Demands and technical developments of clinical flow cytometry with emphasis in quantitative,spectral,and imaging capabilities

As the gold-standard method for single-cell analysis,flow cytometry enables high-throughput and multiple-parameter characterization of individual biological cells.This review highlights the demands for clinical flow cytometry in laboratory hematology(e.g.,diagnoses of minimal residual disease and various types of leukemia),summarizes state-of-the-art clinical flow cytometers(e.g.,FACSLyricTMby Becton Dickinson,DxFLEX by Beckman Coulter),then considers innovative technical improvements in flow cytometry(including quantitative,spectral,and imaging approaches)to address the limitations of clinical flow cytometry in hematology diagnosis.Finally,driven by these clinical demands,future developments in clinical flow cytometry are suggested.

基于微机电系统技术的微电化学地震传感器

介绍了一种新型电化学地震传感器,利用密闭液体(例如,电解质溶液)作为敏感要素,将外界震动引起的活性离子在电极间的不平衡转换成电流输出。通过理论分析和数值仿真,验证此理论方法来研发采用传统微机电系统(MEMS)技术研制的微地震传感器的可行性。基于震动试验台测试得到的实际速度与输出电压幅度的线性关系,研制设备的灵敏度特性为274V/m·s^(-1)(20~80Hz)。研制设备与类似商用产品(MET2003)进行了性能对比测试,实验结果表明,与MET2003相比,研制的设备在对随机震动的响应方面具有更低的功率谱。总之,本文提出的电化学地震传感器可以利用微机电系统技术进行批量生产,与传统电化学地震仪相比具有更出色的性能和更低的功率谱。此新型微传感器可应用于地震监测,提升地震定位、火山喷发和其他地表活动的监测能力。

Au maskless patterning for vacuum packaging using the electrochemical method

The interconnection of wires is an important issue in vacuum-packaged microelectromechanical systems devices because of the difficulties of hermetical sealing and electrical insulation.This paper presents an approach of Au film selective patterning on highly uneven surfaces for wire interconnections of devices in which silicon-oninsulator(SOI)wafers are anodically bonded to glass.The Au film on the handle layer,functioned as an anode,was selectively removed with electrochemical dissolution in a chloride solution.The choice of etchant solution and etching conditions were optimized to improve the process efficiency,resulting in a high yield of gold portions within the via holes for wire interconnection.The proposed wire interconnection technology was employed to fabricate a vacuum-packaged resonant pressure sensor as a proof-of-concept demonstration.Reliable wire bonding and vacuum package were achieved as well as a Q factor that does not decrease over a year.As a platform technology,this method provides a new approach of wire interconnection for vacuum-packaged devices based on SOI–glass anodic bonding.

The Detection of SARS-CoV with SPR Biosensor

SPR (Surface Plasmon Resonance) is an emerging optical biosensor which can monitor the processes at metal interface in real time without labeling requirements.Instrument SPR-2004 can sense two areas in one channel and get two signals at same time in one test.One signal is the graph of the reaction;the other is the graph of reference.SPR biochip is modified with dextran,and only reaction area can be used to immobilize the protein.Two methods of antibody immobilization on chip were tested.One was to immobilize directly,the other was to immobilize protein A firstly and then the antibody was caught by immobilized protein A.The latter was chosen as suitable for retention of the native binding ability with virus of antibody.The latter chip was used to detect SARS-Cov.The signal of detection reached to 60 units within 40 min.It was 55 units even after reference.

