites were theoretically decoupled, and we elaborate on the mechanism enhancing piezoelectric damping through the carbon coating strategy by comparing with the composites with nonpiezoelectric fillers. The as-fabricated core–shell structure having an optimized interface exhibits the proposed PZT@C/PU composite pads with relatively prominent damping ability (loss factor tan δmax= 1.0, tan δRT= 0.3), ductility (400.63%), and sound isolating behavior (transmission loss TL > 23 dB). Moreover, the vibration test results of as-fabricated sandwich structural PZT@C/PU composite damping devices exhibit outstanding vibration attenuating behavior (damping ratio ζ = 0.198). The study herein validates that the carbon shell coated on piezoelectric fillers would effectively increase damping performance of PU-based piezoelectric composites by the enhancement of piezoelectric performance caused by carbon coating piezoelectric fillers, which indicates that this material has potential for future applications in the field of vibration and noise reduction, thereby driving forward and expanding the fundamental understanding in the area of PPCs damping and vibration attenuation.

Cyclosporine A (CsA) is an immunosuppressive drug that is widely used in clinical practice. Due to its narrow therapeutic window and the significant differences between individuals, the therapeutic drug monitoring (TDM) of CsA is required to ensure patient safety. In this study, we screened a novel aptamer, named CsA7, which could specifically recognize CsA, and developed a AuNPs colorimetric aptasensor for the rapid detection of CsA. In the SELEX process, after eight rounds of screening, four aptamer candidate sequences were obtained and subjected to binding affinity and specificity tests. Finally, the CsA7 aptamer (Kd= 41.21 ng mL−1) showed the highest affinity for CsA. Based on CsA7, we also developed a AuNPs colorimetric aptasensor, which had a detection limit of 0.1 ng mL−1and a quantitative range of 0.1–500 ng mL−1and showed good selectivity among CsA and its analogs. According to the results, the CsA7 aptamer provides an alternative recognition molecule to the antibody in biosensor applications and shows great potential for the rapid and convenient detection of CsA.

Testosterone is a steroid hormone that plays an indispensable role in the normal metabolism of organisms. However, exogenous testosterone, even as low as nmol L−1, will harm the human body due to accumulation. In this study, we developed an unlabeled fluorescent sensor for testosterone based on SYBR Green I. SYBR Green I is a fluorescent dye that can be embedded into the G-quadruplex of the testosterone aptamer T5. The fluorescence quenching effect is utilized to achieve quantitative detection, which occurs by the competition between testosterone and SYBR Green I for the T5 aptamer binding sites. In this work, we optimized the detection conditions to make the fluorescent sensor more sensitive and verify the specificity, linear range, and detection ability in the buffer and real water samples. The sensor's LOD and LOQ values were 0.27 nmol L−1and 0.91 nmol L−1, respectively, while the detection range was linear from 0.91 nmol L−1to 2000 nmol L−1. According to the results, the sensor shows high specificity and good performance even in real sample detection such as tap water and river water, providing an alternative method for the quantitative detection of testosterone in the environment, which is more convenient and efficient.

Objectives:Temporal tenosynovial giant cell tumors (TGCTs) are often large and have invaded the middle skull base. It is difficult to protect the important neurovascular structures around the tumor and perform functional reconstruction on the basis of complete tumor resection. This study aimed at analyzing the surgical techniques and functional reconstruction during the operation of complex TGCT of temporal bone and middle skull base. Methods:Five patients with pathologically confirmed TGCT of different complex types in the temporal bone and middle skull base were treated in our hospital from December 2020 to February 2023. We collected and retrospectively analyzed their medical records, including medical imaging, surgical procedures, and follow-up data. Results:The tumors invaded beyond the temporal bone and destroyed the middle skull base in all cases, involving the intracranial space and other important neurovascular structures. The internal carotid artery, infratemporal fossa, pterygopalatine fossa, and parapharyngeal space were also involved in 1 case. All the patients’ tumors were completely removed, and the operations were performed mainly via modified infratemporal fossa approach, or combined with expanded middle cranial fossa approach. All cases with temporal and skull base destruction were repaired using the temporalis muscle flap with no occurrence of intracranial complications. The dura mater, condyle of temporomandibular joint, facial nerve, and internal carotid artery were fully preserved. Normal maxillofacial morphology was also preserved. The air conductive hearing of 2 patients was preserved. Conclusions:We found and summarized some surgical techniques that can help safeguard the important structures around massive TGCTs of temporal bone and middle skull base, and reconstruct the defects after tumor resection. The techniques are effective and feasible.

