Clinical characteristics and prognostic analysis of gastroenteropancreatic neuroendocrine neoplasm(GEP-NEN)

Objective： The aim of the study was to analyze the clinicopathologic characteristics of gastroenteropancreatic neuroendocrine neoplasm （GEP-NEN） and to explore the prognostic factors for patients and differences of immunohisto- chemical markers between neuroendocrine tumor （NET） and neuroendocrine carcinoma （NEC）. Methods： Retrospective reviews were conducted for the charts of 119 patients with GEP-NEN at the Affiliated Hospital of Qingdao University （China） from August 2003 to December 2013. Kaplan-Meier method was used to do the overall survivals analysis for the patients at different levels of predictive factors. Meanwhile, Cox proportional hazard model was used to select independent risk factors of surJival. Analysis of variance was used to compare the expression of immunohistochemical markers among different patho- logical grades. Results：Among 119 patients, pancreas （45/119, 37.82%） and rectum （33/119, 27.73%） were mostly involved. The onset age of GEP-NEN in female group was younger than that of the male group. There were 13 deaths （10.92%） during 18.9 （0.1-133.4） months follow-up period. Multivariate analysis indicated that neural invasion, gender and pathological grades of NET and NEC were independent risk factors. In neuroendocrine neoplasm （NEN）, Syn expression in G2 was higher than G1 and G3, while CgA showed no significant difference. All markers showed no significant differences between NET and NEC. Conclusion： GEP-NEN may occur at multiple sites of digestive system and lack specific clinical manifestations. Syn expression detected for the prognosis of G1, G2 and G3 tumors have clinical significance. Neural invasion, sex and patho- logical grades were independent prognostic factors for GEP-NEN patients. No significant difference was found in different pathological grades of NET and NEC.

Short Term Efficacy of Entecavir in the Treatment of Decompensated Chronic Hepatitis B Cirrhosis

Objective:To explore the effect of entecavir on patients with decompensated chronic hepatitis B cirrhosis.Methods:From October 2007 to December 2019,100 patients with decompensated chronic hepatitis B cirrhosis who were treated in our hospital were selected to carry out this study.The clinical data of the patients were analyzed.According to whether entecavir treatment was carried out,100 patients were divided into two groups,50 cases in the control group and 50 cases in the observation group.The control group was treated with conventional drugs,and the observation group was treated with entecavir.Liver function indexes,liver fibrosis indexes,HBV-DNA negative conversion rate and incidence of adverse reactions were compared between the two groups.Results:Compared with the control group,the liver function indexes of the observation group were lower,P<0.05;Compared with the control group,the observation group was better,P<0.05;The negative rate of HBV-DNA in the observation group was lower than that in the control group(P<0.05);There was no difference in the incidence of adverse reactions between the two groups,P>0.05.Conclusion:Entecavir can not only improve the liver function,but also enhance the shortterm treatment effect,without increasing adverse reactions,and has high safety,which is worthy of recommendation.

Cmtm4 deficiency exacerbates colitis by inducing gut dysbiosis and S100a8/9 expression

The dysfunction of innate immunity components is one of the major drivers for ulcerative colitis(UC),and increasing reports indicate that the gut microbiome serves as an intermediate between genetic mutations and UC development.Here,we find that the IL-17 receptor subunit,CMTM4,is reduced in UC patients and dextran sulfate sodium(DSS)-induced colitis.The deletion of CMTM4(Cmtm4^(-/-))in mice leads to a higher susceptibility to DSS-induced colitis than in wild-type,and the gut microbiome significantly changes in composition.The causal role of the gut microbiome is confirmed with a cohousing experiment.We further identify that S100a8/9 is significantly up-regulated in Cmtm4^(-/-)colitis,with the block of its receptor RAGE that reverses the phenotype associated with the CMTM4 deficiency.CMTM4 deficiency rather suppresses S100a8/9 expression in vitro via the IL17 pathway,further supporting that the elevation of S100a8/9 in vivo is most likely a result of microbial dysbiosis.Taken together,the results suggest that CMTM4 is involved in the maintenance of intestinal homeostasis,suppression of S100a8/9,and prevention of colitis development.Our study further shows CMTM4 as a crucial innate immunity component,confirming its important role in UC development and providing insights into potential targets for the development of future therapies.