A novel microfluidic flow-cytometry for counting numbers of single-cell β-actins

As a house keeping protein with stable expressions, β-actin is used as a loading control in normalization of western blotting. However, the actual numbers of β-actins at the single-cell level remain elusive. Based on a homedeveloped flow cytometry, single-cell numbers of β-actin from 8 cell types(subtypes) and 2 tumour patient samples were quantified as 9.62 ± 4.29 × 105(A549, Ncell= 14,242), 6.46 ± 3.34 × 105(Hep G2, Ncell= 35,932),1.58 ± 0.90 × 106(MCF 10 A, N6 cell= 16,650), 1.08 ± 0.48 × 10(HeLa, Ncell= 26,151), 7.60 ± 4.34 × 105(PC3, Ncell= 11,922), 1.10 ± 0.72 × 106(SACC-83, Ncell= 13,616), 8.58 ± 4.54 × 105(CAL 27, Ncell= 7271),9.00 ± 4.69 × 105(CAL 27-LN2, Ncell= 6222), 8.26 ± 4.48 × 105(Oral Tumour Patient I, Ncell= 359), and8.19 ± 5.12 × 105(Oral Tumour Patient II, Ncell= 175), and were analyzed by statistical approaches including one-way analysis of variance, neural network based pattern recognition and Bayesian estimation, with varied expressions of β-actins among different cell types located. The dataset reported in this study may serve as a reference in future studies of quantitative protein analysis.

Superior vs. Inferior Voting Shares： Price Premium or Discount？

This paper analyzes the price difference between superior voting （SV） and inferior voting （IV） shares for three dual-class firms： Farmer Mac as a big price discount case, Fox as a price similarity case, and Heico as a big price premium case. We show that the price difference is mainly affected by the control benefit, while voting power and liquidity are also relevant factors. We suggest that the control benefit can be revealed by examining share accumulation and firm performance.

A resonant high-pressure microsensor based on a composite pressure-sensitive mechanism of diaphragm bending and volume compression

In this paper,a composite pressure-sensitive mechanism combining diaphragm bending and volume compression was developed for resonant pressure microsensors to achieve high-pressure measurements with excellent accuracy.The composite mechanism was explained,and the sensor structure was designed based on theoretical analysis and finite element simulation.An all-silicon resonant high-pressure microsensor with multiple miniaturized cavities and dual resonators was developed,where dual resonators positioned in two resonant cavities with suitably different widths are used to perform opposite characteristics in pressure and the same characteristics at different temperatures,which can improve pressure sensitivities and realize temperature self-compensation by differential frequency output.The microsensor was fabricated by microfabrication,and the experimental results showed that the sensor had an accuracy of±0.015%full scale(FS)in a pressure range of 0.1~100 MPa and a temperature range of−10~50℃.The pressure sensitivity of the differential frequency was 261.10 Hz/MPa(~2523 ppm/MPa)at a temperature of 20℃,and the temperature sensitivities of the dual resonators were−1.54 Hz/℃(~−14.5 ppm/℃)and−1.57 Hz/℃(~−15.6 ppm/℃)at a pressure of 2 MPa.The differential output had an outstanding stability within±0.02 Hz under constant temperature and pressure.Thus,this research provides a convenient solution for high-pressure measurements because of its advantages,namely,large range,excellent accuracy and stability.

O-methyltransferase CbzMT catalyzes iterative 3,4-dimethylations for carbazomycin biosynthesis

Carbazomycins(1-8)are a subgroup of carbazole derivatives that contain oxygen at the C3 and C4 positions and an unusual asymmetric substitution pattern.Several of these compounds exhibit antifungal and antioxidant activities.To date,no systematic biosynthetic studies have been conducted on carbazomycins.In this study,carbazomycins A and B(1 and 2)were isolated from Streptomyces luteosporeus NRRL 2401 using a one-strain-many-compound(OSMAC)-guided natural product mining screen.A biosynthetic gene cluster(BGC)was iden-tified,and possible biosynthetic pathways for 1 and 2 were proposed.The in vivo genetic manipulation of the O-methyltransferase-encoding gene cbzMT proved indispensable for 1 and 2 biosynthesis.Size exclusion chro-matography indicated that CbzMT was active as a dimer.In vitro biochemical assays confirmed that CbzMT could repeatedly act on the hydroxyl groups at C3 and C4,producing monomethylated 2 and dimethylated 1.Monomethylated carbazomycin B(2)is not easily methylated;however,CbzMT seemingly prefers the dimethy-lation of the dihydroxyl substrate(12)to 1,even with a low conversion efficiency.These findings not only improve the understanding of carbazomycin biosynthesis but also expand the inventory of OMT-catalyzing it-erative methylations on different acceptor sites,paving the way for engineering biocatalysts to synthesize new active carbazomycin derivatives.

