Effective bone regeneration through tissue engineering requires a combination of osteogenic progenitors,osteoinductive biofactors and biocompatible scaffold materials.Mesenchymal stem cells(MSCs)represent the most pro...Effective bone regeneration through tissue engineering requires a combination of osteogenic progenitors,osteoinductive biofactors and biocompatible scaffold materials.Mesenchymal stem cells(MSCs)represent the most promising seed cells for bone tissue engineering.As multipotent stem cells that can self-renew and differentiate into multiple lineages including bone and fat,MSCs can be isolated from numerous tissues and exhibit varied differentiation potential.To identify an optimal progenitor cell source for bone tissue engineering,we analyzed the proliferative activity and osteogenic potential of four commonly-used mouse MSC sources,including immortalized mouse embryonic fibroblasts(iMEF),immortalized mouse bone marrow stromal stem cells(imBMSC),immortalized mouse calvarial mesenchymal progenitors(iCAL),and immortalized mouse adipose-derived mesenchymal stem cells(iMAD).We found that iMAD exhibited highest osteogenic and adipogenic capabilities upon BMP9 stimulation in vitro,whereas iMAD and iCAL exhibited highest osteogenic capability in BMP9-induced ectopic osteogenesis and critical-sized calvarial defect repair.Transcriptomic analysis revealed that,while each MSC line regulated a distinct set of target genes upon BMP9 stimulation,all MSC lines underwent osteogenic differentiation by regulating osteogenesis-related signaling including Wnt,TGF-β,PI3K/AKT,MAPK,Hippo and JAK-STAT pathways.Collectively,our results demonstrate that adipose-derived MSCs represent optimal progenitor sources for cell-based bone tissue engineering.展开更多
OriginalTranslation The avian influenza A(H7N9)virus is a zoonotic virus that is closely associated with live poultry markets.It has caused infections in humans in China since 2013.Five waves of the H7N9 influenza epi...OriginalTranslation The avian influenza A(H7N9)virus is a zoonotic virus that is closely associated with live poultry markets.It has caused infections in humans in China since 2013.Five waves of the H7N9 influenza epidemic occurred in China between March 2013 and September 2017.H7N9 with low-pathogenicity dominated in the first four waves,whereas highly pathogenic H7N9 influenza emerged in poultry and spread to humans during the fifth wave,causing wide concern.Specialists and officials from China and other countries responded quickly,controlled the epidemic well thus far,and characterized the virus by using new technologies and surveillance tools that were made possible by their preparedness efforts.Here,we review the characteristics of the H7N9 viruses that were identified while controlling the spread of the disease.It was summarized and discussed from the perspectives of molecular epidemiology,clinical features,virulence and pathogenesis,receptor binding,T-cell responses,monoclonal antibody development,vaccine development,and disease burden.These data provide tools for minimizing the future threat of H7N9 and other emerging and re-emerging viruses,such as SARS-CoV-2.展开更多
The Circular Electron Positron Collider(CEPC)is a large scientific project initiated and hosted by China,fostered through extensive collaboration with international partners.The complex comprises four accelerators:a 3...The Circular Electron Positron Collider(CEPC)is a large scientific project initiated and hosted by China,fostered through extensive collaboration with international partners.The complex comprises four accelerators:a 30 GeV Linac,a 1.1 GeV Damping Ring,a Booster capable of achieving energies up to 180 GeV,and a Collider operating at varying energy modes(Z,W,H,and tt).The Linac and Damping Ring are situated on the surface,while the subterranean Booster and Collider are housed in a 100 km circumference underground tunnel,strategically accommodating future expansion with provisions for a potential Super Proton Proton Collider(SPPC).The CEPC primarily serves as a Higgs factory.In its baseline design with synchrotron radiation(SR)power of 30 MW per beam,it can achieve a luminosity of 5×10^(34)cm^(-2)s^(-1)per interaction point(IP),resulting in an integrated luminosity of 13 ab^(-1)for two IPs over a decade,producing 2.6 million Higgs bosons.Increasing the SR power to 50 MW per beam expands the CEPC's capability to generate 4.3 million Higgs bosons,facilitating precise measurements of Higgs coupling at sub-percent levels,exceeding the precision expected from the HL-LHC by an order of magnitude.This Technical Design Report(TDR)follows the Preliminary Conceptual Design Report(Pre-CDR,2015)and the Conceptual Design Report(CDR,2018),comprehensively detailing the machine's layout,performance metrics,physical design and analysis,technical systems design,R&D and prototyping efforts,and associated civil engineering aspects.Additionally,it includes a cost estimate and a preliminary construction timeline,establishing a framework for forthcoming engineering design phase and site selection procedures.Construction is anticipated to begin around 2027-2028,pending government approval,with an estimated duration of 8 years.The commencement of experiments and data collection could potentially be initiated in the mid-2030s.展开更多
This article is the tenth series of the Fungal Diversity Notes,where 114 taxa distributed in three phyla,ten classes,30 orders and 53 families are described and illustrated.Taxa described in the present study include ...This article is the tenth series of the Fungal Diversity Notes,where 114 taxa distributed in three phyla,ten classes,30 orders and 53 families are described and illustrated.Taxa described in the present study include one new family(viz.Pseudoberkleasmiaceae in Dothideomycetes),five new genera(Caatingomyces,Cryptoschizotrema,Neoacladium,Paramassaria and Trochilispora)and 71 new species,(viz.Acrogenospora thailandica,Amniculicola aquatica,A.guttulata,Angustimassarina sylvatica,Blackwellomyces lateris,Boubovia gelatinosa,Buellia viridula,Caatingomyces brasiliensis,Calophoma humuli,Camarosporidiella mori,Canalisporium dehongense,Cantharellus brunneopallidus,C.griseotinctus,Castanediella meliponae,Coprinopsis psammophila,Cordyceps succavus,Cortinarius minusculus,C.subscotoides,Diaporthe italiana,D.rumicicola,Diatrypella delonicis,Dictyocheirospora aquadulcis,D.taiwanense,Digitodesmium chiangmaiense,Distoseptispora dehongensis,D.palmarum,Dothiorella styphnolobii,Ellisembia aurea,Falciformispora aquatic,Fomitiporia carpinea,F.lagerstroemiae,Grammothele aurantiaca,G.micropora,Hermatomyces bauhiniae,Jahnula queenslandica,Kamalomyces mangrovei,Lecidella yunnanensis,Micarea squamulosa,Muriphaeosphaeria angustifoliae,Neoacladium indicum,Neodidymelliopsis sambuci,Neosetophoma miscanthi,N.salicis,Nodulosphaeria aquilegiae,N.thalictri,Paramassaria samaneae,Penicillium circulare,P.geumsanense,P.mali-pumilae,P.psychrotrophicum,P.wandoense,Phaeoisaria siamensis,Phaeopoacea asparagicola,Phaeosphaeria penniseti,Plectocarpon galapagoense,Porina sorediata,Pseudoberkleasmium chiangmaiense,Pyrenochaetopsis sinensis,Rhizophydium koreanum,Russula prasina,Sporoschisma chiangraiense,Stigmatomyces chamaemyiae,S.cocksii,S.papei,S.tschirnhausii,S.vikhrevii,Thysanorea uniseptata,Torula breviconidiophora,T.polyseptata,Trochilispora schefflerae and Vaginatispora palmae).Further,twelve new combinations(viz.Cryptoschizotrema cryptotrema,Prolixandromyces australi,P.elongatus,P.falcatus,P.longispinae,P.microveliae,P.neoalardi,P.polhemorum,P.protubera展开更多
At present,natural orifice specimen extraction surgery(NOSES)has attracted more and more attention worldwide,because of its great advantages including minimal cutaneous trauma and post-operative pain,fast post-operati...At present,natural orifice specimen extraction surgery(NOSES)has attracted more and more attention worldwide,because of its great advantages including minimal cutaneous trauma and post-operative pain,fast post-operative recovery,short hospital stay,and positive psychological impact.However,NOSES for the treatment of gastric cancer(GC)is still in its infancy,and there is great potential to improve its theoretical system and clinical practice.Especially,several key points including oncological outcomes,bacteriological concerns,indication selection,and standardized surgical procedures are raised with this innovative technique.Therefore,it is necessary to achieve an international consensus to regulate the implementation of GC-NOSES,which is of great significance for healthy and orderly development of NOSES worldwide.展开更多
