A four-gene signature-derived risk score for glioblastoma:prospects for prognostic and response predictive analyses

Objective: Glioblastoma(GBM) is the most common primary malignant brain tumor regulated by numerous genes, with poor survival outcomes and unsatisfactory response to therapy.Therefore, a robust, multi-gene signature-derived model is required to predict the prognosis and treatment response in GBM.Methods: Gene expression data of GBM from TCGA and GEO datasets were used to identify differentially expressed genes(DEGs)through DESeq2 or LIMMA methods.The DEGs were then overlapped and used for survival analysis by univariate and multivariate COX regression.Based on the gene signature of multiple survival-associated DEGs, a risk score model was established,and its prognostic and predictive role was estimated through Kaplan–Meier analysis and log-rank test.Gene set enrichment analysis(GSEA) was conducted to explore high-risk score-associated pathways.Western blot was used for protein detection.Results: Four survival-associated DEGs of GBM were identified: OSMR, HOXC10, SCARA3, and SLC39A10.The four-gene signature-derived risk score was higher in GBM than in normal brain tissues.GBM patients with a high-risk score had poor survival outcomes.The high-risk group treated with temozolomide chemotherapy or radiotherapy survived for a shorter duration than the low-risk group.GSEA showed that the high-risk score was enriched with pathways such as vasculature development and cell adhesion.Western blot confirmed that the proteins of these four genes were differentially expressed in GBM cells.Conclusions: The four-gene signature-derived risk score functions well in predicting the prognosis and treatment response in GBM and will be useful for guiding therapeutic strategies for GBM patients.

The genomic and epigenetic footprint of local adaptation to variable climates in kiwifruit

A full understanding of adaptive genetic variation at the genomic level will help address questions of how organisms adapt to diverse climates.Actinidia eriantha is a shade-tolerant species,widely distributed in the southern tropical region of China,occurring in spatially heterogeneous environments.In the present study we combined population genomic,epigenomic,and environmental association analyses to infer population genetic structure and positive selection across a climatic gradient,and to assess genomic offset to climatic change for A.eriantha.The population structure is strongly shaped by geography and influenced by restricted gene f low resulting from isolation by distance due to habitat fragmentation.In total,we identified 102 outlier loci and annotated 455 candidate genes associated with the genomic basis of climate adaptation,which were enriched in functional categories related to development processes and stress response;both temperature and precipitation are important factors driving adaptive variation.In addition to single-nucleotide polymorphisms(SNPs),a total of 27 single-methylation variants(SMVs)had significant correlation with at least one of four climatic variables and 16 SMVswere located in or adjacent to genes,several of whichwere predicted to be involved in plant response to abiotic or biotic stress.Gradient forest analysis indicated that the central/east populations were predicted to be at higher risk of future population maladaptation under climate change.Our results demonstrate that local climate factors impose strong selection pressures and lead to local adaptation.Such information adds to our understanding of adaptive mechanisms to variable climates revealed by both population genome and epigenome analysis.

Preparation of TiO_(2) Nano-Flower Coating on Ti Substrates with Good Physical Sterilization Effect and Biocompatibility

We report a facile solution method to form titanium oxide(TiO_(2))nano-flower structure on the titanium(Ti)substrates for realizing good physical sterilization and biocompatibility.We first prepare TiO_(2) nanotubes(NT)with a diameter of about 80-100 nm and a length of about 5μm on Ti substrates by anodization,which is utilized as precursor.Then,we employ immersion treatment in different concentrations of phosphoric acid solution at 75℃ for 5 h to realize the transformation from TiO_(2) NT to TiO_(2) nano-flower structure.In addition,we studied the effects of phosphoric acid concentration(1 wt%,2.5 wt%,5 wt% and 10 wt%)on the TiO_(2) nano-flower structure,and the antibacterial properties and biocompatibility of the TiO_(2) nano-flower structure.The results show that TiO_(2) nano-flower structure become larger and thicker with the increase in the phosphoric acid concentration,and the thickness of the coating can reach 6.88μm.Meanwhile,the TiO_(2) nano-flower structure shows good physical sterilization effect,especially for the TiO_(2) nano-flower structure formed in 10 wt%H^(3)PO_(4) solution,the antibacterial rate can reach 95%.In addition,the TiO_(2) nano-flower structure have no toxicity to the osteoblasts and support cell growth.