Objectives:To study the feasibility of reserving the endolymphatic sac in the cerebellopontine angle (CPA) and the fundus of the internal auditory canal (IAC) by the retrolabyrinthine approach. Design:Single-center retrospective study. Methods:Through 3-dimensional preoperative computed tomography reconstruction, vestibular schwannoma (VS) resection was performed using a retrolabyrinthine approach with preservation of the endolymphatic sac in selected patients, and hearing and facial nerve functions were followed to assess the feasibility of this operation and the effectiveness of function preservation. Results:VS was completely removed in all cases and the postoperative detectable hearing retention rate (AAO-HNS hearing rating grade A, B, and C) was 80% (4/5). Postoperative facial nerve function was well preserved (HB grade I), no leakage of cerebrospinal fluid or other cranial complications was observed in all patients, and no recurrence was observed during follow-up. Conclusions:With less trauma and a promising route for hearing preservation and facial nerve functions, the retrolabyrinthine approach is a potential choice for the treatment of VS located in the IAC-CPA.

Actinomycetes is an abundant resource for discovering a large number of lead compounds, which play an important role in microbial drug discovery. Compared to terrestrial microorganisms, marine actinomycetes have unique metabolic pathways because of their special living environment, which has the potential to produce a variety of bioactive substances. In this paper, secondary metabolites isolated from marine actinomycetes are reviewed (2013-2018), most of which exhibited cytotoxic, antibacterial, and antiviral biological activities.

Objective:The aim of this study was to investigate the methylenetetrahydrofolate reductase (MTHFR) gene rs1801133 C>T polymorphisms and lung cancer susceptibility by pooling openly published data.

Siloxane coatings for surfaces are essential in many scientific and industrial applications. We describe a straightforward gas-phase evaporation technique in inert atmosphere and introduce a practical and reliable silanization protocol adaptable to different silane types. The primary aim of depositing ultrathin siloxane films on surfaces is to enable a reproducible and homogenous surface functionalization without agglomeration effects during the layer formation. To realize high-quality and large-area coatings, it is fundamental to understand the reaction conditions of the silanes, the process of the siloxane layer formation, and the possible influence of the substrate morphology. We used three typical silane types to exemplify the potential and versatility of our process: aminopropyltriethoxysilane, glycidoxypropyltrimethoxysilane, and 1H,1H,2H,2H-perfluorooctyl-trichlorosilane. The ultrathin siloxane layers, which are generally difficult to characterize, were precisely investigated with high-resolution surface-characterization methods to verify our concept in terms of reproducibility and coating quality. Our results show that this gas-phase evaporation protocol is easily adaptable to all three, widely used silane types also enabling a large-area upscale.

The Notch signaling pathway regulates stem cell proliferation and differentiation in multiple tissues and organs, and is required for tissue maintenance. However, the role of Notch in regulation of olfactory epithelium (OE) progenitor/stem cells to maintain tissue function is still not clear. A recent study reported that leucine‐rich repeat‐containing G‐protein‐coupled receptor 5 (Lgr5) is expressed in globose basal cells (GBCs) localized in OE. Through lineage tracing in vivo, we found that Lgr5+cells act as progenitor/stem cells in OE. The generation of daughter cells from Lgr5+progenitor/stem cells is delicately regulated by the Notch signaling pathway, which not only controls the proliferation of Lgr5+cells and their immediate progenies but also affects their subsequent terminal differentiation. In conditionally cultured OE organoids in vitro, inhibition of Notch signaling promotes neuronal differentiation. Besides, OE lesion through methimazole administration in mice induces generation of more Notch1+cells in the horizontal basal cell (HBC) layer, and organoids derived from lesioned OE possesses more proliferative Notch1+HBCs. In summary, we concluded that Notchsignaling regulates Lgr5+GBCs by controlling cellular proliferation and differentiation as well as maintaining epithelial cell homeostasis in normal OE. Meanwhile, Notch1also marks HBCs in lesioned OE and Notch1+HBCs are transiently present in OE after injury. This implies that Notch1+cells in OE may have dual roles, functioning as GBCs in early development of OE and HBCs in restoring the lesioned OE. StemCells2018;36:1259–1272 Notch signaling regulates proliferation and differentiation of Lgr5+olfactory epithelium basal cells. (A):Notch1 marks Lgr5+ basal cells in olfactory epithelium (OE). (B):Notch activation in vivo enhances proliferation. (C):Notch activation keeps more cells at progenitor and immature state as well as induces generation of more supporting cells and less mature sensory neurons. (D, E):Notch inhibition by DAPT treatment promotes generation of Tuj1+ neuronal cells and decreases the number of p63+ cells in OE organoids compared with that in DMSO control. (F, G):DAPT treatment decreases ratio of Ki67+ proliferative cells and increases OMP+ mature sensory neurons in OE organoids. (H, I):Lesion leads to more Notch1+ICAM1+ horizontal basal cells in OE. (J):OE organoids express Lgr5‐mRNA. (K):Organoids from lesioned epithelium contains more Notch1+ cells. (L):More Notch1+ICAM+Ki67+ proliferative horizontal basal cells are generated in organoids from lesioned epithelium.

