When Glanzmann thrombasthenia encounters antithrombin defi ciency: how do we balance the risk and benefi t of antithrombotic therapy?

Glanzmann’s thrombasthenia(GT)is an inherited autosomal recessive bleeding disorder,resulting from mutations in the ITGA2B and ITGB3 genes,that lead to a defect in the platelet membrane integrinαIIbβ3.[1]As integrinαIIbβ3 plays an important role in thrombus formation,the clinical manifestation of GT includes bleeding(mostly mucocutaneous)and purpura.For this reason,patients with GT are typically thought to be unlikely to suffer from thromboembolic incidents.Antithrombin is an anticoagulant that inhibits thrombin and is activated factor X and other serine proteases in the coagulation cascade.[2]Antithrombin deficiency is an autosomal dominant hereditary disease with an approximate prevalence of 1/500 in the overall population.[3]In contrast to the hemorrhagic tendency of GT,patients with antithrombin deficiency are at increased risk of thromboembolism,especially in the venous system.Herein,we describe a rare case of GT and antithrombin deficiency coexisting in a single patient.Rivaroxaban was used for the treatment of pulmonary embolism(PE)and deep vein thrombosis(DVT).

Improvement in discharge characteristics and energy yield of ozone generation via configuration optimization of a coaxial dielectric barrier discharge reactor

Dielectric barrier discharge (DBD) has been widely employed in ozone generation.However,the technology still exhibits relatively low energy yield (E_(Y)) referring to its theoretical value.In this work,E_(Y)of ozone generation was improved by optimizing the mesh number,electrode length,and dielectric material in a coaxial DBD reactor with two wire mesh electrodes.Meanwhile,the discharge characteristics were investigated to elucidate the effect of reactor configuration on E_(Y).Results showed that the discharge characteristics were improved by increasing the mesh number,electrode length,and relative permittivity.When the mesh number was increased from 40 to 100,an improvement of approximately 48%in E_(Y) was obtained.Additionally,higher E_(Y) values were obtained using corundum as the dielectric material relative to polytetrafluoroethylene and quartz.Ultimately,E_(Y) in the optimal DBD reactor could reach 326.77 g·(k W·h)^(-1).Compared with the reported DBD reactor,the coaxial DBD reactor with the mesh electrode and the dielectric material of corundum could effectively improve E_(Y),which lays a foundation for the design of high-efficiency coaxial DBD reactor.

非晶二氧化钛超薄纳米片用于稳定的高倍率锂储存

嵌入型金属氧化物由于降低了低电压下锂沉积风险,作为负极材料在可充电锂离子电池中广泛使用。然而,这类电极材料较低的能量密度、功率密度及循环稳定性差限制了其快充的能力。我们设计合成了一种具备良好电化学循环稳定性的非晶二氧化钛纳米片,在500 mA·g^(-1)的电流密度下循环200圈后具有231 mA·h·g^(-1)的比容量,在6 A·g^(-1)的高电流密度下经过1000圈循环后保持了156.7 mA·h·g^(-1)的比容量。非晶二氧化钛纳米片高倍率性能的提升归因于开放的高度各向同性的结构特性,降低了离子迁移能垒,确保了离子可用性,降低了嵌入后材料的体积变化。本研究表明非晶化是一种有望开发具有高倍率性能的传统金属氧化物电极材料的策略。