Wnt signaling plays a major role in regulating cell proliferation and differentiation.The Wnt ligands are a family of 19 secreted glycoproteins that mediate their signaling effects via binding to Frizzled receptors an...Wnt signaling plays a major role in regulating cell proliferation and differentiation.The Wnt ligands are a family of 19 secreted glycoproteins that mediate their signaling effects via binding to Frizzled receptors and LRP5/6 coreceptors and transducing the signal either throughβ-catenin in the canonical pathway or through a series of other proteins in the nonca-nonical pathway.Many of the individual components of both canonical and noncanonical Wnt signaling have additional functions throughout the body,establishing the complex interplay between Wnt signaling and other signaling pathways.This crosstalk between Wnt signaling and other pathways gives Wnt signaling a vital role in many cellular and organ processes.Dys-regulation of this system has been implicated in many diseases affecting a wide array of organ systems,including cancer and embryological defects,and can even cause embryonic lethality.The complexity of this system and its interacting proteins have made Wnt signaling a target for many therapeutic treatments.However,both stimulatory and inhibitory treatments come with potential risks that need to be addressed.This review synthesized much of the current knowl-edge on the Wnt signaling pathway,beginning with the history of Wnt signaling.It thoroughly described the different variants of Wnt signaling,including canonical,noncanonical Wnt/PCP,and the noncanonical Wnt/Ca2+pathway.Further description involved each of its components and their involvement in other cellular processes.Finally,this review explained the various other pathways and processes that crosstalk with Wnt signaling.展开更多
Recent advances in deep sequencing technologies have revealed that,while less than 2%of the human genome is transcribed into mRNA for protein synthesis,over 80%of the genome is transcribed,leading to the production of...Recent advances in deep sequencing technologies have revealed that,while less than 2%of the human genome is transcribed into mRNA for protein synthesis,over 80%of the genome is transcribed,leading to the production of large amounts of noncoding RNAs(ncRNAs).It has been shown that ncRNAs,especially long non-coding RNAs(lncRNAs),may play crucial regulatory roles in gene expression.As one of the first isolated and reported lncRNAs,H19 has gained much attention due to its essential roles in regulating many physiological and/or pathological processes including embryogenesis,development,tumorigenesis,osteogen-esis,and metabolism.Mechanistically,H19 mediates diverse regulatory functions by serving as competing endogenous RNAs(CeRNAs),Igf2/H19 imprinted tandem gene,modular scaffold,cooperating with H19 antisense,and acting directly with other mRNAs or lncRNAs.Here,we summarized the current understanding of H19 in embryogenesis and development,cancer development and progression,mesenchymal stem cell lineage-specific differentiation,and metabolic diseases.We discussed the potential regulatory mechanisms underlying H19’s func-tions in those processes although more in-depth studies are warranted to delineate the exact molecular,cellular,epigenetic,and genomic regulatory mechanisms underlying the physiolog-ical and pathological roles of H19.Ultimately,these lines of investigation may lead to the development of novel therapeutics for human diseases by exploiting H19 functions.展开更多
Intestinal cancers are developed from intestinal epithelial stem cells(ISCs)in intestinal crypts through a multi-step process involved in genetic mutations of oncogenes and tumor suppressor genes.ISCs play a key role ...Intestinal cancers are developed from intestinal epithelial stem cells(ISCs)in intestinal crypts through a multi-step process involved in genetic mutations of oncogenes and tumor suppressor genes.ISCs play a key role in maintaining the homeostasis of gut epithelium.In 2009,Sato et al established a three-dimensional culture system,which mimicked the niche microenvironment by employing the niche factors,and successfully grew crypt ISCs into organoids or Mini-guts in vitro.Since then,the intestinal organoid technology has been used to delineate cellular signaling in ISC biology.However,the cultured organoids consist of heterogeneous cell populations,and it was technically challenging to introduce genomic changes into three-dimensional organoids.Thus,there was a technical necessity to develop a twodimensional ISC culture system for effective genomic manipulations.In this study,we established a conditionally immortalized mouse intestinal crypt(ciMIC)cell line by using a piggyBac transposon-based SV40 T antigen expression system.We showed that the ciMICs maintained long-term proliferative activity under two-dimensional niche factor-containing culture condition,retained the biological characteristics of intestinal epithelial stem cells,and could form intestinal organoids in three-dimensional culture.While in vivo cell implantation tests indicated that the ciMICs were non-tumorigenic,the ciMICs overexpressing oncogenic b-catenin and/or KRAS exhibited high proliferative activity and developed intestinal adenoma-like pathological features in vivo.Collectively,these findings strongly suggested that the engineered ciMICs should be used as a valuable tool cell line to dissect the genetic and/or epigenetic underpinnings of intestinal tumorigenesis.展开更多
AIMTo evaluate outcomes of combined pars plana vitrectomy and Baerveldt glaucoma implant (PPV-BGI) placement for refractory glaucoma.METHODSThe medical records of 92 eyes (89 patients) that underwent PPV-BGI were retr...AIMTo evaluate outcomes of combined pars plana vitrectomy and Baerveldt glaucoma implant (PPV-BGI) placement for refractory glaucoma.METHODSThe medical records of 92 eyes (89 patients) that underwent PPV-BGI were retrospectively reviewed, including 43 eyes with neovascular glaucoma (NVG) and 49 eyes with other types of glaucoma (non-NVG).RESULTSOutcome measures were visual acuity (VA), intraocular pressure (IOP), glaucoma medical therapy, complications, and success [VA>hand motions (HM), IOP≥6 mm Hg and ≤21 mm Hg, no subsequent glaucoma surgery]. Cumulative success rates for the non-NVG group and NVG group were 79% and 40% at 1y, respectively (P=0.038). No difference in the rates of surgical success were found between pars plana and anterior chamber tube placement. Preoperative IOP (mean±SD) was 30.3±11.7 mm Hg in the Non-NVG group and 40.0±10.6 mm Hg in the NVG group, and IOP was reduced to 15±9.5 mm Hg in the non-NVG group and 15±10.5 mm Hg in the NVG at 1y. Number of glaucoma medications (mean±SD) decreased from 2.7±1.3 in the non-NVG group and 2.8±1.3 in the NVG group preoperatively to 0.76±1.18 in the non-NVG group and 0.51±1.00 in the NVG group at 1y. Improvement in VA of ≥2 Snellen lines was observed in 25 (27%) eyes, although only 33% of non-NVG eyes and 2.3% of NVG eyes maintained VA better than 20/200 at 1y. Nonclearing vitreous hemorrhage was the most common postoperative complication occurring in 16 (17%) eyes, and postoperative suprachoroidal hemorrhages developed in 5 (5.4%) eyes.CONCLUSIONPPV-BGI is a viable surgical option for eyes with refractory glaucoma, but visual outcomes are frequently poor because of ocular comorbidities, especially in eyes with NVG. The location of tube placement does not influence surgical outcome and should be left to the discretion of the surgeon.展开更多
