Multi-level prediction of substance use: Interaction of white matter integrity, resting-state connectivity and inhibitory control measured repeatedly in every-day life.

Substance use disorders are characterized by inhibition deficits related to disrupted connectivity in white matter pathways, leading via interaction to difficulties in resisting substance use. By combining neuroimaging with smartphone-based ecological momentary assessment (EMA), we questioned how biomarkers moderate inhibition deficits to predict use. Thus, we aimed to assess white matter integrity interaction with everyday inhibition deficits and related resting-state network connectivity to identify multi-dimensional predictors of substance use. Thirty-eight patients treated for alcohol, cannabis or tobacco use disorder completed 1 week of EMA to report substance use five times and complete Stroop inhibition testing twice daily. Before EMA tracking, participants underwent resting state functional MRI and diffusion tensor imaging (DTI) scanning. Regression analyses were conducted between mean Stroop performances and whole-brain fractional anisotropy (FA) in white matter. Moderation testing was conducted between mean FA within significant clusters as moderator and the link between momentary Stroop performance and use as outcome. Predictions between FA and resting-state connectivity strength in known inhibition-related networks were assessed using mixed modelling. Higher FA values in the anterior corpus callosum and bilateral anterior corona radiata predicted higher mean Stroop performance during the EMA week and stronger functional connectivity in occipital-frontal-cerebellar regions. Integrity in these regions moderated the link between inhibitory control and substance use, whereby stronger inhibition was predictive of the lowest probability of use for the highest FA values. In conclusion, compromised white matter structural integrity in anterior brain systems appears to underlie impairment in inhibitory control functional networks and compromised ability to refrain from substance use.

Tunable Macroscopic Alignment of Self-Assembling Peptide Nanofibers.

Progress in the design and synthesis of nanostructured self-assembling systems has facilitated the realization of numerous nanoscale geometries, including fibers, ribbons, and sheets. A key challenge has been achieving control across multiple length scales and creating macroscopic structures with nanoscale organization. Here, we present a facile extrusion-based fabrication method to produce anisotropic, nanofibrous hydrogels using self-assembling peptides. The application of shear force coinciding with ion-triggered gelation is used to kinetically trap supramolecular nanofibers into aligned, hierarchical macrostructures. Further, we demonstrate the ability to tune the nanostructure of macroscopic hydrogels through modulating phosphate buffer concentration during peptide self-assembly. In addition, increases in the nanostructural anisotropy of fabricated hydrogels are found to enhance their strength and stiffness under hydrated conditions. To demonstrate their utility as an extracellular matrix-mimetic biomaterial, aligned nanofibrous hydrogels are used to guide directional spreading of multiple cell types, but strikingly, increased matrix alignment is not always correlated with increased cellular alignment. Nanoscale observations reveal differences in cell-matrix interactions between variably aligned scaffolds and implicate the need for mechanical coupling for cells to understand nanofibrous alignment cues. In total, innovations in the supramolecular engineering of self-assembling peptides allow us to decouple nanostructure from macrostructure and generate a gradient of anisotropic nanofibrous hydrogels. We anticipate that control of architecture at multiple length scales will be critical for a variety of applications, including the bottom-up tissue engineering explored here.

Anisotropic power-law viscoelasticity of living cells is dominated by cytoskeletal network structure.

