Rational Engineering of Secondary Metabolic Pathways in a Heterologous Host to Enable the Biosynthesis of Hibarimicin Derivatives with Enhanced Anti-Melanomic Activity

A 61-kb biosynthetic gene cluster(BGC),which is accountable for the biosynthesis of hibarimicin(HBM)B from Microbispora rosea subsp.hibaria TP-A0121,was heterologously expressed in Streptomyces coelicolor M1154,which generated a trace of the target products but accumulated a large amount of shunt products.Based on rational analysis of the relevant secondary metabolism,directed engineering of the biosynthetic pathways resulted in the high production of HBM B,as well as new HBM derivates with improved antitumor activity.These results not only establish a biosynthetic system to effectively synthesize HBMs-a class of the largest and most complex Type-Ⅱpolyketides,with a unique pseudo-dimeric structure-but also set the stage for further engineering and deep investigation of this complex biosynthetic pathway toward potent anticancer drugs.

Polymer Fiber Rigid Network with High Glass Transition Temperature Reinforces Stability of Organic Photovoltaics

Organic photovoltaics(OPVs)need to overcome limitations such as insufficient thermal stability to be commercialized.The reported approaches to improve stability either rely on the development of new materials or on tailoring the donor/acceptor morphology,however,exhibiting limited applicability.Therefore,it is timely to develop an easy method to enhance thermal stability without having to develop new donor/acceptor materials or donor–acceptor compatibilizers,or by introducing another third component.Herein,a unique approach is presented,based on constructing a polymer fiber rigid network with a high glass transition temperature(T_(g))to impede the movement of acceptor and donor molecules,to immobilize the active layer morphology,and thereby to improve thermal stability.A high-T_(g) one-dimensional aramid nanofiber(ANF)is utilized for network construction.Inverted OPVs with ANF network yield superior thermal stability compared to the ANF-free counterpart.The ANF network-incorporated active layer demonstrates significantly more stable morphology than the ANF-free counterpart,thereby leaving fundamental processes such as charge separation,transport,and collection,determining the device efficiency,largely unaltered.This strategy is also successfully applied to other photovoltaic systems.The strategy of incorporating a polymer fiber rigid network with high T_(g) offers a distinct perspective addressing the challenge of thermal instability with simplicity and universality.

Kinematics of Terrestrial Locomotion in Mole Cricket Gryllotalpa orientalis

The fore leg of mole cricket （Orthoptera： Glyllotalpidae） has developed into claw for digging and excavating. As the result of having a well-suited body and appendages for living underground, mole cricket still needs to manoeuvre on land in some cases with some kinds of gait. In this paper, the three-dimensional kinematics information of mole cricket in terrestrial walking was recorded by using a high speed 3D video recording system. The mode and the gait of the terrestrial walking mole cricket were investigated by analyzing the kinematics parameters, and the kinematics coupling disciplines of each limb and body were discussed. The results show that the locomotion gait of mole cricket in terrestrial walking belongs to a distinctive alternating tripod gait. We also found that the fore legs of a mole cricket are not as effective as that of common hexapod insects, its middle legs and body joints act more effective in walking and turning which compensate the function of fore legs. The terrestrial lo-comotion of mole cricket is the result of biological coupling of three pairs of legs, the distinctive alternating tripod gait and the trunk locomotion.

Application and development of the pulsed plasma thruster

The application and development of pulsed plasma thrusters(PPTs)in recent years are reviewed in this paper.The advantages of PPTs are discussed.The schematics,propulsion performance parameters and key physical processes of PPTs are described.Some representative PPT products and flight systems developed in recent years are presented to show the performance of the PPT.Studies about how electrode structures,discharge circuits,propellant materials,energy discharge method,propellant feed method,ignition method and number of thruster heads influence the PPT performance are presented and analyzed.The ignitor design method,ignition process and propellant carbonization are introduced to discuss the reliability and lifetime issues in PPTs.The modeling methods of the discharge circuit,as well as ablation,ionization and acceleration in PPTs are presented.Finally,the application of PPTs in the future is analyzed and some suggestions for PPT development are proposed.