Modes of genetic adaptations underlying functional innovations in the rumen

The rumen is the hallmark organ of ruminants and hosts a diverse ecosystem of microorganisms that facilitates efficient digestion of plant fibers.We analyzed 897 transcriptomes from three Cetartiodactyla lineages:ruminants,camels and cetaceans,as well as data from ruminant comparative genomics and functional assays to explore the genetic basis of rumen functional innovations.We identified genes with relatively high expression in the rumen,of which many appeared to be recruited from other tissues.These genes show functional enrichment in ketone body metabolism,regulation of microbial community,and epithelium absorption,which are the most prominent biological processes involved in rumen innovations.Several modes of genetic change underlying rumen functional innovations were uncovered,including coding mutations,genes newly evolved,and changes of regulatory elements.We validated that the key ketogenesis rate-limiting gene(HMGCS2)with five ruminant-specific mutations was under positive selection and exhibits higher synthesis activity than those of other mammals.Two newly evolved genes(LYZ1 and DEFB1)are resistant to Gram-positive bacteria and thereby may regulate microbial community equilibrium.Furthermore,we confirmed that the changes of regulatory elements accounted for the majority of rumen gene recruitment.These results greatly improve our understanding of rumen evolution and organ evo-devo in general.

Building a sequence map of the pig pan-genome from multiple de novo assemblies and Hi-C data

Pigs were domesticated independently in the Near East and China,indicating that a single reference genome from one individual is unable to represent the full spectrum of divergent sequences in pigs worldwide.Therefore,12 de novo pig assemblies from Eurasia were compared in this study to identify the missing sequences from the reference genome.As a result,72.5 Mb of nonredundant sequences(~3% of the genome)were found to be absent from the reference genome(Sscrofa11.1)and were defined as pan-sequences.Of the pan-sequences,9.0 Mb were dominant in Chinese pigs,in contrast with their low frequency in European pigs.One sequence dominant in Chinese pigs contained the complete genic region of the tazarotene-induced gene 3(TIG3)gene which is involved in fatty acid metabolism.Using flanking sequences and Hi-C based methods,27.7% of the sequences could be anchored to the reference genome.The supplementation of these sequences could contribute to the accurate interpretation of the 3D chromatin structure.A web-based pan-genome database was further provided to serve as a primary resource for exploration of genetic diversity and promote pig breeding and biomedical research.

Ultracompact meta-imagers for arbitrary all-optical convolution

Electronic digital convolutions could extract key features of objects for data processing and information identification in artificial intelligence,but they are time-cost and energy consumption due to the low response of electrons.Although massless photons enable high-speed and low-loss analog convolutions,two existing all-optical approaches including Fourier fItering and Green's function have either limited functionality or bulky volume,thus restricting their applications in smart systems.Here,we report aloptical convolutional computing with a metasurface-singlet or-doublet imager,considered as the third approach,where its point spread function is modified arbitrarily via a complex-amplitude meta-modulator that enables functionality-unlimited kernels.Beyond one-and two-dimensional spatial differentiation,we demonstrate real-time,parallel,and analog convolutional processing of optical and biological specimens with challenging pepper-salt denoising and edge enhancement,which significantly enrich the toolkit of all-optical computing.Such meta-imager approach bridges multi-functionality and high-integration in all-optical convolutions,meanwhile possessing good architecture compatibility with digital convolutional neural networks.

An atlas of CNV maps in cattle, goat and sheep

Copy number variation(CNV)is the most prevalent type of genetic structural variation that has been recognized as an important source of phenotypic variation in humans,animals and plants.However,the mechanisms underlying the evolution of CNVs and their function in natural or artificial selection remain unknown.Here,we generated CNV region(CNVR)datasets which were diverged or shared among cattle,goat,and sheep,including 886 individuals from 171 diverse populations.Using 9 environmental factors for genome-wide association study(GWAS),we identified a series of candidate CNVRs,including genes relating to immunity,tick resistance,multi-drug resistance,and muscle development.The number of CNVRs shared between species is significantly higher than expected(P<0.00001),and these CNVRs may be more persist than the single nucleotide polymorphisms(SNPs)shared between species.We also identified genomic regions under long-term balancing selection and uncovered the potential diversity of the selected CNVRs close to the important functional genes.This study provides the evidence that balancing selection might be more common in mammals than previously considered,and might play an important role in the daily activities of these ruminant species.

BGVD:An Integrated Database for Bovine Sequencing Variations and Selective Signatures

Next-generation sequencing has yielded a vast amount of cattle genomic data for global characterization of population genetic diversity and identification of genomic regions under natural and artificial selection.However,efficient storage,querying,and visualization of such large datasets remain challenging.Here,we developed a comprehensive database,the Bovine Genome Variation Database(BGVD).It provides six main functionalities:gene search,variation search,genomic signature search,Genome Browser,alignment search tools,and the genome coordinate conversion tool.BGVD contains information on genomic variations comprising^60.44 M SNPs,~6.86 M indels,76,634 CNV regions,and signatures of selective sweeps in 432 samples from modern cattle worldwide.Users can quickly retrieve distribution patterns of these variations for 54 cattle breeds through an interactive source of breed origin map,using a given gene symbol or genomic region for any of the three versions of the bovine reference genomes(ARS-UCD1.2,UMD3.1.1,and Btau5.0.1).Signals of selection sweep are displayed as Manhattan plots and Genome Browser tracks.To further investigate and visualize the relationships between variants and signatures of selection,the Genome Browser integrates all variations,selection data,and resources,from NCBI,the UCSC Genome Browser,and Animal QTLdb.Collectively,all these features make the BGVD a useful archive for in-depth data mining and analyses of cattle biology and cattle breeding on a global scale.BGVD is publicly available at http://animal.nwsuaf.edu.cn/BosVar.

