Enhancing the Photosensitivity of Hypocrellin A by Perylene Diimide Metallacage‑Based Host–Guest Complexation for Photodynamic Therapy

The development of supramolecular hosts which can efficiently encapsulate photosensitizers to improve the photodynamic efficacy holds great promise for cancer therapy.Here,we report two perylene diimide-based metallacages that can form stable host–guest complexes with planar conjugated molecules including polycyclic aromatic hydrocarbons and photosensitizers(hypocrellin A).Such host–guest complexation not only prevents the aggregation of photosensitizers in aqueous environments,but also offers fluorescence resonance energy transfer(FRET)from the metallacage to the photosensitizers to further improve the singlet oxygen generation(Φ_(Δ)=0.66).The complexes are further assembled with amphiphilic polymers,forming nanoparticles with improved stability for anticancer study.Both in vitro and in vivo studies indicate that the nanoparticles display excellent anticancer activities upon light irradiation,showing great potential for cancer photodynamic therapy.This study provides a straightforward and effective approach for enhancing the photosensitivity of conventional photosensitizers via host–guest complexation-based FRET,which will open a new avenue for host–guest chemistry-based supramolecular theranostics.

Third-order elastic, piezoelectric, and dielectric constants

The definitions of the third-order elastic,piezoelectric,and dielectric constants and the properties of the associated tensors are discussed.Based on the energy conservation and coordinate transformation,the relations among the third-order constants are obtained.Furthermore,the relations among the third-order elastic,piezoelectric,and dielectric constants of the seven crystal systems and isotropic materials are listed in detail.These third-order constants relations play an important role in solving nonlinear problems of elastic and piezoelectric materials.It is further found that all third-order piezoelectric constants are 0 for 15 kinds of point groups,while all third-order dielectric constants are 0 for 16 kinds of point groups as well as isotropic material.The reason is that some of the point groups are centrally symmetric,and the other point groups are high symmetry.These results provide the foundation to measure these constants,to choose material,and to research nonlinear problems.Moreover,these results are helpful not only for the study of nonlinear elastic and piezoelectric problems,but also for the research on flexoelectric effects and size effects.

Nanoparticle-induced drag reduction for polyacrylamide in turbulent flow with high Reynolds numbers

Although having been increasingly studied, there is still controversy as to when the addition of nanoparticles could improve the drag reduction performance of polymer drag reducer and particularly what is the underlying mechanism from the fluid dynamics viewpoint. The drag reduction effects of adding SiO_(2) nanoparticles to various polymer polyacrylamide(PAM) solutions were examined in this work.The optimal combination of SiO_(2) nanoparticles with cationic polyacrylamide was confirmed.Interestingly,the addition of SiO_(2) nanoparticles to cationic polyacrylamide solution was shown to be quite efficient for reducing drag, but only at higher flow rates with Reynolds numbers more than 6000, below which the nanoparticle addition is even negative. The addition of SiO_(2) nanoparticles to the PAM solution is supposed to play a dual role. The first is an increase in flow resistance caused by the Brownian motion of nanoparticles, while the second is a decrease in flow resistance caused by acting as nodes to protect the polymer chain from shear-induced breaking under high shear action. At optimal nanoparticle concentration and under higher Reynolds numbers, the later effect is dominant, which could improve the drag reduction performance of polymer drag reducers. Our work should serve as a guide for the application of natural gas fracturing, where the flow rate is frequently very high.