Complex field network-coded cooperation based on multi-user detection in wireless networks

Cooperative communication can achieve spatial diversity gains,and consequently combats signal fading due to multipath propagation in wireless networks powerfully.A novel complex field network-coded cooperation（CFNCC） scheme based on multi-user detection for the multiple unicast transmission is proposed.Theoretic analysis and simulation results demonstrate that,compared with the conventional cooperation（CC） scheme and network-coded cooperation（NCC） scheme,CFNCC would obtain higher network throughput and consumes less time slots.Moreover,a further investigation is made for the symbol error probability（SEP） performance of CFNCC scheme,and SEPs of CFNCC scheme are compared with those of NCC scheme in various scenarios for different signal to noise ratio（SNR） values.

Locally Minimum Storage Regenerating Codes in Distributed Cloud Storage Systems

In distributed cloud storage systems, inevitably there exist multiple node failures at the same time. The existing methods of regenerating codes, including minimum storage regenerating(MSR) codes and minimum bandwidth regenerating(MBR) codes, are mainly to repair one single or several failed nodes, unable to meet the repair need of distributed cloud storage systems. In this paper, we present locally minimum storage regenerating(LMSR) codes to recover multiple failed nodes at the same time. Specifically, the nodes in distributed cloud storage systems are divided into multiple local groups, and in each local group(4, 2) or(5, 3) MSR codes are constructed. Moreover, the grouping method of storage nodes and the repairing process of failed nodes in local groups are studied. Theoretical analysis shows that LMSR codes can achieve the same storage overhead as MSR codes. Furthermore, we verify by means of simulation that, compared with MSR codes, LMSR codes can reduce the repair bandwidth and disk I/O overhead effectively.

Volumetric Langmuir probe mapping of a transient pulsed plasma thruster plume

The triple Langmuir probe enables measurements of the transient plasma parameters over time at a point of interest.We demonstrate how these measurements can be easily combined to obtain a visualization of the overall plasma behavior of a pulsed plasma thruster.Through this,it is possible to identify features in the expansion of the plasma such as the canting angle of the plume.We also identified the early arrival of a negatively canted low-density plasma plume.The 2D profiles also reveal data that would otherwise be obscured by other planes in optical measurements.

Thermal radiation properties of PTFE plasma

To illuminate the thermal transfer mechanism of devices adopting polytetrafluoroethylene（PTFE） as ablation materials,the thermal radiation properties of PTFE plasma are calculated and discussed based on local thermodynamic equilibrium（LTE） and optical thin assumptions.It is clarified that line radiation is the dominant mechanism of PTFE plasma.The emission coefficient shows an opposite trend for both wavelength regions divided by 550 nm at a temperature above15 000 K.The emission coefficient increases with increasing temperature and pressure.Furthermore,it has a good log linear relation with pressure.Equivalent emissivity varies complexly with temperature,and has a critical point between 20 000 K to 25 000 K.The equivalent cross points of the average ionic valence and radiation property are about 10 000 K and 15 000 K for fully single ionization.

Experimental investigation on the evolution of plasma properties in the discharge channel of a pulsed plasma thruster

Pulsed plasma thrusters(PPTs)are an attractive form of micro-thrusters due to advantages such as their compactness and lightweight design compared to other electric propulsion systems.Experimental investigations on their plasma properties are beneficial in clarifying the complex process of plasma evolution during the micro-second pulse discharge of a PPT.In this work,the multi-dimensional evolutions of the light intensity of the PPT plasma with wavelength,time,and position were identified.The plasma pressure was obtained using an iterative process with composition calculations.The results show that significant ion recombination occurred in the discharge channel since the line intensities of CII,CIII,CIV,and FII decreased and those of CI and FI increased as the plasma moved downstream.At the center of the discharge channel,the electron temperature and electron density were in the order of 10000 K and 1017 cm-3,respectively.These had maximum values of 13750 K and 2.3?×?1017 cm-3 and the maximum temperature occurred during the first half-cycle while the maximum number density was measured during the second half-cycle.The estimated plasma pressure was in the order of 105 Pa and exhibited a maximum value of 2.69?×?105 Pa.