During physiological and pathological processes, cells experience significant morphological alterations with the re-arrangement of cytoskeletal filaments, resulting in anisotropic viscoelasticity. Here, a structure-based cell model is proposed to study the anisotropic viscoelastic mechanical behaviors of living cells. We investigate how cell shape affects its creep responses in longitudinal and perpendicular directions. It is shown that cells exhibit power-law rheological behavior in both longitudinal and perpendicular directions under step stress, with a more solid-like behavior along the longitudinal direction. We reveal that the cell volume and cytoskeletal filament orientation, which have been neglected in most existing models, play a critical role in regulating cellular anisotropic viscoelasticity. The stiffness of the cell in both directions increases linearly with increasing its aspect ratio, due to the decrease of cell volume. Moreover, the increase in the cell's aspect ratio produces the aggregation of cytoskeletal filaments along the longitudinal direction, resulting in higher stiffness in this direction. It is also shown that the increase in cell's aspect ratio corresponds to a process of cellular ordering, which can be quantitatively characterized by the orientational entropy of cytoskeletal filaments. In addition, we present a simple yet robust method to establish the relationship between cell's aspect ratio and cell volume, thus providing a theoretical framework to capture the anisotropic viscoelastic behavior of cells. This study suggests that the structure-based cell models may be further developed to investigate cellular rheological responses to external mechanical stimuli and may be extended to the tissue scale. STATEMENT OF SIGNIFICANCE: The viscoelastic behaviors of cells hold significant importance in comprehending the roles of mechanical forces in embryo development, invasion, and metastasis of cancer cells. Here, a structure-based cell model is proposed to study the anisotropic viscoelastic mechanical behaviors of living cells. Our study highlights the crucial role of previously neglected factors, such as cell volume and cytoskeletal filament orientation, in regulating cellular anisotropic viscoelasticity. We further propose an orientational entropy of cytoskeletal filaments to quantitatively characterize the ordering process of cells with increasing aspect ratios. Moreover, we derived the analytical interrelationships between cell aspect ratio, cell stiffness, cell volume, and cytoskeletal fiber orientation. This study provides a theoretical framework to describe the anisotropic viscoelastic mechanical behavior of cells.

Nanoparticle Anisotropy Increases Targeting Interactions on Live-Cell Membranes.

This paper describes how branch lengths of anisotropic nanoparticles can affect interactions between grafted ligands and cell-membrane receptors. Using live-cell, single-particle tracking, we found that DNA aptamer-gold nanostar nanoconstructs with longer branches showed improved binding efficacy to human epidermal growth factor receptor 2 (HER2) on cancer cell membranes. Inhibiting nanoconstruct-HER2 binding promoted nonspecific interactions, which increased the rotational speed of long-branched nanoconstructs but did not affect that of short-branched constructs. Bivariate analysis of the rotational and translational dynamics showed that longer branch lengths increased the ratio of targeting to nontargeting interactions. We also found that longer branches increased the nanoconstruct-cell interaction times before internalization and decreased intracellular trafficking velocities. Differences in binding efficacy revealed by single-particle dynamics can be attributed to the distinct protein corona distributions on short- and long-branched nanoconstructs, as validated by transmission electron microscopy. Minimal protein adsorption at the high positive curvature tips of long-branched nanoconstructs facilitated binding of DNA aptamer ligands to HER2. Our study reveals the significance of nanoparticle branch length in regulating local chemical environment and interactions with live cells at the single-particle level.

ECL cytosensor for sensitive and label-free detection of circulating tumor cells based on hierarchical flower-like gold microstructures.

The development of sensitive and efficient cell sensing strategies to detect circulating tumor cells (CTCs) in peripheral blood is crucial for the early diagnosis and prognostic assessment of cancer clinical treatment. Herein, an array of hierarchical flower-like gold microstructures (HFGMs) with anisotropic nanotips was synthesized by a simple electrodeposition method and used as a capture substrate to construct an ECL cytosensor based on the specific recognition of target cells by aptamers. The complex topography of the HFGMs array not only catalyzed the enhancement of ECL signals, but also induced the cells to generate more filopodia, improving the capture efficiency and shortening the capture time. The effect of topographic roughness on cell growth and adhesion propensity was also investigated, while the cell capture efficiency was proposed to be an important indicator affecting the accuracy of the ECL cytosensor. In addition, the capture of cells on the electrode surface increased the steric hindrance, which caused ECL signal changes in the Ru(bpy)32+ and TPrA system, realizing the quantitative detection of MCF-7 cells. The detection range of the sensor was from 102 to 106 cells mL-1 and the detection limit was 18 cells mL-1. The proposed detection method avoids the process of separation, labeling and counting, which has great potential for sensitive detection in clinical applications.

A novel indicator to predict the outcome of percutaneous stereotactic radiofrequency rhizotomy for trigeminal neuralgia patients: diffusivity metrics of MR-DTI.