The physiological changes and the mechanism of stress tolerance in tomato were studied under low temperature and low light conditions. Two growth chamber experiments evaluated three temperatures regimes under standard...The physiological changes and the mechanism of stress tolerance in tomato were studied under low temperature and low light conditions. Two growth chamber experiments evaluated three temperatures regimes under standard and relatively low illumination levels with three tomato genotypes. Both experiments used a completely randomized split-plot design (CRD), with temperature regime as the main plot and tomato genotype as the split-plot. The three tomato varieties were “Fenyan No.1”, “SV0313TG”, and “Ousa”. In both experiments, activity of superoxide dismutase (SOD) and peroxidases (POD) in tomato seedlings decreased under low temperature regime and the combination of low temperature and low light. Decreasing temperature had the greatest effect on the increase in enzyme activity. Decrease in POD activity was the greatest under low light and low temperature. The concentration of malondialdehyde (MDA) in plant tissue also decreased under low temperature (20°C/10°C day/night) compared to the standard temperature control (25°C/16°C day/night), but increased at 15°C/5°C day/night temperatures in both experiments and was the greatest under the lowest light and temperature conditions. In both experiments, proline concentrations were the greatest under the standard light intensity (30,000 lux), and proline concentrations increased as temperature decreased. The content of soluble sugar decreased under only low temperature stress but increased under double stresses. The relative value of osmotic potential increased a little under low temperature stress but decreased under double stresses.展开更多
Here,we report the identification of Histoplasma causing an unexplained disease cluster in Matthews Ridge,Guyana.In March 2019,14 employees of Chongqing Bosai Mining Company,China,working in a manganese mining of Guya...Here,we report the identification of Histoplasma causing an unexplained disease cluster in Matthews Ridge,Guyana.In March 2019,14 employees of Chongqing Bosai Mining Company,China,working in a manganese mining of Guyana,had unexplained fever,and two of them died.We obtained lung and brain tissues as well as the blood samples from the two deceased cases(patient No.1 and 2),and bronchoscopy lavages and cerebrospinal fluid samples from one severe case(patient No.3),respectively.All samples were tested by pathological examination,high-throughput sequencing,and real-time PCR.Pathological detection showed the presence of spore-like structures in the lung tissue of patient No.1,indicating a fungal infection in this patient.Nanopore sequencing identified the existing of H.capsulatum in the lung tissue sample within 13 h.Next-generation sequencing identified specific fragments of H.capsulatum in all of the samples tested(lung,brain and blood serum from the deceased cases,and plasma from the severe case).Real-time PCR assays did not reveal any viral infection related to transmission from bat feces.We conclude that H.capsulatum was the causative pathogen of this disease cluster based on epidemiologic,clinical,pathological and nucleic acid evidence.展开更多
Studies on influenza virus by Chinese Academy of Sciences(CAS)could be traced back as early as 2005 by the CAS Key Laboratory of Pathogenic Microbiology and Immunology(CASPMI),who discovered that Qinghai-like Clade 2....Studies on influenza virus by Chinese Academy of Sciences(CAS)could be traced back as early as 2005 by the CAS Key Laboratory of Pathogenic Microbiology and Immunology(CASPMI),who discovered that Qinghai-like Clade 2.2H5N1 subtype highly pathogenic avian influenza virus(HPAIV)first caused severe outbreak in wild birds in Qinghai Lake(Liu et al.,2005).展开更多
Age-related macular degeneration(AMD)is characterized by complex interactions between genetic and environmental factors.Here we genotyped the selected 25 single-nucleotide polymorphisms(SNPs)in 983 cases with advanced...Age-related macular degeneration(AMD)is characterized by complex interactions between genetic and environmental factors.Here we genotyped the selected 25 single-nucleotide polymorphisms(SNPs)in 983 cases with advanced AMD and 271 cases with intermediate AMD and build an AMD life-risk score model for assessment of progression from intermediate to advanced AMD.We analyzed the performance of the prediction model for geographic atrophy progressors or choroidal neovascularization progressors versus non-progressors based on the 25 SNPs plus body mass index and smoking status.Our results suggest that a class prediction algorithm can be used for the risk assessment of progression from intermediate to late AMD stages.The algorithm could also be potentially applied for therapeutic response,and toward personalized care and precision medicine.展开更多
The authors regret that an image assembly(copy/paste)error in Figure 3D,in which the image for the organoid of"Primary MiCs"group was erroneously duplicated with an image of primary MICs that was previously ...The authors regret that an image assembly(copy/paste)error in Figure 3D,in which the image for the organoid of"Primary MiCs"group was erroneously duplicated with an image of primary MICs that was previously published.The corrected figure is shown below.As shown in the corrected Figure 3D,this error does not adversely impact the conclusion of the original work.The authors would like to apologise forany inconvenience caused.展开更多
Plasmid DNA(pDNA)isolation from bacterial cells is one of the most common and critical steps in molecular cloning and biomedical research.Almost all pDNA purification in-volves disruption of bacteria,removal of membra...Plasmid DNA(pDNA)isolation from bacterial cells is one of the most common and critical steps in molecular cloning and biomedical research.Almost all pDNA purification in-volves disruption of bacteria,removal of membrane lipids,proteins and genomic DNA,purifi-cation of pDNA from bulk lysate,and concentration of pDNA for downstream applications.While many liquid-phase and solid-phase pDNA purification methods are used,the final pDNA preparations are usually contaminated with varied degrees of host RNA,which cannot be completely digested by RNase A.To develop a simple,cost-effective,and yet effective method for RNA depletion,we investigated whether commercially available size selection magnetic beads(SSMBs),such as Mag-Bind®TotalPure NGS Kit(or Mag-Bind),can completely deplete bacterial RNA in pDNA preparations.In this proof-of-principle study,we demonstrated that,compared with RNase A digestion and two commercial plasmid affinity purification kits,the SSMB method was highly efficient in depleting contaminating RNA from pDNA minipreps.Gene transfection and bacterial colony formation assays revealed that pDNA purified from SSMB method had superior quality and integrity to pDNA samples cleaned up by RNase A digestion and/or commercial plasmid purification kits.We further demonstrated that the SSMB method completely depleted contaminating RNA in large-scale pDNA samples.Furthermore,the Mag-bind-based SSMB method costs only 5-10%of most commercial plasmid purification kits on a per sample basis.Thus,the reported SSMB method can be a valuable and inexpensive tool for the removal of bacterial RNA for routine pDNA preparations.展开更多
The onsite next generation sequencing(NGS)of Ebola virus(EBOV)genomes during the 2013–2016 Ebola epidemic in Western Africa provides an opportunity to trace the origin,transmission,and evolution of this virus.Herein,...The onsite next generation sequencing(NGS)of Ebola virus(EBOV)genomes during the 2013–2016 Ebola epidemic in Western Africa provides an opportunity to trace the origin,transmission,and evolution of this virus.Herein,we have diagnosed a cohort of EBOV patients in Sierra Leone in 2015,during the late phase of the outbreak.The surviving EBOV patients had a recovery process characterized by decreasing viremia,fever,and biochemical parameters.EBOV genomes sequenced through the longitudinal blood samples of these patients showed dynamic intra-host substitutions of the virus during acute infection,including the previously described short stretches of 13 serial TNC mutations.Remarkably,within individual patients,samples collected during the early phase of infection possessed Ts at these nucleotide sites,whereas they were replaced by Cs in samples collected in the later phase,suggesting that these short stretches of TNC mutations could emerge independently.In addition,up to a total of 35 nucleotide sites spanning the EBOV genome were mutated coincidently.Our study showed the dynamic intra-host adaptation of EBOV during patient recovery and gave more insight into the complex EBOV-host interactions.展开更多
