SMARCA4/BRG1缺陷型非小细胞肺癌的临床病理特点和治疗策略

SWI/SNF复合体是一个含有10~15个亚基的多蛋白复合体,参与重要的细胞进程和功能调控,突变频率较高,最常见的突变亚基为SMARCA4/BRG1。SMARCA4/BRG1缺失的非小细胞肺癌(SMARCA4-deficient non-small lung cancer,SMARCA4-dNSCLC)具有恶性程度高、肿瘤发展迅速、生存率低等特点。SMARCA4-dNSCLC经常发生SMARCA4和KRAS、TP53、KEAP1、STK11共突变的情况,但ALK、EGFR、ROS1等常见突变几乎均为阴性,因此传统的肺癌治疗模式对SMARCA4-dNSCLC效果有限,新型治疗策略的出现或是解决问题的关键。本文将对SMARCA4-dNSCLC的临床病理特点和新型治疗策略进行综述。

Modal structure and propagation of internal tides in the northeastern South China Sea

The evolution of energy, energy flux and modal structure of the internal tides (ITs) in the northeastern South China Sea is examined using the measurements at two moorings along a cross-slope section from the deep continental slope to the shallow continental shelf. The energy of both diurnal and semidiurnal ITs clearly shows a ~14-day spring-neap cycle, but their phases lag that of barotropic tides, indicating that ITs are not generated on the continental slope. Observations of internal tidal energy flux suggest that they may be generated at the Luzon Strait and propagate west-northwest to the continental slope in the northwestern SCS. Because the continental slope is critical-supercritical with respect to diurnal ITs, about 4.6 kJ/m^2 of the incident energy and 8.7 kW/m of energy flux of diurnal ITs are reduced from the continental slope to the continental shelf. In contrast, the semidiurnal internal tides enter the shelf because of the sub-critical topography with respect to semidiurnal ITs. From the continental slope to the shelf, the vertical structure of diurnal ITs shows significant variation, with dominant Mode 1 on the deep slope and dominant higher modes on the shelf. On the contrary, the vertical structure of the semidiurnal ITs is stable, with dominant Mode 1.

Modified parameterization for near-inertial waves

The near-inertial waves(NIWs)are important for energy cascade in the ocean.They are usually significantly reinforced by strong winds,such as typhoon.Due to relatively coarse resolutions in contemporary climate models,NIWs and associated ocean mixing need to be parameterized.In this study,a parameterization for NIWs proposed by Jochum in 2013(J13 scheme),which has been widely used,is compared with the observations in the South China Sea,and the observations are treated as model outputs.Under normal conditions,the J13 scheme performs well.However,there are noticeable discrepancies between the J13 scheme and observations during typhoon.During Typhoon Kalmaegi in 2014,the inferred value of the boundary layer is deeper in the J13 scheme due to the weak near-inertial velocity shear in the vertical.After typhoon,the spreading of NIWs beneath the upper boundary layer is much faster than the theoretical prediction of inertial gravity waves,and this fast process is not rendered well by the J13 scheme.In addition,below the boundary layer,NIWs and associated diapycnal mixing last longer than the direct impacts of typhoon on the sea surface.Since the energy dissipation and diapycnal mixing below the boundary layer are bounded to the surface winds in the J13 scheme,the prolonged influences of typhoon via NIWs in the ocean interior are missing in this scheme.Based on current examination,modifications to the J13 scheme are proposed,and the modified version can reduce the discrepancies in the temporal and vertical structures of diapycnal mixing.

Tides and Turbulent Mixing in the North of Taiwan Island

Microstructure and hydrological profiles were collected along two cross-shelf sections from the deep slope to the shallow water in the north of Taiwan Island in the summer of 2006.While the tidal currents on the shelf were dominated by the barotropic tide with the current ellipse stretched across the shelf,significant internal tides were observed on the slope.The depth-mean turbulent kinetic energy(TKE)dissipation rate on the shelf was 10^-6W kg^-1,corresponding to a diapycnal diffusivity of 10^-2 m^2s^-1.The depth-mean TKE dissipation rate on the slope was 1×10^-7 Wkg^-1,with diapycnal diffusivity of 3×10^-4m^2s^-1.The shear instability associated with internal tides largely contributed to the TKE dissipation rate on the slope from the surface to 150 m,while the enhanced turbulence on the shelf was dominated by tidal or residual current dissipations caused by friction in the thick bottom boundary layer(BBL).In the BBL,the Ekman currents associated with the northeastward Taiwan Warm Current were identified,showing a near-bottom velocity spiral,which agreed well with the analytical bottom Ekman solution.