MOSS:An Open Conversational Large Language Model

Conversational large language models(LLMs)such as ChatGPT and GPT-4 have recently exhibited remarkable capabilities across various domains,capturing widespread attention from the public.To facilitate this line of research,in this paper,we report the development of MOSS,an open-sourced conversational LLM that contains 16 B parameters and can perform a variety of instructions in multi-turn interactions with humans.The base model of MOSS is pre-trained on large-scale unlabeled English,Chinese,and code data.To optimize the model for dialogue,we generate 1.1 M synthetic conversations based on user prompts collected through our earlier versions of the model API.We then perform preference-aware training on preference data annotated from AI feedback.Evaluation results on real-world use cases and academic benchmarks demonstrate the effectiveness of the proposed approaches.In addition,we present an effective practice to augment MOSS with several external tools.Through the development of MOSS,we have established a complete technical roadmap for large language models from pre-training,supervised fine-tuning to alignment,verifying the feasibility of chatGPT under resource-limited conditions and providing a reference for both the academic and industrial communities.Model weights and code are publicly available at https://github.com/OpenMOSS/MOSS.

Full lifetime demonstration of a Micro-Cathode-Arc thruster evolution characteristics

Ground lifetime test is the most crucial experiment to assess the performance,reliability.and flight qualification of electric propulsion,and it can bring new insights for understanding the operation characteristics.This work demonstrates a full lifetime test of 140000 cycles on a Micro-Cathode-Arc Thruster(μCAT)with 160μs charging time and 86 mJ charging energy.A four-probe resistivity measurement method is utilized to investigate variations in the conductive film thickness and resistivity throughout the thruster lifespan.Direct film parameters show that the lifetime of theμCAT can be divided into three stages.In the initial stage,the film thickness decreases by 1.2μm and the resistivity increases significantly due to the high discharge intensity and intense film ablation;In the steady stage,the change of the film thickness is within 5%,and the resistivity of the film increases slowly from 0.050Ω·mm to 0.223Ω·mm.In the end stage,the resistivity exponentially increases from 0.223Ω·mm to 1.176Ω·mm,with the increase accounting for 81%,ultimately resulting in the failure of the thruster open circuit.Additionally,the evolution of discharge parameters,and the variation of plume parameters are measured throughout the life-time.The discharge characteristics also show significant differences in the duration of voltage and current in these three stages.The results of plume shape and plasma parameters are also well con-sistent with the discharge parameters and film state.These results suggest that,for evaluating the steady stage lifetime of thrusters,the film thickness is the best indicator compared to the variations in resistivity and voltage-current characteristics.For the end stage,the plasma plume morphology.discharge duration,and plume parameters can conveniently and clearly characterize the thruster failures and irregularity.

High toughness and CMAS resistance of REAlO_(3)/RE_(2)Zr_(2)O_(7)(RE=La,Nd,Sm,Eu,Gd,and Dy)composites with eutectic composition for thermal barrier coatings

