Odd dynamics of living chiral crystals.

Active crystals are highly ordered structures that emerge from the self-organization of motile objects, and have been widely studied in synthetic1,2 and bacterial3,4 active matter. Whether persistent  crystalline order can emerge  in groups of autonomously developing multicellular organisms is currently unknown. Here we show that swimming starfish embryos spontaneously assemble into chiral crystals that span thousands of spinning organisms and persist for tens of hours. Combining experiments, theory and simulations, we demonstrate that the formation, dynamics and dissolution of these living crystals are controlled by the hydrodynamic properties and the natural development of embryos. Remarkably, living chiral crystals exhibit self-sustained chiral oscillations as well as various unconventional deformation response behaviours recently predicted for odd elastic materials5,6. Our results provide direct experimental evidence for how non-reciprocal interactions between autonomous multicellular components may facilitate non-equilibrium phases of chiral active matter.

Bifurcation instructed design of multistate machines.

We propose a design paradigm for multistate machines where transitions from one state to another are organized by bifurcations of multiple equilibria of the energy landscape describing the collective interactions of the machine components. This design paradigm is attractive since, near bifurcations, small variations in a few control parameters can result in large changes to the system's state providing an emergent lever mechanism. Further, the topological configuration of transitions between states near such bifurcations ensures robust operation, making the machine less sensitive to fabrication errors and noise. To design such machines, we develop and implement a new efficient algorithm that searches for interactions between the machine components that give rise to energy landscapes with these bifurcation structures. We demonstrate a proof of concept for this approach by designing magnetoelastic machines whose motions are primarily guided by their magnetic energy landscapes and show that by operating near bifurcations we can achieve multiple transition pathways between states. This proof of concept demonstration illustrates the power of this approach, which could be especially useful for soft robotics and at the microscale where typical macroscale designs are difficult to implement.

Exosome detection via the ultrafast-isolation system: EXODUS.

Exosomes have shown great potential in disease diagnostics and therapeutics. However, current isolation approaches are burdensome and suffer from low speed, yield and purity, limiting basic research and clinical applications. Here, we describe an efficient exosome detection method via the ultrafast-isolation system (EXODUS) that allows automated label-free purification of exosomes from varied biofluids. We obtained the ultra-efficient purification of exosomes by negative pressure oscillation and double coupled harmonic oscillator-enabled membrane vibration. Our two coupled oscillators generate dual-frequency transverse waves on the membranes, enabling EXODUS to outperform other isolation techniques in speed, purity and yield. We demonstrated EXODUS by purifying exosomes from urine samples of 113 patients and validated the practical relevance in exosomal RNA profiling with the high-resolution capability and high-throughput analysis.

Association Between Serum Neurofilament Light Chain and Neurochemistry Deficits in Patients with Spinocerebellar Ataxia Type 3.

Extensive evidence supports the claim that the serum neurofilament light chain (sNfL) can be used as a biomarker to monitor disease severity in patients with spinocerebellar ataxia type 3 (SCA3). However, little is known about the associations between sNfL levels and neurochemical alterations in SCA3 patients. In this study, we performed a cross-sectional study to analyze the association between sNfL and brain metabolic changes in SCA3 patients. The severity of ataxia was assessed by using the Scale for the Assessment and Rating of Ataxia (SARA) and the International Cooperative Ataxia Rating Scale (ICARS). The sNfL levels and brain metabolic changes, represented by N-acetyl aspartate (NAA)/creatine (Cr) and choline complex (Cho)/Cr ratios, were measured by a single-molecule array and proton magnetic resonance spectroscopy, respectively. In this cohort, we observed consistently elevated sNfL levels and reduced brain metabolites in the cerebellar hemispheres, dentate nucleus, and cerebellar vermis. However, this correlation was further validated in the cerebellar cortex after analysis using pairwise comparisons and a Bonferroni correction. Taken together, our results further confirmed that sNfL levels were increased in SCA3 patients and were negatively correlated with metabolic changes in the cerebellar cortex. Our data also support the idea that sNfL levels are a promising potential complementary biomarker for patients with SCA3.

High-performance laser power converts for wireless information transmission applications.