Magnetic resonance-diffusion tensor imaging (MR-DTI) has been used in the microvascular decompression and gamma knife radiosurgery in trigeminal neuralgia (TN) patients; however, use of percutaneous stereotactic radiofrequency rhizotomy (PSR) to target an abnormal trigeminal ganglion (ab-TG) is unreported. Fractional anisotropy (FA), mean and radial diffusivity (MD and RD, respectively), and axial diffusivity (AD) of the trigeminal nerve (CNV) were measured in 20 TN patients and 40 healthy control participants immediately post PSR, at 6-months, and at 1 year. Longitudinal alteration of the diffusivity metrics and any correlation with treatment effects, or prognoses, were analyzed. In the TN group, either low FA (value < 0.30) or a decreased range compared to the adjacent FA (dFA) > 17% defined an ab-TG. Two-to-three days post PSR, all 15 patients reported decreased pain scores with increased FA at the ab-TG (P < 0.001), but decreased MD and RD (P < 0.01 each). Treatment remained effective in 10 of 14 patients (71.4%) and 8 of 12 patients (66.7%) at the 6-month and 1-year follow-ups, respectively. In patients with ab-TGs, there was a significant difference in treatment outcomes between patients with low FA values (9 of 10; 90%) and patients with dFA (2 of 5; 40%) (P < 0.05). MR-DTI with diffusivity metrics correlated microstructural CNV abnormalities with PSR outcomes. Of all the diffusivity metrics, FA could be considered a novel objective quantitative indicator of treatment effects and a potential indicator of PSR effectiveness in TN patients.

Microfluidic-assisted formulation of cell membrane-camouflaged anisotropic nanostructures.

Anisotropic gold (Au) nanostructures have been widely explored for various nanomedicine applications. While these nanomaterials have shown great promise for disease theranostics, particularly for cancer diagnosis and treatment, the utilization and clinical translation of anisotropic Au nanostructures have been limited by their high phagocytic uptake and clearance and low cancer targeting specificity. Numerous efforts have thus been made toward mitigating these challenges. Many conventional strategies, however, rely on all-synthetic materials, involve complex chemical processes, or have low product throughput and reproducibility. Herein, by integrating cell membrane coating and microfluidic technologies, a high-throughput bioinspired approach for synthesizing biomimetic anisotropic Au nanostructures with minimized phagocytic uptake and improved cancer cell targeting is reported. Through continuous hydrodynamic flow focusing, mixing, and sonication, Au nanostructures are encapsulated within the macrophage and cancer cell membrane vesicles effectively. The fabricated nanostructures are uniform and highly stable in serum. Importantly, the macrophage membrane vesicle-encapsulated Au nanostructures can be preferentially internalized by breast cancer cells, but not by macrophages. Overall, this study has demonstrated the feasibility of employing an integrated microfluidic-sonication technique to formulate uniform and highly stable biomimetic anisotropic nanostructures for enhanced cancer theranostic applications.

Anisotropic Elastomer Ionomer Composite-Based Strain Sensors: Achieving High Sensitivity and Wide Detection for Human Motion Detection and Wireless Transmission.

Anisotropic strain sensors capable of multidirectional sensing are crucial for advanced sensor applications in human motion detection. However, current anisotropic sensors encounter challenges in achieving a balance among high sensitivity, substantial stretchability, and a wide linear detection range. To address these challenges, a facile freeze-casting strategy was employed to construct oriented filler networks composed of carbon nanotubes and conductive carbon black within a brominated butyl rubber ionomer (iBIIR) matrix. The resulting anisotropic sensor based on the iBIIR composites exhibited distinct gauge factors (GF) in the parallel and vertical directions (GF∥ = 4.91, while GF⊥ = 2.24) and a broad linear detection range over a strain range of 190%. This feature enables the sensor to detect various human activities, including uniaxial pulse, finder bending, elbow bending, and cervical spine movements. Moreover, the ion-cross-linking network within the iBIIR, coupled with strong π-cation interactions between the fillers and iBIIR macromolecules, imparted high strength (12.3 MPa, nearly twice that of pure iBIIR) and an ultrahigh elongation at break (>1800%) to the composites. Furthermore, the sensor exhibited exceptional antibacterial effectiveness, surpassing 99% against both Escherichia coli and Staphylococcus aureus. Notably, the sensor was capable of wireless sensing. It is anticipated that anisotropic sensors will have extensive application prospects in flexible wearable devices.