Prediction of app usage and location of smartphone users is an interesting problem and active area of research. Several smartphone sensors such as GPS, accelerometer, gyroscope, microphone, camera and Bluetooth make it easier to capture user behavior data and use it for appropriate analysis. However, differences in user behavior and increasing number of apps have made such prediction a challenging problem. In this article, a prediction approach that takes smartphone user behavior into consideration is proposed. The proposed approach is illustrated using data from over 30000 users from a leading IT company in China by first converting data in to recency, frequency, and monetary variables and then performing cluster analysis to capture user behavior. Prediction models are then developed for each cluster using a training dataset and their performance is assessed using a test dataset. The study involves ten different categories of apps and four different regions in Beijing. The proposed app usage prediction and next location prediction approach has provided interesting results.

The purpose of this study was to evaluate the utility of EBUS-TNA for mediastinal mass or suspected lung cancer patients with mediastinal or hilar lymph node enlarged. Further to investigate the clinical value of EBUS-TBNA combining with immunohistochemistry and genotype in lung cancer.

MicroRNAs (miRNAs) are a class of short noncoding RNA that play important regulatory roles in living organisms. These RNA molecules are implicated in the development and progression of malignant diseases such as cancer and are closely associated with cell aging. Findings demonstrating that microRNA is associated with aging in macrophages have nevertheless rarely been reported. This study’s objective was to investigate if miRNA-34 is linked to aging process of macrophages. We built a cell aging model in mouse RAW264.7 macrophages using d-galactose and determined the expression levels of miRNA-34a, miRNA-34b, and miRNA-34c in aging and normal macrophages by fluorescence quantitative polymerase chain reaction (q-PCR). We predicted a target gene of miRNA-34 using biological information techniques and constructed the recombinant plasmid pGL3-E2f3 for the putative target gene E2f3. The expression level of miRNA-34b was 5.23 times higher in aging macrophages than in normal macrophages. The luciferase activity decreased by nearly 50 % in cells transfected with miRNA-34b mimics, while no significant decrease in luciferase activity was noted in cells transfected with the miRNA-34b inhibitor or unrelated sequences. Our findings provide the groundwork for further research into the molecular mechanisms whereby miRNA-34b regulates the aging of macrophages. miRNA-34b is associated with the aging of RAW264.7 macrophages, and E2f3 is a target gene of miRNA-34b.

Objective To evaluate the performance of GeneXpert MTB/RIF in diagnosing pulmonary tuberculosis (TB) in China.Methods This cross-sectional study included sputum specimens of 240 suspected TB cases. Specimens were examined by light microscopy for the presence of acid-fast bacilli, which were cultured by the BACTEC MGIT 960 (M960) system and detected by the GeneXpert MTB/RIF assay. The positive rate, sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and average turnaround time of methods were evaluated.Results The positive rate was 36.6% (87/238) for the GeneXpert MTB/RIF assay and 34.0% (81/238) by M960 culture, with no significant difference between methods (χ2 = 0.33, p > 0.05). According to culture results, sensitivity of the GeneXpert MTB/RIF assay was 84.0% (68/81), specificity was 87.8% (129/147), the PPV was 78.2% (68/87), and the NPV was 87.2% (129/148). The agreement for results between Gene Xpert MTB/RIF and the M960 system was 82.8% and the Kappa value was 0.73.Conclusion The GeneXpert MTB/RIF assay is a simple, rapid, and accurate test for detecting Mycobacterium tuberculosisin sputum specimens.