When querying databases containing sensitive information,the privacy of individuals stored in the database has to be guaranteed.Such guarantees are provided by differentially private mechanisms which add controlled no...When querying databases containing sensitive information,the privacy of individuals stored in the database has to be guaranteed.Such guarantees are provided by differentially private mechanisms which add controlled noise to the query responses.However,most such mechanisms do not take into consideration the valid range of the query being posed.Thus,noisy responses that fall outside of this range may potentially be produced.To rectify this and therefore improve the utility of the mechanism,the commonly-used Laplace distribution can be truncated to the valid range of the query and then normalized.However,such a data-dependent operation of normalization leaks additional information about the true query response,thereby violating the differential privacy guarantee.Here,we propose a new method which preserves the differential privacy guarantee through a careful determination of an appropriate scaling parameter for the Laplace distribution.We adapt the privacy guarantee in the context of the Laplace distribution to account for data-dependent normalization factors and study this guarantee for different classes of range constraint configurations.We provide derivations of the optimal scaling parameter(i.e.,the minimal value that preserves differential privacy)for each class or provide an approximation thereof.As a result of this work,one can use the Laplace distribution to answer queries in a range-adherent and differentially private manner.To demonstrate the benefits of our proposed method of normalization,we present an experimental comparison against other range-adherent mechanisms.We show that our proposed approach is able to provide improved utility over the alternative mechanisms.展开更多
By analyzing the structures of circuits,a novel approach for signal probability estimation of very large-scale integration(VLSI)based on the improved weighted averaging algorithm(IWAA)is proposed.Considering the failu...By analyzing the structures of circuits,a novel approach for signal probability estimation of very large-scale integration(VLSI)based on the improved weighted averaging algorithm(IWAA)is proposed.Considering the failure probability of the gate,first,the first reconvergent fan-ins corresponding to the reconvergent fan-outs were identified to locate the important signal correlation nodes based on the principle of homologous signal convergence.Secondly,the reconvergent fan-in nodes of the multiple reconverging structure in the circuit were identified by the sensitization path to determine the interference sources to the signal probability calculation.Then,the weighted signal probability was calculated by combining the weighted average approach to correct the signal probability.Finally,the reconvergent fan-out was quantified by the mixed-calculation strategy of signal probability to reduce the impact of multiple reconvergent fan-outs on the accuracy.Simulation results on ISCAS85 benchmarks circuits show that the proposed method has approximate linear time-space consumption with the increase in the number of the gate,and its accuracy is 4.2%higher than that of the IWAA.展开更多
Misoprostol (Cytotec, Pfizer) is a prostaglandin E1 analogue widely used in labor induction. Understanding of potential risks of misoprostol in labor induction is lacking as the drug is used off-label in most countrie...Misoprostol (Cytotec, Pfizer) is a prostaglandin E1 analogue widely used in labor induction. Understanding of potential risks of misoprostol in labor induction is lacking as the drug is used off-label in most countries. A 35-year-old G3P2 woman with post-date pregnancy at 40 + 3 weeks was induced using titrated oral misoprostol. Following delivery, post-partum hemorrhage was noted and, upon discovery of a uterine wall rupture due to congenital weakness of the myometrium, emergency abdominal total hysterectomy was conducted. Following surgery, the patient made a full recovery and was discharged. The main contraindications for misoprostol in labor induction are a scarred uterus or multipara greater than 4. Uterine wall weakness should be considered as a potential contraindication. Extreme vigilance is required in use of misoprostol for labor induction.展开更多
基金by research grants from the Natural Science Foundation of China(82102696 to JF)the Chongqing Bayu Young Scholar Award(JF),the 2019 Chongqing Support Program for Entrepreneurship and Innovation(No.cx2019113 to JF)+4 种基金the 2019 Funding for Postdoctoral Research(Chongqing Human Resources and Social Security Bureau No.298 to JF),the National Institutes of Health(CA226303 to TCH,and DE030480 to RRR)supported by the Medical Scientist Training Program of the National Institutes of Health(T32 GM007281)supported in part by The University of Chicago Cancer Center Support Grant(P30CA014599)the National Center for Advancing Translational Sciences of the National Institutes of Health through Grant Number UL1TR002389-07.
文摘Effective bone regeneration through tissue engineering requires a combination of osteogenic progenitors,osteoinductive biofactors and biocompatible scaffold materials.Mesenchymal stem cells(MSCs)represent the most promising seed cells for bone tissue engineering.As multipotent stem cells that can self-renew and differentiate into multiple lineages including bone and fat,MSCs can be isolated from numerous tissues and exhibit varied differentiation potential.To identify an optimal progenitor cell source for bone tissue engineering,we analyzed the proliferative activity and osteogenic potential of four commonly-used mouse MSC sources,including immortalized mouse embryonic fibroblasts(iMEF),immortalized mouse bone marrow stromal stem cells(imBMSC),immortalized mouse calvarial mesenchymal progenitors(iCAL),and immortalized mouse adipose-derived mesenchymal stem cells(iMAD).We found that iMAD exhibited highest osteogenic and adipogenic capabilities upon BMP9 stimulation in vitro,whereas iMAD and iCAL exhibited highest osteogenic capability in BMP9-induced ectopic osteogenesis and critical-sized calvarial defect repair.Transcriptomic analysis revealed that,while each MSC line regulated a distinct set of target genes upon BMP9 stimulation,all MSC lines underwent osteogenic differentiation by regulating osteogenesis-related signaling including Wnt,TGF-β,PI3K/AKT,MAPK,Hippo and JAK-STAT pathways.Collectively,our results demonstrate that adipose-derived MSCs represent optimal progenitor sources for cell-based bone tissue engineering.
基金This study was supported by the Shenzhen Science and Technology Research and Development Project(No.JCYJ201604271519-20801)Innovation Unit for Emerging and Re-emerging Virus Adaptive Evolution Study and the Applications in Disease Control(No.2019-I2M-5-009)+3 种基金National Mega-projects for Infectious Diseases(No.2020ZX10001016-005-001)W.J.L.is supported by the Excellent Young Scientist Program of the NSFC(No.81822040)and Beijing New-star Plan of Science and Technology(No.Z181100006218080)H.X.is supported by Tianjin Synthetic Biotechnology Innovation Capacity Improvement Project(No.TSBICIP-KJGG-004-04)G.F.G.is a leading principal investigator of the National Natural Science Foundation of China Innovative Research Group(No.81621091).