Synergistic antibacterial activity of physical-chemical multi-mechanism by TiO2 nanorod arrays for safe biofilm eradication on implant

Treatment of implant-associated infection is becoming more challenging,especially when bacterial biofilms form on the surface of the implants.Developing multi-mechanism antibacterial methods to combat bacterial biofilm infections by the synergistic effects are superior to those based on single modality due to avoiding the adverse effects arising from the latter.In this work,TiO2 nanorod arrays in combination with irradiation with 808 nearinfrared(NIR)light are proven to eradicate single specie biofilms by combining photothermal therapy,photodynamic therapy,and physical killing of bacteria.The TiO2 nanorod arrays possess efficient photothermal conversion ability and produce a small amount of reactive oxygen species(ROS).Physiologically,the combined actions of hyperthermia,ROS,and puncturing by nanorods give rise to excellent antibacterial properties on titanium requiring irradiation for only 15 min as demonstrated by our experiments conducted in vitro and in vivo.More importantly,bone biofilm infection is successfully treated efficiently by the synergistic antibacterial effects and at the same time,the TiO2 nanorod arrays improve the new bone formation around implants.In this protocol,besides the biocompatible TiO2 nanorod arrays,an extra photosensitizer is not needed and no other ions would be released.Our findings reveal a rapid bacteria-killing method based on the multiple synergetic antibacterial modalities with high biosafety that can be implemented in vivo and obviate the need for a second operation.The concept and antibacterial system described here have large clinical potential in orthopedic and dental applications.

全球变暖导致易诱发臭氧污染的强地面太阳辐射频率增加

世界卫生组织2021年提出了新的臭氧标准,不仅加严了原有的短期暴露标准,还增加了暖季峰值的长期暴露指标.2019年秋季我国发生了大范围臭氧污染事件,特别是珠三角地区臭氧浓度异常增加最为突出,导致其暖季峰值超标,并且2019年长时间臭氧污染事件增幅更大.本文发现地面太阳辐射与臭氧年际变化相关性远高于其他气象因子,即使在温度较低时,较强的太阳辐射依然可促进高臭氧浓度累积.数值模式显示强太阳辐射驱动天然源大幅增加,不仅促进臭氧浓度升高,更重要的是,对于长时间臭氧污染事件频率增加大于短期污染事件,从而大大促进臭氧超标天数的增加.结合高分辨率地球系统模式和多模式比较计划,一致揭示在全球变暖下中国东部、美国东南部、欧洲各国,未来地面太阳辐射显著增加.通过将秋季地面太阳辐射日异常标准化,构建了臭氧气象指数,可有效揭示高臭氧浓度,阐明在北半球多个易发生臭氧污染区域,高臭氧气象指数天气发生频率显著增加,即利于高臭氧污染发生的气象条件在全球变暖下可能会更加频繁地发生.

Sources and characteristics of fine particles over the Yellow Sea and Bohai Sea using online single particle aerosol mass spectrometer

Marine aerosols over the East China Seas are heavily polluted by continental sources. During the Chinese Comprehensive Ocean Experiment in November 2012, size and mass spectra of individual atmospheric particles in the size range from 0.2 to 2.0 μm were measured on board by a single particle aerosol mass spectrometer （SPAMS）. The average hourly particle number （PN） was around 4560 ＋ 3240 in the South Yellow Sea （SYS）, 2900 ± 3970 in the North Yellow Sea （NYS）, and 1700 ± 2220 in the Bohai Sea （BS）. PN in NYS and BS varied greatly over 3 orders of magnitude, while that in SYS varied shghtly. The size distributions were fitted with two log-normal modes. Accumulation mode dominated in NYS and BS, especially during episodic periods. Coarse mode particles played an important role in SYS. Particles were dassifled using an adaptive resonance theory based neural network algorithm （ART-2a）. Six particle types were identified with secondary-containing, aged sea-salt, soot-like, biomass burning, fresh sea-salt, and lead-containing particles accounting for 32%, 21%, 18%, 16%, 4%, and 3% of total PN, respectively. Aerosols in BS were relatively enriched in particles from anthropogenic sources compared to SYS, probably due to emissions from more developed upwind regions and indicating stronger influence of continental outflow on marine environment. Variation of source types depended mainly on origins of transported air masses. This study examined rapid changes in PN, size distribution and source types of fine particles in marine atmospheres. It also demonstrated the effectiveness of hi,h-time-resolution source apportionment by ART-2a.