SUMO1 regulates post-infarct cardiac repair based on cellular heterogeneity

Small ubiquitin-related modifier(SUMOylation)is a dynamic post-translational modification that maintains cardiac function and can protect against a hypertrophic response to cardiac pressure overload.However,the function of SUMOylation after myocardial infarction(MI)and the molecular details of heart cell responses to SUMO1 deficiency have not been determined.In this study,we demonstrated that SUMO1 protein was inconsistently abundant in different cell types and heart regions after MI.However,SUMO1 knockout significantly exacerbated systolic dysfunction and infarct size after myocardial injury.Single-nucleus RNA sequencing revealed the differential role of SUMO1 in regulating heart cells.Among cardiomyocytes,SUMO1 deletion increased the Nppa^(+)Nppb^(+)Ankrd1^(+)cardiomyocyte subcluster pro-portion after MI.In addition,the conversion of fibroblasts to myofibroblasts subclusters was inhibited in SUMO1 knockout mice.Importantly,SUMO1 loss promoted proliferation of endothelial cell subsets with the ability to reconstitute neovascularization and expressed angiogenesis-related genes.Computational analysis of ligand/receptor interactions suggested putative pathways that mediate cardiomyocytes to endothelial cell communication in the myocardium.Mice preinjected with cardiomyocyte-specific AAV-SUMO1,but not the endothelial cell-specific form,and exhibited ameliorated cardiac remodeling following MI.Collectively,our results identified the role of SUMO1 in cardiomyocytes,fibroblasts,and endothelial cells after MI.These findings provide new insights into SUMO1 involvement in the patho-genesis of MI and reveal novel therapeutic targets.

Characterization and mitigation option of greenhouse gas emissions from lactating Holstein dairy cows in East China

Background:This study investigated greenhouse gas(GHG)emission characteristics of lactating Holstein dairy cows in East China and provided a basis for formulating GHG emission reduction measures.GreenFeed system was used to measure the amount of methane(CH_(4))and carbon dioxide(CO_(2))emitted by the cows through respiration.Data from a commercial cow farm were used to observe the effects of parity,body weight,milk yield,and milk component yield on CH_(4) and CO_(2) emissions.Results:Mean herd responses throughout the study were as follows:111 cows completed all experimental processes,while 42 cows were rejected because they were sick or had not visited the GreenFeed system 20 times.On average,lactating days of cows was 138±19.04 d,metabolic weight was 136.5±9.5 kg,parity was 2.8±1.0,dry matter intake(DMI)was 23.1±2.6 kg/d,and milk yield was 38.1±6.9 kg/d.The GreenFeed system revealed that CH_(4) production(expressed in CO_(2) equivalent,CO_(2)-eq)was found to be 8304 g/d,CH_(4)_(CO_(2)−eq)/DMI was 359 g/kg,CH_(4)_(CO_(2)−eq)/energy-corrected milk(ECM)was 229.5 g/kg,total CO_(2) production(CH_(4) production plus CO_(2) production)was 19,201 g/d,total CO_(2)/DMI was 831 g/kg,and total CO_(2)/ECM was 531 g/kg.The parity and metabolic weight of cows had no significant effect on total CO_(2) emissions(P>0.05).Cows with high milk yield,milk fat yield,milk protein yield,and total milk solids yield produced more total CO_(2)(P<0.05),but their total CO_(2) production per kg of ECM was low(P<0.05).The total CO_(2)/ECM of the medium and high milk yield groups was 17%and 27%lower than that of the low milk yield group,respectively.Conclusions:The parity and body condition had no effect on total CO_(2) emissions,while the total CO_(2)/ECM was negatively correlated with milk yield,milk fat yield,milk protein yield,and total milk solids yield in lactating Holstein dairy cows.Measurement of total CO_(2) emissions of dairy cows in the Chinese production system will help establish regional or national GHG inventories and develop mitigation approaches to dairy production regimes.

Organic anion transporters also mediate the drug–drug interaction between imipenem and cilastatin

This study aimed to clarify that organic anion transporters(OATs)mediate the drug–drug interaction(DDI)between imipenem and cilastatin.After co-administration with imipenem,the plasma concentrations and the plasma concentration-time curve(AUC)of cilastatin were significantly increased,while renal clearance and cumulative urinary excretion of cilastatin were decreased.At the same time,imipenem significantly inhibited the uptake of cilastatin in rat kidney slices and in human OAT1(hOAT1)-HEK293 and human OAT3(hOAT3)-HEK293 cells.Probenecid,p-aminohippurate,and benzylpenicillin inhibited the uptake of imipenem and cilastatin in rat kidney slices and in hOAT1-and hOAT3-HEK 293 cells,respectively.The uptakes of imipenem and cilastatin in hOAT1-and hOAT3-HEK 293 cells were significantly higher than that in mock-HEK-293 cells.Moreover,the K m values of cilastatin were increased in the presence of imipenem with unchanged V max,indicating that imipenem inhibited the uptake of cilastatin in a competitive manner.When imipenem and cilastatin were co-administered,the level of imipenem was higher compared with imipenem alone both in vivo and in vitro.But,cilastatin significantly inhibited the uptake of imipenem when dehydropeptidase-1(DPEP1)was silenced by RNAi technology in hOAT1-and hOAT3-HEK 293 cells.In conclusion,imipenem and cilastatin are the substrates of OAT1 and OAT3.OAT1 and OAT3 mediate the DDI between imipenem and cilastatin.Meanwhile,cilastatin also reduces the hydrolysis of imipenem by inhibiting the uptake of imipenem mediated by OAT1 and OAT3 in the kidney as a complement.