文摘OriginalTranslation The avian influenza A(H7N9)virus is a zoonotic virus that is closely associated with live poultry markets.It has caused infections in humans in China since 2013.Five waves of the H7N9 influenza epidemic occurred in China between March 2013 and September 2017.H7N9 with low-pathogenicity dominated in the first four waves,whereas highly pathogenic H7N9 influenza emerged in poultry and spread to humans during the fifth wave,causing wide concern.Specialists and officials from China and other countries responded quickly,controlled the epidemic well thus far,and characterized the virus by using new technologies and surveillance tools that were made possible by their preparedness efforts.Here,we review the characteristics of the H7N9 viruses that were identified while controlling the spread of the disease.It was summarized and discussed from the perspectives of molecular epidemiology,clinical features,virulence and pathogenesis,receptor binding,T-cell responses,monoclonal antibody development,vaccine development,and disease burden.These data provide tools for minimizing the future threat of H7N9 and other emerging and re-emerging viruses,such as SARS-CoV-2.
基金support from diverse funding sources,including the National Key Program for S&T Research and Development of the Ministry of Science and Technology(MOST),Yifang Wang's Science Studio of the Ten Thousand Talents Project,the CAS Key Foreign Cooperation Grant,the National Natural Science Foundation of China(NSFC)Beijing Municipal Science&Technology Commission,the CAS Focused Science Grant,the IHEP Innovation Grant,the CAS Lead Special Training Programthe CAS Center for Excellence in Particle Physics,the CAS International Partnership Program,and the CAS/SAFEA International Partnership Program for Creative Research Teams.
文摘The Circular Electron Positron Collider(CEPC)is a large scientific project initiated and hosted by China,fostered through extensive collaboration with international partners.The complex comprises four accelerators:a 30 GeV Linac,a 1.1 GeV Damping Ring,a Booster capable of achieving energies up to 180 GeV,and a Collider operating at varying energy modes(Z,W,H,and tt).The Linac and Damping Ring are situated on the surface,while the subterranean Booster and Collider are housed in a 100 km circumference underground tunnel,strategically accommodating future expansion with provisions for a potential Super Proton Proton Collider(SPPC).The CEPC primarily serves as a Higgs factory.In its baseline design with synchrotron radiation(SR)power of 30 MW per beam,it can achieve a luminosity of 5×10^(34)cm^(-2)s^(-1)per interaction point(IP),resulting in an integrated luminosity of 13 ab^(-1)for two IPs over a decade,producing 2.6 million Higgs bosons.Increasing the SR power to 50 MW per beam expands the CEPC's capability to generate 4.3 million Higgs bosons,facilitating precise measurements of Higgs coupling at sub-percent levels,exceeding the precision expected from the HL-LHC by an order of magnitude.This Technical Design Report(TDR)follows the Preliminary Conceptual Design Report(Pre-CDR,2015)and the Conceptual Design Report(CDR,2018),comprehensively detailing the machine's layout,performance metrics,physical design and analysis,technical systems design,R&D and prototyping efforts,and associated civil engineering aspects.Additionally,it includes a cost estimate and a preliminary construction timeline,establishing a framework for forthcoming engineering design phase and site selection procedures.Construction is anticipated to begin around 2027-2028,pending government approval,with an estimated duration of 8 years.The commencement of experiments and data collection could potentially be initiated in the mid-2030s.
基金the Foreign Experts Bureau of Yunnan Province,Foreign Talents Program(2018,Grant No.YNZ2018002)Thailand Research grants entitled Biodiversity,phylogeny and role of fungal endophytes on above parts of Rhizophora apiculata and Nypa fruticans(Grant No.RSA5980068)+14 种基金the future of specialist fungi in a changing climate:baseline data for generalist and specialist fungi associated with ants,Rhododendron species and Dracaena species(Grant No.DBG6080013)Impact of climate change on fungal diversity and biogeography in the Greater Mekong Subregion(Grant No.RDG6130001)Chiang Mai University for the award of visiting ProfessorCAS President’s International Fellowship Initiative(PIFI)for funding his postdoctoral research(Grant No.2018PC0006)the National Science Foundation of China(NSFC,project code 31750110478)supported by the Graduate Program for the Undiscovered Taxa of Koreain part by the Project on Survey and Discovery of Indigenous Fungal Species of Korea funded by NIBR and Project on Discovery of Fungi from Freshwater and Collection of Fungarium funded by NNIBR of the Ministry of Environment(MOE)in part carried out with the support of Cooperative Research Program for Agriculture Science and Technology Development(PJ013744),Rural Development Administration,Republic of Koreain part supported by the BK21 plus program through the National Research Foundation(NRF)funded by the Ministry of Education of Korea.Jian-Kui Liu thanks the National Natural Science Foundation of China(NSFC 31600032)the CNPq(Conselho Nacional de Desenvolvimento Cientifico e Tecnologico)for a research grant(309058/2015-5)funding for collecting trips(401186/2014-8)a collaborative project with RL as Special Visiting Professor(314570/2014-4)Funding for phylogenetic work on Graphidaceae was provided by a grant from the National Science Foundation(NSF)to The Field Museum:DEB-1025861"ATM-Assembling a taxonomic monograph:The lichen family Graphidaceae"PI Thorsten Lumbsch,CoPI Robert Luckingthe CAPES,CNPq,and FAPEMIG for financial support and ICMBio
文摘This article is the tenth series of the Fungal Diversity Notes,where 114 taxa distributed in three phyla,ten classes,30 orders and 53 families are described and illustrated.Taxa described in the present study include one new family(viz.Pseudoberkleasmiaceae in Dothideomycetes),five new genera(Caatingomyces,Cryptoschizotrema,Neoacladium,Paramassaria and Trochilispora)and 71 new species,(viz.Acrogenospora thailandica,Amniculicola aquatica,A.guttulata,Angustimassarina sylvatica,Blackwellomyces lateris,Boubovia gelatinosa,Buellia viridula,Caatingomyces brasiliensis,Calophoma humuli,Camarosporidiella mori,Canalisporium dehongense,Cantharellus brunneopallidus,C.griseotinctus,Castanediella meliponae,Coprinopsis psammophila,Cordyceps succavus,Cortinarius minusculus,C.subscotoides,Diaporthe italiana,D.rumicicola,Diatrypella delonicis,Dictyocheirospora aquadulcis,D.taiwanense,Digitodesmium chiangmaiense,Distoseptispora dehongensis,D.palmarum,Dothiorella styphnolobii,Ellisembia aurea,Falciformispora aquatic,Fomitiporia carpinea,F.lagerstroemiae,Grammothele aurantiaca,G.micropora,Hermatomyces bauhiniae,Jahnula queenslandica,Kamalomyces mangrovei,Lecidella yunnanensis,Micarea squamulosa,Muriphaeosphaeria angustifoliae,Neoacladium indicum,Neodidymelliopsis sambuci,Neosetophoma miscanthi,N.salicis,Nodulosphaeria aquilegiae,N.thalictri,Paramassaria samaneae,Penicillium circulare,P.geumsanense,P.mali-pumilae,P.psychrotrophicum,P.wandoense,Phaeoisaria siamensis,Phaeopoacea asparagicola,Phaeosphaeria penniseti,Plectocarpon galapagoense,Porina sorediata,Pseudoberkleasmium chiangmaiense,Pyrenochaetopsis sinensis,Rhizophydium koreanum,Russula prasina,Sporoschisma chiangraiense,Stigmatomyces chamaemyiae,S.cocksii,S.papei,S.tschirnhausii,S.vikhrevii,Thysanorea uniseptata,Torula breviconidiophora,T.polyseptata,Trochilispora schefflerae and Vaginatispora palmae).Further,twelve new combinations(viz.Cryptoschizotrema cryptotrema,Prolixandromyces australi,P.elongatus,P.falcatus,P.longispinae,P.microveliae,P.neoalardi,P.polhemorum,P.protubera
文摘At present,natural orifice specimen extraction surgery(NOSES)has attracted more and more attention worldwide,because of its great advantages including minimal cutaneous trauma and post-operative pain,fast post-operative recovery,short hospital stay,and positive psychological impact.However,NOSES for the treatment of gastric cancer(GC)is still in its infancy,and there is great potential to improve its theoretical system and clinical practice.Especially,several key points including oncological outcomes,bacteriological concerns,indication selection,and standardized surgical procedures are raised with this innovative technique.Therefore,it is necessary to achieve an international consensus to regulate the implementation of GC-NOSES,which is of great significance for healthy and orderly development of NOSES worldwide.
