Re-Designing Cellulosic Core-Shell Composite Fibers for Advanced Photothermal and Thermal-Regulating Performance.

Flexible fibers and textiles featuring photothermal conversion and storage capacities are ideal platforms for solar-energy utilization and wearable thermal management. Other than using fossil-fuel-based synthetic fibers, re-designing natural fibers with nanotechnology is a sustainable but challenging option. Herein, advanced core-shell structure fibers based on plant-based nanocelluloses are obtained using a facile co-axial wet-spinning process, which has superior photothermal and thermal-regulating performances. Besides serving as the continuous matrix, nanocelluloses also have two other important roles: dispersing agent when exfoliating molybdenum disulfide (MoS2), and stabilizer for phase change materials (PCM) in the form of Pickering emulsion. Consequently, the shell layer contains well-oriented nanocelluloses and MoS2, and the core layer contains a high content of PCM in a leak-proof encapsulated manner. Such a hierarchical cellulosic supportive structure leads to high mechanical strength (139 MPa), favorable flexibility, and large latent heat (92.0 J g-1), surpassing most previous studies. Furthermore, the corresponding woven cloth demonstrates satisfactory thermal-regulating performance, high solar-thermal conversion and storage efficiency (78.4-84.3%), and excellent long-term performance. In all, this work paves a new way to build advanced structures by assembling nanoparticles and polymers for functional composite fibers in advanced solar-energy-related applications.

Simultaneous bond-selective deuterium-based isotopic labeling sensing with disposable ultra-miniature CARS fiber probe.

Deuterium-based isotopic labeling is an important technique for tracking cellular metabolism with the Raman signals analysis of low-wavenumber (LW) C-D bonds and high-wavenumber (HW) C-H bonds. We propose and demonstrate a disposable ultra-miniature fiber probe to detect LW and HW coherent anti-Stokes Raman scattering (CARS) spectra for deuterated compounds simultaneously and bond-selectively sensing. The 10.78 µm diameter disposable fiber probe, comprised of focusing taper as fiber probe head and time-domain walk-off eliminating fiber section with designed length, realizes wide-frequency-interval dual Stokes pulse delivering and focusing. The fiber probe enables quantitative concentration determination with resolution down to 11 mM. The chemical vibration modes of LW region C-D bonds and HW region C-H bonds of the mixture samples of organic compounds and their deuterated counterparts in a simulated cell are simultaneously excited and characterized. The CARS disposable fiber probe introduces a promising handle for in vivo biochemical detection based on isotopic labeling sensing.

Development and functional characterization of novel fully human anti-CD19 chimeric antigen receptors for T-cell therapy.

Impressive outcomes have been achieved by chimeric antigen receptor (CAR)-T cell therapy using murine-derived single-chain variable fragment (scFv) FMC63 specific for CD19 in patients with B cell malignancies. However, evidence suggests that human anti-mouse immune responses might be responsible for poor persistence and dysfunction of CAR-T cells, leading to poor outcomes or early tumor recurrence. Substituting a fully human scFv for murine-derived scFv may address this clinically relevant concern. In this study, we discovered two human anti-CD19 scFv candidates through an optimized protein/cell alternative panning strategy and evaluated their function in CAR-T cells and CD19/CD3 bispecific antibody formats. The two clones exhibited excellent cytotoxicity in CAR-T cells and bispecific antibodies in vitro compared with the benchmarks FMC63 CAR-T cells and blinatumomab. Furthermore, Clone 78-BBz CAR-T cells exhibited similar in vivo antitumor activity to FMC63-BBz CAR-T cells. Our results indicate that Clone 78-BBz CAR has excellent efficacy and safety profile and is a good candidate for clinical development.

Heterogeneous-frequency-dual-pulse chain and weak FBG array for quasi-distributed acoustic sensing with improved response bandwidth.

By continuously injecting four groups of heterogeneous frequency dual pulses into the sensing fiber with weak fiber Bragg gratings (WFBGs), a quasi-distributed acoustic sensing method based on frequency-division multiplexing is proposed. Each group of pulses generates interference signals with different carrier frequencies after being reflected by the WFBGs. Through the discrete Fourier transform phase demodulation method, each carrier frequency interference signal is demodulated and then the phase is spliced. The feasibility of this method is theoretically analyzed, and a detection with a bandwidth of 2 kHz is realized on a 70 km sensing fiber with a spatial resolution of 10 m.

Optical fiber laser refractometer based on an open microcavity Mach-Zehnder interferometer with an ultra-low detection limit.

A fiber laser refractometer based on an open microcavity Mach-Zehnder interferometer (OMZI) is proposed. The open microcavity is constructed by embedding a segment single-mode fiber (SMF) into two multi-mode fiber (MMF) joints with lateral offset for liquid sample, which has the advantages of micro sensing element and easy fabrication. The transmission characteristics of the MMF-assisted OMZI are investigated by simulating and manufacturing the OMZIs with different microcavity lengths and offset distances. By inserting the MMF-assisted OMZI into the erbium-doped fiber ring laser (FRL) cavity, the lasing wavelength can be used to detect the refractive index (RI) change of the medium in the microcavity. Experimental results show a high sensitivity of -2953.444 nm/RIU within the measurement range of 1.33302∼1.33402. More importantly, with the combination of OMZI and FRL, the proposed fiber laser refractometer realizes ultra-low detection limit (DL) and high-quality factor Q, which are two orders of magnitude better than that of previous reports.