Analysis and Improvement of an Efficient Controlled Quantum Secure Direct Communication and Authentication Protocol

The controlled quantum secure direct communication(CQSDC)with authentication protocol based on four particle cluster states via quantum one-time pad and local unitary operations is cryptanalyzed.It is found that there are some serious security issues in this protocol.An eavesdropper(Eve)can eavesdrop on some information of the identity strings of the receiver and the controller without being detected by the selective-CNOT-operation(SCNO)attack.By the same attack,Eve can also steal some information of the secret message that the sender transmits.In addition,the receiver can take the same kind of attack to eavesdrop on some information of the secret message out of the control of the controller.This means that the requirements of CQSDC are not satisfied.At last,we improve the original CQSDC protocol to a secure one.

The Quantum Approximate Algorithm for Solving Traveling Salesman Problem

The Quantum Approximate Optimization Algorithm(QAOA)is an algorithmic framework for finding approximate solutions to combinatorial optimization problems.It consists of interleaved unitary transformations induced by two operators labelled the mixing and problem Hamiltonians.To fit this framework,one needs to transform the original problem into a suitable form and embed it into these two Hamiltonians.In this paper,for the well-known NP-hard Traveling Salesman Problem(TSP),we encode its constraints into the mixing Hamiltonian rather than the conventional approach of adding penalty terms to the problem Hamiltonian.Moreover,we map edges(routes)connecting each pair of cities to qubits,which decreases the search space significantly in comparison to other approaches.As a result,our method can achieve a higher probability for the shortest round-trip route with only half the number of qubits consumed compared to IBM Q’s approach.We argue the formalization approach presented in this paper would lead to a generalized framework for finding,in the context of QAOA,high-quality approximate solutions to NP optimization problems.

钛合金-芳纶纤维复合材料单搭接接头的失效形式

采用钛合金与芳纶纤维复合材料制备同质与异质材料单搭接胶接接头。利用数字图像相关技术、万能试验机、光学显微镜等手段,对拉伸载荷下的接头应变、极限载荷与破坏模式进行表征,分析不同搭接材料接头应变场及胶接性能,研究了钛合金-芳纶纤维复合材料接头失效形式。结果表明,在拉伸载荷下,钛合金-芳纶纤维复合材料接头复合材料应变远大于钛合金应变,搭接区域外部应变大于搭接区域内应变;接头偏移及被胶接件变形高于钛合金或芳纶纤维复合材料同质接头,承载能力较低;搭接区域复合材料端头剥离及剪切应力集中,是接头的薄弱部位,易出现渐进失效;破坏模式主要为复合材料层间破坏与钛合金-胶层界面破坏,芳纶纤维丝束承受剥离或剪切力断裂。

Responses of soil CH_(4) fluxes to nitrogen addition in two tropical montane rainforests in southern China