基金supported in part by research grants from the National Institutes of Health(No.CA226303 to TCH and No.DE030480 to RRR)the American Shoulder and Elbow Surgeons PJI Research Grant(LLS).JF was supported in part by research grants from the Natural Science Foundation of China(No.82102696)+4 种基金the 2019 Science and Technology Research Plan Project of Chongqing Education Commission(China)(No.KJQN201900410)the 2019 Funding for Postdoctoral Research(Chongqing Human Resources and Social Security Bureau No.298)WW was supported by the Medical Scientist Training Program of the National Institutes of Health(No.T32 GM007281)This project was also supported in partby The University of Chicago Cancer Center Support Grant(No.P30CA014599)the National Center for Advancing Translational Sciences(NCATS)of the National Institutes of Health through Grant Number 5UL1TR002389.
文摘Wnt signaling plays a major role in regulating cell proliferation and differentiation.The Wnt ligands are a family of 19 secreted glycoproteins that mediate their signaling effects via binding to Frizzled receptors and LRP5/6 coreceptors and transducing the signal either throughβ-catenin in the canonical pathway or through a series of other proteins in the nonca-nonical pathway.Many of the individual components of both canonical and noncanonical Wnt signaling have additional functions throughout the body,establishing the complex interplay between Wnt signaling and other signaling pathways.This crosstalk between Wnt signaling and other pathways gives Wnt signaling a vital role in many cellular and organ processes.Dys-regulation of this system has been implicated in many diseases affecting a wide array of organ systems,including cancer and embryological defects,and can even cause embryonic lethality.The complexity of this system and its interacting proteins have made Wnt signaling a target for many therapeutic treatments.However,both stimulatory and inhibitory treatments come with potential risks that need to be addressed.This review synthesized much of the current knowl-edge on the Wnt signaling pathway,beginning with the history of Wnt signaling.It thoroughly described the different variants of Wnt signaling,including canonical,noncanonical Wnt/PCP,and the noncanonical Wnt/Ca2+pathway.Further description involved each of its components and their involvement in other cellular processes.Finally,this review explained the various other pathways and processes that crosstalk with Wnt signaling.
基金supported by the National Natural Science Foundation of China(NSFC)(No.82002312,81972069)supported in part by research grants from the National Institutes of Health,USA(No.CA226303 to TCH,No.DE030480 to RRR)+10 种基金supported by the Science and Technology Research Program of Chongqing Education Commission,China(No.KJQN202100431,KJZD-M202100401)the Top Talent Award from The First Affiliated Hospital of Chongqing Medical University,China(No.BJRC2021-04)Cultivation Program of Postdoctoral Research of The First Affiliated Hospital of Chongqing Medical University,China(No.CYYY-BSHPYXM-202202)supported by a post-doctoral fellowship from Chongqing Medical University and rewarded by China Postdoctoral Science Foundation(No.2022M720605)supported in part by research grants from the 2019 Science and Technology Project of Chongqing Education Commission,China(No.KJQN201900410)the 2019 Funding for Postdoctoral Research(Chongqing Human Resources and Social Security Bureau No.298)the Natural Science Foundation of China(No.82102696)supported by the Medical Scientist Training Program of the National Institutes of Health,USA(No.T32 GM007281)supported in part by The University of Chicago Cancer Center Support Grant,USA(No.P30CA014599)the National Center for Advancing Translational Sciences(NCATS)of the National Institutes of Health,USA(No.5UL1TR002389)supported by the Mabel Green Myers Research Endowment Fund and The University of Chicago Orthopedics Alumni Fund.
文摘Recent advances in deep sequencing technologies have revealed that,while less than 2%of the human genome is transcribed into mRNA for protein synthesis,over 80%of the genome is transcribed,leading to the production of large amounts of noncoding RNAs(ncRNAs).It has been shown that ncRNAs,especially long non-coding RNAs(lncRNAs),may play crucial regulatory roles in gene expression.As one of the first isolated and reported lncRNAs,H19 has gained much attention due to its essential roles in regulating many physiological and/or pathological processes including embryogenesis,development,tumorigenesis,osteogen-esis,and metabolism.Mechanistically,H19 mediates diverse regulatory functions by serving as competing endogenous RNAs(CeRNAs),Igf2/H19 imprinted tandem gene,modular scaffold,cooperating with H19 antisense,and acting directly with other mRNAs or lncRNAs.Here,we summarized the current understanding of H19 in embryogenesis and development,cancer development and progression,mesenchymal stem cell lineage-specific differentiation,and metabolic diseases.We discussed the potential regulatory mechanisms underlying H19’s func-tions in those processes although more in-depth studies are warranted to delineate the exact molecular,cellular,epigenetic,and genomic regulatory mechanisms underlying the physiolog-ical and pathological roles of H19.Ultimately,these lines of investigation may lead to the development of novel therapeutics for human diseases by exploiting H19 functions.
文摘Intestinal cancers are developed from intestinal epithelial stem cells(ISCs)in intestinal crypts through a multi-step process involved in genetic mutations of oncogenes and tumor suppressor genes.ISCs play a key role in maintaining the homeostasis of gut epithelium.In 2009,Sato et al established a three-dimensional culture system,which mimicked the niche microenvironment by employing the niche factors,and successfully grew crypt ISCs into organoids or Mini-guts in vitro.Since then,the intestinal organoid technology has been used to delineate cellular signaling in ISC biology.However,the cultured organoids consist of heterogeneous cell populations,and it was technically challenging to introduce genomic changes into three-dimensional organoids.Thus,there was a technical necessity to develop a twodimensional ISC culture system for effective genomic manipulations.In this study,we established a conditionally immortalized mouse intestinal crypt(ciMIC)cell line by using a piggyBac transposon-based SV40 T antigen expression system.We showed that the ciMICs maintained long-term proliferative activity under two-dimensional niche factor-containing culture condition,retained the biological characteristics of intestinal epithelial stem cells,and could form intestinal organoids in three-dimensional culture.While in vivo cell implantation tests indicated that the ciMICs were non-tumorigenic,the ciMICs overexpressing oncogenic b-catenin and/or KRAS exhibited high proliferative activity and developed intestinal adenoma-like pathological features in vivo.Collectively,these findings strongly suggested that the engineered ciMICs should be used as a valuable tool cell line to dissect the genetic and/or epigenetic underpinnings of intestinal tumorigenesis.