The application of 3D printing in the development of RECIST standard for evaluating tumor efficacy

Three-dimensional(3D)printing technology,as a novel technical method,can convert conventional computed tomography(CT)or magnetic resonance imaging(MRI)scans to computer-aided design files and develop a 2D spatial structure into a 3D imaging structure.In recent years,the technology has been widely used in numerous areas,including head and neck surgery,orthopedics,and bio-medicinal research.This article uses examples of 3D printed tumor models to develop Response Evaluation Criteria In Solid Tumors(RECIST)standards to evaluate the changes in tumors.RECIST standard is currently recognized as the standard for assessment of chemotherapy.Under the RECIST standard,changes occurring in tumors before and after the surgery,are evaluated.The assessment depends upon a CT evaluation of the changes in the lesions with the largest diameters.In addition,the disease progression and stability of remission is also assessed.Three-dimensional printing technology is more intuitive in the evaluation of changes to human tumors following chemotherapy and targeted therapy.However,a few reports are available.

Haploidentical hematopoietic cell transplantation with or without an unrelated cord blood unit for adult acute myeloid leukemia:a multicenter,randomized,open-label,phase 3 trial

Coinfusion of unrelated cord blood(UCB)units in haploidentical hematopoietic cell transplantation(haplo-HCT)(haplo-cord HCT)for hematopoietic malignancies showed promising results in previous reports,but the efficiency of haplo-cord HCT in acute myeloid leukemia(AML)still lacks sufficient evidence.This multicenter,randomized,phase 3 trial(ClinicalTrials.gov NCT03719534)aimed to assess the efficacy and safety of haplo-cord HCT in AML patients.A total of 268 eligible patients aged 18-60 years,diagnosed with measurable residual disease in AML(excluding acute promyelocytic leukemia),with available haploidentical donors and suitable for allotransplantation,were randomly allocated(1:1)to receive haplo-cord HCT(n=134)or haplo-HCT(n=134).The 3-year overall survival(OS)was the primary endpoint in this study.Overall median follow-up was 36.50 months(IQR 24.75-46.50).The 3-year OS of Haplo-cord HCT group was better than haplo-HCT group(80.5%,95%confidence interval[CI]:73.7-87.9 vs.67.8%95%CI 60.0-76.5,p=0.013).Favorable progression-free survival(70.3%,95%CI 62.6-78.8 vs.57.6%,95%CI 49.6-67.0,p=0.012)and cumulative incidence of relapse(12.1%,95%CI 12.0-12.2 vs.30.3%,95%CI 30.1-30.4,p=0.024)were observed in haplo-cord HCT group.Grade 3-4 adverse events(AEs)within two years posttransplantation in the two groups were similar.Haplo-cord HCT patients exhibited a faster cumulative incidence of neutrophil recovery(p=0.026)and increased T-cell reconstitution in the early period posttransplantation.Haplo-cord HCT can improve OS in AML patients without excessive AEs,which may exert additional benefits for recipients of haplo-HCT.

Blood-derived factors to brain communication in brain diseases

Brain diseases,mainly including acute brain injuries,neurodegenerative diseases,and mental disorders,have posed a significant threat to human health worldwide.Due to the limited regenerative capability and the existence of the blood–brain barrier,the brain was previously thought to be separated from the rest of the body.Currently,various cross-talks between the central nervous system and peripheral organs have been widely described,including the brain-gut axis,the brain-liver axis,the brain-skeletal muscle axis,and the brain-bone axis.Moreover,several lines of evidence indicate that leveraging systemic biology intervention approaches,including but not limited to lifestyle interventions,exercise,diet,blood administration,and peripheral immune responses,have demonstrated a significant influence on the progress and prognosis of brain diseases.The advancement of innovative proteomic and transcriptomic technologies has enriched our understanding of the nuanced interplay between peripheral organs and brain diseases.An array of novel or previously underappreciated blood-derived factors have been identified to play pivotal roles in mediating these communications.In this review,we provide a comprehensive summary of blood-to-brain communication following brain diseases.Special attention is given to the instrumental role of blood-derived signals,positing them as significant contributors to the complex process of brain diseases.The insights presented here aim to bridge the current knowledge gaps and inspire novel therapeutic strategies for brain diseases.