基于基因组挖掘的农抗120活性成分制霉菌素和丰加霉素的发现和鉴定

【目的】分析刺孢吸水链霉菌北京变种(农抗120产生菌)基因组和次级代谢产物组分,研究并鉴定农抗120产生菌中未被发现的活性组分。【方法】利用antiSMASH在线分析农抗120产生菌Streptomyces hygrospinosusvar.beijingensis基因组信息,锁定可能的制霉菌素和丰加霉素生物合成基因簇。利用HPLC和LC-MS等分析方法对农抗120产生菌发酵产物进行分析,同时利用制霉菌素和丰加霉素标准品作为对照,以鉴定该菌株代谢组分中的次级代谢产物。此外,通过构建目标基因簇大片段缺失突变株,并对所得突变株发酵产物进行检测,以确定生物合成基因簇与目的代谢产物的对应关系。【结果】本研究综合利用基因组序列分析、基因缺失突变株构建以及代谢产物检测方法,鉴定了农抗120产生菌中制霉菌素和丰加霉素两种活性成分,并确定了负责这些化合物合成的基因簇。【结论】本研究所构建的多重基因簇失活突变株为挖掘刺孢吸水链霉菌北京变种更多的天然次级代谢产物奠定了基础。

Climatic and lake environmental changes in the Serling Co region of Tibet over a variety of timescales

The Serling Co region is located at the transitional zone of the interaction between the Indian monsoon and the westerlies over the Tibetan Plateau. The Serling Co lake covers a water area of2,389 km2(June 2017) in a 45,530 km2drainage basin. Under the dramatic hydro-meteorological changes on the Tibetan Plateau in recent decades, and complex hydrological compositions of rivers and lakes in the basin, the lake area expanded by 43%, from1,667 km2in 1976, to 2,389 km2in 2017 (1)In 2014 it surpassed Nam Co as the largest lake on the Tibetan Plateau [2], and exerts significant effect on regional environmental conditions.

Pollen-inferred Holocene vegetation and climate histories in Taro Co,southwestern Tibetan Plateau

A 310-cm-long sediment core,covering the last10,200 years,was collected from Taro Co on the southwestern Tibetan Plateau and analyzed for pollen,grain size and total inorganic carbon content.The pollen data showed that vegetation changed from alpine steppe to alpine meadow during 10,200–8,900 cal a BP,to alpine steppe dominated by Artemisia during 8,900–7,400 cal a BP,to alpine meadow during 7,400–3,300 cal a BP and to alpine steppe after 3,300 cal a BP.Correspondingly,the pollen,grain size and total inorganic carbon content results revealed climatic change in this area over four stages.The initial stage was from 10,200 to 8,900 cal a BP,during which the climate changed from cold-dry to warm-humid.The second stage(8,900–7,400 cal a BP)was characterized by a warm and dry climate.However,at approximately7,400 cal a BP,the climate began to become cold and humid,which continued until 3,300 cal a BP.The last stage,from 3,300 cal a BP to present,was characterized as cold and increasingly arid.Climatic events of the early and mid-late Holocene showed that the area was significantly affected by the westerlies.However,the mid-Holocene climate in Taro Co was controlled by the Indian monsoon.The mid-late Holocene depositional environment record of Taro Co was very important to further elaborate the degree of influence by the westerlies or Indian monsoon.

In-situ water quality investigation of the lakes on the Tibetan Plateau

The lakes on the Tibetan Plateau(TP)account for 57%of the total lake area in China[1],which is a key component of the Asia water tower[2-4].A recent study showed that there are 1424 lakes greater than 1 km^(2) on the TP,while the total lake area reached 5.0-10^(4)±791.4 km^(2) in 2018[5].Most lakes on the TP are closed and are less disturbed by human activities than the other inland water bodies in China.

