硬纤维瘤的分子发病机制和治疗进展

硬纤维瘤(desmoidtumor,DT)是一种罕见的局部侵袭性肿瘤,无转移能力,但具有浸润性生长及局部复发的倾向,可严重影响患者功能,造成沉重的临床负担甚至死亡。近20年来,该病的治疗理念发生了巨变,从传统的积极手术转变为以主动监测为一线治疗的保守策略,治疗手段也更加丰富,呈现多学科管理的发展趋势。相关研究指出DT的发病与Wnt及Notch信号通路失调有关,以nirogacestat为代表的多款针对其发病机制的新型药物正在研发中,有望成为该病未来治疗的新方向。本文就DT的分子发病机制和治疗进展进行综述,为该病的临床治疗及未来研究提供依据和方向。

Population genetic insights into the conservation of common walnut(Juglans regia)in Central Asia

The common walnut(Juglans regia)is one of the most economically important nut trees cultivated worldwide.Despite its importance,no comprehensive evaluation of walnut tree population genetics has been undertaken across the range where it originated,Central Asia.In this study,we investigated the genetic diversity and population structure of 1082 individuals from 46 populations across Central Asia.We found moderate genetic diversity of J.regia across Central Asia,with 46 populations clustered into three groups with a weak relationship between genetic and geographic distance.Our findings reveal that the western Himalaya might be the core region of common walnut genetic diversity in Central Asia and that,except for two populations in Gongliu Wild Walnut Valley,humans might have introduced walnut populations to Xinjiang,China.The observed distribution of the genetic landscape has probably been affected by historical climate fluctuation,breeding system,and prolonged anthropogenic activity.We propose the conservation of the core genetic diversity resources in the western Himalaya and pay special attention to populations from Gongliu in Xinjiang.These findings enhance our understanding of the genetic variation throughout the distribution range of J.regia in Central Asia,which will provide a key prerequisite for evidence-based conservation and management.

Effect of ZSM-5 zeolite morphology on the catalytic performance of the alkylation of toluene with methanol

A series of ZSM-5 zeolites, with the morphologies of sphere, sphere with cubic particles on the surface, and cubic particles, were synthesized by hydrothermal method using n-butylamine as the template, assisted by the addition of NaC1 and crystal seed. X-ray diffraction （XRD）, scanning electron microscope （SEM）, X-ray fluorescence （XRF） and temperature-programmed desorption of ammonia （NH3-TPD） were used to characterize these samples. The samples were tested with toluene methylation reaction. The modified sample composed of spherical particles with 3 μm crystal particles on the surface had a para-xylene selectivity of 95% and maintained 79% of the initial conversion after running the reaction for 50 h. This modified samole showed the best stability amonz the tested three modified samoles.

Recent advances on the membrane processes for CO_2 separation

Membrane separation technology has popularized rapidly and attracts much interest in gas industry as a promising sort of newly chemical separation unit operation. In this paper, recent advances on membrane processes for CO_2 separation are reviewed. The researches indicate that the optimization of operating process designs could improve the separation performance, reduce the energy consumption and decrease the cost of membrane separation systems. With the improvement of membrane materials recently,membrane processes are beginning to be competitive enough for CO_2 separation, especially for postcombustion CO_2 capture, biogas upgrading and natural gas carbon dioxide removal, compared with the traditional separation methods. We summarize the needs and most promising research directions for membrane processes for CO_2 separation in current and future membrane applications. As the time goes by, novel membrane materials developed according to the requirement proposed by process optimization with increased selectivity and/or permeance will accelerate the industrialization of membrane process in the near future. Based on the data collected in a pilot scale test, more effort could be made on the optimization of membrane separation processes. This work would open up a new horizon for CO_2 separation/Capture on Carbon Capture Utilization and Storage(CCUS).

Hierarchical Optimization of Landing Performance for Lander with Adaptive Landing Gear

A parameterized dynamics analysis model of legged lander with adaptive landing gear was established. Based on the analysis model, the landing performances under various landing conditions were analyzed by the optimized Latin hypercube experimental design method. In order to improve the landing performances, a hierarchical optimization method was proposed considering the uncertainty of landing conditions. The optimization problem was divided into a higher level(hereafter the "leader") and several lower levels(hereafter the "follower"). The followers took condition?ing factors as design variables to find out the worst landing conditions, while the leader took bu er parameters as design variables to better the landing performance under worst conditions. First of all, sensitivity analysis of landing conditioning factors was carried out according to the results of experimental design. After the sensitive factors were screened out, the response surface models were established to reflect the complicated relationships between sensi?tive conditioning factors, bu er parameters and landing performance indexes. Finally, the response surface model was used for hierarchical optimization iteration to improve the computational e ciency. After selecting the optimum bu er parameters from the solution set, the dynamic model with the optimum parameters was simulated again under the same landing conditions as the simulation before. After optimization, nozzle performance against damage is improved by 5.24%, the acceleration overload is reduced by 5.74%, and the primary strut improves its performance by 21.10%.