A phage display library of variable domain of the heavy chain only antibody or nanobody (Nb) was constructed after immunizing a bactrian camel with testosterone. With the smaller molecular size (15 kDa), improved solubility, good stability, high affinity, specificity, and lower immunogenicity, Nbs are a promising tool in the next generation of diagnosis and medical applications. Testosterone is a reproductive hormone, playing an important role in normal cardiac function and being the highly predictive marker for many diseases. Herein, a simple and sensitive immunosensor based on electrochemical impedance spectroscopy (EIS) and Nbs was successfully developed for the determination of testosterone. We successfully isolated the antitestosterone Nbs from an immune phage display library. Moreover, one of the Nbs was biotinylated according to in vivo BirA system, which showed the highest production yield and the most stable case. Further, the EIS immunosensor was set up for testosterone detection by applying the biotinylated antitestosterone Nb. As a result, the biosensor exhibited a linear working range from 0.05 to 5 ng mL–1with a detection limit of 0.045 ng mL–1. In addition, the proposed immunosensor was successfully applied in determining testosterone in serum samples. In conclusion, the proposed immunosensor revealed high specificity of testosterone detection and showed as a potential approach for sensitive and accurate diagnosis of testosterone.

In the present work, a sensitive electrochemical aptasensor was designed for the detection of adenosine triphosphate (ATP) with hemin/graphene oxide nanosheets (HGNs). Firstly, the ATP aptamer was self-assembled on gold electrode surface, and then HGNs were captured to the modified electrode by π-π stacking. The captured HGNs could catalyze the disproportionation reaction of H2O2, and produced a detectable electrochemical signal by chronoamperometry. ATP was competitively bound to aptamer which led to the release of HGNs from the electrode surface after adding ATP. The decrease of the electrochemical signal, which was calculated by the difference of amperometric responses before and after incubation of ATP, provided a quantitative signal for ATP detection. A linear correlation was achieved between the difference of the amperometric responses and the logarithmic concentration of ATP ranging from 0.5 to 100 nM with a detection limit of 0.08 nM. Besides, the aptasensor also exhibited good selectivity toward ATP against other analogs.

Recent studies have shown that the phosphorylation and dephosphorylation of ULK1 and ATG13 are related to autophagy activity. Although ATG16L1 is absolutely required for autophagy induction by affecting the formation of autophagosomes, the post-translational modification of ATG16L1 remains elusive. Here, we explored the regulatory mechanism and role of ATG16L1 phosphorylation for autophagy induction in cardiomyocytes. We showed that ATG16L1 was a phosphoprotein, because phosphorylation of ATG16L1 was detected in rat cardiomyocytes during hypoxia/reoxygenation (H/R). We not only demonstrated that CSNK2 (casein kinase 2) phosphorylated ATG16L1, but also identified the highly conserved Ser139 as the critical phosphorylation residue for CSNK2. We further established that ATG16L1 associated with the ATG12-ATG5 complex in a Ser139 phosphorylation-dependent manner. In agreement with this finding, CSNK2 inhibitor disrupted the ATG12-ATG5-ATG16L1 complex. Importantly, phosphorylation of ATG16L1 on Ser139 was responsible for H/R-induced autophagy in cardiomyocytes, which protects cardiomyocytes from apoptosis. Conversely, we determined that wild-type PPP1 (protein phosphatase 1), but not the inactive mutant, associated with ATG16L1 and antagonized CSNK2-mediated phosphorylation of ATG16L1. Interestingly, one RVxF consensus site for PPP1 binding in the C-terminal tail of ATG16L1 was identified; mutation of this site disrupted its association with ATG16L1. Notably, CSNK2 also associated with PPP1, but ATG16L1 depletion impaired the interaction between CSNK2 and PPP1. Collectively, these data identify ATG16L1 as a bona fide physiological CSNK2 and PPP1 substrate, which reveals a novel molecular link from CSNK2 to activation of the autophagy-specific ATG12-ATG5-ATG16L1 complex and autophagy induction.