Although rare earth zirconates(RE_(2)Zr_(2)O_(7))have garnered attention as viable candidates for thermal barrier coatings(TBCs),they suffer from low fracture toughness and accelerated calcium–magnesium–alumina–silicate(CMAS)melt corrosion at high service temperatures,which impedes their practical application.In this work,we developed a series of REAlO_(3)/RE_(2)Zr_(2)O_(7)(RE=La,Nd,Sm,Eu,Gd,and Dy)composites with a eutectic composition that not only significantly enhanced the fracture toughness by more than 40%relative to that of RE_(2)Zr_(2)O_(7)but also exhibited improved resistance to CMAS corrosion.The increase in toughness arises from multiple mechanisms,such as ferroelastic toughening,fine-grain strengthening,and residual stress toughening,all of which trigger more crack defects and energy consumption.Additionally,the CMAS penetration depth of the REAlO_(3)/RE_(2)Zr_(2)O_(7)composites is approximately 36%lower than that of RE_(2)Zr_(2)O_(7).Al–O constituents in composites can capture CaO,SiO_(2),and MgO in CMAS melts and increase their viscosity,resulting in enhanced CMAS corrosion resistance.The thermophysical properties of the REAlO_(3)/RE_(2)Zr_(2)O_(7)composites were also investigated,and their coefficient of thermal expansion and thermal conductivity are comparable to those of 7–8 wt%Y_(2)O_(3)partially stabilized ZrO2(YSZ),indicating their potential as TBC materials.

A brief review of alternative propellants and requirements for pulsed plasma thrusters in micropropulsion applications

Technological miniaturization has enabled the development of small satellites weighing as little as 1 kg.Unfortunately,there is still a lack of suitable efficient micropropulsion systems at these scales.The pulsed plasma thruster is a structurally simple form of electric propulsion.This simplicity also makes it ideally suited for miniaturization.Its history can be traced back to applications in satellites that are much larger than micro/nano-satellites.The vast majority of modern pulsed plasma thrusters use solid polytetrafluoroethylene(PTFE)as a propellant.Unfortunately,at lower discharge energy levels such as those necessitated by the power limitations of micro/nano-satellites,PTFE has a tendency to exhibit carbon deposition,which can ultimately lead to thruster failure.In this new era of small satellites,it is important to consider alternative propellants in the miniaturization of pulsed plasma thrusters.This brief review discusses the needs and limitations of small satellites and alternative propellants that may be able to meet these needs.Such propellants may be able to offer advantages such as a longer thruster lifetime,a higher specific impulse,or a higher thrust-topower ratio.This would enable the development of different types of pulsed plasma thrusters that can be tailored towards specific mission requirements.

A leaf vein-like hierarchical silver grids transparent electrode towards high-performance flexible electrochromic smart windows

As essential components of numerous flexible and wearable optoelectronic devices,the flexible transparent conducting electrodes(TCEs)with sufficient optical transmittance and electric conductivity become more and more important.In this work,we fabricated a large-area flexible TCE based on leaf vein-like hierarchical metal grids(HMG)comprising of mesoscale"trunk"and microscale"branches".The selfformed branched grids made the conducting paths distributing uniformly while the laser-etching trunk grids enabled to transport the collected electrons across long-distance.The Ag HMG exhibited high optical transmittance(-81%)with low sheet resistance(1.36Ωsq-1,which could be simply optimized through adjusting the grids’widths,spaces,and the sizes of the TiO2 colloidal crackle patterns.In addition,on the basis of such advanced HMG electrode,flexible electrochromic devices(ECDs)with remarkable cyclic performance were fabricated.The HMG with high transparency,conductivity,and flexibility provides a promising TCE for the next-generation flexible and wearable optoelectronic devices.

Effect of the microbial lipopeptide on tumor cell lines: apoptosis induced by disturbing the fatty acid composition of cell membrane