Chromosome-level genome assemblies of five Prunus species and genome-wide association studies for key agronomic traits in peach

Prunus species include many important perennial fruit crops,such as peach,plum,apricot,and related wild species.Here,we report de novo genome assemblies for five species,including the cultivated species peach(Prunus persica),plum(Prunus salicina),and apricot(Prunus armeniaca),and the wild peach species Tibetan peach(Prunus mira)and Chinese wild peach(Prunus davidiana).The genomes ranged from 240 to 276 Mb in size,with contig N50 values of 2.27−8.30Mb and 25,333−27,826 protein-coding gene models.As the phylogenetic tree shows,plum diverged from its common ancestor with peach,wild peach species,and apricot~7 million years ago(MYA).We analyzed whole-genome resequencing data of 417 peach accessions,called 3,749,618 high-quality SNPs,577,154 small indels,31,800 deletions,duplications,and inversions,and 32,338 insertions,and performed a structural variant-based genome-wide association study(GWAS)of key agricultural traits.From our GWAS data,we identified a locus associated with a fruit shape corresponding to the OVATE transcription factor,where a large inversion event correlates with higher OVATE expression in flat-shaped accessions.Furthermore,a GWAS revealed a NAC transcription factor associated with fruit developmental timing that is linked to a tandem repeat variant and elevated NAC expression in early-ripening accessions.We also identified a locus encoding microRNA172d,where insertion of a transposable element into its promoter was found in double-flower accessions.Thus,our efforts have suggested roles for OVATE,a NAC transcription factor,and microRNA172d in fruit shape,fruit development period,and floral morphology,respectively,that can be connected to traits in other crops,thereby demonstrating the importance of parallel evolution in the diversification of several commercially important domesticated species.In general,these genomic resources will facilitate functional genomics,evolutionary research,and agronomic improvement of these five and other Prunus species.We believe that structural variant-based GWASs can also be used in other plants,animal species,and humans and be combined with deep sequencing GWASs to precisely identify candidate genes and genetic architecture components.

Multi-Label Chinese Comments Categorization: Comparison of Multi-Label Learning Algorithms

Multi-label text categorization refers to the problem of categorizing text througha multi-label learning algorithm. Text classification for Asian languages such as Chinese isdifferent from work for other languages such as English which use spaces to separate words.Before classifying text, it is necessary to perform a word segmentation operation to converta continuous language into a list of separate words and then convert it into a vector of acertain dimension. Generally, multi-label learning algorithms can be divided into twocategories, problem transformation methods and adapted algorithms. This work will usecustomer's comments about some hotels as a training data set, which contains labels for allaspects of the hotel evaluation, aiming to analyze and compare the performance of variousmulti-label learning algorithms on Chinese text classification. The experiment involves threebasic methods of problem transformation methods: Support Vector Machine, Random Forest,k-Nearest-Neighbor;and one adapted algorithm of Convolutional Neural Network. Theexperimental results show that the Support Vector Machine has better performance.

Mechanism analysis and improved model for stick-slip friction behavior considering stress distribution variation of interface

Studying the evolution of interface contact state, revealing the “black box” behavior in interface friction and establishing a more accurate friction model are of great significance to improve the prediction accuracy of mechanical system performance. Based on the principle of total reflection, a visual analysis technology of interface contact behavior is proposed. Considering the dynamic variation of stress distribution in interface contact, we analyze the nonlinear characteristics of contact parameters in different stages of stick-slip process using the above-mentioned experimental technology. Then,we find that the tangential stiffness of the interface is not a fixed value during the stick-slip process and the stress distribution variation is one of the important factors affecting the tangential stiffness of interface. Based on the previous experimental results, we present an improved stick-slip friction model, considering the change of tangential stiffness and friction coefficient caused by the stress distribution variation. This improved model can characterize the variation characteristics of contact parameters in different stages of stick-slip process, whose simulation results are in good agreement with the experimental data. This research may be valuable for improving the prediction accuracy of mechanical system performance.