Comparing the effects of dual-task training and single-task training on walking,balance and cognitive functions in individuals with Parkinson’s disease:A systematic review

Background:This systematic review aimed to examine whether dual-task(DT)training was superior to single-task(ST)training in improving DT walking,balance and cognitive functions for individuals with Parkinson’s disease(PD).Methods:Literature search was performed in the following electronic databases:PubMed,the Cochrane Library,Web of Science,and Metstr covering inception to May 10,2023.And in order to facilitate comparison across trials,we calculated the effect size(Hedges’g)of gait,balance,cognitive,and other parameters under both ST and DT conditions,using the mean change score and standard deviation(SD)of change score of the experimental and control groups.Randomized controlled trials that examined the effects of DT motor and cognitive training in individuals with Parkinson’s disease were included for this systematic review.Results:A total of 214 participants recruited from six articles(actually five trials)were involved in this review.In terms of walking ability,only double support time and stride time variability showed significant between-group difference(Hedges’g=0.34,0.18,respectively).Compared to ST training group,DT training group had a more improvement effect in laboratory balance measurement(Hedges’g=0.18,1.25),but no significant improvement in clinical balance measurement.No significant between-group differences were observed,thus its training effect on cognitive function was inconclusive.Conclusions:The DT training failed to achieve promising results better than ST training in improving DT walking and balance functions for individuals with PD.Any firm conclusion cannot be drawn at present,due to the limited number of eligible publications.Larger sample size and high-quality studies are needed to investigate the effectiveness of DT training in individuals with PD.

Structural changes in the conversion of an Arabidopsis outward-rectifying K^(+) channel into an inward-rectifying channel

Dear Editor,By using cryo-electron microscopy and electrophysiology,this study characterizes the structural and functional dynamics of the K+outward-rectifying channel SKOR in Arabidopsis and the structural changes associated with a double mutation that transforms SKOR into an inward-rectifying K+channel,SKDM.These findings have implications for understanding and manipulating crop K+nutrition.

Enhancing Variant Calling in Whole-exome Sequencing Data Using Population-matched Reference Genomes

Whole-exome sequencing(WES)data are frequently used for cancer diagnosis and genome-wide association studies(GWAS),based on high-coverage read mapping,informative variant calling,and high-quality reference genomes.The center position of the currently used genome assembly,GRCh38,is now challenged by two newly published telomere-to-telomere(T2T)genomes,T2T-CHM13 and T2T-YAO,and it becomes urgent to have a comparative study to test population specificity using the three reference genomes based on real case WES data.Here,we report our analysis along this line for 19 tumor samples collected from Chinese patients.The primary comparison of the exon regions among the three references reveals that the sequences in up to∼1%of target regions in T2T-YAO are widely diversified from GRCh38 and may lead to off-target in sequence capture.However,T2T-YAO still outperforms GRCh38 by obtaining 7.41%of more mapped reads.Due to more reliable read-mapping and closer phylogenetic relationship with the samples than GRCh38,T2T-YAO reduces half of variant calls of clinical significance which are mostly benign,while maintaining sensitivity in identifying pathogenic variants.T2T-YAO also outperforms T2T-CHM13 in reducing calls of Chinese-specific variants.Our findings highlight the critical need for employing population-specific reference genomes in genomic analysis to ensure accurate variant analysis and the significant benefits of tailoring these approaches to the unique genetic background of each ethnic group.

声表面波谐振器频率-温度行为分析

声表面波(SAW)器件以其优良的性能广泛应用于雷达、通讯和日常用品等领域.然而,随着器件工作频率的不断升高,温度对器件频率稳定性的影响也越来越严重.因此,研究声表面波器件的温度效应,并在变温情况下保持SAW器件的频率稳定性至关重要.论文采用增量型的拉格朗日方程分析受温度影响的声表面波频率漂移问题.用频率-温度系数(TCF)作为评价频率-温度行为的标准.设计了一个具有温度补偿层的双层SAW谐振器模型,降低了器件的频率-温度系数.通过尺寸优化,LiNbO_3-AlN结构的SAW谐振器在25℃(参考温度)下的频率-温度系数TCF接近0 ppm/℃.SAW谐振器的波长为4μm,谐振频率为1214.9 MHz.

