First Total Synthesis of a Naturally Occurring Iodinated 5′-Deoxyxylofuranosyl Marine Nucleoside

4-Amino-7-(5′-deoxy-β-D-xylofuranosyl)-5-iodo-pyrrolo[2,3-d]pyrimidine 1, an unusual naturally occurring marine nucleoside isolated from an ascidan, Diplosoma sp., was synthesized from D-xylose in seven steps with 28% overall yield on 10 g scale. The key step was Vorbrüggen glycosylation of 5-iodo-pyrrolo[2,3-d]pyrimidine with 5-deoxy-1,2-O-diacetyl-3-O-benzoyl-D-xylofuranose. Its absolute configuration was confirmed

Laser solid-phase synthesis of single-atom catalysts

From Springer Nature via Jisc Publications RouterHistory: received 2021-01-22, rev-recd 2021-06-25, registration 2021-07-19, accepted 2021-07-19, pub-electronic 2021-08-18, online 2021-08-18, collection 2021-12Publication status: PublishedAbstract: Single-atom catalysts (SACs) with atomically dispersed catalytic sites have shown outstanding catalytic performance in a variety of reactions. However, the development of facile and high-yield techniques for the fabrication of SACs remains challenging. In this paper, we report a laser-induced solid-phase strategy for the synthesis of Pt SACs on graphene support. Simply by rapid laser scanning/irradiation of a freeze-dried electrochemical graphene oxide (EGO) film loaded with chloroplatinic acid (H2PtCl6), we enabled simultaneous pyrolysis of H2PtCl6 into SACs and reduction/graphitization of EGO into graphene. The rapid freezing of EGO hydrogel film infused with H2PtCl6 solution in liquid nitrogen and the subsequent ice sublimation by freeze-drying were essential to achieve the atomically dispersed Pt. Nanosecond pulsed infrared (IR; 1064 nm) and picosecond pulsed ultraviolet (UV; 355 nm) lasers were used to investigate the effects of laser wavelength and pulse duration on the SACs formation mechanism. The atomically dispersed Pt on graphene support exhibited a small overpotential of −42.3 mV at −10 mA cm−2 for hydrogen evolution reaction and a mass activity tenfold higher than that of the commercial Pt/C catalyst. This method is simple, fast and potentially versatile, and scalable for the mass production of SACs

Cardiac Sca-1+ cells are not intrinsic stem cells for myocardial development, renewal and repair

Background: For over a decade, Sca-1+ cells within the mouse heart have been widely recognized as a stem cell population with multipotency that can give rise to cardiomyocytes, endothelial cells and smooth muscle cells in vitro and after cardiac grafting. However, the developmental origin and authentic nature of these cells remain elusive. Methods: Here, we used a series of high-fidelity genetic mouse models to characterize the identity and regenerative potential of cardiac resident Sca-1+ cells. Results: With these novel genetic mouse models, we found that Sca-1 does not label cardiac precursor cells during early embryonic heart formation. Postnatal cardiac resident Sca-1+ cells are in fact a pure endothelial cell population. They retain endothelial properties and exhibit minimal cardiomyogenic potential during development, normal aging and upon ischemic injury. Conclusions: Our study provides definitive insights into the nature of cardiac resident Sca-1+ cells. The observations challenge the current dogma that cardiac resident Sca-1+ cells are intrinsic stem cells for myocardial development, renewal and repair and suggest that the mechanisms of transplanted Sca-1+ cells in heart repair need to be reassessed

Ankyrin Repeats of ANKRA2 Recognize a PxLPxL Motif on the 3M Syndrome Protein CCDC8

SummaryPeptide motifs are often used for protein-protein interactions. We have recently demonstrated that ankyrin repeats of ANKRA2 and the paralogous bare lymphocyte syndrome transcription factor RFXANK recognize PxLPxL/I motifs shared by megalin, three histone deacetylases, and RFX5. We show here that that CCDC8 is a major partner of ANKRA2 but not RFXANK in cells. The CCDC8 gene is mutated in 3M syndrome, a short-stature disorder with additional facial and skeletal abnormalities. Two other genes mutated in this syndrome encode CUL7 and OBSL1. While CUL7 is a ubiquitin ligase and OBSL1 associates with the cytoskeleton, little is known about CCDC8. Binding and structural analyses reveal that the ankyrin repeats of ANKRA2 recognize a PxLPxL motif at the C-terminal region of CCDC8. The N-terminal part interacts with OBSL1 to form a CUL7 ligase complex. These results link ANKRA2 unexpectedly to 3M syndrome and suggest novel regulatory mechanisms for histone deacetylases and RFX7

Genomic selection analysis of morphological and adaptation traits in Chinese indigenous dog breeds