Development of Anisotropic Electrically Conductive GNP-Reinforced PCL-Collagen Scaffold for Enhanced Neurogenic Differentiation under Electrical Stimulation.

The internal electric field of the human body plays a crucial role in regulating various biological processes, such as, cellular interactions, embryonic development and the healing process. Electrical stimulation (ES) modulates cytoskeleton and calcium ion activities to restore nervous system functioning. When exposed to electrical fields, stem cells respond similarly to neurons, muscle cells, blood vessel linings, and connective tissue (fibroblasts), depending on their environment. This study develops cost-effective electroconductive scaffolds for regenerative therapy. This was achieved by incorporating carboxy functionalized graphene nanoplatelets (GNPs) into a Polycaprolactone (PCL)-collagen matrix. ES was used to assess the scaffolds' propensity to boost neuronal differentiation from MSCs. This study reported that aligned GNP-reinforced PCL-Collagen scaffolds demonstrate substantial MSC differentiation with ES. This work effectively develops scaffolds using a simple, cost-effective synthesis approach. The direct coupling approach generated a homogeneous electric field to stimulate cells cultured on GNP-reinforced scaffolds. The scaffolds exhibited improved mechanical and electrical characteristics, as a result of the reinforcement with carbon nanofillers. In vitro results suggest that electrical stimulation helps differentiation of mesenchymal stem-like cells (MSC-like) towards neuronal. This finding holds great potential for the development of effective treatments for tissue injuries related to the nervous system.

Dynamic monitoring of radiation-induced white matter microstructure injury in nasopharyngeal carcinoma via high-angular resolution diffusion imaging.

PURPOSE: To investigate white matter microstructural abnormalities caused by radiotherapy in nasopharyngeal carcinoma (NPC) patients using MRI high-angular resolution diffusion imaging (HARDI). METHODS: We included 127 patients with pathologically confirmed NPC: 36 in the pre-radiotherapy group, 29 in the acute response period (post-RT-AP), 23 in the early delayed period (post-RT-ED) group, and 39 in the late-delayed period (post-RT-LD) group. HARDI data were acquired for each patient, and dispersion parameters were calculated to compare the differences in specific fibre bundles among the groups. The Montreal Neurocognitive Assessment (MoCA) was used to evaluate neurocognitive function, and the correlations between dispersion parameters and MoCA were analysed. RESULTS: In the right cingulum frontal parietal bundles, the fractional anisotropy value decreased to the lowest level post-RT-AP and then reversed and increased post-RT-ED and post-RT-LD. The mean, axial, and radial diffusivity were significantly increased in the post-RT-AP (p < 0.05) and decreased in the post-RT-ED and post-RT-LD groups to varying degrees. MoCA scores were decreased post-radiotherapy than those before radiotherapy (p = 0.005). MoCA and mean diffusivity exhibited a mild correlation in the left cingulum frontal parahippocampal bundle. CONCLUSIONS: White matter tract changes detected by HARDI are potential biomarkers for monitoring radiotherapy-related brain damage in NPC patients.

The use of NADH anisotropy to investigate mitochondrial cristae alignment.