In lung cancer, antiangiogenic treatment targeting tumor endothelial cells (ECs) provides a survival advantage. To fully elucidate the behavior of ECs in a tumor microenvironment, high-purity (>98%) normal, paratumor-, and tumor-derived CD105+ECs were purified from lung squamous cell carcinoma by incubating cells with anti-CD105 antibody-coated magnetic beads. These cells exhibited typical EC characteristics. Totally, 1765 proteins were identified with high confidence by isobaric stable isotope tags and two-dimensional LC/MS/MS (iTRAQ-2DLC/MS/MS). In particular, 178 and 162 proteins were differentially expressed in paratumor- and tumor-derived ECs, respectively, compared to normal ECs. The up- and down-regulation trends showed good interassay correlation. Using gene ontology, they were classified into genes involved in major reprogramming of cellular metabolic processes, oxidative stress response, redox homeostasis, apoptosis, and platelet degranulation/activation. Moreover, tumor angiogenesis-initiating ECs appeared to acquire distinct properties. For example, cell migration and regulation of smooth muscle cell migration of paratumor-derived ECs were significantly faster than that of normal and tumor-derived ECs. Among them, two migration-associated proteins, neuropilin 1 and platelet-derived growth factor receptor β predominantly expressed in ECs of paratumor from 16 patients with lung squamous cell carcinoma, were identified as potential biomarkers for antiangiogenic therapy.

AbstractOxidation of tertiary amines to tertiary amine N-oxides was achieved in moderate to high yields, by using Fe2O3as catalyst, with molecular oxygen in the presence of isovaleraldehyde under mild conditions.

AbstractOxidation of sulfides to sulfoxides and sulfones was achieved in moderate to high yields with a good selectivity, by using Fe2O3, MnO2, Cu(OH)2and Cu(OAc)2as catalyst, with molecular oxygen in the presence of isovaleraldehyde under mild conditions.

AbstractA novel method for the epoxidation of cyclohexene using molecular oxygen (latm) and aldehyde in the presence of Fe2O3is presented. The yields of epoxide highly increased by using this method.

An efficient, six-step stereocontrolled total synthesis of the antifungal agent strobilurin B is reported and was based on a convergent bi-directional coupling featuring a hetero-bis-1,4-metallated pentadiene system as the linchpin.

Mesenchymal niche cells instruct activity of tissue-resident stem and progenitor cell populations. Epithelial stem cells in hair follicles (HFs) have region-specific activity, which may arise from intrinsic cellular heterogeneity within mesenchymal dermal papilla (DP) cells. Here we show that expression of Hoxcgenes is sufficient to reprogram mesenchymal DP cells and alter the regenerative potential of epithelial stem cells. Hoxcgene expression in adult skin dermis closely correlates with regional HF regeneration patterns. Disrupting the region-specific expression patterns of Hoxcgenes, by either decreasing their epigenetic repression via Bmi1loss or inducing ectopic interactions of the Hoxclocus with an active epigenetic region, leads to precocious HF regeneration. We further show that a single Hoxcgene is sufficient to activate dormant DP niches and promote regional HF regeneration through canonical Wnt signaling. Altogether, these results reveal that Hoxcgenes bestow mesenchymal niches with tissue-level heterogeneity and plasticity.

ABSTRACTLow fusion efficiency and nominal activity of fusion cells (FCs) restrict the clinical application of dendritic cell (DC)/tumor fusion cells. Collagen I (Col I) is an interstitial collagen with a closely-knit structure used to repair damaged cell membranes. This study evaluated whether Col I could improve the fusion efficiency of polyethylene glycol (PEG)-induction and enhance the immunogenicity of fusion vaccine. DC/B16 melanoma and controlled DC/H22 hepatoma cell fusions were induced by PEG with or without Col I. Col I/PEG treatment increased the levels of DC surface molecules and the secretion of lactate, pro- and anti-inflammatory cytokines in fusion cells. Col I/PEG-treated FCs enhanced T-cell proliferation and cytotoxic T lymphocyte activity. The Col I-prepared fusion vaccine obviously suppressed tumor growth and prolonged mice survival time. Thus Col I treatment could significantly improve the efficiency of PEG-induced DC/tumor fusion and enhance the anticancer activity of the fusion vaccine. This novel fusion strategy might promote the clinical application of DC/tumor fusion immunotherapy.