Observations of semidiurnal M 2 internal tidal parametric subharmonic instability in the northeastern South China Sea

Near-diurnal vertically-standing waves with high vertical wavenumbers k z were observed in the velocity and shear fi elds from a set of 75-d long ADCP moored in the northeastern South China Sea(SCS)away from the“critical”latitude of 28.8°.These enhanced near-diurnal internal waves followed a fortnightly spring-neap cycle.However,they always happened during semidiurnal spring tides rather than diurnal springs although strong diurnal internal tides with the fortnightly spring-neap cycle were prevailing,suggesting that they were generated via subharmonic instability(PSI)of dominant semidiurnal M 2 internal tides.When two semidiurnal internal tidal waves with opposite vertical propagation direction intersected,both semidiurnal subharmonic and super harmonic waves were largely intensifi ed.The observed maximum diurnal velocity amplitudes were up to 0.25 m/s.The kinetic energy and shear spectra further suggested that frequencies of daughter waves were not always perfectly equal to M 2/2.The superposition of two daughter waves with nearly equal frequencies and nearly opposite k z in a PSI-triad leaded to the vertically-standing waves.

Identification of a novel MYO1D variant associated with laterality defects,congenital heart diseases,and sperm defects in humans

The establishment of left–right asymmetry is a fundamental process in animal development.Interference with this process leads to a range of disorders collectively known as laterality defects,which manifest as abnormal arrangements of visceral organs.Among patients with laterality defects,congenital heart diseases(CHD)are prevalent.Through multiple model organisms,extant research has established that myosin-Id(MYO1D)deficiency causes laterality defects.This study investigated over a hundred cases and identified a novel biallelic variant of MYO1D(NM_015194:c.1531G>A;p.D511N)in a consanguineous family with complex CHD and laterality defects.Further examination of the proband revealed asthenoteratozoospermia and shortened sperm.Afterward,the effects of the D511N variant and another known MYO1D variant(NM_015194:c.2293C>T;p.P765S)were assessed.The assessment showed that both enhance the interaction withβ-actin and SPAG6.Overall,this study revealed the genetic heterogeneity of this rare disease and found that MYO1D variants are correlated with laterality defects and CHD in humans.Furthermore,this research established a connection between sperm defects and MYO1D variants.It offers guidance for exploring infertility and reproductive health concerns.The findings provide a critical basis for advancing personalized medicine and genetic counseling.

Advances in research of the mid-deep South China Sea circulation

The South China Sea(SCS)is a large marginal sea connecting the Indian and Pacific oceans.Under the factors of monsoons,strait transport,and varied bathymetry,the SCS presents a three-layer structure and strong diapycnal mixing which is far greater than that in the open ocean.Theoretical analysis and observations reveal that internal tides,internal solitary waves,and strong winds are the sources of the strong mixing in the northern SCS.A major consequence of the strong mixing is an active mid-deep circulation system.This system promotes exchange of water between the SCS and adjacent oceans,and also regulates the upper layer of wind-driven circulation,making the 3 dimensional SCS circulation clearly different from that in other tropical and subtropical marginal seas.The mass transport capacity of the mid-deep circulation has a substantial impact on marine sedimentation,the biogeochemical cycle,and other processes in the SCS.This paper summarizes the recent advances in middeep sea circulation dynamics of the SCS,and discusses the opportunities and challenges in this area.

Identifying viruses from metagenomic data using deep learning

Background:The recent development of metagenomic sequencing makes it possible to massively sequence microbial genomes including viral genomes without the need for laboratory culture.Existing reference-based and gene homology-based methods are not efficient in identifying unknown viruses or short viral sequences from metagenomic data.Methods:Here we developed a reference-free and alignment-free machine learning method,DeepVirFinder,for identifying viral sequences in metagenomic data using deep learning.Results'.Trained based on sequences from viral RefSeq discovered before May 2015,and evaluated on those discovered after that date,DeepVirFinder outperformed the state-of-the-art method VirFinder at all contig lengths,achieving AUROC 0.93,0.95,0.97,and 0.98 for 300,500,1000,and 3000 bp sequences respectively.Enlarging the training data with additional millions of purified viral sequences from metavirome samples further improved the accuracy for identifying virus groups that are under-represented.Applying DeepVirFinder to real human gut metagenomic samples,we identified 51,138 viral sequences belonging to 175 bins in patients with colorectal carcinoma(CRC).Ten bins were found associated with the cancer status,suggesting viruses may play important roles in CRC.Conclusions:Powered by deep learning and high throughput sequencing metagenomic data,DeepVirFinder significantly improved the accuracy of viral identification and will assist the study of viruses in the era of metagenomics.