Background:Atmospheric nitrogen(N)deposition is projected to increase in the next few decades,which may have a marked impact on soil-atmosphere CH_(4) fluxes.However,the impacts of increased atmospheric N depositions on soil CH_(4) flux in tropical rainforests are still poorly understood.From January 2015 to December 2018,a field experiment was conducted in a primary tropical montane rainforest(PTMR)and a secondary tropical montane rainforest(STMR)in southern China to quantify the impact of N additions at four levels(N0:0 kg N⋅ha^(-1)⋅year^(-1);N25:25 kg N⋅ha^(-1)⋅year^(-1);N50:50 kg N⋅ha^(-1)⋅year^(-1);N100:100 kg N⋅ha^(-1)⋅year^(-1)on soil CH_(4) flux.Results:Four years of measurements showed clear seasonal variations in CH_(4) flux in all treatment plots for both forest types(PTMR and STMR),with lower rates of soil CH_(4) uptake during the wet season and higher rates of soil CH_(4) uptake during the dry season.Soil CH_(4) uptake rates were significantly and negatively correlated with both soil temperature and soil moisture for both forest types.Annual CH_(4) uptake for the N0 plots from the PTMR and STMR soils were2.20 and1.98 kg N⋅ha^(-1)⋅year^(-1),respectively.At the PTMR site,mean CH_(4) uptake compared with the N0 treatment was reduced by 19%,29%,and 36%for the N25,N50,and N100 treatments,respectively.At the STMR site,mean CH_(4) uptake compared with the N0 treatment was reduced by 15%,18%,and 38%for the N25,N50,and N100 treatments,respectively.High level N addition had a stronger inhibitory impact on soil CH_(4) uptake than did the low level N addition.Conclusion:Our data suggest that soil CH_(4) uptake in tropical rainforests is sensitive to N deposition.If atmospheric N deposition continues to increase in the future,the soil CH_(4) sink strength of tropical rainforests may weaken further.

Parameter Group Optimization by Combining CUBE with Surface Filtering and Its Application

Shallow water multi-beam echo sounders(MBESs)are characterized by their high resolution and high density,and MBES data processing is a hotspot in modern marine surveying.The Combined Uncertainty and Bathymetry Estimator(CUBE)is the mainstream MBES data processing algorithm,although little is known about its core theories and parameters.In this paper,the basic principle,mathematical model,key parameters,and main processing steps of CUBE are described systematically.A parameter group optimization method that combines CUBE with a surface filter is established.Additionally,an example is given that shows the steps for parameter group optimization,including selection of a typical area,parameter group testing,and comparative analysis,and the method is then applied to shallow water MBES data processing.The results show that the method can improve the accuracy and efficiency of automatic data processing effectively,and it is thus of engineering application value.

Piperacillin enhances the inhibitory effect of tazobactam on β-lactamase through inhibition of organic anion transporter 1/3 in rats

To assess the mechanism of the pharmacokinetic interaction between piperacillin and tazobactam,renal excretion and pharmacokinetic studies of piperacillin/tazobactam were investigated in normal and bacteremia rats.A bacteremia model was established to investigate the pharmacokinetic properties of piperacillin and tazobactam under different conditions.Renal slices were taken to examine the uptake of piperacillin and tazobactam.Pharmacokinetic studies ofβ-lactamase in rats were performed to study the contribution of rOat1/3 to the inhibition of tazobactam onβ-lactamase.The AUC(from 2.93±0.58 to 6.52±1.44 mg·min/ml)and the plasma clearance(CL P)(from 2.41±1.20 to 0.961±0.212 ml/min/kg)of tazobactam were both altered after the intravenous coadministration of piperacillin and tazobactam in the bacteremia rats.The renal clearance(CL R)of tazobactam decreased from 1.30±0.50 to 0.361±0.043 ml/min/kg.In summary,there was a beneficial interaction between piperacillin and tazobactam mediated by rOat1 and rOat3.Piperacillin enhances the inhibitory effect of tazobactam onβ-lactamase through the inhibition of rOat1 and rOat3 in rats.The contribution rate of rOat1/3 for the synergistic effect was 20%when the two drugs were coadministered.

The transporters of intestinal tract and techniques applied to evaluate interactions between drugs and transporters

Most drug products on the global pharmaceutical market are administered orally.The absorption of oral drug in the intestine is an important factor to determine the drug bioavailability.There are many intestinal transporters expressed on the small intestine and the transporters can be classified into two major families,SLC family and ABC family.They mediate drug absorption,distribution,excretion and drugedrug interaction.Understanding the transport mechanism can improve the effectivity and safety of drug and guide clinical rational use of drugs.The roles of drug transporters can be assessed in vitro and in vivo,using techniques spanning from cellular expression systems to gene knockout animals.The purposes of this article were to introduce the main transporters in the intestinal tract,to explain the transport mechanism and to compare the limitations and applications of techniques used to evaluate interactions of drugs and transporters.