Regulation of TiO_(2) nanoarrays on titanium implants for enhanced osteogenic activity and immunomodulation

The surface topography of implants plays a major role in osteogenesis and immunomodulation.In this study,three types of TiO_(2) nanoarrays including nanorod arrays with a diameter of 45 nm(TiO_(2)-N),nanorod arrays with a diameter of 60 nm(TiO_(2)-N N),and nanocone arrays(TiO_(2)-NW)are prepared on titanium and the behavior of bone marrow stromal cells(BMSCs)and polarization of macrophages are studied.Compared to the planar titanium control,TiO_(2) nanoarrays facilitate osteogenesis of BMSCs and stimulate the pro-healing M2 phenotype.However,adhesion,spreading,proliferation,and osteogenic differentiation of BMSCs are more pronounced on TiO_(2)-N N than both TiO_(2)-N and TiO_(2)-NW.TiO_(2)-NN also produces the best immune microenvironment,while TiO_(2)-NW is more favorable than TiO_(2)-NN from the viewpoint of cell adhesion and spreading of osteoblasts.

Spatiotemporal trends of PM_(2.5) and its major chemical components at urban sites in Canada

To evaluate the effectiveness of emission control regulations designed for reducing air pollution, chemically resolved PM_(2.5) data have been collected across Canada through the National Air Pollution Surveillance network in the past decade. 24-hr time integrated PM_(2.5) collected at seven urban and two rural sites during 2010-2016 were analyzed to characterize geographical and seasonal patterns and associated potential causes. Site-specific seven-year mean gravimetric PM_(2.5) mass concentrations ranged from 5.7 to 9.6 μg/m^(3). Seven-year mean concentrations of SO_(4)^(2-), NO_(3)^(-), NH_(4)^(+), organic carbon(OC), and elemental carbon(EC) were in the range of 0.68 to 1.6, 0.21 to 1.5, 0.27 to 0.71, 1.1 to 1.9, and 0.37 to 0.71 μg/m^(3), accounting for 10.8%-18.1%, 3.7%-16.7%, 4.7%-7.4%, 18.4%-21.0%, and 6.4%-10.6%, respectively, of gravimetric PM_(2.5) mass. PM_(2.5) and its five major chemical components showed higher concentrations in southeastern Canada and lower values in Atlantic Canada, with the seven-year mean ratios between the two regions being on the order of 1.7 for PM_(2.5) and 1.8-7.1 for its chemical components. When comparing the concentrations between urban and rural sites within the same region, those of SO_(4)^(2-) and NH_(4)^(+) were comparable, while those of NO_(3)^(-), OC, and EC were around 20%, 40%-50%, and 70%-80%, respectively, higher at urban than rural sites, indicating the regional scale impacts of SO_(4)^(2-) and NH_(4)^(+) and effects of local sources on OC and EC. Monthly variations generally showed summertime peaks for SO_(4)^(2-) and wintertime peaks for NO_(3)^(-), but those of NH_(4)^(+), OC, and EC exhibited different seasonality at different locations.

Pyroptotic macrophages stimulate the SARS-CoV-2-associated cytokine storm

Coronavirus disease 2019(COVID-19)is an unprecedented pandemic caused by severe acute respiratory syndrome coronavirus 2(SARS-CoV-2).As of 22 February 2021,the worldwide pandemic has resulted in more than 110 million cases and 2.4 million deaths.1 Clinical investigation of COVID-19 patients has shown that a systemic cytokine storm can occur,especially in severe cases.2 Treatment of the SARS-CoV-2-associated cytokine storm with tocilizumab3 or anakinra4 has been shown to immediately improve the clinical outcome in most severe and critical COVID-19 patients.These data highlight the systemic cytokine storm as an important exacerbating event in severe COVID-19;however,our understanding of the molecular mechanisms involved in the initiation of the SARS-CoV-2-associated cytokine storm is limited.In the present study,we uncovered a reasonable explanation for cytokine storm initiation through the analysis of 13 autopsy samples from severe COVID-19 patients.

SRSF1通过可变剪接调控小鼠减数分裂期间的同源染色体配对和联会

同源染色体配对和联会是第一次减数分裂过程中的重要环节.然而,可变剪接(AS)在同源染色体配对和联会中发挥作用的基本机制仍不清楚.本文揭示了SRSF1对于同源染色体配对和联会中的AS和基因表达至关重要.小鼠生精细胞中Srsf1的缺失导致同源染色体配对和联会异常,引发非阻塞性无精子症(NOA).在同源染色体识别、端粒介导的染色体移动以及联会复合体(SC)组装过程中,SRSF1与TRA2B和U2AF2相互作用,直接结合并通过AS调控Dmc1、Sycp1和Sun1的表达.总之,本研究揭示了在同源染色体配对和联会中SRSF1介导的转录后调控的关键作用,为阐明雄性减数分裂转录后调控的分子网络提供理论依据.

