Nanotechnologies meeting natural sources:Engineered lipoproteins for precise brain disease theranostics

Biological nanotechnologies have provided considerable opportunities in the management of malignancies with delicate design and negligible toxicity,from preventive and diagnostic to therapeutic fields.Lipoproteins,because of their inherent blood-brain barrier permeability and lesion-homing capability,have been identified as promising strategies for high-performance theranostics of brain diseases.However,the application of natural lipoproteins remains limited owing to insufficient accumulation and complex purification processes,which can be critical for individual therapeutics and clinical translation.To address these issues,lipoprotein-inspired nano drug-delivery systems(nano-DDSs),which have been learned from nature,have been fabricated to achieve synergistic drug delivery involving site-specific accumulation and tractable preparation with versatile physicochemical functions.In this review,the barriers in brain disease treatment,advantages of state-of-the-art lipoprotein-inspired nano-DDSs,and bio-interactions of such nano-DDSs are highlighted.Furthermore,the characteristics and advanced applications of natural lipoproteins and tailor-made lipoprotein-inspired nano-DDSs are summarized.Specifically,the key designs and current applications of lipoprotein-inspired nano-DDSs in the field of brain disease therapy are intensively discussed.Finally,the current challenges and future perspectives in the field of lipoprotein-inspired nano-DDSs combined with other vehicles,such as exosomes,cell membranes,and bacteria,are discussed.

Effect of carboxymethyl konjac glucomannan coating on curcumin-loaded multilayered emulsion:stability evaluation

The stability against various environmental stresses of the curcumin-loaded secondary and tertiary emulsions that was emulsified by whey protein isolate(WPI)and coated by chitosan(CHI),carboxymethyl konjac glucomannan(CMKGM),or their combination through layer-by-layer assembly was investigated.Generally,the multilayered emulsions were destabilized in high Na Cl concentrations or medium p H that could interrupt the electrostatic interaction between the three polyelectrolytes or deprotonate CHI,indicating that electrostatic interaction played an important role in the stability of emulsions.Compared with the primary emulsion that was solely stabilized by WPI,extra coating with CHI and CMKGM generally increased the stability of the emulsion against repeated freezing-thawing,improved the retention of curcumin against heating,UV irradiation,and long-term storage,and the effects were more remarkable in the tertiary emulsion with CMKGM locating in the outmost layer.Since CMKGM has shown the colon-targeted delivery potency,the multilayered emulsions assembled by layer-by-layer deposition,especially the tertiary emulsion,could be used as an effective carrier for the targeted delivery of curcumin.

Expanding the targeting scope of CRISPR/Cas9-mediated genome editing by Cas9 variants in Brassica

CRISPR/Cas9,presently the most widely used genome editing technology,has provided great potential for functional studies and plant breeding.However,the strict requirement for a protospacer adjacent motif(PAM)has hindered the application of the CRISPR/Cas9 system because the number of targetable genomic sites is limited.Recently,the engineered variants Cas9-NG,SpG,and SpRY,which recognize non-canonical PAMs,have been successfully tested in plants(mainly in rice,a monocot).In this study,we evaluated the targeted mutagenesis capabilities of these Cas9 variants in two important Brassica vegetables,Chinese cabbage(Brassica rapa spp.pekinensis)and cabbage(Brassica oleracea var.capitata).Both Cas9-NG and SpG induced efficient mutagenesis at NGN PAMs,while SpG outperformed Cas9-NG at NGC and NGT PAMs.SpRY achieved efficient editing at almost all PAMs(NRN>NYN),albeit with some self-targeting activity at transfer(T)-DNA sequences.And SpRY-induced mutants were detected in cabbage plants in a PAM-less fashion.Moreover,an adenine base editor was developed using SpRY and TadA8e deaminase that induced A-to-G conversions within target sites using non-canonical PAMs.Together,the toolboxes developed here induced successful genome editing in Chinese cabbage and cabbage.Our work further expands the targeting scope of genome editing and paves the way for future basic research and genetic improvement in Brassica.