The object of this study was to investigate the effect of the long-term application fertilizer on soil total sulphur and valid sulphur. The results showed that applying fertilizer can improve total sulphur and valid sulphur. In comparison with the low level of nitrogen fertilization treatment, the high one total sulphur and valid sulphur were obviously increased by 29.41% and 19.0%, respectively. Compared with in application of different levels nitrogen and the low level of organic fertilizer, the high level treatment total sulphur and valid sulphur contents were significantly increased by 10.73% and 23.47% than the low one. In application of organic fertilization can also improve total sulphur and valid sulphur The total sulphur and valid sulphur content were higher than organic fertilization only treatment 34.14% and 455.89% in comparison with high levels of organic fertilization mix with nitrogen, phosphorous and potassium fertilization treatment.

BackgroundAnthocyanins have been proven to be beneficial to the eyes. However, information is scarce about the effects of purple sweet potato (Ipomoea batatas, L.) anthocyanin (PSPA), a class of anthocyanins derived from purple sweet potato roots, on visual health.ObjectiveThe aim of this study was to investigate whether PSPA could have influences on the growth characteristics (cellular morphology, survival, and proliferation) of human retinal pigment epithelial (RPE) cells, which perform essential functions for the visual process.MethodsThe RPE cell line D407 was used in the present study. The cytotoxicity of PSPA was assessed by MTT assay. Then, cellular morphology, viability, cell cycle, Ki67expression, and PI3K/MAPK activation of RPE cells treated with PSPA were determined.ResultsPSPA exhibited dose-dependent promotion of RPE cell proliferation at concentrations ranging from 10 to 1,000 µg/ml. RPE cells treated with PSPA demonstrated a predominantly polygonal morphology in a mosaic arrangement, and colony-like cells displayed numerous short apical microvilli and typical ultrastructure. PSPA treatment also resulted in a better platform growing status, statistically higher viability, an increase in the S-phase, and more Ki67+ cells. However, neither pAkt nor pERK were detected in either group.ConclusionsWe found that PSPA maintained high cell viability, boosted DNA synthesis, and preserved a high percentage of continuously cycling cells to promote cell survival and division without changing cell morphology. This paper lays the foundation for further research about the damage-protective activities of PSPA on RPE cells or human vision.

BackgroundL-Arabinose is a non-caloric sugar, which could affect glucose and lipid metabolism and suppress obesity. However, few reports have described the effect of L-arabinose in metabolic syndrome, a combination of medical disorders that increase the risk of diabetes and cardiovascular disease.ObjectiveThis study was conducted to explore the effects of L-arabinose in rats with metabolic syndrome induced by a high-carbohydrate, high-fat (HCHF) diet.MethodsAfter the rat model for metabolic syndrome was successfully established, L-arabinose was administrated by oral gavage for 6 weeks. The biochemical index and histological analysis were measured, and the expression levels of genes related to fatty acid metabolism were analyzed using real-time PCR.ResultsFollowing treatment with L-arabinose, metabolic syndrome rats had an obvious reduction in body weight, systolic blood pressure, diastolic blood pressure, fasting blood glucose, triglycerides, total cholesterol, serum insulin, TNF-α, and leptin. Further study showed that treatment with L-arabinose significantly increased the expression of mRNA for hepatic CPT-1α and PDK4, but the expression of mRNA for hepatic ACCα was reduced.ConclusionsThis work suggests that L-arabinose could lower body weight, Lee's index, and visceral index and improve dyslipidemia, insulin resistance, inflammation, and viscera function, which indicate that it might be a promising candidate for therapies combating metabolic syndrome.

Here, we discuss the intimate relationship that exists between malignant and tumor-associated cells, providing a new strategy for targeted diagnosis and therapy via the screening of single-chain antibodies and aptamers that interact with target cells.

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.