Corrosion behavior,antibacterial ability,and osteogenic activity of Zn-incorporated Ni-Ti-O nanopore layers on NiTi alloy

Development of bone fixation devices with excellent corrosion resistance,antibacterial ability,and osteogenic activity is critical for promoting fracture healing.In this study,Zn-incorporated nanopore(NP)layers were prepared on the NiTi alloy through anodization and hydrothermal treatment.Results show that Zn can be evenly incorporated into the NP layers in the form of ZnTiO_(2).The Zn-incorporated samples exhibit good corrosion resistance and significantly reduce Ni^(2+)release.Meanwhile,the samples can continuously release Zn^(2+),which is responsible for excellent long-term antibacterial ability.Furthermore,the synergetic effect of Zn^(2+) release and nanoporous structure of the NP layers endues the NiTi alloy excellent osteogenic activity,as verified by upregulated alkaline phosphatase activity,secretion of type I collagen,and extracellular matrix mineralization.Therefore,Zn-incorporated Ni-Ti-O NP layers have great potential as biomedical coatings of NiTi-based implant materials.

Self-assembled nanosheets on NiTi alloy facilitate endothelial cell function and manipulate macrophage immune response

Stenting has been widely adopted for the treatment of cardiovascular diseases,but the complications such as in-stent restenosis and late stent thrombosis cannot be completely avoided,which are closely related to endothelial dysfunction and inflammatory response.In the present work,oxide nanosheets were grown on the surface of nearly equiatomic Ni Ti alloy by alkaline corrosion(AC),aiming at yielding favorable endothelial functionality and immune microenvironment.The results show nanosheets mainly composed of TiO_(2),Ni(OH)_(2),and K_(2)TiO_(3)can be grown on the alloy in KOH solution of 2.5–15 M at room temperature.The AC-treated samples significantly promote endothelial cell(EC)functionality such as proliferation,migration,NO production,VEGF secretion,and angiogenesis.In addition,the sample grown in KOH of 15 M can switch macrophages to an anti-inflammatory M2 phenotype and up-regulate the gene expression of VEGF to facilitate EC functionality.These results demonstrate that the nanosheets can directly and indirectly up-regulate EC functionality,possibly leading to rapid re-endothelialization of the stents thus addressing the stent-related complications.

Roles of SO_2 oxidation in new particle formation events

The oxidation of SO2 is commonly regarded as a major driver for new particle formation（NPF） in the atmosphere. In this study, we explored the connection between measured mixing ratio of SO2 and observed long-term（duration 〉 3 hr） and short-term（duration〈 1.5 hr） NPF events at a semi-urban site in Toronto. Apparent NPF rates（J30） showed a moderate correlation with the concentration of sulfuric acid（[H2SO4]） calculated from the measured mixing ratio of SO2 in long-term NPF events and some short-term NPF events（Category I）（R^2= 0.66）. The exponent in the fitting line of J30~ [H2SO4]nin these events was1.6. It was also found that SO2 mixing ratios varied a lot during long-term NPF events,leading to a significant variation of new particle counts. In the SO2-unexplained short-term NPF events（Category II）, analysis showed that new particles were formed aloft and then mixed down to the ground level. Further calculation results showed that sulfuric acid oxidized from SO2 probably made a negligible contribution to the growth of 〉 10 nm new particles.

The genome sequencing and comparative analysis of a wild kiwifruit Actinidia eriantha

The current kiwifruit industry is mainly based on the cultivars derived from the species Actinidia chinensis(Ac)which may bring risks such as canker disease.Introgression of desired traits from wild relatives is an important method for improving kiwifruit cultivars.Actinidia eriantha(Ae)is a particularly important taxon used for hybridization or introgressive breeding of new kiwifruit cultivars because of its valued species-specific traits.Here,we assembled a chromosome-scale high-quality genome of a Ae sample which was directly collected from its wild populations.Our analysis revealed that 41.3%of the genome consists of repetitive elements,comparable to the percentage in Ac and Ae cultivar“White”genomes.The genomic structural variation,including the presence/absence-variation(PAV)of genes,is distinct between Ae and Ac,despite both sharing the same two kiwifruit-specific whole genome duplication(WGD)events.This suggests that a post-WGD divergence mechanism occurred during their evolution.We further investigated genes involved in ascorbic acid biosynthesis and disease-resistance of Ae,and we found introgressive genome could contribute to the complex relationship between Ae and other representative kiwifruit taxa.Collectively,the Ae genome offers valuable genetic resource to accelerate kiwifruit breeding applications.