Climatic significance of n-alkanes and their compound-specific dD values from lake surface sediments on the Southwestern Tibetan Plateau

The content and hydrogen isotope ratios of n-alkanes extracted from recent lake surface sediments sampled from nine lakes in three different climate zones on the Southwestern Tibetan Plateau were analyzed.Values were compared with n-alkanes in plants from lake drainages,and dD values of meteoric water,lake water,and mean annual precipitation.The results showed that n-C23was predominantly derived from aquatic plants,and n-C27–n-C33from terrestrial higher plants.The average carbon chain length of n-C27–n-C33(ACL27–33)was positively correlated with the mean annual precipitation.dD values of the long-chain n-alkanes n-C29and n-C31of terrestrial origin(varying between-214%and-169%,and-226%and-185%,respectively)were inversely correlated with mean annual precipitation;but in accordance with the average annual variations in dD(OIPC),dD values of n-C31were strongly related to the dD values of growing season meteoric water(R2=0.74).The large difference between dD values of n-C23of aquatic origin and n-C31(an average of about 27%)demonstrates the enrichment of the lake water dD compared to precipitation,caused by strong evaporation in the semiarid–arid areas of the southwestern Tibetan Plateau.Average value of en C25 31=p(-95%)is evidently higher than the value observed in European wet regions(-128%);besides,en C31(about-116%)is constant along the study transect(SD=9),which indicates that n-C31is a useful proxy for the environment.

Wearable and flexible electrochemical sensors for sweat analysis:a review

Flexible wearable sweat sensors allow continuous,real-time,noninvasive detection of sweat analytes,provide insight into human physiology at the molecular level,and have received significant attention for their promising applications in personalized health monitoring.Electrochemical sensors are the best choice for wearable sweat sensors due to their high performance,low cost,miniaturization,and wide applicability.Recent developments in soft microfluidics,multiplexed biosensing,energy harvesting devices,and materials have advanced the compatibility of wearable electrochemical sweat-sensing platforms.In this review,we summarize the potential of sweat for medical detection and methods for sweat stimulation and collection.This paper provides an overview of the components of wearable sweat sensors and recent developments in materials and power supply technologies and highlights some typical sensing platforms for different types of analytes.Finally,the paper ends with a discussion of the challenges and a view of the prospective development of this exciting field.

A new finding on the prevalence of rapid water warming during lake ice melting on the Tibetan Plateau

The Tibetan Plateau(TP)is home to about 1400 lakes with areas greater than 1 km2[1].A trend towards warmer and wetter conditions on the TP has resulted in substantial expansion of the lake area since the mid-1990s,which has attracted widespread attention[1-3].Meanwhile,climate change can alter lake ice duration and lake mixing regimes[4].

Asymmetries of Positive Feedback Trading in Individual Stocks:Evidences from China

The paper investigates the positive feedback trading phenomenon of individual stocks in China’s stock market.Heterogeneous regression models and a non-parametric Sentana-Wadhwani model are developed and applied to prove the existence of rise-favor asymmetric feedback trading.This result is consistent with the reality of China’s stock market,that is,the herding behavior of irrational retail investors has a significant influence on the market.However,the result is in contrast with the stylized findings using market indices.Further empirical research shows that this distinction could be explained by the average effect of indices.The asymmetries of positive feedback trading caused by heterogeneous feedback trading and the uneven distributed retail trading in individual stocks,are covered by the weighted average effect in indices.Therefore,the indices exhibit a different asymmetric pattern from that of individual stocks.