Interactive hepatic parenchymal transection simulation with haptic feedback

Background Liver resection involves surgical removal of a portion of the liver.It is used to treat liver tumors and liver injuries.The complexity and high-risk nature of this surgery prevents novice doctors from practicing it on real patients.Virtual surgery simulation was developed to simulate surgical procedures to enable medical professionals to be trained without requiring a patient,a cadaver,or an animal.Therefore,there is a strong need for the development of a liver resection surgery simulation system.We propose a real-time simulation system that provides realistic visual and tactile feedback for hepatic parenchymal transection.Methods The tetrahedron structure and cluster-based shape matching are used for physical model construction,topology update of a three-dimensional liver model soft deformation simulation,and haptic rendering acceleration.During the liver parenchyma separation simulation,a tetrahedral mesh is used for surface triangle subdivision and surface generation of the surgical wound.The shape-matching cluster is separated via component detection on an undirected graph constructed using the tetrahedral mesh.Results In our system,cluster-based shape matching is implemented on a GPU,whereas haptic rendering and topology updates are implemented on a CPU.Experimental results show that haptic rendering can be performed at a high frequency(>900Hz),whereas mesh skinning and graphics rendering can be performed at 45fps.The topology update can be executed at an interactive rate(>10Hz)on a single CPU thread.Conclusions We propose an interactive hepatic parenchymal transection simulation method based on a tetrahedral structure.The tetrahedral mesh simultaneously supports physical model construction,topology update,and haptic rendering acceleration.

A multi-parameter-induced activation of gas therapeutic platform to remarkably amplify photodynamic therapy efficacy

Gas therapy(GT)combined with photodynamic therapy(PDT)is an effective strategy to compensate for the PDT limitation caused by the hypoxic tumor microenvironment,which can greatly improve PDT efficacy.The uncontrolled leakage of gas molecules during delivery seriously hinders its practical biological application.Herein,we report a multifunction nanomedicine that enables precise gas therapy(including carbon monoxide(CO)release and H_(2)S depletion)using a multi-parameter-induced activation gas release strategy,enlarging the PDT efficacy.This nanomedicine uses a disulfide bond to covalently link a photosensitizer with the CO donor 3-hydroxyflavone(3-HF).The disulfide bond can be specifically consumed in H_(2)S-rich tumor areas,releasing the CO donor(3-HF),and also depleting H_(2)S.More importantly,the photo-controlled production of^(1)O_(2)can induce 3-HF precise release of CO in the tumor location.Such H_(2)S,light,and^(1)O_(2)multi-parameter-induced activation of gas release strategy ensures the accuracy of GT to amplify PDT efficiency.As expected,in vitro and in vivo investigations show that GT makes up for the PDT limitation,exhibiting the highest tumor therapeutic effect.This multi-parameter-activated design strategy provides a new way to improve the precision and efficacy of multimodal synergistic therapy of tumors.

The secretory Candida effector Sce1 licenses fungal virulence by masking the immunogenicβ-1,3-glucan and promoting apoptosis of the host cells

Candida albicans deploys a variety of mechanisms such as morphological switch and elicitor release to promote virulence.However,the intricate interactions between the fungus and the host remain poorly understood,and a comprehensive inventory of fungal virulence factors has yet to be established.In this study,we identified a C.albicans secretory effector protein Sce1,whose induction and secretion are associated with vagina‐simulative conditions and chlamydospore formation.Sequence alignment showed that Sce1 belongs to a Pir family in C.albicans,which is conserved across several fungi and primarily characterized as aβ‐glucan binding protein in the Saccharomyces cerevisiae.Mechanically,Sce1 is primarily localized to the cell wall in a cleaved form as an alkali‐labileβ‐1,3‐glucan binding protein and plays a role in maskingβ‐glucan in acidic environments and chlamydospores,a feature that might underline C.albicans'ability to evade host immunity.Further,a cleaved short form of Sce1 protein could be released into extracellular compartments and presented in bone marrow‐derived macrophages infected with chlamydospores.This cleaved short form of Sce1 also demonstrated a unique ability to trigger the caspases‐8/9‐dependent apoptosis in various host cells.Correspondingly,genetic deletion of SCE1 led to dampened vaginal colonization of C.albicans and diminished fungal virulence during systemic infection.The discovery of Sce1 as a versatile virulence effector that executes at various compartments sheds light on the fungus–host interactions and C.albicans pathogenesis.