The CUL-4A ubiquitination machinery regulates the stability of HOXA9 by promoting its ubiquinitation and proteasome-dependent degradation. Our previous study showed the perturbation of CUL-4A biosysthesis in 32D cells by RNA-mediated interference increased an accumulation of HOXA9, and impaired G-CSF-induced terminal differentiation to granulocytes. HOXA9 is preferentially expressed in primitive hematopoietic cells and downregulates with differentiation. In this study, a lentiviral vector expressed both CUL-4A shRNA and GFP was constructed and was used to transduce cord blood (CB) CD34+ cells (GFP-shCUL-4A-CD34+ cells). The ability of GFP-shCUL-4A-CD34+ cells to form CFC colonies, to differentiate into myeloid, erythroid, B-lymphoid and T-lymphoid cells in vitro, and to engraft in irradiated NOD/SCID mice was evaluated. Our results showed that knockdown of CUL-4A m-RNA dramatically inhibited hematopoisis both in vivo and in vitro. In the CFC assay, FACS-sorted GFPbright-shCUL-4A-CD34+ cell formed fewer colonies (5%) that were smaller size (<500 cells/colonies) relative to progeny of GFPbright-CD34+ cells. In contrast, FACS-sorted GFPdim-shCUL-4A-CD34+ cells produced only 50% less colonies than the control GFPdim-CD34+ cells. However, GFPdim-shCUL-4A-CD34+ cells had 30% more colonies with <500 cells/colony but 82% less colonies with >500 cells/colony comparing to that of GFPdim-CD34+ cells. After transplanting the GFP-shCUL-4A-CD34+ cells into irradiated NOD/SCID mice for 6 weeks, GFP-shCUL-4A-CD45+ cells decreased more than 80% in the mouse bone marrow. These human GFP-shCUL-4A CD45 + cells were capable of forming GFP+-CFC but with >80% reduction in their potency. No reduction in % of GFP-CD45+ cells and GFP+-CFC was observed in the GFP-CD34+ cells group pre- and post-transplantation. The in vitro culture systems showed that knockdown of CUL-4A mRNA in CB CD34+ cells resulted in the developmental impairment in monocytic, megakaryocytic, erythroid, B lymphoid and T-lymphoid lineages. This impairment is a time- and shCUL-4A dose-dependent process. Further study using cell cycle analysis indicated that transduction of CUL-4A shRNA to HL-60 or CD34+ cells induced apoptosis. Our results, for the first time, demonstrate an essential role of the CUL-4A ubiquitin ligase in maintaining cell survival to ensure proper differentiation of normal human stem and progenitor cells into different hematopoietic lineages both in vivo and in vitro.

The CUL-4A ubiquitination machinery regulates the stability of HOXA9 by promoting its ubiquinitation and proteasome-dependent degradation. Our previous study showed the perturbation of CUL-4A biosysthesis in 32D cells by RNA-mediated interference increased an accumulation of HOXA9, and impaired G-CSF-induced terminal differentiation to granulocytes. HOXA9 is preferentially expressed in primitive hematopoietic cells and downregulates with differentiation. In this study, a lentiviral vector expressed both CUL-4A shRNA and GFP was constructed and was used to transduce cord blood (CB) CD34+cells (GFP-shCUL-4A-CD34+cells). The ability of GFP-shCUL-4A-CD34+cells to form CFC colonies, to differentiate into myeloid, erythroid, B-lymphoid and T-lymphoid cells in vitro,and to engraft in irradiated NOD/SCID mice was evaluated. Our results showed that knockdown of CUL-4A m-RNA dramatically inhibited hematopoisis both in vivoand in vitro. In the CFC assay, FACS-sorted GFPbright-shCUL-4A-CD34+cell formed fewer colonies (5%) that were smaller size (<500 cells/colonies) relative to progeny of GFPbright-CD34+cells. In contrast, FACS-sorted GFPdim-shCUL-4A-CD34+cells produced only 50% less colonies than the control GFPdim-CD34+cells. However, GFPdim-shCUL-4A-CD34+cells had 30% more colonies with <500 cells/colony but 82% less colonies with >500 cells/colony comparing to that of GFPdim-CD34+cells. After transplanting the GFP-shCUL-4A-CD34+cells into irradiated NOD/SCID mice for 6 weeks, GFP-shCUL-4A-CD45+cells decreased more than 80% in the mouse bone marrow. These human GFP-shCUL-4A CD45 +cells were capable of forming GFP+-CFC but with >80% reduction in their potency. No reduction in % of GFP-CD45+cells and GFP+-CFC was observed in the GFP-CD34+cells group pre- and post-transplantation. The in vitroculture systems showed that knockdown of CUL-4A mRNA in CB CD34+cells resulted in the developmental impairment in monocytic, megakaryocytic, erythroid, B lymphoid and T-lymphoid lineages. This impairment is a time- and shCUL-4A dose-dependent process. Further study using cell cycle analysis indicated that transduction of CUL-4A shRNA to HL-60 or CD34+cells induced apoptosis. Our results, for the first time, demonstrate an essential role of the CUL-4A ubiquitin ligase in maintaining cell survival to ensure proper differentiation of normal human stem and progenitor cells into different hematopoietic lineages both in vivoand in vitro.

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