Seasonal variations in the composition and functional profiles of gut microbiota reflect dietary changes in plateau pikas

Seasonal variations in gut microbiota of small mammals and how they are influenced by environmental variables are relatively poorly understood.We sampled 162 wild plateau pikas(Ochotona curzoniae)in 4 seasons over 2 and a half years and recorded the air temperature,precipitation,and nutrient content in edible vegetation at the sampling site.After conducting 16S rRNA and shotgun metagenomic sequencing,we found that the highest alpha diversity,the relative abundance of Firmicutes,and the simplest co-occurrence network occurred in winter,whereas the highest relative abundance of Proteobacteria and the most complex network structure were observed in spring.The highest relative abundance of Verrucomicrobiota and Spirochaetota was seen in summer and autumn,respectively.Air temperature,precipitation,and the contents of crude protein,crude fiber,and polysaccharide in vegetation had significant effects on the seasonal changes in gut microbiota.Diet contributed more to microbial variation than climatic factors.Metagenomic analysis revealed that the amino acid metabolism pathway and axillary activity enzymes were most abundant in summer,while abundance of carbohydrate-binding modules and carbohydrate esterases was highest in spring.These microbial variations were related to the changes in dietary nutrition,indicating that gut microbiota of plateau pika contribute to the efficient use of food resources.This study provides new evidence of how external environmental factors affect the intestinal environment of small mammals.

Mechanism of keyhole pore formation in metal additive manufacturing

During metal additive manufacturing,the porosity of the as-built part deteriorates the mechanical property and even hinders the further application of metal additive manufacturing.Particularly,the mechanisms of keyhole pores associated with the keyhole fluctuation are not fully understood.To reveal the mechanisms of the keyhole pores formation,we adopt a multiphysics thermal-fluid flow model incorporating heat transfer,liquid flow,metal evaporation,Marangoni effect,and Darcy’s law to simulate the keyhole pore formation process,and the results are validated with the in situ X-ray images.The simulation results present the instant bubble formation due to the keyhole instability and motion of the instant bubble pinning on the solidification front.Furthermore,comparing the keyhole pore formation under different laser scanning speeds shows that the keyhole pore is sensitive to the manufacturing parameters.Additionally,the simulation under a low ambient pressure shows the feasibility of improving the keyhole stability to reduce and even avoid the formation of keyhole pores.

Effect of assisted transverse magnetic field on distortion behavior of thin-walled components in WEDM process

Machining performance of thin-walled components made by aeronautical difficult-toprocess materials is a significant issue in the aviation manufacturing industry.Although wire electric discharge machining-low speed(WEDM-LS)is one of typical non-contact machining processes without macro cutting force,which does well in removing hardness and brittleness materials via pulsed discharge at high temperature,but few researchers have studied the thermal distortion behavior leading to a considerable geometric error in the WEDM-LS of thin-walled components.In this paper,a transverse magnetic field assisted method is applied for affecting the uniformity of discharge point distribution so as to reduce the distortion in WEDM-LS processing thin-wall component.First,the generation mechanism of this new distortion behavior and the impact mechanism of transverse magnetic field(TMF)on distortion are demonstrated by theoretical analysis.In order to further figure out the distortion behavior in the TMF-WEDM process,a new thermophysical model considering the discharge point distribution is established to simulate temperature field,residual stress field and distortion profiles.Then a large number of Taguchi experiments are carried out to investigate the influences of process parameters including pulse discharge energy(pulse on time,pulse off time,and current)and magnetic field strength on distortion in WEDM-LS.To comparatively analyze simulated and experimental results,the accuracy of established thermophysical model is verified within a relative error of 18.38%in distortion.Moreover,it can be revealed that transverse magnetic field contribute to significantly improve the longitudinal distribution uniformity with maximum increase of 12.32%at magnetic field strength:0.15 T,leading to significant reductions of 32.77%in distortion and 22.68%in recast layer.Eventually,we also presented the variation of residual stress and recast layer along thickness direction under different distortion behavior,which are in good agreement with that of distortion behavior.