Laser Power Converters (LPCs) are components of the laser wireless power transmission (LWPT) system receiving laser power. This paper proposes a comprehensive test method that employs continuous, pulse-pause, and short-time techniques to evaluate the performance of six-junction GaAs LPCs operating with an optical input at 808 nm. Additionally, we investigate the performance of LPCs with different areas and achieve a conversion efficiency over 60%. Furthermore, we apply LPCs with varying areas to wireless information transmission and successfully achieve a response time of 1.7 µs.

Evaluation of Relationships between Corticospinal Excitability and Somatosensory Deficits in the Acute and Subacute Phases of Stroke.

BACKGROUND: Somatosensory deficits are common symptoms post stroke. Repetitive transcranial magnetic stimulation (rTMS) over the motor cortex is able to promote motor rehabilitation, whereby its impact on somatosensory functioning remains unknown. This study was designed to evaluate the association between somatosensory deficits and corticospinal excitability following stroke, with the purpose to provide insights on rTMS interventions for the management of somatosensory deficits. METHODS: Somatosensory functioning and corticospinal excitability (motor-evoked potential, MEP; cortical silence period, CSP) were evaluated from a group of sixteen patients with unilateral ischemic stroke in the acute or subacute phase. RESULTS: Results indicated that the uncommon presentation of larger MEPs in ipsilesional vs. contralesional motor cortex was associated with worse somatosensory function compared to those with a smaller MEP in ipsilesional motor cortex. Moreover, increased MEP ratio (ipsilesional vs. contralesional motor cortex) was associated with better somatosensory function in patients with well-preserved somatosensory function. CONCLUSIONS: In well-recovered patients, an increased MEP ratio between the ipsilesional and contralesional motor cortex could be an indicator of improved somatosensory functioning following stroke.

Age of Synchronization Minimization Algorithms in Wireless Networks with Random Updates under Throughput Constraints.

This study considers a wireless network where multiple nodes transmit status updates to a base station (BS) through a shared bandwidth-limited channel. Considering the random arrival of status updates, we measure the data freshness with the age of synchronization (AoS) metric; specifically, we use the time elapsed since the latest synchronization as a metric. The objective of this study is to minimize the weighted sum of the average AoS of the entire network while meeting the minimum throughput requirement of each node. We consider both the central scheduling scenario and the distributed scheduling scenario. In the central scheduling scenario, we propose the optimal stationary randomized policy when the transmission feedback is unavailable and the max-weight policy when it is available. In the distributed scenario, we propose a distributed policy. The complexity of the three scheduling policies is significantly low. Numerical simulations show that the policies can satisfy the throughput constraint in the central controlling scenario and the AoS performance of the max-weight policy is close to the lower bound.

[Application of strigolactone analogs in storage of Gastrodia elata].

This study explored the preservation effect of strigolactone analogs on Gastrodia elata tubers and screened out the suitable preservation measures of G. elata to provide a safer and more effective method for its storage and preservation. Fresh G. elata tubers were treated with 7FGR24, 2,4-D isooctyl ester, and maleic hydrazide, respectively. The growth of flower buds, the activities of CAT, and MDA, and the content of gastrodin and p-hydroxybenzyl alcohol were measured to compare the effects of different compounds on the storage and preservation of G. elata. The effects of different storage temperatures on the preservation of 7FGR24 were compared and analyzed. The gibberellin signal transduction receptor gene GeGID1 was cloned, and the effect of 7FGR24 on the expression level of GeGID1 was analyzed by quantitative polymerase chain reaction(qPCR). The toxicity of the G. elata preservative 7FGR24 was analyzed by intragastric administration in mice to evaluate its safety. The results showed that compared with 2,4-D isooctyl ester and maleic hydrazide, 7FGR24 treatment had a significant inhibitory effect on the growth of G. elata flower buds, and the CAT enzyme activity of G. elata was the highest, indicating that its preservation effect was stronger. Different storage temperatures had different effects on the preservation of G. elata, and the preservation effect was the strongest at 5 ℃. The open reading frame(ORF) of GeGID1 gene was 936 bp in length, and its expression level was significantly down-regulated after 7FGR24 treatment, indicating that 7FGR24 may inhibit the growth of flower buds by inhibiting the gibberellin signal of G. elata, thereby exerting a fresh-keeping effect. Feeding preservative 7FGR24 had no significant effect on the behavior and physiology of mice, indicating that it had no obvious toxicity. This study explored the application of the strigolactone analog 7FGR24 in the storage and preservation of G. elata and preliminarily established a method for the storage and preservation of G. elata, laying a foundation for the molecular mechanism of 7FGR24 in the storage and preservation of G. elata.