Biodegradable porous Zn-1Mg-3βTCP scaffold for bone defect repair:In vitro and in vivo evaluation

Zn-based materials are promising as bone repair materials,but their poor mechanical property and bioactivity as well as low degradation rate render the potential application.Rational structural and material design can address the concerns.In this study,porous Zn-1 wt.%Mg-3 vol.%β-TCP scaffolds with 40%and 60%preset porosities were fabricated via heating-press sintering using NaCl particles as space holders,and their mechanical properties,in vitro degradation behavior,cytotoxicity and in vivo osteogenic activities were evaluated.The results showed that the actual porosities of the scaffolds were 22%and 50%.Mg exists in the form of Zn 2 Mg and Zn 11 Mg 2,whileβ-TCP evenly distributed in the matrix.The compressive yield strength of scaffolds ranges from approximately 58.46 to 71.04 MPa,which is close to that of cancellous bone.The in vitro degradation tests showed that the corrosion rate of the scaffolds was in the range of about 2.73-4.28 mm y^(-1).Moreover,the scaffolds not only provided great space for osteoblasts adhesion and proliferation in vitro but also possessed favorable degradability and osteogenic activity in vivo.The porous Zn-1 wt.%Mg-3 vol.%β-TCP scaffolds manifest reliable mechanical properties,desirable degradability,and osteogenic activity,which are promising as next-generation bone repair materials.

Investigating the impact of air pollution on AMI and COPD hospital admissions in the coastal city of Qingdao,China

Air pollution has been widely associated with adverse effects on the respiratory and cardiovascular systems.We investigated the relationship between acute myocardial infarction(AMI),chronic obstructive pulmonary disease(COPD)and air pollution exposure in the coastal city of Qingdao,China.Air pollution in this region is characterized by inland and oceanic transportation sources in addition to local emission.We examined the influence of PM_(2.5),PM_(10),NO_(2),SO_(2),CO and O_(3) concentrations on hospital admissions for AMI and COPD from October 1,2014,to September 30,2018,in Qingdao using a Poisson generalized additive model(GAM).We found that PM_(2.5),PM_(10),NO_(2),SO_(2) and CO exhibited a significant short-term(lag 1 day)association with AMI in the singlepollutant model among older adults(>65 years old)and females,especially during the cold season(October to March).In contrast,only NO2 and SO2 had clear cumulative lag associations with COPD admission for females and those over 65 years old at lag 01 and lag 03,respectively.In the twopollutant model,the exposure-response relationship fitted by the two-pollutant model did not change significantly.Our findings indicated that there is an inflection point between the concentration of certain air pollutants and the hospital admissions of AMI and COPD even under the linear assumption,indicative of the benefits of reducing air pollution vary with pollution levels.This study has important implications for the development of policy for air pollution control in Qingdao and the public health benefits of reducing air pollution levels.

Elevated Kir2.1/nuclear N2ICD defines a highly malignant subtype of non-WNT/SHH medulloblastomas

Medulloblastoma(MB)is one of the most common childhood malignant brain tumors(WHO grade IV),traditionally divided into WNT,SHH,Group 3,and Group 4 subgroups based on the transcription profiles,somatic DNA alterations,and clinical outcomes.Unlike WNT and SHH subgroup MBs,Group 3 and Group 4 MBs have similar transcriptomes and lack clearly specific drivers and targeted therapeutic options.The recently revised WHO Classification of CNS Tumors has assigned Group 3 and 4 to a provisional non-WNT/SHH entity.In the present study,we demonstrate that Kir2.1,an inwardly-rectifying potassium channel,is highly expressed in non-WNT/SHH MBs,which promotes tumor cell invasion and metastasis by recruiting Adam10 to enhance S2 cleavage of Notch2 thereby activating the Notch2 signaling pathway.Disruption of the Notch2 pathway markedly inhibited the growth and metastasis of Kir2.1-overexpressing MB cell-derived xenograft tumors in mice.Moreover,Kir2.1^(high)/nuclear N2ICD^(high)MBs are associated with the significantly shorter lifespan of the patients.Thus,Kir2.1^(high)/nuclear N2ICD^(high)can be used as a biomarker to define a novel subtype of non-WNT/SHH MBs.Our findings are important for the modification of treatment regimens and the development of novel-targeted therapies for non-WNT/SHH MBs.