Microbial lipopeptides play an important role in apoptosis induction of tumor cells.However,there is little knowledge about the relationship between apoptosis induction and membrane fatty acids.The present study focused on the effects of lipopeptides produced by Bacillus subtilis HSO121 on Bcap-37 cell lines.3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl(MTT)colorimetric assay and surface tension measurements,showed that the critical micelle concentration(CMC)was a critical level for the inhibitory activity of lipopeptides on the growth of Bcap-37 cells.Under the CMC,the order of least to greatest cytotoxicity effect on cancer cell lines by lipopeptides is C13-lipopeptide<C14-lipopepitde<C15-lipopeptide.Above CMC,all lipopeptides directly exert cytolytic activity.The flow cytometric analysis and Hoechst33258 staining experiments confirmed the apoptosis of Bcap-37 cell lines induced by lipopeptides in a dose-dependent manner.This apoptosis was associated with a significant decrease of the unsaturated degree of the cellular fatty acids of Bcap-37 cell lines due to the changes in the cellular fatty acids composition induced by the lipopeptide treatment.These results indicated that disturbance of the cellular fatty acid composition of breast cancer cell lines were related to in the cell apoptosis.Furthermore,significant difference in IC50 values of tumor cells and normal cell showed that the lipopeptide exerted selective cytotoxicity on the cancer cells.Thus HSO121 lipopeptides may have potential applications as an anticancer leads.

酮基合酶AlpRQ影响醌那霉素的产量

【背景】角蒽环类聚酮化合物醌那霉素生物合成基因簇包含了两套酮基合酶(KS_(α)和KS_(β))的编码基因,即alpA,alpB和alpR,alpQ,AlpA和AlpB被证明是醌那霉素合成过程中必需的酮基合酶,而AlpR和AlpQ则被认为与别的化合物的合成相关。【目的】鉴于alpR和alpQ和必需基因alpS在醌那霉素合成基因簇上紧密相邻,本研究旨在确定它们与醌那霉素生物合成的相关性。【方法】PCR-targeting在细菌人工染色体(BAC)文库质粒上进行多基因敲除,构建好的文库质粒再导入通用宿主Streptomyces albus J1074中进行异源表达,并用高效液相色谱(HPLC)检测突变株和野生型菌株的发酵产物。【结果】AlpR和AlpQ对醌那霉素的合成没有直接影响,但是敲除AlpRQ突变株的发酵液中醌那霉素的产量显著提高了。【结论】AlpR和AlpQ很有可能是另一Ⅱ型聚酮化合物的KS_(α)和KS_(β),它们与AlpA和AlpB竞争共同的合成前体。本研究还证明了AlpR和AlpQ并不能替代AlpA和AlpB的功能。

天蓝色链霉菌孢子色素whiE在大肠杆菌中的异源生物合成

【目的】在大肠杆菌中完整重构孢子色素whiE的生物合成途径,分离纯化表达体系中合成的新化合物,并解析whiE的生物合成途径。【方法】构建whiE-ORFII、whiE-ORFVII和whiE-ORFI的单基因重组质粒,SDS-PAGE检测蛋白表达情况;借助Xba I与Spe I互为同尾酶的特性,实现多基因组合串联;构建好的重组质粒再导入大肠杆菌菌株BAP1中进行异源表达,并用高效液相色谱(HPLC)检测发酵产物;依次使用正相硅胶柱和反向半制备柱分离发酵产物,四级杆飞行时间质谱仪(Q-TOFMS)鉴定发酵产物分子量。【结果】whiE-ORFII、whiE-ORFVII和whiE-ORFI均获得可溶性表达;这3个基因单个串联到菌株BTw95中均未检测到新的产物生成;而whiE-ORFII和whiE-ORFVII、whiE-ORFI和whiE-ORFVII双基因组合以及三基因组合串联到BTw95中可检测得到两种化合物ZYC-1和ZYC-2。在负离子模式下进行Q-TOFMS检测,ZYC-1的[M-H]-为419.0748,推测分子式为C_(23)H_(16)O_(8);ZYC-2的[M-H]-为465.0743,推测分子式为C_(24)H_(18)O_(10)。【结论】本研究推进了孢子色素whiE生物合成途径在大肠杆菌中的异源重构,分离鉴定了2个十二酮II型聚酮化合物,并推测了孢子色素whiE的生物合成途径。

Effect of size and crystalline phase of TiO2 nanotubes on cell behaviors: A high throughput study using gradient TiO2 nanotubes