[Research progress in strigolactones and application prospect in medicinal plants].

Strigolactones(SLs) are a class of sesquiterpenoids derived from the carotenoid biosynthesis pathway with the core carbon skeleton consisting of tricyclic lactone(ABC tricyclic ring) and α,ß-unsaturated furan ring(D ring). SLs are widely distributed in higher plants and are symbiotic signals between plants and Arbuscular mycorrhiza(AM), which play key roles in the evolution of plant colonizing terrestrial habitats. As a new type of plant hormone, SLs possess such important biological functions as inhibiting shoot branching(tillers), regulating root architecture, promoting secondary growth, and improving plant stress resistance. Therefore, SLs have attracted wide attention. The biological functions of SLs are not only closely related to the formation of "excellent shape and quality" of Chinese medicinal materials but also have important practical significance for the production of high-quality medicinal materials. However, SLs have been currently widely studied in model plants and crops such as Oryza sativa and Arabidopsis thaliana, and few related studies have been reported on SLs in medicinal plants, which need to be strengthened. This review focused on the latest research progress in the isolation and identification, biological and artificial synthesis pathways, biosynthesis sites and transport modes, signal transduction pathways and mechanisms, and biological functions of SLs, and prospected the research on the regulation mechanism of SLs in the growth and development of medicinal plants and their related application on targeted regulation of Chinese herbal medicine production, which is expected to provide some references for the in-depth research on SLs in the field of Chinese medicinal resources.

[Cloning and gene function of dicarboxylate-tricarboxylate carrier protein in Gastrodia elata].

The gene GeDTC encoding the dicarboxylate-tricarboxylate carrier protein in Gastrodia elata was cloned by specific primers which were designed based on the transcriptome data of G. elata. Bioinformatics analysis on GeDTC gene was carried out by using ExPASY, ClustalW, MEGA, etc. Positive transgenic plants and potato minituber were obtained by virtue of the potato genetic transformation system. Agronomic characters, such as size, weight, organic acid content, and starch content, of potato minituber were tested and analyzed and GeDTC gene function was preliminarily investigated. The results showed that the open reading frame of GeDTC gene was 981 bp in length and 326 amino acid residues were encoded, with a relative molecular weight of 35.01 kDa. It was predicted that the theoretical isoelectric point of GeDTC protein was 9.83, the instability coefficient was 27.88, and the average index of hydrophilicity was 0.104, which was indicative of a stable hydrophilic protein. GeDTC protein had a transmembrane structure and no signal peptide and was located in the inner membrane of mitochondria. The phylogenetic tree showed that GeDTC was highly homologous with DTC proteins of other plant species, among which GeDTC had the highest homology with DcDTC(XP＿020675804.1) in Dendrobium candidum, reaching 85.89%. GeDTC overexpression vector pCambia1300-35Spro-GeDTC was constructed by double digests, and transgenic potato plants were obtained by Agrobacterium-mediated gene transformation. Compared with the wild-type plants, transgenic potato minituber harvested by transplanting had smaller size, lighter weight, lower organic acid content, and no significant difference in starch content. It is preliminarily induced that GeDTC is the efflux channel of tricarboxylate and related to the tuber development, which lays a foundation for further elucidating the molecular mechanism of G. elata tuber development.

Achieving Highly Reversible Zinc Anodes via N, N-Dimethylacetamide Enabled Zn-Ion Solvation Regulation.