The decrease of salinity in lakes on the Tibetan Plateau between 2000 and 2019 based on remote sensing model inversions

Salinity is an essential factor of lake water environments and aquatic systems.It is also sensitive to climatic changes and human activities based on concentration variations of solved minerals.However,there are few consecutively temporal studies on lake salinity variations on the Tibetan Plateau because the harsh environmental conditions make it diffcult to carry out in-situ observations for several lakes.In this study.we constructed a remote sensing retrieval model for lake salinity based on 87 in-situ lake investigations;moreover,interannual lake salinity and associated variations from 152 lakes larger than 50 km2 were analyzed on the Tibetan Plateau.A significant decreasing trend in lake salinity was observed between 2000 and 2019(p<0.01).The spatial variation of lake salinity was negatively correlated with lake area changes,and the optical characteristics of salt mineral solutions were generally positively correlated with mineral concentration based on the absorption coefficients of ionic solutions.The decreasing trend of lake salinity was not directly affected by the.precipitation,but was,potentially dominated by the expanding lake water volume.This study improves the understanding of regional water environmental changes and management efficacy of water resources.

Netrin-3 Suppresses Diabetic Neuropathic Pain by Gating the Intra-epidermal Sprouting of Sensory

tDiabetic neuropathic pain(DNP)is the most common disabling complication of diabetes.Emerging evi-dence has linked the pathogenesis of DNP to the aberrant sprouting of sensory axons into the epidermal area;however,the underlying molecular events remain poorly understood.Here we found that an axon guidance molecule,Netrin-3(Ntn-3),was expressed in the sensory neurons of mouse dorsal root ganglia(DRGs),and downregulation of Ntn-3 expression was highly correlated with the severity of DNP in a diabetic mouse model.Genetic ablation of Ntn-3 increased the intra-epidermal sprouting of sensory axons and worsened the DNP in diabetic mice.In contrast,the elevation of Ntn-3 levels in DRGs significantly inhibited the intra-epidermal axon sprouting and alleviated DNP in diabetic mice.In con-clusion,our studies identified Ntn-3 as an important regula-tor of DNP pathogenesis by gating the aberrant sprouting of sensory axons,indicating that Ntn-3 is a potential druggable target for DNP treatment.

A Method to Adjust Dielectric Property of SiC Powder in the GHz Range

The SiC powders by AI or N doping have been synthesized by combustion synthesis, using AI powder and NH4Cl powder as the dopants and polytetrafluoroethylene as the chemical activator. Characterization by X-ray diffraction, Raman spectrometer, scanning electron microscopy and energy dispersive spectrometer demonstrates the formation of Al doped SiC, N doped SiC and the AI and N co-doped SiC solid solution powders, respectively. The electric permittivities of prepared powders have been determined in the frequency range of 8.2-12.4 GHz. It indicates that the electric permittivities of the prepared SiC powders have been improved by the pure AI or N doping and decrease by the AI and N co-doping. The paper presents a method to adjust dielectric property of SiC powders in the GHz range.

P2-type layered high-entropy oxides as sodium-ion cathode materials

P2-type layered oxides with the general Na-deficient composition Na_(x)TMO_(2)(x<1,TM:transition metal)are a promising class of cathode materials for sodium-ion batteries.The open Na+transport pathways present in the structure lead to low diffusion barriers and enable high charge/discharge rates.However,a phase transition from P2 to O2 structure occurring above 4.2 V and metal dissolution at low potentials upon discharge results in rapid capacity degradation.In this work,we demonstrate the positive effect of configurational entropy on the stability of the crystal structure during battery operation.Three different compositions of layered P2-type oxides were synthesized by solid-state chemistry,Na_(0.67)(Mn_(0.55)Ni_(0.21)Co_(0.24))O_(2),Na_(0.67)(Mn_(0.45)Ni_(0.18)Co_(0.24)Ti_(0.1)Mg_(0.03))O_(2) and Na_(0.67)(Mn_(0.45)Ni_(0.18)Co_(0.18)Ti_(0.1)Mg_(0.03)Al_(0.04)Fe_(0.02))O_(2) with low,medium and high configurational entropy,respectively.The high-entropy cathode material shows lower structural transformation and Mn dissolution upon cycling in a wide voltage range from 1.5 to 4.6 V.Advanced operando techniques and post-mortem analysis were used to probe the underlying reaction mechanism thoroughly.Overall,the high-entropy strategy is a promising route for improving the electrochemical performance of P2 layered oxide cathodes for advanced sodium-ion battery applications.