A Modified Enrichment Method to Construct Microsatellite Library from Plateau Pika Genome(Ochotona curzoniae)

A microsatellite-enriched library of plateau pika （Ochotona curzoniae） was constructed according to the strong affinity between biotin and streptavidin. Firstly, genomic DNA was fragmented by ultrasonication, which is a major improvement over traditional methods. Linker-ligated DNA fragments were hybridized with biotinylated microsatellite probes, and then were subjected to streptavidin-coated magnetic beads. PCR amplification was performed to obtain double-stranded DNA fragments containing microsatellites. Ligation and transformation were carried out by using the pGEM-T Vector System I and Escherichia coli DH10B competent cells. Sequencing results showed that 80.2% of clones contained microsatellite repeat motif. Several modifications make this protocol time-efficient and technically easier than the traditional ones; particularly, composition and relative abundance of microsatellite repeats in plateau pika genome were truly represented through the optimized PCR conditions. This method has also been successfully applied to construct microsatellite-enriched genomic libraries of Chinese hamster （Cricetulus griseus） and small abalone [Haliotis diversicolor （Reeve）] with high rates of positive clones, demonstrating its feasibility and stability.

基于碳纳米管的光伏电池

碳纳米管具有独特的一维结构和优异的光电特性,是构建光伏电池的理想材料。本文主要综述了近年来碳纳米管基光伏电池的结构设计、制备方法以及碳纳米管在器件中的不同功能应用。首先概述了碳纳米管的结构和光电特性,重点讨论了碳纳米管作为光电转换材料、导电电极和载流子传输层等功能层时器件的原理、制作方法及优缺点,介绍了碳纳米管在微型光伏电池、碳纳米管/硅异质结光伏电池、染料敏化光伏电池、钙钛矿光伏电池、有机光伏电池以及柔性光伏电池中的应用,最后总结了碳纳米管基光伏电池的优势和挑战,以期为新型碳基光伏电池的设计和制作提供思路和参考。

Discovery of a Potent Botulinum Neurotoxin A Inhibitor ZM299 with Effective Protections in Botulism Mice

Botulinum neurotoxins serotype A(BoNT/A)is the deadliest toxins known to humans and the"Category A"agent for bioterrorism.Over the past 20 years,significant efforts have been put forth to develop effective inhibitors of BoNT/A.Unfortunately,few identified inhibitors possess noteworthy efficacy against BoNT/A in vivo.Here,we performed a high-throughput virtual screening based on the structure-based docking simulations and found a novel potent scaffold 2-thionicotinate that inhibits the BoNT/A light chain(LC).We then synthesized and optimized a novel series of 2-thionicotinate derivatives and comprehensively evaluated their activity against BoNT/A in vitro and in vivo.An optimized compound ZM299 effectively exhibits anti-BoNT/A activity in primary neurons and displayed remarkably therapeutic efficacy against BoNT/A in vivo,which could raise the survival rate of intoxicated mice to 100%(12/12)after lethal doses of BoNT/A exposures.These findings demonstrate that 2-thionicotinates is a promising scaffold for producing more effective anti-BoNT/A analogs,and compound ZM299 is worthy of further preclinical evaluation as a drug candidate for the treatment of botulism.

Identification of the receptor of oncolytic virus M1 as a therapeutic predictor for multiple solid tumors

Over the last decade,oncolytic virus(OV)therapy has shown its promising potential in tumor treatment.The fact that not every patient can benefit from it highlights the importance for defining biomarkers that help predict patients’responses.As particular self-amplifying biotherapeutics,the anti-tumor effects of OVs are highly dependent on the host factors for viral infection and replication.By using weighted gene co-expression network analysis(WGCNA),we found matrix remodeling associated 8(MXRA8)is positively correlated with the oncolysis induced by oncolytic virus M1(OVM).