The research of TiO2 nanotubes(TNTs)in the field of biomedicine has been increasingly active.However,given the diversity of the nanoscale dimension and controversial reports,our understanding of the structure-property relationships of TNTs is not yet complete.In this paper,gradient TNTs with a wide diameter range of 20-350 nm were achieved by bipolar electrochemistry and utilized for a thorough high-throughput study of the effect of nanotube dimension and crystalline phase on protein adsorption and cell behaviors.Results indicated that protein adsorption escalated with nanotube dimension whereas cell proliferation and differentiation are preferred on small diameter(<70 nm)nanotubes.Large diameter anatase nanotubes had higher adsorption of serum proteins than as-prepared ones.But only as-prepared small diameter nanotubes presented slightly higher cell proliferation than corresponding annealed nanotubes whereas there was no discernible difference between as-prepared and annealed nanotubes on cell differentiation for the entire gradient.Those findings replenish previous research about how cell responses to TNTs with a wide diameter range and provide scientific guidance for the optimal design of biomedical materials.

COPEX:co-evolutionary crystal structure prediction algorithm for complex systems

Crystal structure prediction has been widely used to accelerate the discovery of new materials in recent years.Up to this day,it remains a challenge to predict the stable stoichiometries and structures of ternary or more complex systems due to the explosive increase of the size of the chemical and configurational space.Numerous novel materials with a series of unique characteristics are expected to be found in this virgin territory while new algorithms to predict crystal structures in complex systems are urgently called for.Inspired by co-evolution in biology,here we propose a co-evolutionary algorithm,which we name COPEX,and which is based on the well-known evolutionary algorithm USPEX.Within this proposed algorithm,a few USPEX calculations for ternary systems and multiple for energetically-favored pseudobinary or fixed-composition systems are carried out in parallel,and coevolution is achieved by sharing structural information on the fittest individuals among different USPEX sub-processes during the joint evolution.We have applied the algorithm to W–Cr–B,Mg–Si–O,and Hf–Ta–C,three very different systems,and many ternary compounds have been identified.Our results clearly demonstrate that the COPEX algorithm combines efficiency and reliability even for complex systems.

Ultralow oxygen ion diffusivity in pyrochlore-type La_(2)(Zr_(0.7)Ce_(0.3))_(2)O_(7)

Thermally grown oxides(TGOs)at the ceramic top-coat/metallic bond-coat interface are a pressing chal-lenge in advanced thermal barrier coating(TBC)systems as they can affect the performance and ser-vice lifetime of TBCs.Thus,developing novel TBC materials with ultralow oxygen ion diffusivity is very urgent.In this study,we reported the diffusive properties of oxygen ions in a novel pyrochlore-type La_(2)(Zr_(0.7)Ce_(0.3))_(2)O_(7)(LZ7C3)material.The measured ionic conductivity and atomistic simulation revealed that the oxygen ion diffusivity in LZ7C3 grains is two orders of magnitude lower than that in conventional 8 wt.%yttria-stabilized zirconia(8YSZ)grains.This is due to the relatively high energy barrier for oxygen hopping in LZ7C3.In addition,it was found that enhancing the order distribution of cations is a strategy to reduce the intrinsic oxygen diffusion of pyrochlore-type oxides.On the other hand,we observed that La^(3+) cations segregate at the grain boundaries(GBs)of LZ7C3,which results in the electrostatic poten-tial at GBs being comparable to that in the bulk.Furthermore,we found that the oxygen ion diffusion is facilitated at the GBs of LZ7C3 due to the stretched O-Zr/Ce bond and the low coordination at GBs.How-ever,the segregations of Y^(3+)cations and the increase in the number of oxygen vacancies resulted in the formation of an electrostatic layer at the GBs of 8YSZ,which shielded the oxygen ion diffusion.Despite this,the oxygen ion diffusivity in LZ7C3 was still considerably less than that in conventional 8YSZ.This study offers a stepping stone toward utilizing pyrochlore-type LZ7C3 materials as advanced TBCs at high temperatures.