The significant morphological differences and abundant germplasm resources of Chinese indigenous dog breeds can be attributed to the diverse geographical environment, including plateaus, mountains, and a long history of raising dogs. The combination of both natural and artificial selection during the past several thousand years has led to hundreds of dog breeds with distinct morphological traits and environmental adaptations. China is one of the earliest countries to domesticate dogs and there are more than 50 ancient indigenous dog breeds. In this study, the run of homozygosity (ROH) and proportion of the autosomal genome covered by ROHs (FROH) were calculated for 10 dog breeds that are the most representative Chinese indigenous dogs based on 170K SNP microarray. The results of FROH showed that the Chuandong hound dogs (HCSSC) have the highest level of inbreeding among the tested breeds. The inbreeding in HCSSC occurred more recently than the Liangshan dogs (SCLSQ) dogs because of more numbers of long ROHs in HCSSC dogs, and the former also have higher inbreeding degree. In addition, there are significant differences in the inbreeding degree among different subpopulations of the same breed, such as the Thin dogs from Shaanxi and Shandong province. To explore genome-wide selection signatures among different breeds, including coat color, ear shape, and altitude adaptability, we performed genome selection analyses of FST and cross population extended haplotype homozygosity (XP-EHH). For the coat color, the FST analysis between Xiasi dogs (XSGZ) and HCSSC dogs was performed and identified multiple genes involved in coat color, hair follicle, and bone development, including MC1R, KITLG, SOX5, RSPO2, and TBX15. For the plateau adaptability, we performed FST and XP-EHH analyses between dogs from Tibet (Tibetan Mastiffs and Nyingchi dogs) and plain regions (Guangxi Biwei dogs GXBWQ and Guandong Sharpei dogs). The results showed the EPAS1 gene in dogs from Tibet undergo strong selection. Multiple genes identified for selection signals based on different usage of dogs. Furthermore, the results of ear shape analyses showed that MSRB3 was likely to be the main gene causing the drop ear of domestic dogs. Our study provides new insights into further understanding of Chinese indigenous dogs

CDBA: a novel multi-branch feature fusion model for EEG-based emotion recognition

EEG-based emotion recognition through artificial intelligence is one of the major areas of biomedical and machine learning, which plays a key role in understanding brain activity and developing decision-making systems. However, the traditional EEG-based emotion recognition is a single feature input mode, which cannot obtain multiple feature information, and cannot meet the requirements of intelligent and high real-time brain computer interface. And because the EEG signal is nonlinear, the traditional methods of time domain or frequency domain are not suitable. In this paper, a CNN-DSC-Bi-LSTM-Attention (CDBA) model based on EEG signals for automatic emotion recognition is presented, which contains three feature-extracted channels. The normalized EEG signals are used as an input, the feature of which is extracted by multi-branching and then concatenated, and each channel feature weight is assigned through the attention mechanism layer. Finally, Softmax was used to classify EEG signals. To evaluate the performance of the proposed CDBA model, experiments were performed on SEED and DREAMER datasets, separately. The validation experimental results show that the proposed CDBA model is effective in classifying EEG emotions. For triple-category (positive, neutral and negative) and four-category (happiness, sadness, fear and neutrality), the classification accuracies were respectively 99.44% and 99.99% on SEED datasets. For five classification (Valence 1—Valence 5) on DREAMER datasets, the accuracy is 84.49%. To further verify and evaluate the model accuracy and credibility, the multi-classification experiments based on ten-fold cross-validation were conducted, the elevation indexes of which are all higher than other models. The results show that the multi-branch feature fusion deep learning model based on attention mechanism has strong fitting and generalization ability and can solve nonlinear modeling problems, so it is an effective emotion recognition method. Therefore, it is helpful to the diagnosis and treatment of nervous system diseases, and it is expected to be applied to emotion-based brain computer interface systems

A Two-Year Surveillance of 2009 Pandemic Influenza A (H1N1) in Guangzhou, China: From Pandemic to Seasonal Influenza?

In this two-years surveillance of 2009 pandemic influenza A (H1N1) (pH1N1) in Guangzhou, China, we reported here that the scale and duration of pH1N1 outbreaks, severe disease and fatality rates of pH1N1 patients were significantly lower or shorter in the second epidemic year (May 2010-April 2011) than those in the first epidemic year (May 2009-April 2010) (P<0.05), but similar to those of seasonal influenza (P>0.05). Similar to seasonal influenza, pre-existing chronic pulmonary diseases was a risk factor associated with fatal cases of pH1N1 influenza. Different from seasonal influenza, which occurred in spring/summer seasons annually, pH1N1 influenza mainly occurred in autumn/winter seasons in the first epidemic year, but prolonged to winter/spring season in the second epidemic year. The information suggests a tendency that the epidemics of pH1N1 influenza may probably further shift to spring/summer seasons and become a predominant subtype of seasonal influenza in coming years in Guangzhou, China