Although aqueous zinc-ion batteries (ZIBs) are promising for scalable energy storage application, the actual performance of ZIBs is hampered by the irreversibility. Optimization of electrolyte composition is a relatively practical and facile way to improve coulombic efficiency (CE) and Zn plating/stripping reversibility of ZIBs. N,N-Dimethylacetamide (DMA) has a higher Gutmann donor number (DN) than that of H2 O, abundant polar groups, and economic price. Herein, a mixture electrolyte containing 10 vol% DMA and ZnSO4 , which has an enhanced Zn reversibility almost fourfold higher than that of pure ZnSO4 electrolyte, is demonstrated. The density functional theory (DFT) calculation and spectroscopic analysis reveal DMA has the ability to reconstruct the solvation structure of Zn2+ and capture free water molecules via forming Hbonds. The inhibited dendrite growth on Zn anode is further clarified by an in situ characterization. This work provides a feasible way for the development of long-lifespan ZIBs.

Role for Biochemical Assays and Kayser-Fleischer Rings in Diagnosis of Wilson's Disease.

BACKGROUND & AIMS: Wilson disease is an autosomal recessive disorder that impairs copper homeostasis and is caused by homozygous or compound heterozygous mutations in ATP7B, which encodes a copper-transporting P-type ATPase. Patients have variable clinical manifestations and laboratory test results, resulting in diagnostic dilemmas. We aimed to identify factors associated with symptoms and features of Wilson disease from a large cohort, over 15 years. METHODS: We collected data from 715 patients (529 with symptoms, 146 without symptoms, and 40 uncategorized) and a genetic confirmation of Wilson's disease (mean age of diagnosis, 18.84 years), recruited from 3 hospitals in China from 2004 through 2019. We analyzed clinical data along with serum levels of ceruloplasmin (available from 636 patients), 24-hr urinary copper excretion (collected from 131 patients), Kayser-Fleisher rings (copper accumulation in eyes, with neurologic data from 355 patients), and magnetic resonance imaging (MRI) abnormalities. Differences among the groups were analyzed using 1-way analysis of variance followed by Tukey multiple comparison test. RESULTS: Of the 529 patients with symptoms, 121 had hepatic features, 355 had neurologic features, 28 had osteomuscular features (premature osteoarthritis, skeletal deformities, and pathological bone fractures), and 25 had psychiatric symptoms. Age of onset was significantly younger in patients with hepatic (16.94 ± 1.03 years; P = .0105) or osteomuscular features (13 ± 1.33 years; P = .0001) than patients with neurological features (19.48 ± 0.46 years). Serum levels of ceruloplasmin differed among asymptomatic patients and patients with osteomuscular or neurologic symptoms of Wilson disease. Serum levels of ceruloplasmin ranged from 18.93 mg/L to approximately 120.00 mg/L (quantiles of 0.025 to approximately 0.975). Fifty-one of 131 patients (39%) had urinary copper excretion levels below 100 µg/24 hr; there was significant variation in levels of urinary copper excretion between patients older than 14 years vs 14 years or younger. Of the 355 patients with neurologic features, 244 patients (69%) had abnormal findings from MRI and Kayser-Fleisher rings; only 1 patient with abnormal findings from brain MRI was negative for Kayser-Fleisher rings. CONCLUSIONS: Serum level of ceruloplasmin, 24-hour urinary copper excretion, and Kayser-Fleisher rings can be used to identify patients who might have Wilson disease. Patients with serum levels of ceruloplasmin below 120 mg/L and children with urinary copper excretion above 40 µg should undergo genetic testing for Wilson's disease. Patients with movement disorders and brain MRI abnormalities without Kayser-Fleisher rings are not likely to have Wilson disease.

A Novel Immunosuppressant, Luteolin, Modulates Alloimmunity and Suppresses Murine Allograft Rejection.