Life may be expressed as the flow of electrons, protons, and other ions, resulting in large potential difference. It is also highly photo-sensitive, as a large proportion of the redox capable molecules it relies on are chromophoric. It is thus suggestive that a key organelle in eukaryotes, the mitochondrion, constantly adapt their morphology as part of the homeostatic process. Studying unstained in vivo nano-scale structure in live cells is technically very challenging. One option is to study a central electron carrier in metabolism, reduced nicotinamide adenine dinucleotide (NADH), which is fluorescent and mostly located within mitochondria. Using one and two-photon absorption (340-360 nm and 730 nm, respectively), fluorescence lifetime imaging and anisotropy spectroscopy of NADH in solution and in live cells, we show that mitochondria do indeed appear to be aligned and exhibit high anisotropy (asymmetric directionality). Aqueous solution of NADH showed an anisotropy of ~ 0.20 compared to fluorescein or coumarin of < 0.1 and 0.04 in water respectively and as expected for small organic molecules. The anisotropy of NADH also increased further to 0.30 in the presence of proteins and 0.42 in glycerol (restricted environment) following two-photon excitation, suggesting more ordered structures. Two-photon NADH fluorescence imaging of Michigan Cancer Foundation-7 (MCF7) also showed strong anisotropy of 0.25 to 0.45. NADH has a quantum yield of fluorescence of 2% compared to more than 40% for photoionisation (electron generation), when exposed to light at 360 nm and below. The consequence of such highly ordered and directional NADH patterns with respect to electron ejection upon ultra-violet (UV) excitation could be very informative-especially in relation to ascertaining the extent of quantum effects in biology, including electron and photonic cascade, communication and modulation of effects such as spin and tunnelling.

Optical Sensor System for 3D Jones Matrix Reconstruction of Optical Anisotropy Maps of Self-Assembled Polycrystalline Soft Matter Films.

Our work uses a polarization matrix formalism to analyze and algorithmically represent optical anisotropy by open dehydration of blood plasma films. Analytical relations for Jones matrix reconstruction of optical birefringence maps of protein crystal networks of dehydrated biofluid films are found. A technique for 3D step-by-step measurement of the distributions of the elements of the Jones matrix or Jones matrix images (JMI) of the optically birefringent structure of blood plasma films (BPF) has been created. Correlation between JMI maps and corresponding birefringence images of dehydrated BPF and saliva films (SF) obtained from donors and prostate cancer patients was determined. Within the framework of statistical analysis of layer-by-layer optical birefringence maps, the parameters most sensitive to pathological changes in the structure of dehydrated films were found to be the central statistical moments of the 1st to 4th orders. We physically substantiated and experimentally determined the sensitivity of the method of 3D polarization scanning technique of BPF and SF preparations in the diagnosis of endometriosis of uterine tissue.

Selective Induction of Molecular Assembly to Tissue-Level Anisotropy on Peptide-Based Optoelectronic Cardiac Biointerfaces.

The conduction efficiency of ions in excitable tissues and of charged species in organic conjugated materials both benefit from having ordered domains and anisotropic pathways. In this study, a photocurrent-generating cardiac biointerface is presented, particularly for investigating the sensitivity of cardiomyocytes to geometrically comply to biomacromolecular cues differentially assembled on a conductive nanogrooved substrate. Through a polymeric surface-templated approach, photoconductive substrates with symmetric peptide-quaterthiophene (4T)-peptide units assembled as 1D nanostructures on nanoimprinted polyalkylthiophene (P3HT) surface are developed. The 4T-based peptides studied here can form 1D nanostructures on prepatterned polyalkylthiophene substrates, as directed by hydrogen bonding, aromatic interactions between 4T and P3HT, and physical confinement on the nanogrooves. It is observed that smaller 4T-peptide units that can achieve a higher degree of assembly order within the polymeric templates serve as a more efficient driver of cardiac cytoskeletal anisotropy than merely presenting aligned -RGD bioadhesive epitopes on a nanotopographic surface. These results unravel some insights on how cardiomyocytes perceive submicrometer dimensionality, local molecular order, and characteristics of surface cues in their immediate environment. Overall, the work offers a cardiac patterning platform that presents the possibility of a gene modification-free cardiac photostimulation approach while controlling the conduction directionality of the biotic and abiotic components.

Effect of collagen fibril orientation on the anisotropic properties of peri-implant bone.