Response to Pegylated Interferon Plus Ribavirin in Patients with Hepatitis C Virus Genotype 6a Infection from Guangdong and Guangxi Province of China

Aim. Our aim is to survey the treatment effect of PEG-IFN plus ribavirin in patients infected with HCV genotype 6a in Guangdong and Guangxi province of China and investigate best course of antiviral treatment for patients with HCV-6a infection. Methods. 515 eligible patients received subcutaneous 180 μg PEG-IFNα-2a or 1.5 μg/kg PEG-IFNα-2b once weekly plus oral ribavirin. Primary outcome was SVR by intention-to-treat analysis. Secondary outcome was RVR, cEVR, ETR, and relapse rate. Results. SVR in patients with HCV-6a infection treated for 48 weeks was comparable to that in patients with HCV-2/3 infection (80.9% versus 82.5%, p=0.812) and higher than that in patients with HCV-1b infection (80.9% versus 67.2%, p=0.014). ETR (98.9% versus 90.6%, p=0.016), virological response at month 3 of end-of- treatment (88.8% versus 76.6%, p=0.044), SVR (80.9% versus 65.6%, p=0.032), and virological response at month 12 of end-of-treatment (76.4% versus 60.9%, p=0.04) in patients with HCV-6a infection treated for 48 weeks were higher than those in patients with HCV-6a infection treated for 24 weeks. Conclusion. SVR in patients with HCV-6a treated for 48 weeks was comparable to that in patients with HCV-2/3 infection and higher than that in patients with HCV-1b infection; patients with HCV-6a infection treated for 48 weeks had a superior treatment response than patients treated for 24 weeks

Enhanced Osseointegration of Hierarchically Structured Ti Implant with Electrically Bioactive SnO₂-TiO₂ Bilayered Surface

The poor osseointegration of Ti implant significantly compromise its application in load-bearing bone repair and replacement. Electrically bioactive coating inspirited from heterojunction on Ti implant can benefit osseointegration but cannot avoid the stress shielding effect between bone and implant. To resolve this conflict, hierarchically structured Ti implant with electrically bioactive SnO2–TiO2 bilayered surface has been developed to enhance osseointegration. Benefiting from the electric cue offered by the built-in electrical field of SnO2–TiO2 heterojunction and the topographic cue provided by the hierarchical surface structure to bone regeneration, the osteoblastic function of basic multicellular units around the implant is significantly improved. Because the individual TiO2 or SnO2 coating with uniform surface exhibits no electrical bioactivity, the effects of electric and topographic cues to osseointegration have been decoupled via the analysis of in vivo performance for the placed Ti implant with different surfaces. The developed Ti implant shows significantly improved osseointegration with excellent bone–implant contact, improved mineralization of extracellular matrix, and increased push-out force. These results suggest that the synergistic strategy of combing electrical bioactivity with hierarchical surface structure provides a new platform for developing advanced endosseous implants

IL-17A Synergizes with IFN-γ to Upregulate iNOS and NO Production and Inhibit Chlamydial Growth

IFN-γ-mediated inducible nitric oxide synthase (iNOS) expression is critical for controlling chlamydial infection through microbicidal nitric oxide (NO) production. Interleukin-17A (IL-17A), as a new proinflammatory cytokine, has been shown to play a protective role in host defense against Chlamydia muridarum (Cm) infection. To define the related mechanism, we investigated, in the present study, the effect of IL-17A on IFN-γ induced iNOS expression and NO production during Cm infection in vitro and in vivo. Our data showed that IL-17A significantly enhanced IFN-γ-induced iNOS expression and NO production and inhibited Cm growth in Cm-infected murine lung epithelial (TC-1) cells. The synergistic effect of IL-17A and IFN-γ on Chlamydia clearance from TC-1 cells correlated with iNOS induction. Since one of the main antimicrobial mechanisms of activated macrophages is the release of NO, we also examined the inhibitory effect of IL-17A and IFN-γ on Cm growth in peritoneal macrophages. IL-17A (10 ng/ml) synergizes with IFN-γ (200 U/ml) in macrophages to inhibit Cm growth. This effect was largely reversed by aminoguanidine (AG), an iNOS inhibitor. Finally, neutralization of IL-17A in Cm infected mice resulted in reduced iNOS expression in the lung and higher Cm growth. Taken together, the results indicate that IL-17A and IFN-γ play a synergistic role in inhibiting chlamydial lung infection, at least partially through enhancing iNOS expression and NO production in epithelial cells and macrophages