文摘AIMTo evaluate outcomes of combined pars plana vitrectomy and Baerveldt glaucoma implant (PPV-BGI) placement for refractory glaucoma.METHODSThe medical records of 92 eyes (89 patients) that underwent PPV-BGI were retrospectively reviewed, including 43 eyes with neovascular glaucoma (NVG) and 49 eyes with other types of glaucoma (non-NVG).RESULTSOutcome measures were visual acuity (VA), intraocular pressure (IOP), glaucoma medical therapy, complications, and success [VA>hand motions (HM), IOP≥6 mm Hg and ≤21 mm Hg, no subsequent glaucoma surgery]. Cumulative success rates for the non-NVG group and NVG group were 79% and 40% at 1y, respectively (P=0.038). No difference in the rates of surgical success were found between pars plana and anterior chamber tube placement. Preoperative IOP (mean±SD) was 30.3±11.7 mm Hg in the Non-NVG group and 40.0±10.6 mm Hg in the NVG group, and IOP was reduced to 15±9.5 mm Hg in the non-NVG group and 15±10.5 mm Hg in the NVG at 1y. Number of glaucoma medications (mean±SD) decreased from 2.7±1.3 in the non-NVG group and 2.8±1.3 in the NVG group preoperatively to 0.76±1.18 in the non-NVG group and 0.51±1.00 in the NVG group at 1y. Improvement in VA of ≥2 Snellen lines was observed in 25 (27%) eyes, although only 33% of non-NVG eyes and 2.3% of NVG eyes maintained VA better than 20/200 at 1y. Nonclearing vitreous hemorrhage was the most common postoperative complication occurring in 16 (17%) eyes, and postoperative suprachoroidal hemorrhages developed in 5 (5.4%) eyes.CONCLUSIONPPV-BGI is a viable surgical option for eyes with refractory glaucoma, but visual outcomes are frequently poor because of ocular comorbidities, especially in eyes with NVG. The location of tube placement does not influence surgical outcome and should be left to the discretion of the surgeon.
文摘The physiological changes and the mechanism of stress tolerance in tomato were studied under low temperature and low light conditions. Two growth chamber experiments evaluated three temperatures regimes under standard and relatively low illumination levels with three tomato genotypes. Both experiments used a completely randomized split-plot design (CRD), with temperature regime as the main plot and tomato genotype as the split-plot. The three tomato varieties were “Fenyan No.1”, “SV0313TG”, and “Ousa”. In both experiments, activity of superoxide dismutase (SOD) and peroxidases (POD) in tomato seedlings decreased under low temperature regime and the combination of low temperature and low light. Decreasing temperature had the greatest effect on the increase in enzyme activity. Decrease in POD activity was the greatest under low light and low temperature. The concentration of malondialdehyde (MDA) in plant tissue also decreased under low temperature (20°C/10°C day/night) compared to the standard temperature control (25°C/16°C day/night), but increased at 15°C/5°C day/night temperatures in both experiments and was the greatest under the lowest light and temperature conditions. In both experiments, proline concentrations were the greatest under the standard light intensity (30,000 lux), and proline concentrations increased as temperature decreased. The content of soluble sugar decreased under only low temperature stress but increased under double stresses. The relative value of osmotic potential increased a little under low temperature stress but decreased under double stresses.
基金This work was supported by grants from the China MegaProjects for Infectious Disease(2018ZX10713-002,2018ZX10711001,2017ZX10104001,and 2017ZX10302301-004-002).
文摘Here,we report the identification of Histoplasma causing an unexplained disease cluster in Matthews Ridge,Guyana.In March 2019,14 employees of Chongqing Bosai Mining Company,China,working in a manganese mining of Guyana,had unexplained fever,and two of them died.We obtained lung and brain tissues as well as the blood samples from the two deceased cases(patient No.1 and 2),and bronchoscopy lavages and cerebrospinal fluid samples from one severe case(patient No.3),respectively.All samples were tested by pathological examination,high-throughput sequencing,and real-time PCR.Pathological detection showed the presence of spore-like structures in the lung tissue of patient No.1,indicating a fungal infection in this patient.Nanopore sequencing identified the existing of H.capsulatum in the lung tissue sample within 13 h.Next-generation sequencing identified specific fragments of H.capsulatum in all of the samples tested(lung,brain and blood serum from the deceased cases,and plasma from the severe case).Real-time PCR assays did not reveal any viral infection related to transmission from bat feces.We conclude that H.capsulatum was the causative pathogen of this disease cluster based on epidemiologic,clinical,pathological and nucleic acid evidence.
基金supported by the National Key R&D Program of China(2016YFE0205800)National Science and Technology Major Project(2016ZX10004222)+5 种基金Emergency Technology Research Issue on Prevention and Control for Human Infection with A(H7N9)Avian Influenza Virus(10600100000015001206)intramural special grants for influenza virus research from the Chinese Academy of Sciences(KJZD-EWL15)Tianjin Research Program of the Application Foundation and Advanced Technology(14JCYBJC24400)the research project RFBR 17-04-01919a leading principal investigator of the NSFC Innovative Research Group(81621091)supported by the Youth Innovation Promotion Association of Chinese Academy of Sciences(CAS)(2017122)
文摘Studies on influenza virus by Chinese Academy of Sciences(CAS)could be traced back as early as 2005 by the CAS Key Laboratory of Pathogenic Microbiology and Immunology(CASPMI),who discovered that Qinghai-like Clade 2.2H5N1 subtype highly pathogenic avian influenza virus(HPAIV)first caused severe outbreak in wild birds in Qinghai Lake(Liu et al.,2005).
基金The study was partially supported by NSFC(81300778,81271020)973 program(2012CB917304)+1 种基金863 Program(2014AA021604)NIH(R01EY024134,R01HG008135,R01EY018660,R01EY021374)and VA Merit Award.
文摘Age-related macular degeneration(AMD)is characterized by complex interactions between genetic and environmental factors.Here we genotyped the selected 25 single-nucleotide polymorphisms(SNPs)in 983 cases with advanced AMD and 271 cases with intermediate AMD and build an AMD life-risk score model for assessment of progression from intermediate to advanced AMD.We analyzed the performance of the prediction model for geographic atrophy progressors or choroidal neovascularization progressors versus non-progressors based on the 25 SNPs plus body mass index and smoking status.Our results suggest that a class prediction algorithm can be used for the risk assessment of progression from intermediate to late AMD stages.The algorithm could also be potentially applied for therapeutic response,and toward personalized care and precision medicine.
文摘The authors regret that an image assembly(copy/paste)error in Figure 3D,in which the image for the organoid of"Primary MiCs"group was erroneously duplicated with an image of primary MICs that was previously published.The corrected figure is shown below.As shown in the corrected Figure 3D,this error does not adversely impact the conclusion of the original work.The authors would like to apologise forany inconvenience caused.