美国推进教师信息技术能力发展策略及启示

教师是国家教育信息化发展中的关键要素之一。相较于我国主要关注中小学教师的信息技术能力,美国在教师信息技术能力发展,特别是职前教师信息技术能力培养方面的政策规划和举措值得我国借鉴。本文重点分析了自2016年美国发布第五个国家教育技术计划(NETP16)以来美国国家政策规划、教师信息技术能力标准建设以及在职和职前教师信息技术能力发展方面的典型实践动态,探究了美国教师信息技术能力发展策略以及对我国当前教师信息技术能力发展的重要启示。研究结果表明,转变教师角色,鼓励其利用信息技术支持学生的学习已成为教师信息技术能力发展的方向。此外,为在职教师提供持续、嵌入式的信息技术能力发展支持,重视职前教师信息技术能力培养并改革职前教师培养的课程体系,加强高校与中小学校的合作,职前职后培养一体化以及不断提升和更新高校教师的信息技术能力,都是我国促进教师信息技术能力持续发展可以借鉴的重要策略。

Robust and Passive Motion Detection with COTS WiFi Devices

Device-free Passive（DfP） detection has received increasing attention for its ability to support various pervasive applications. Instead of relying on variable Received Signal Strength（RSS）, most recent studies rely on finer-grained Channel State Information（CSI）. However, existing methods have some limitations, in that they are effective only in the Line-Of-Sight（LOS） or for more than one moving individual. In this paper, we analyze the human motion effect on CSI and propose a novel scheme for Robust Passive Motion Detection（R-PMD）. Since traditional low-pass filtering has a number of limitations with respect to data denoising, we adopt a novel Principal Component Analysis（PCA）-based filtering technique to capture the representative signals of human motion and extract the variance profile as the sensitive metric for human detection. In addition, existing schemes simply aggregate CSI values over all the antennas in MIMO systems. Instead, we investigate the sensing quality of each antenna and aggregate the best combination of antennas to achieve more accurate and robust detection. The R-PMD prototype uses off-the-shelf WiFi devices and the experimental results demonstrate that R-PMD achieves an average detection rate of 96.33% with a false alarm rate of 3.67%.

The efficacy and safety of three types of combination therapies in patients with moderate to very severe COPD: a systematic review and meta-analysis

Inhaled drugs,including long-acting muscarinic antagonists(LAMAs),long-actingβ2-agonists(LABAs)and inhaled corticosteroids(ICSs),are the main therapeutic options for patients with chronic obstructive pulmonary disease(COPD).We conducted a systematic review and meta-analysis to compare the efficacy and safety of LAMA+LABA+ICS,LAMA+LABA and LABA+ICS therapies.The Pubmed,Embase and Cochrane Library databases were searched for randomized controlled trials(RCTs)comparing the efficacy(moderate-to-severe exacerbations,lung function and quality of life)and safety(adverse events(AEs),severe adverse events(SAEs),withdrawals due to AEs,deaths and pneumonia)of LAMA+LABA+ICS,LAMA+LABA and LABA+ICS in COPD patients.Two investigators independently searched eligible studies and extracted relevant information.The data were analyzed using the Review Manager software,and the quality of included studies was assessed using the Cochrane risk of bias tool.A total of 27 studies were included,and majority of the studies showed low risk of bias.Moderate-to-severe exacerbations were lower after LAMA+LABA+ICS therapy compared with the LABA+ICS(RR=0.66;95%CI:0.59–0.74)and LAMA+LABA therapies(RR=0.88;95%CI:0.82–0.94).Lung function was significantly improved after LAMA+LABA+ICS compared with LAMA+ICS treatment.FEV1,peak FEV1 and trough FEV1 were significantly increased by 100 mL,150 mL and 120 mL,respectively,in LAMA+LABA+ICS therapy compared with LAMA+ICS.In addition,LAMA+LABA therapy resulted in increased FEV1,peak FEV1 and trough FEV1 by 80 mL,90 mL and 70 mL,respectively,compared with LAMA+ICS.SGRQ-total score was used to assess quality of life of COPD patients,which indicated that LAMA+LABA+ICS therapy was associated with slightly greater decrease compared with LABA+ICS(MD=–1.33;95%CI:–2.35 to–0.30).No significant differences were found across all three treatment combinations in term of AEs,SAEs,withdrawals due to AEs and deaths.However,the risk of pneumonia was higher in the triple therapy group than that in the LABA+ICS(RR=1.16;95%CI:1.01–1.33)or LAMA+LABA(RR=1.31;95%CI:1.06–1.62)groups,and significantly lower in the LAMA+LABA group compared with LABA+ICS(RR=0.64;95%CI:0.54–0.76).LAMA+LABA+ICS therapy offered greater efficacy and comparable safety compared with the LAMA+LABA or LABA+ICS therapies.However,triple therapy could increase the risk of pneumonia compared with LAMA+LABA or LABA+ICS therapies.People who have higher risk of pneumonia should carefully consider the use of triple therapy.LAMA+LABA therapy offered greater efficacy and lower risk of pneumonia to LABA+ICS therapy.Collectively,LAMA+LABA therapy might be a better choice than LABA+ICS.