Unraveling the ethylene carbonate effect on the electro-chemical/thermosafety features for practical LiNi_(0.9)Co_(0.05)Mn_(0.05)O_(2)||graphite pouch cells

With the continuous development of the electrification industry,the development of high-specific batteries has attracted much attention.However,the safety of lithiumion batteries is currently unable to meet the market demand due to poor thermal stability.Solving the thermal issues is crucial to improve battery safety.Ethylene carbonate(EC)not only plays an important interfacial film-forming role,but also poses safety risks in terms of reactivity.In this work,we conducted a series of gradient experiments utilizing different EC amounts and verified the effect of reducing EC on battery performance.A strategy is also proposed to design a new electrolyte.Ethyl methyl carbonate(EMC)is used instead of EC as the main solvent to improve the thermal safety of the battery,while salts and additives are used to dominate the film formation to improve the cycling stability of the battery under high voltages(4.5 V,~90%after 200 cycles).This work paves a new avenue for the development of novel electrolyte systems.

An Interfacial Gel Electrode Patch with Tunable Hydrogen Bond Network for Electromyographic Sensing and Discrimination

The sensitivity and fidelity of surface electromyography(sEMG)signal monitoring is critical for muscle status and fatigue assessment,prosthetic control,and gesture recognition.However,the incompatible skin-electrode interface and complex electrophysiological environment restrict the sensitive acquisition and accurate analysis of sEMG signals.Focused on the impedance of the skin-electrode interface issue,we developed an interfacial gel electrode patch with a tunable hydrogen bond network to simultaneously achieve a conformal interface,suitable adhesion,and high conductivity for sEMG signal monitoring.By exploiting hydroxyethylidene diphosphonic acid(HEDP)and 2-hydroxyphosphono-acetic acid(HPAA)as hydrogen bonding regulators were introduced into the polyvinyl alcohol(PVA)-based hydrogel network to regulate the hydrogen bond cross-linking network.As a result,the balance of elastic modulus,adhesion,and electrical conductivity of PVA-HEDP-HPAA(PHH)hydrogel are achieved.The reliable electrodeskin interface is manipulated to achieve conformal contact by matching the elastic modulus,reducing the gap of electrode-skin interface by adhesion,and promoting ion and electron conduction by electrical conductivity.The PHH electrode patches exhibit a lower interfacial impedance(12.56 kΩ)and a signal-to-noise ratio of 38.09±1.28 dB for accurate analysis of muscle strength and evaluation of the fatigue state.With the assistance of the artificial neural network algorithm,seven gestures can be recognized with 100%prediction accuracy.The interfacial gel electrode patch contributes a bio-matching electrophysiological platform for prosthetic control,human–machine interaction,and clinical or athletic auxiliary monitoring.

Mold-free self-assembled scalable microlens arrays with ultrasmooth surface and record-high resolution

Microlens arrays(MLAs)based on the selective wetting have opened new avenues for developing compact and miniaturized imaging and display techniques with ultrahigh resolution beyond the traditional bulky and volumetric optics.However,the selective wetting lenses explored so far have been constrained by the lack of precisely defined pattern for highly controllable wettability contrast,thus limiting the available droplet curvature and numerical aperture,which is a major challenge towards the practical high-performance MLAs.Here we report a mold-free and self-assembly approach of mass-production of scalable MLAs,which can also have ultrasmooth surface,ultrahigh resolution,and the large tuning range of the curvatures.The selective surface modification based on tunable oxygen plasma can facilitate the precise pattern with adjusted chemical contrast,thus creating large-scale microdroplets array with controlled curvature.The numerical aperture of the MLAs can be up to 0.26 and precisely tuned by adjusting the modification intensity or the droplet dose.The fabricated MLAs have high-quality surface with subnanometer roughness and allow for record-high resolution imaging up to equivalently 10,328 ppi,as we demonstrated.This study shows a cost-effective roadmap for mass-production of high-performance MLAs,which may find applications in the rapid proliferating integral imaging industry and high-resolution display.