In orthopedic and dental surgery, the implantation of biomaterials within the bone to restore the integrity of the treated organ has become a standard procedure. Their long-term stability relies on the osseointegration phenomena, where bone grows onto and around metallic implants, creating a bone-implant interface. Bone is a highly hierarchical material that evolves spatially and temporally during this healing phase. A deeper understanding of its biomechanical characteristics is needed, as they are determinants for surgical success. In this context, we propose a multiscale homogenization model to evaluate the effective elastic properties of bone as a function of the distance from the implant, based on the tissue's structure and composition at lower scales. The model considers three scales: hydroxyapatite foam (nanoscale), ultrastructure (microscale), and tissue (mesoscale). The elastic properties and the volume fraction of the elementary constituents of bone matrix (mineral, collagen, and water), the orientation of the collagen fibril relative to the implant surface, and the mesoscale porosity constitute the input data of the model. The effect of a spatiotemporal variation in the collagen fibrils' orientation on the bone anisotropic properties in the proximity of the implant was investigated. The findings revealed a strong variation of the components of the effective elasticity tensor of the bone as a function of the distance from the implant. The effective elasticity appears to be primarily sensitive to the porosity (mesoscale) rather than to the collagen fibrils' orientation (sub-micro scale). However, the orientation of the fibrils has a significant influence on the isotropy of the bone. When analyzing the symmetry properties of the effective elasticity tensor, the ratio between the isotropic and hexagonal components is determined by a combination of the porosity and the fibrils' orientation. A decrease in porosity leads to a decrease in bone isotropy and, in turn, an increase in the impact of the fibrils' orientation. These results demonstrate that the collagen fibril orientation should be taken into account to properly describe the effective elastic anisotropy of bone at the organ scale.

Mueller matrix-based characterization of cervical tissue sections: a quantitative comparison of polar and differential decomposition methods.

Significance: Quantitative optical polarimetry has received considerable recent attention owing to its potential for being an efficient diagnosis and characterizing tool with potential applications in biomedical research and various other disciplines. In this regard, it is crucial to validate various Mueller matrix (MM) decomposition methods, which are utilized to extract and quantify the intrinsic individual polarization anisotropy properties of various complex optical media. Aim: To quantitatively compare the performance of both polar and differential MM decomposition methods for probing the structural and morphological changes in complex optical media through analyzing their intrinsic individual polarization parameters, which are extracted using the respective decomposition algorithms. We also intend to utilize the decomposition-derived anisotropy parameters to distinguish among the cervical tissues with different grades of cervical intraepithelial neoplasia (CIN) and to characterize the healing efficiency of an organic crystal. Approach: Polarization MM of the cervical tissues with different grades of CIN and the different stages of the self-healing crystal are recorded with a home-built MM imaging setup in the transmission detection geometry with a spatial resolution of ≈400 nm. The measured MMs are then processed with both the polar and differential MM decomposition methods to extract the individual polarization parameters of the respective samples. The derived polarization parameters are further analyzed to validate and compare the performance of both the MM decomposition methods for probing and characterizing the structural changes in the respective investigated optical media through their decomposition-derived intrinsic individual polarization properties. Results: Pronounced differences in the decomposed-derived polarization anisotropy parameters are observed for cervical tissue sections with different grades of CIN. While a significant increase in the depolarization parameter (Δ) is obtained with the increment of CIN stages for both the polar [Δ=0.32 for CIN grade one (CIN-I) and Δ=0.53 for CIN grade two (CIN-II))] and differential (Δ=0.35 for CIN-I and Δ=0.56 for CIN-II) decomposition methods, a trend reversal is seen for the linear diattenuation parameter (dL), indicating the structural distortion in the cervical morphology due to the CIN disease. More importantly, with the differential decomposition algorithm, the magnitude of the derived dL parameter decreases from 0.26 to 0.19 with the progression of CIN, which was not being probed by the polar decomposition method. Conclusion: Our results demonstrate that the differential decomposition of MM holds certain advantages over the polar decomposition method to characterize and probe the structural changes in the cervical tissues with different grades of CIN. Although the quantified individual polarization parameters obtained through both the MM decomposition methods can be used as useful metrics to characterize various optical media, in case of complex turbid media such as biological tissues, incorporation of the differential decomposition technique may yield more efficient information. Also, the study highlights the utilization of MM polarimetry with an appropriate decomposition technique as an efficient diagnostic and characterizing tool in the realm of biomedical clinical research, and various other disciplines.