MANF brakes TLR4 signaling by competitively binding S100A8 with S100A9 to regulate macrophage phenotypes in hepatic fibrosis

The mesencephalic astrocyte-derived neurotrophic factor(MANF)has been recently identified as a neurotrophic factor,but its role in hepatic fibrosis is unknown.Here,we found that MANF was upregulated in the fibrotic liver tissues of the patients with chronic liver diseases and of mice treated with CCl4.MANF deficiency in either hepatocytes or hepatic mono-macrophages,particularly in hepatic mono-macrophages,clearly exacerbated hepatic fibrosis.Myeloid-specific MANF knockout increased the population of hepatic Ly6C^(high)macrophages and promoted HSCs activation.Furthermore,MANF-sufficient macrophages(from WT mice)transfusion ameliorated CCl4-induced hepatic fibrosis in myeloid cells-specific MANF knockout(MKO)mice.Mechanistically,MANF interacted with S100A8 to competitively block S100A8/A9 heterodimer formation and inhibited S100A8/A9-mediated TLR4-NF-κB signal activation.Pharmacologically,systemic administration of recombinant human MANF significantly alleviated CCl_(4)-induced hepatic fibrosis in both WT and hepatocytes-specific MANF knockout(HKO)mice.This study reveals a mechanism by which MANF targets S100A8/A9-TLR4 as a“brake”on the upstream of NF-κB pathway,which exerts an impact on macrophage differentiation and shed light on hepatic fibrosis treatment.

A bioinspired,self-powered,flytrap-based sensor and actuator enabled by voltage triggered hydrogel electrodes

Because of its adaptive interfacial property,soft sensors/actuators can be used to perform more delicate tasks than their rigid counterparts.However,plant epidermis with a waxy cuticle layer challenges stable and high-fidelity non-invasive electrophysiology since the conventional electrodes are invasive,easily detached from plants,and require complicated setup procedures.Here,we report a bioinspired sensor and actuator created by using a conformable electrode interface as an electrical modulation unit on a Venus flytrap.Our conformable electrode,by employing an adhesive hydrogel layer,can achieve the merits of low impedance,stretchable,biocompatible,reusable,and transparent enough for normal chlorophyll activity to occur.Owing to the high sensitivity of a flytrap to a triggering mechanical stimulation,a plant sensor matrix based on flytraps has been demonstrated by capturing the stimulated action potential(AP)signals from upper epidermis,which can orient honeybee colonies by their touch during collecting nectar.Moreover,via frequency-dependent AP modulation,an autonomous on-demand actuation on a flytrap is realized.The flytrap actuator can be controlled to responsively grasp tiny objects by the modulated signals triggered by a triboelectric nanogenerator(TENG).This work paves a way of developing autonomous plant-based sensors and actuators toward smart agriculture and intelligent robots.

Bioengineering extracellular vesicles as novel nanocarriers towards brain disorders

Despite noteworthy technological progress and promising preclinical trials,brain disorders are still the leading causes of death globally.Extracellular vesicles(EVs),nano-/micro-sized membrane vesicles carrying bioactive molecules,are involved in cellular communication.Based on their unique properties,including superior biocompatibility,non-immunogenicity,and blood-brain barrier(BBB)penetration,EVs can shield their cargos from immune clearance and transport them to specific site,which have attracted increasing interests as novel nanocarriers for brain disorders.However,considering the limitations of native EVs,such as poor encapsulation efficiency,inadequate targeting capability,uncontrolled drug release,and limited production,researchers bioengineer EVs to fully exploit the clinical potential.Herein,this review initially describes the basic properties,biogenesis,and uptake process of EVs from different subtypes.Then,we highlight the application of EVs derived from different sources for personalized therapy and novel strategies to construct bioengineered EVs for enhanced diagnosis and treatment of brain disorders.Besides,it also presents a systematic comparison between EVs and other brain-targeted nanocarriers.Finally,existing challenges and future perspectives of EVs have been discussed,hoping to bolster the research from benchtop to bedside.