肝内胆管细胞癌外科治疗疗效分析

目的探讨手术切除治疗肝内胆管细胞癌(intrahepatic cholangiocarcinoma,ICC)的临床疗效及分析影响预后的危险因素。方法回顾性分析2015年1月1日至2021年4月30日于安徽医科大学第一附属医院普外科接受手术切除的ICC患者的临床资料。结果67例获得完整随访,最终纳入本研究中。截止至2022年4月30日,中位随访时间14(1~60)个月,53例(79.1%)肿瘤复发,52例(77.6%)死亡,其中49例(73.1%)死于肿瘤复发,全组1、2、3年累积的无瘤和总体生存率分别为35.6%、19.6%、16.8%和53.7%、32.4%、20.8%。无微血管侵犯组总体生存率显著优于有微血管侵犯组(χ^(2)=5.916,P=0.015)。CA19-9≥1000 U/ml是影响ICC术后无瘤生存时间的独立危险因素。CA19-9≥1000 U/ml、术中失血量≥600 ml、微血管侵犯和肿瘤复发是影响ICC术后总体生存时间的独立危险因素。结论单发ICC肿瘤,当肿瘤直径≤5 cm且考虑无微血管侵犯时,可积极推荐手术切除,能够取得较为满意的手术效果。

α-酮酸、异腈和水的电化学三组分合成α-酮酰胺

电化学有机合成使用无痕的电子替代化学氧化还原试剂,是一种环境友好的合成方法.利用碘化钾作为电解质和催化剂,乙腈和水的混合溶液作为溶剂,在非分离式电解池中实现了α-酮酸、异腈和水的电化学脱羧酰基化和接力水合反应,高效合成了一系列的α-酮酰胺化合物.该电化学反应无需使用化学氧化剂,无需过渡金属催化剂,具有反应条件温和等优点.

响应面法优化鹿茸胶原蛋白制备抗氧化肽的水解条件

以鹿茸中下段胶原蛋白为酶解底物,用木瓜蛋白酶酶解制备小分子抗氧化肽,以清除1,1-二苯基-2-苦基肼基(DPPH·)自由基的能力为指标,采用响应面法优化酶水解条件。结果表明,最优实验条件为时间56 min,酶添加量1.40wt%,pH=5.60,温度60℃。该条件下所得抗氧化肽对DPPH·自由基的清除率为83.09%。用超滤膜、半制备色谱柱和超高效液相色谱-质谱联用仪分级分离获得分子量0.2~0.6 kDa的具有最高抗氧化活性的多肽,其具有与头段类似的保健功效,更易被人体吸收,且易进一步加工和储存。

Microstructural evolution and defect formation in a powder metallurgy nickel-based superalloy processed by selective laser melting

In this study,the selective laser melting(SLM)technology has been employed to manufacture a nickelbased superalloy which was conventionally prepared through powder metallurgy(PM)route.The microstructural features and defects were systematically investigated both prior to and after heat treatment and compared with the PM counterpart.Both solidification cracking and liquation cracking were observed in the SLM specimen in which the grain misorientation and low melting point(γ+γ')eutectic played a vital role in their formation mechanism.Columnar grains oriented along building direction were ubiquitous,corresponding to strong<001>fiber texture.Solidification cell structures and melt pools are pervasive and noγ'precipitates were detected at about 10 nm scale before heat treatment.After supersolvus solution and two-step aging treatments,high volume fractionγ'precipitates emerged and their sizes and morphologies were comparable to those in PM alloy.<001>texture is relieved and columnar grains tend to become more equiaxed due to static recrystallization process and grain boundary migration events.Significant annealing twins formed in SLM alloy and are clarified as a consequence of recrystallization.Our results provide fundamental understandings for the SLM PM nickel-based superalloy both before and after heat treatment and demonstrate the potential to fabricate this group of alloys using SLM technology.

HEMS-enabled transactive flexibility in real-time operation of three-phase unbalanced distribution systems

This paper proposes a coordinated two-stage real-time market mechanism in an unbalanced distribution system which can utilize flexibility service from home energy management system(HEMS)to alleviate line congestion,voltage violation,and substation-level power imbalance.At the grid level,the distribution system operator(DSO)computes the distribution locational marginal prices(DLMPs)and its energy,loss,congestion,and voltage violation components through comprehensive sensitivity analyses.By using the DLMP components in a firststage optimization problem,the DSO generates two price signals and sends them to HEMS to seek flexibility service.In response to the request of DSO,each home-level HEMS computes a flexibility range by incorporating the prices of DSO in its own optimization problem.Due to future uncertainties,the HEMS optimization problem is modeled as an adaptive dynamic programming(ADP)to minimize the total expected cost and discomfort of the household over a forward-looking horizon.The flexibility range of each HEMS is then used by the DSO in a second-stage optimization problem to determine new optimal dispatch points which ensure the efficient,reliable,and congestionfree operation of the distribution system.Lastly,the second-stage dispatch points are used by each HEMS to constrain its maximum consumption level in a final ADP to assign consumption level of major appliances such as energy storage,heating,ventilation and air-conditioning,and water heater.The proposed method is validated on an IEEE 69-bus system with a large number of regular and HEMS-equipped homes in each phase.