GGVD:A goat genome variation database for tracking the dynamic evolutionary process of selective signatures and ancient introgressions

Understanding the evolutionary history and adaptive process depends on the knowledge that we can acquire from both ancient and modern genomic data.With the availability of a deluge of whole-genome sequencing data from ancient and modern goat samples,a user-friendly database making efficient reuse of these important resources is needed.Here,we use the genomes of 208 modern domestic goats,24 bezoars,46 wild ibexes,and 82 ancient goats to present a comprehensive goat genome variation database(GGVD).GGVD hosts a total of~41.44 million SNPs,~5.14 million indels,6,193 selected loci,and 112 introgression regions.Users can freely visualize the frequency of genomic variations in geographical maps,selective sweeps in interactive tables,Manhattan plots,or line charts,as well as the heatmap patterns of the SNP genotype.Ancient data can be shown in haplotypes to track the state of genetic variants of selection and introgression events in the early,middle,and late stages.For facilitating access to sequence features,the UCSC Genome Browser,BLAT,BLAST,Lift Over,and pcadapt are also integrated into GGVD.GGVD will be a convenient tool for population genetic studies and molecular marker designing in goat breeding programs,and it is publicly available at http://animal.nwsuaf.edu.cn/Goat Var.

Pathogen-associated T follicular helper cell plasticity is critical in anti-viral immunity

T follicular helper(Tfh)cells are critical in providing help for B cells in the germinal center reaction.Tfh cell plasticity,especially with regard to their expression of effector Th cytokines,has been described,but lacks in-depth analysis with genetic approaches.In this study,we systemically compared transcriptomic profiles of Tfh cells derived from various types of immune responses and found gene clusters corresponding to effector Th cells were differentially induced in response to pathogens or immune responses.Of special interest,a subset of Tfh cells producing IFN-γwas generated in an influenza virus infection,partially dependent on the innate cytokine IL-12.Lineage-tracing mouse model revealed unique developmental regulation of IFN-γ~+Tfh cells,while selective ablation of these cells impaired the induction of Ig G2c~+germinal center B cells and the control of influenza infection.These results indicate that pathogen-associated Tfh cell plasticity is necessary for host immunity,which has implications in vaccine design.

Free-ranging Sichuan snub-nosed monkeys Rhinopithecus roxellana： Neophobia, neophilia, or both？

We studied the responsiveness of the Sichuan snub-nosed monkey Rhinopithecus roxellana, an arboreal Old World monkey, to the presence of novel stimuli associated with familiar food. We also determined differences in responses by age and sex. Results showed that monkeys exhibited neophilia and neophobia simultaneously when facing novel stimuli. Age affected the response to novel stimuli significantly, with immature individuals responding to novel stimuli most frequently and infants least frequently. No significant differences were observed for sex, although females were more responsive to the novel object than were males. Our results support the ＂readiness to eat＂ hypothesis that the presence of a novel object can increase latencies to consume familiar food .

Bovine HSD17B8 gene and its relationship with growth and meat quality traits

17 β-Hydroxysteroid dehydrogenase type 8 （HSD17B8） is an important regulator of lipid and steroid metabolism. In the present study, we aimed to assess the effects of HSD17B8 on growth and meat quality traits in cattle. Transcription profile analysis showed that HSD17B8 was primarily expressed in the salpinx, liver, and testis. Meanwhile, we identified three SNPs （SNPI： intron 1-A91G; SNP2： exon 1-A90G; and SNP3： intron 8-A86G） of the bovine HSD17B8 gene and investigated its haplotype frequencies and linkage disequilibrium. The detected SNPs were found associated with growth traits （body weight, body length, height at withers, heart girth, hip width, and average daily gain） in native cattle populations （Nanyang and Jiaxian） as well as the meat quality traits （Warner- Bratzler shear force, rib area, dressing percentage, carcass weight, and backfat thickness） in commercial breeds （Angus, Hereford, Limousin, Luxi, Simmental, and Jinnan）. Our results provided evidence that polymorphisms in the HSD17B8 gene were associated with growth traits and meat quality traits. Moreover, our findings might be used for marker-assisted selection in beef cattle breeding program