Design and 3D Printing of Graded Bionic Metamaterial Inspired by Pomelo Peel for High Energy Absorption

Light-weight,high-strength metamaterials with excellent specific energy absorption(SEA)capabilities are sig-nificant for aerospace and automobile.The SEA of metamaterials largely depends on the material and structural design.Herein,inspired by the superior impact resistance of pomelo peel for protecting the pulp and the elevated SEA ability of a functionally graded structure,a graded bionic polyhedron metamaterial(GBPM)was designed and realized by 3D printing using a soft material(photosensitive resin)and a hard material(Ti-6Al-4V).Guided by compression tests and numerical simulations,the elevated SEA ability was independent of the materials.The fluctuation region appeared in hard-material-fabricated bionic polyhedron metamaterial(BPMs)and was absent in soft-material-fabricated BPMs in the stress-strain curves,resulting in the growth rate of the SEA value of the soft-material-fabricated GBPM being enhanced by 5.9 times compared with that of the hard-material-fabricated GBPM.The SEA values of soft-and hard-material-fabricated GBPM were 1.89 and 44.16 J/g,which exceed those of most soft-and hard-material-fabricated metamaterials reported in previous studies.These findings can guide the design of metamaterials with high energy absorption to resist external impacts.

Determination of void boundary in a packed bed by laser attenuation measurement

Voids are important regions in some industrial processes,particularly in the iron-making process,because a void is a zone in which gas-solid heat transfer and reactions occur.This paper presents a 3D experimental study of void formation measurement with 2D projection in a packed bed using an optical method.By developing an experimental laser-attenuation scanning method,invisible voids that form in a packed bed can be detected and identified as relatively stable ellipsoids.The effects of various operational parameters on void formation are analyzed in terms of the resulting void sizes and shapes.The results show that the void shape that forms in the packed bed is close to an ellipsoid and is relatively stable.The void size is positively correlated with the blast volume rate and is negatively correlated with the blowpipe diameter.The blowpipe depth has no significant effect on either the void formation or size.The blast angle affects the void location strongly;when this angle is increased,the void moves upward.The information and methods obtained in this experiment are significant in aiding understanding of the mechanism of void formation in gas-solid reactors.

Head-to-head comparison of PSMA PET/CT and mpMRI for detecting biochemical recurrence of prostate cancer: A systematic review and meta-analysis

Objectives This study aimed to evaluate the performance of prostate-specific membrane antigen positron emission tomography/computed tomography(PSMA PET/CT)in comparison to multiparametric magnetic resonance imaging(mpMRI)for detecting biochemical recurrence of prostate cancer(PCa).Materials and methods We conducted a comprehensive search for articles published in PubMed,Web of Science,Embase,and the Cochrane Library,spanning the inception of the database until October 26,2022,which included head-to-head comparisons of PSMA PET/CT and mpMRI for assessing the biochemical recurrence of PCa.Results A total of 5 studies including 228 patients were analyzed.The overall positivity rates of PSMA PET/CT and mpMRI for detecting biochemical recurrence of PCa after final treatment were 0.68(95%confidence interval[CI],0.52–0.89)and 0.56(95%CI,0.36–0.88),respectively.The positivity rates of PSMA PET/CT and mpMRI for detecting local recurrence,lymph node metastasis,and bone metastases were 0.37(95%CI,0.30–0.47)and 0.38(95%CI,0.22–0.67),0.44(95%CI,0.35–0.56)and 0.25(95%CI,0.17–0.35),and 0.19(95%CI,0.11–0.31)and 0.12(95%CI,0.05–0.25),respectively.Compared with mpMRI,PSMA PET/CT exhibited a higher positivity rate for detecting biochemical recurrence and lymph node metastases,and no significant difference in the positivity rate of local recurrence was observed between these 2 imaging modalities.Conclusions Compared with mpMRI,PSMA PET/CT appears to have a higher positivity rate for detecting biochemical recurrence of PCa.Although both imaging methods showed similar positivity rates of detecting local recurrence,PSMA PET/CT outperformed PSMA PET/CT in detecting lymph node involvement and overall recurrence.