Feasibility study on application of volume acid fracturing technology to tight gas carbonate reservoir development

How to effectively develop tight-gas carbonate reservoir and achieve high recovery is always a problem for the oil and gas industry.To solve this problem,domestic petroleum engineers use the combination of the successful experiences of North American shale gas pools development by stimulated reservoir volume(SRV)fracturing with the research achievements of Chinese tight gas development by acid fracturing to propose volume acid fracturing technology for fractured tightgas carbonate reservoir,which has achieved a good stimulation effect in the pilot tests.To determine what reservoir conditions are suitable to carry out volume acid fracturing,this paper firstly introduces volume acid fracturing technology by giving the stimulation mechanism and technical ideas,and initially analyzes the feasibility by the comparison of reservoir characteristics of shale gas with tight-gas carbonate.Then,this paper analyzes the validity and limitation of the volume acid fracturing technology via the analyses of control conditions for volume acid fracturing in reservoir fracturing performance,natural fracture,horizontal principal stress difference,orientation of insitu stress and natural fracture,and gives the solution for the limitation.The study results show that the volume acid fracturing process can be used to greatly improve the flow environment of tight-gas carbonate reservoir and increase production;the incremental or stimulation response is closely related with reservoir fracturing performance,the degree of development of natural fracture,the small intersection angle between hydraulic fracture and natural fracture,the large horizontal principal stress difference is easy to form a narrow fracture zone,and it is disadvantageous to create fracture network,but the degradable fiber diversion technology may largely weaken the disadvantage.The practices indicate that the application of volume acid fracturing process to the tight-gas carbonate reservoir development is feasible in the Ordovician Majiagou Formation of lower Paleozoic,which is of great significance and practical value for domestic tight-gas carbonate reservoir development and studies in the future.

Black-phosphorus-based junctions and their optoelectronic device applications

Black phosphorus(BP)has attracted significant attention owing to its unique structure and preeminent photoelectric properties,which can be utilized to create novel junctions.Based on different BP-based junctions,versatile optoelectronic devices have been fabricated and investigated in recent years,providing a fertile library for the characteristics of BP-based junctions and their optoelectronic applications.This review summarizes diverse BP-based junctions and their optoelectronic device applications.We firstly introduce the structure and properties of BP.Then,we emphatically describe the formation,properties,and optoelectronic device applications of the BP-based junctions including heterojunctions of BP and other two-dimensional(2D)semiconductors,BP p–n homojunctions,and BP/metal Schottky junctions.Finally,the challenge and prospect of the development and application of BP-based junctions are discussed.This timely review gives a snapshot of recent research breakthroughs in BP-based junctions and optoelectronic devices based on them,which is expected to provide a comprehensive vision for the potential of BP in the optoelectronic field.

The effect of high-involvement human resource management practices on supply chain resilience and operational performance

Supply chain(SC)resilience is an increasingly important topic for practitioners and academics because it is a competitive weapon for firms to cope with sC disruptive risks.This study examines the impact of high-involvement human resource management practices on SC resilience from the ability-motivation-opportunity perspective.It also examines the relationship between the dimensions of sC resilience and operational performance.Based on data collected from 206 Chinese manufacturers,the proposed hypotheses were tested using structural equation modeling.The results indicated that employee participation played the most powerful role in improving supplier,customer,and internal resilience.Moreover,employee skills only facilitate internal and customer resilience but have no significant impact on supplier resilience.By contrast,employee incentives do not influence the dimension of sC resilience.It was also found that both internal and customer resilience have positive effects on operational performance,while supplier resilience has no significant effect.The findings contribute to literature and practice.