基金supported in part by research grants from the China Postdoctoral Science Foundation(2019M663446 to ZZ)the Postdoctoral Program of the Natural Science Foundation of Chongqing,China(cstc2019jcyj-bsh0006 to ZZ)+6 种基金WW was supported by the Medical Scientist Training Program of the National Institutes of Health(T32 GM007281)This project was also supported in part by The University of Chicago Cancer Center Support Grant(P30CA014599)the National Center for Advancing Translational Sciences of the National Institutes of Health through Grant Number UL1 TR000430TCH was supported by the Mabel Green Myers Research Endowment Fund and The University of Chicago Orthopaedics Alumni Fund.Funding sources were not involved in the study designin the collection,analysis and interpretation of datain the writing of the reportand in the decision to submit the paper for publication.
文摘Plasmid DNA(pDNA)isolation from bacterial cells is one of the most common and critical steps in molecular cloning and biomedical research.Almost all pDNA purification in-volves disruption of bacteria,removal of membrane lipids,proteins and genomic DNA,purifi-cation of pDNA from bulk lysate,and concentration of pDNA for downstream applications.While many liquid-phase and solid-phase pDNA purification methods are used,the final pDNA preparations are usually contaminated with varied degrees of host RNA,which cannot be completely digested by RNase A.To develop a simple,cost-effective,and yet effective method for RNA depletion,we investigated whether commercially available size selection magnetic beads(SSMBs),such as Mag-Bind®TotalPure NGS Kit(or Mag-Bind),can completely deplete bacterial RNA in pDNA preparations.In this proof-of-principle study,we demonstrated that,compared with RNase A digestion and two commercial plasmid affinity purification kits,the SSMB method was highly efficient in depleting contaminating RNA from pDNA minipreps.Gene transfection and bacterial colony formation assays revealed that pDNA purified from SSMB method had superior quality and integrity to pDNA samples cleaned up by RNase A digestion and/or commercial plasmid purification kits.We further demonstrated that the SSMB method completely depleted contaminating RNA in large-scale pDNA samples.Furthermore,the Mag-bind-based SSMB method costs only 5-10%of most commercial plasmid purification kits on a per sample basis.Thus,the reported SSMB method can be a valuable and inexpensive tool for the removal of bacterial RNA for routine pDNA preparations.
基金supported by the Megaproject for Infectious Disease Research of China(2016ZX10004222-003)the research of Ebola pathogen from the National Natural Science Foundation of China(NSFC,81590763)+4 种基金National Key Research and Development Program of China(2016YFC1200200 to Y.Shu)the Distinguished Young Scientist Program of the NSFC(81525017 to Y.Shu)the Excellent Young Scientist Program of the NSFC(81822040 to W.J.Liu)the Taishan Scholar Project of Shandong Province(ts201511056 to W.Shi)G.F.Gao is a primary principal investigator of the NSFC Innovative Research Group(81621091).
文摘The onsite next generation sequencing(NGS)of Ebola virus(EBOV)genomes during the 2013–2016 Ebola epidemic in Western Africa provides an opportunity to trace the origin,transmission,and evolution of this virus.Herein,we have diagnosed a cohort of EBOV patients in Sierra Leone in 2015,during the late phase of the outbreak.The surviving EBOV patients had a recovery process characterized by decreasing viremia,fever,and biochemical parameters.EBOV genomes sequenced through the longitudinal blood samples of these patients showed dynamic intra-host substitutions of the virus during acute infection,including the previously described short stretches of 13 serial TNC mutations.Remarkably,within individual patients,samples collected during the early phase of infection possessed Ts at these nucleotide sites,whereas they were replaced by Cs in samples collected in the later phase,suggesting that these short stretches of TNC mutations could emerge independently.In addition,up to a total of 35 nucleotide sites spanning the EBOV genome were mutated coincidently.Our study showed the dynamic intra-host adaptation of EBOV during patient recovery and gave more insight into the complex EBOV-host interactions.
基金supported by the Natural Sciences and Engineering Research Council of Canada(NSERC)under Grant Nos.RGPIN-2020-06482,RGPIN-2016-06253 and CGSD2-503941-2017.
文摘When querying databases containing sensitive information,the privacy of individuals stored in the database has to be guaranteed.Such guarantees are provided by differentially private mechanisms which add controlled noise to the query responses.However,most such mechanisms do not take into consideration the valid range of the query being posed.Thus,noisy responses that fall outside of this range may potentially be produced.To rectify this and therefore improve the utility of the mechanism,the commonly-used Laplace distribution can be truncated to the valid range of the query and then normalized.However,such a data-dependent operation of normalization leaks additional information about the true query response,thereby violating the differential privacy guarantee.Here,we propose a new method which preserves the differential privacy guarantee through a careful determination of an appropriate scaling parameter for the Laplace distribution.We adapt the privacy guarantee in the context of the Laplace distribution to account for data-dependent normalization factors and study this guarantee for different classes of range constraint configurations.We provide derivations of the optimal scaling parameter(i.e.,the minimal value that preserves differential privacy)for each class or provide an approximation thereof.As a result of this work,one can use the Laplace distribution to answer queries in a range-adherent and differentially private manner.To demonstrate the benefits of our proposed method of normalization,we present an experimental comparison against other range-adherent mechanisms.We show that our proposed approach is able to provide improved utility over the alternative mechanisms.
基金The National Natural Science Foundation of China(No.61502422)the Natural Science Foundation of Zhejiang Province(No.LY18F020028,LQ15F020006)the Natural Science Foundation of Zhejiang University of Technology(No.2014XY007)
文摘By analyzing the structures of circuits,a novel approach for signal probability estimation of very large-scale integration(VLSI)based on the improved weighted averaging algorithm(IWAA)is proposed.Considering the failure probability of the gate,first,the first reconvergent fan-ins corresponding to the reconvergent fan-outs were identified to locate the important signal correlation nodes based on the principle of homologous signal convergence.Secondly,the reconvergent fan-in nodes of the multiple reconverging structure in the circuit were identified by the sensitization path to determine the interference sources to the signal probability calculation.Then,the weighted signal probability was calculated by combining the weighted average approach to correct the signal probability.Finally,the reconvergent fan-out was quantified by the mixed-calculation strategy of signal probability to reduce the impact of multiple reconvergent fan-outs on the accuracy.Simulation results on ISCAS85 benchmarks circuits show that the proposed method has approximate linear time-space consumption with the increase in the number of the gate,and its accuracy is 4.2%higher than that of the IWAA.
文摘Misoprostol (Cytotec, Pfizer) is a prostaglandin E1 analogue widely used in labor induction. Understanding of potential risks of misoprostol in labor induction is lacking as the drug is used off-label in most countries. A 35-year-old G3P2 woman with post-date pregnancy at 40 + 3 weeks was induced using titrated oral misoprostol. Following delivery, post-partum hemorrhage was noted and, upon discovery of a uterine wall rupture due to congenital weakness of the myometrium, emergency abdominal total hysterectomy was conducted. Following surgery, the patient made a full recovery and was discharged. The main contraindications for misoprostol in labor induction are a scarred uterus or multipara greater than 4. Uterine wall weakness should be considered as a potential contraindication. Extreme vigilance is required in use of misoprostol for labor induction.