Molecular glues modulate protein functions by inducing protein aggregation:A promising therapeutic strategy of small molecules for disease treatment

Molecular glues can specifically induce aggregation between two or more proteins to modulate biological functions.In recent years,molecular glues have been widely used as protein degraders.In addition,however,molecular glues play a variety of vital roles,such as complex stabilization,interactome modulation and transporter inhibition,enabling challenging therapeutic targets to be druggable and offering an exciting novel approach for drug discovery.Since most molecular glues are identified serendipitously,exploration of their systematic discovery and rational design are important.In this review,representative examples of molecular glues with various physiological functions are divided into those mediating homo-dimerization,homo-polymerization and hetero-dimerization according to their aggregation modes,and we attempt to elucidate their mechanisms of action.In particular,we aim to highlight some biochemical techniques typically exploited within these representative studies and classify them in terms of three stages of molecular glue development:starting point,optimization and identification.

An Assessment of Flexibility Reserves in Stochastic Modeling at Multiple Timescales

Due to recent technological achievements,stochastic optimization,which inherently captures the uncertainty of intermittent resources,is being used to capture the variability and uncertainty of wind and solar resources.However,due to persistent computational limitations,it is not practical to consider all possible variable generation scenarios.As a result,a reduced number of most likely scenarios is usually considered.While this helps reduce the computational burden,it also leaves the system operator vulnerable to some risk.In order to address this issue,this paper aims at providing insight into using an explicit reserve requirement in a stochastic modeling framework in order to provide system operators with greater confidence in stochastic dispatch solutions.This is accomplished by simulating a modified version of the IEEE 118 bus system in a fully stochastic,multi-timescale framework with flexibility reserve requirements.Results show that utilizing a stochastic flexibility reserve requirement within the stochastic modeling framework offers the most reliability benefit.

Placental Development and Pregnancy-Associated Diseases

Serving as the interface between the fetal and maternal environments during gestation,the placenta plays critical roles in the protection of the developing fetus and the maintenance of maternal health.The placenta is primarily derived from the embryonic trophectoderm which differentiates into various subtypes of trophoblast cells through villous and extravillous pathways.The interactions among trophoblasts and multiple decidual cells and immune cells at the maternal-fetal interface fundamentally form the functional units of the placenta,which are responsible for blood perfusion and maternal-fetal material exchange,immune tolerance,and the regulation of pregnancy adaptation.Defects in placental development and functional maintenance are in tight association with adverse pregnancy outcomes such as preeclampsia.In this article,we review recent advances on human trophoblast cell differentiation and the construction of placental functional units and discuss the placental and maternal factors that may contribute to the occurrence of preeclampsia.

Short-term forecasts and long-term mitigation evaluations for the COVID-19 epidemic in Hubei Province,China

As an emerging infectious disease,the 2019 coronavirus disease(COVID-19)has developed into a global pandemic.During the initial spreading of the virus in China,we demonstrated the ensemble Kalman filter performed well as a short-term predictor of the daily cases reported in Wuhan City.Second,we used an individual-level network-based model to reconstruct the epidemic dynamics in Hubei Province and examine the effectiveness of non-pharmaceutical interventions on the epidemic spreading with various scenarios.Our simulation results show that without continued control measures,the epidemic in Hubei Province could have become persistent.Only by continuing to decrease the infection rate through 1)protective measures and 2)social distancing can the actual epidemic trajectory that happened in Hubei Province be reconstructed in simulation.Finally,we simulate the COVID-19 transmission with non-Markovian processes and show how these models produce different epidemic trajectories,compared to those obtained with Markov processes.Since recent studies show that COVID-19 epidemiological parameters do not follow exponential distributions leading to Markov processes,future works need to focus on non-Markovian models to better capture the COVID-19 spreading trajectories.In addition,shortening the infectious period via early case identification and isolation can slow the epidemic spreading significantly.