An allograft is rejected in the absence of any immunosuppressive treatment because of vigorous alloimmunity and thus requires extensive immunosuppression for its survival. Although there are many conventional immunosuppressants for clinical use, it is necessary to seek alternatives to existing drugs, especially in case of transplant patients with complicated conditions. Luteolin, a natural ingredient, exists in many plants. It exhibits multiple biological and pharmacological effects, including anti-inflammatory properties. In particular, luteolin has been shown to upregulate CD4+CD25+ regulatory T cells (Tregs) in the context of airway inflammation. However, it remains unknown whether luteolin regulates alloimmune responses. In this study, we demonstrated that luteolin significantly prolonged murine skin allograft survival, ameliorated cellular infiltration, and downregulated proinflammatory cytokine gene expression in skin allografts. Furthermore, luteolin increased the percentage of CD4+Foxp3+ Tregs while reducing frequency of mature dendritic cells and CD44highCD62Llow effector CD4+/CD8+ T cells posttransplantation. It also suppressed the proliferation of T cells and their production of cytokines IFN-γ and IL-17A in vitro while increasing IL-10 level in the supernatant. Moreover, luteolin promoted CD4+Foxp3+ Treg generation from CD4+CD25- T cells in vitro. Depleting Tregs largely, although not totally, reversed luteolin-mediated extension of allograft survival. More importantly, luteolin inhibited AKT/mTOR signaling in T cells. Thus, for the first time, to our knowledge, we found that luteolin is an emerging immunosuppressant as an mTOR inhibitor in allotransplantation. This finding could be important for the suppression of human allograft rejection, although it remains to be determined whether luteolin has an advantage over other conventional immunosuppressants in suppression of allograft rejection.

Optimizing Age Penalty in Time-Varying Networks with Markovian and Error-Prone Channel State.

In this paper, we consider a scenario where the base station (BS) collects time-sensitive data from multiple sensors through time-varying and error-prone channels. We characterize the data freshness at the terminal end through a class of monotone increasing functions related to Age of information (AoI). Our goal is to design an optimal policy to minimize the average age penalty of all sensors in infinite horizon under bandwidth and power constraint. By formulating the scheduling problem into a constrained Markov decision process (CMDP), we reveal the threshold structure for the optimal policy and approximate the optimal decision by solving a truncated linear programming (LP). Finally, a bandwidth-truncated policy is proposed to satisfy both power and bandwidth constraint. Through theoretical analysis and numerical simulations, we prove the proposed policy is asymptotic optimal in the large sensor regime.

High-Efficiency Separation of Extracellular Vesicles from Lipoproteins in Plasma by Agarose Gel Electrophoresis.

Isolation and purification of extracellular vesicles (EVs) from plasma is essential to understand the EV circulation mechanism and discover biomarkers for the early detection of diseases. However, the size range of lipoprotein particles such as high density lipoprotein (HDL), low density lipoprotein (LDL), and very low density lipoprotein (VLDL) overlap that of EVs, making it difficult to remove lipoproteins from EVs. Here, we propose a method for the high efficiency separation of EVs in plasma using agarose gel electrophoresis based on their differences in size and zeta potential properties. Electrophoresis track assays revealed that EVs propagate more slowly than HDL but more quickly than LDL and VLDL in 1% agarose gel with pH 7.4 Tris-Acetate-EDTA (TAE) buffer. The size and morphology of the electrophoresis-recovered products were characterized to be consistent with typical EVs. In addition, the biological function of recovered EVs was investigated with cell uptake tests. The feasibility of this method was further verified with human plasma samples. In summary, this technique has the potential to become a convenient and efficient approach for high-purity EV separation.

Three-dimensional manipulation of single cells using surface acoustic waves.

The ability of surface acoustic waves to trap and manipulate micrometer-scale particles and biological cells has led to many applications involving "acoustic tweezers" in biology, chemistry, engineering, and medicine. Here, we present 3D acoustic tweezers, which use surface acoustic waves to create 3D trapping nodes for the capture and manipulation of microparticles and cells along three mutually orthogonal axes. In this method, we use standing-wave phase shifts to move particles or cells in-plane, whereas the amplitude of acoustic vibrations is used to control particle motion along an orthogonal plane. We demonstrate, through controlled experiments guided by simulations, how acoustic vibrations result in micromanipulations in a microfluidic chamber by invoking physical principles that underlie the formation and regulation of complex, volumetric trapping nodes of particles and biological cells. We further show how 3D acoustic tweezers can be used to pick up, translate, and print single cells and cell assemblies to create 2D and 3D structures in a precise, noninvasive, label-free, and contact-free manner.

Quantitation of Intact Proteins in Human Plasma Using Top-Down Parallel Reaction Monitoring-MS.