Synthesis and Optical Properties of Polyaryl 2-(Pyridin-2-yl)phenol-Based Four-Coordinate Organoboron Complexes

Comprehensive Summary A family of polyaryl 2-(pyridin-2-yl)phenol-based four-coordinate organoboron complexes were prepared in good yields via deconstructive cycloaromatization of indolizines,cyclopropenones,and boric acids.The photoluminescence measurements have revealed that these N,Oπ-conjugated tetracoordinate boron complexes display bright fluorescence,large Stokes shifts,and good quantum yields(Φlum=0.15-0.45).In addition,the DFT calculations were carried out to deepen the understanding of the electronic structures and optoelectronic properties of these structurally unprecedented tetracoordinate boron complexes.

Emerging monoelemental 2D materials(Xenes)for biosensor applications

Currently,numerous monoelemental two-dimensional(2D)materials,called Xenes,have been discovered,including graphyne(GD),silicene,germanene,arsenene,borophene.Their structures,fabrication methods,as well as properties have been extensively explored.Based on their single-element composition,high optical response capability,excellent electrical-optical properties,large specific surface area(SSA)and easy modification,Xenes have been widely used in photoelectric applications(detection,modulation,light processing)and biomedicine(biological sensing,drug loading,bioimaging,etc.).Especially in the field of biomedicine,Xenes are expected to induce a great breakthrough.In this review,we introduce the structural characteristics,synthesis and modification methods of several common Xenes respectively.The general properties including optical,electronic,physical and chemical properties of Xenes are summarized.Their diverse utilization as biosensors for nucleic acid sequencing,bioactive detection,cancer diagnosis,etc.are also explicitly explored.Finally,the challenges and future perspectives of Xenes in biosensor are discussed.

Cilastatin protects against imipenem-induced nephrotoxicity via inhibition of renal organic anion transporters(OATs)

Imipenem is a carbapenem antibiotic. However, Imipenem could not be marketed owing to its instability and nephrotoxicity until cilastatin, an inhibitor of renal dehydropeptidase-I(DHP-I),was developed. In present study, the potential roles of renal organic anion transporters(OATs) in alleviating the nephrotoxicity of imipenem by cilastatin were investigated in vitro and in rabbits. Our results indicated that imipenem and cilastatin were substrates of h OAT1 and h OAT3. Cilastatin inhibited h OAT1/3-mediated transport of imipenem with IC50 values comparable to the clinical concentration, suggesting the potential to cause a clinical drug–drug interaction(DDI). Moreover,imipenem exhibited h OAT1/3-dependent cytotoxicity, which was alleviated by cilastatin and probenecid. Furthermore, cilastatin and probenecid ameliorated imipenem-induced rabbit acute kidney injury, and reduced the renal secretion of imipenem. Cilastatin and probenecid inhibited intracellular accumulation of imipenem and sequentially decreased the nephrocyte toxicity in rabbit primary proximal tubule cells. Renal OATs, besides DHP-I, was also the target of interaction between imipenem and cilastatin, and contributed to the nephrotoxicity of imipenem. This therefore gives in part the explanation about the mechanism by which cilastatin protected against imipenem-induced nephrotoxicity. Thus, OATs can potentially be used as a therapeutic target to avoid the renal adverse reaction of imipenem in clinic.

锂离子电池电解液功能性添加剂设计及应用

为提高锂离子电池的电化学性能,开发适合不同电解液的功能性添加剂是重要手段之一。功能性添加剂可以在不增加电池成本的情况下,显著改变电池的电化学性能,如改善循环性能,提高可逆容量和电解液电导率。本文分别从溶剂和添加剂两方面进行系统分析,介绍了锂离子电池电解液功能性添加剂的现状与进展,并提出面临的问题。本文以功能性添加剂的不同官能团为出发点,分析其作用机理,并分类探讨了阻燃添加剂、高电压添加剂等的优缺点、应用和前景。最后对锂离子电池电解液的溶剂及其添加剂的发展进行了展望。