Extracellular Matrix-Bioinspired Anisotropic Topographical Cues of Electrospun Nanofibers: A Strategy of Wound Healing through Macrophage Polarization.

The skin serves as the body's outermost barrier and is the largest organ, providing protection not only to the body but also to various internal organs. Owing to continuous exposure to various external factors, it is susceptible to damage that can range from simple to severe, including serious types of wounds such as burns or chronic wounds. Macrophages play a crucial role in the entire wound-healing process and contribute significantly to skin regeneration. Initially, M1 macrophages infiltrate to phagocytose bacteria, debris, and dead cells in fresh wounds. As tissue repair is activated, M2 macrophages are promoted, reducing inflammation and facilitating restoration of the dermis and epidermis to regenerate the tissue. This suggests that extracellular matrix (ECM) promotes cell adhesion, proliferation, migrationand macrophage polarization. Among the numerous strategies, electrospinning is a versatile technique for obtaining ECM-mimicking structures with anisotropic and isotropic topologies of micro/nanofibers. Various electrospun biomaterials influence macrophage polarization based on their isotropic or anisotropic topologies. Moreover, these fibers possess a high surface-area-to-volume ratio, promoting the effective exchange of vital nutrients and oxygen, which are crucial for cell viability and tissue regeneration. Micro/nanofibers with diverse physical and chemical properties can be tailored to polarize macrophages toward skin regeneration and wound healing, depending on specific requirements. This review describes the significance of micro/nanostructures for activating macrophages and promoting wound healing.

Emergence of periodic circumferential actin cables from the anisotropic fusion of actin nanoclusters during tubulogenesis.

The periodic circumferential cytoskeleton supports various tubular tissues. Radial expansion of the tube lumen causes anisotropic tensile stress, which can be exploited as a geometric cue. However, the molecular machinery linking anisotropy to robust circumferential patterning is poorly understood. Here, we aim to reveal the emergent process of circumferential actin cable formation in a Drosophila tracheal tube. During luminal expansion, sporadic actin nanoclusters emerge and exhibit circumferentially biased motion and fusion. RNAi screening reveals the formin family protein, DAAM, as an essential component responding to tissue anisotropy, and non-muscle myosin II as a component required for nanocluster fusion. An agent-based model simulation suggests that crosslinkers play a crucial role in nanocluster formation and cluster-to-cable transition occurs in response to mechanical anisotropy. Altogether, we propose that an actin nanocluster is an organizational unit that responds to stress in the cortical membrane and builds a higher-order cable structure.

[Correlation between postoperative microstructural changes in cerebral white matter and early postoperative cognitive function in patients undergoing meningioma resection].

Objective: To analyze the correlation between microstructure changes in cerebral white matter before and after surgery and early postoperative cognitive function in patients undergoing meningioma resection. Methods: A total of 17 patients who underwent their first meningioma resection at Xuanwu Hospital of Capital Medical University from April 2022 to April 2023 were prospectively included as observation group, with 5 males and 12 females, aged (56.4±7.3) years. Another 15 age- and education-matched patients with cerebral benign tumor were recruited as control group during the same period, with 5 males and 10 females, aged (55.2±8.0) years. Neuropsychological tests (NST), mainly including auditory verbal learning test of Huashan version (AVLT-H), the Montreal cognitive assessment-basic (MoCA-B), clock drawing task-30 (CDT-30), shape trails test-B (STT-B) and animal fluence test (AFT), were conducted at 1 day before surgery, 1 day and within 3-4 days after surgery in the observation group. Simultaneously, magnetic resonance imaging (MRI) scans were performed to collect diffusion tensor imaging (DTI) images at 1 day before surgery and within 3-4 days after surgery. The same NST were conducted at 1 day, 3 days and 6 days after admission in the control group to adjust for learning effects from repeated tests. The microstructure changes of the whole brain white matter were evaluated at the group level by using tract-based spatial statistics (TBSS) technology, including changes of fractional anisotropy (FA), mean diffusion (MD), axial diffusion (AD), and radial diffusion (RD). Then, correlation was performed between DTI indicators with statistically significant and cognitive function. Results: After adjusting for the learning effects, the AVLT-H (R), MoCA-B, and CDT-30 scores decreased, and the evaluation time of STT-B prolonged after surgery in patients with meningioma. And their perioperative decreased values were -0.78 (95%CI:-3.28--0.28) points, -2.22 (95%CI:-4.22--0.72) points, -2.74 (95%CI:-5.29--0.19) points, and 61.49 (95%CI: 5.71-117.27) seconds, respectively, with statistically significant differences (all P<0.05). Group level analysis of TBSS based on DTI images showed decreased FA mainly in the right superior cerebellar peduncle, left posterior limb of internal capsule and genu of corpus callosum, and increased RD mainly in the left anterior corona radiata in patients undergoing meningioma resection, with statistically significant differences (all PFWE<0.05). Linear correlation showed that the perioperative decreased values of FA in genu of corpus callosum and right superior cerebellar peduncle were positively correlated with the perioperative decreased values of AVLT-H (L) after adjusting for learning effects (r=0.72, 0.52, all PFWE<0.05). Conclusions: Patients undergoing meningioma resection are at risk of postoperative cognitive decline. Perioperative decreased values of FA in genu of corpus callosum and right superior cerebellar peduncle based on DTI images are positively correlated with the perioperative decreased values of AVLT-H (L) after adjusting for learning effects.