Direct quantitation of proteins in complex biological matrices by mass spectrometry remains a challenge. Here, we describe a novel top-down parallel reaction monitoring-mass spectrometry (PRM-MS) assay, enabled by microflow LC-nanospray MS using a silicon microfluidic LC-MS chip. We demonstrated direct analysis of intact proteins such as somatropin in human plasma, achieving sensitivity (0.1-1.0 fmole) and speed (1-5 min) on par with enzyme-linked immunosorbent assay (ELISA).

Mangiferin Attenuates Murine Lupus Nephritis by Inducing CD4+Foxp3+ Regulatory T Cells via Suppression of mTOR Signaling.

BACKGROUND/AIMS: Lupus nephritis (LN) is an autoimmune glomerulonephritis that frequently develops secondary to systemic lupus erythematosus. Patients with LN require extensive treatments with global immunosuppressive agents. However, long-term treatment with conventional immunosuppressants may cause various side effects. Therefore, it's important to seek alternative drugs for treating LN. Here we aimed to investigate the immunoregulatory effects of mangiferin (MG), an ingredient that was originally extracted from natural herbs, including Mangifera Indica Linn. and Rhizoma Anemarrhenae. METHODS: FasL-deficient B6/ gld mice were used as a spontaneous LN model. The serum anti-dsDNA Ab and creatinine levels were analyzed via ELISA. Renal histology and immunopathology were determined using H&E and PAS staining, immunofluorescence (IgG and C3), and IHC staining (CD3 and a-SMA). Cytokine gene expression was measured by RT-PCR assays while effector T cells and Tregs were enumerated by flow analysis. Finally, the proliferation and apoptosis of T cells were measured by CFSE staining and flow analysis while their mTOR signaling was detected through Western blotting. RESULTS: We found that administration of MG ameliorated LN in lupus-prone B6/gld mice by reducing the urinary protein and serum creatinine levels, diminishing T cell infiltration in kidneys and improving renal immunopathology. MG also significantly lowered the percentages of CD44highCD62Llow effector T cells in B6/gld mice. Importantly, treatments with MG augmented CD4+FoxP3+ Treg frequencies in spleens, lymph nodes and kidneys of B6/gld mice. It also induced CD4+FoxP3+ Tregs from CD3+ T cells in vitro and promoted Treg proliferation. Furthermore, it inhibited CD3+ T cell proliferation in vitro and suppressed their phosphorylation of mTOR and its downstream P70S6K. However, MG did not promote T cell apoptosis, implying that it is not cytotoxic. Depletion of CD4+CD25+FoxP3+ Tregs in B6/gld mice abrogated its therapeutic effects on LN. CONCLUSION: MG exerts a novel therapeutic effect on murine LN via upregulating CD4+FoxP3+ Tregs, downregulating mTOR/p70S6K pathway and improving renal immunopathology. It may be useful for treating LN in clinic.

Standing Surface Acoustic Wave (SSAW)-Based Fluorescence-Activated Cell Sorter.

Microfluidic fluorescence-activated cell sorters (µFACS) have attracted considerable interest because of their ability to identify and separate cells in inexpensive and biosafe ways. Here a high-performance µFACS is presented by integrating a standing surface acoustic wave (SSAW)-based, 3D cell-focusing unit, an in-plane fluorescent detection unit, and an SSAW-based cell-deflection unit on a single chip. Without using sheath flow or precise flow rate control, the SSAW-based cell-focusing technique can focus cells into a single file at a designated position. The tight focusing of cells enables an in-plane-integrated optical detection system to accurately distinguish individual cells of interest. In the acoustic-based cell-deflection unit, a focused interdigital transducer design is utilized to deflect cells from the focused stream within a minimized area, resulting in a high-throughput sorting ability. Each unit is experimentally characterized, respectively, and the integrated SSAW-based FACS is used to sort mammalian cells (HeLa) at different throughputs. A sorting purity of greater than 90% is achieved at a throughput of 2500 events s-1 . The SSAW-based FACS is efficient, fast, biosafe, biocompatible and has a small footprint, making it a competitive alternative to more expensive, bulkier traditional FACS.