Baseline symptom-related white matter tracts predict individualized treatment response to 12-week antipsychotic monotherapies in first-episode schizophrenia.

There is significant heterogeneity in individual responses to antipsychotic drugs, but there is no reliable predictor of antipsychotics response in first-episode psychosis. This study aimed to investigate whether psychotic symptom-related alterations in fractional anisotropy (FA) and mean diffusivity (MD) of white matter (WM) at the early stage of the disorder may aid in the individualized prediction of drug response. Sixty-eight first-episode patients underwent baseline structural MRI scans and were subsequently randomized to receive a single atypical antipsychotic throughout the first 12 weeks. Clinical symptoms were evaluated using the eight "core symptoms" selected from the Positive and Negative Syndrome Scale (PANSS-8). Follow-up assessments were conducted at the 4th, 8th, and 12th weeks by trained psychiatrists. LASSO regression model and cross-validation were conducted to examine the performance of baseline symptom-related alterations FA and MD of WM in the prediction of individualized treatment outcome. Fifty patients completed both clinical follow-up assessments by the 8th and 12th weeks. 30 patients were classified as responders, and 20 patients were classified as nonresponders. At baseline, the altered diffusion properties of fiber tracts in the anterior thalamic radiation, corticospinal tract, callosum forceps minor, longitudinal fasciculi (ILF), inferior frontal-occipital fasciculi (IFOF) and superior longitudinal fasciculus (SLF) were related to the severity of symptoms. These abnormal fiber tracts, especially the ILF, IFOF, and SLF, significantly predicted the response to antipsychotic treatment at the individual level (AUC = 0.828, P < 0.001). These findings demonstrate that early microstructural WM changes contribute to the pathophysiology of psychosis and may serve as meaningful individualized predictors of response to antipsychotics.

Macro-indentation testing of soft biological materials and assessment of hyper-elastic material models from inverse finite element analysis.

Mechanical characterization of hydrogels and ultra-soft tissues is a challenging task both from an experimental and material parameter estimation perspective because they are much softer than many biological materials, ceramics, or polymers. The elastic modulus of such materials is within the 1 - 100 kPa range, behaving as a hyperelastic solid with strain hardening capability at large strains. In the current study, indentation experiments have been performed on agarose hydrogels, bovine liver, and bovine lymph node specimens. This work reports on the reliable determination of the elastic modulus by indentation experiments carried out at the macro-scale (mm) using a spherical indenter. However, parameter identification of the hyperelastic material properties usually requires an inverse finite element analysis due to the lack of an analytical contact model of the indentation test. Hence a comprehensive study on the spherical indentation of hyperelastic soft materials is carried out through robust computational analysis. Neo-Hookean and first-order Ogden hyperelastic material models were found to be most suitable. A case study on known anisotropic hyperelastic material showed the inability of the inverse finite element method to uniquely identify the whole material parameter set.