Virtual-block-array phase analysis for distributed acoustic sensors with a high signal-to-noise ratio reconstruction waveform.

A virtual-block-array phase analysis method is proposed for the fiber-optic distributed acoustic sensor. The sensing fiber is divided into a serial of discrete virtual blocks according to the pulse spatial length. The phase variation caused by acoustic events is obtained by combining the operation of the temporal differential process between traces and local spatial average in virtual blocks. The linear frequency-modulated probe pulse produces phase compensation effects at the event location. High signal-to-noise ratio (SNR) measurement is verified by simulation and experiment. The reconstructed waveform of 1.5 kHz sinusoidal signal showed a root mean square error of 0.0359 and an SNR of 47.28 dB.

Wall-thickness-controlled microbubble fabrication for WGM-based application.

We present a wall-thickness-controlled microbubble fabrication model for whispering-gallery-mode (WGM)-based application. The process of fabricating the model is divided into three sequenced steps: geometry size change of the microcapillary during drawing, expanding the process under internal injection air pressure, and microcapillary waist swell into a microbubble. Experiments were carried out to verify the effectiveness of the model. Experiment results show that wall thickness can reach 1.28 µm-1.46 µm at different injection pressure ranges of 50 kPa. The expected wall thickness of the microbubble can be achieved by changing injection pressure while keeping the diameter, which helps to prepare the required microbubble for practical application.

Multi-channel optical fiber refractometer based on tree topology structure.

A multi-channel optical fiber refractometer based on S fiber taper (SFT) cascaded with fiber Bragg grating (FBG) is proposed and experimentally demonstrated. The compact SFT acts as an in-line Mach-Zehnder interferometer (MZI) to be used as a band-pass filter (BPF) to tailor the FBG reflection, whose transmission spectrum is sensitive to the surrounding refractive index (SRI). Thus, the peak power of the FBG reflection is modulated by the SRI. The three-channel SRI monitor can be achieved by discriminating the different center wavelength and peak power variation of the FBG reflections. Experimental results show that the RI sensitivities of Channels 1, 2, and 3 are 345.54, 349.57, and 463.60 dB/RIU, respectively. Moreover, the temperature cross-sensitivity can be solved by interrogating the center wavelength of the FBG reflection.

Simultaneous refractive index and temperature measurement using nested fiber balloon rings.

A simple all-fiber sensor based on nested fiber balloon rings (FBRs) for simultaneous refractive index (RI) and temperature measurement is proposed and demonstrated. The FBR is easily fabricated by properly bending a section of single-mode fiber. The FBR with a smaller bending radius is embedded in a bigger one. Because the two separate interference dips have different RI and temperature sensitivities, which are formed by individual FBRs, the RI and temperature can be simultaneously measured by interrogating the wavelength shifts of the two interference dips. This sensor has the advantages of convenient fabrication, economical materials, probe structure, and high sensitivity and can be a candidate for simultaneous measurement of RI and temperature.

Hypermethylation of DDAH2 promoter contributes to the dysfunction of endothelial progenitor cells in coronary artery disease patients.

BACKGROUND: Circulating endothelial progenitor cells (EPCs) may be a biomarker for vascular function and cardiovascular risk in patients with coronary artery disease (CAD). Dimethylarginine dimethylaminohydrolase 2 (DDAH2) regulates the function of EPCs. This study aimed to examine whether hypermethylation of DDAH2 promoter contributes to impaired function of EPCs in CAD patients. METHODS: Peripheral blood mono-nuclear cells from 25 CAD patients and 15 healthy volunteers were collected and differentiated into EPCs. EPCs were tested for their adhesive capability. DDAH2 mRNA expression was analyzed by real-time PCR, and the methylation of DDAH2 promoter was detected by bisulfite genomic sequencing. RESULTS: DDAH2 promoter in EPCs from CAD patients was hypermethylated and the methylation level was negatively correlated to DDAH2 mRNA level and adhesion function of EPCs. Homocysteine impaired the adhesion function of EPCs, accompanied by lower DDAH2 expression and higher methylation level of DDAH2 promoter, compared to controls. These effects of homocysteine were reversed by pretreatment with Aza, an inhibitor of DNA methyltransferase. CONCLUSION: Hypermethylation in DDAH2 promoter is positively correlated to the dysfunction of EPCs in CAD patients. Homocysteine disrupts EPCs function via inducing the hypermethylation of DDAH2 promoter, suggesting a key role of epigenetic mechanism in the progression of atherosclerosis.

Hollow-microsphere-integrated optofluidic immunochip for myocardial infarction biomarker microanalysis.

This work developed an optofluidic immunochip that uses whispering gallery mode with fiber laser enhancement, for the rapid detection of a key biomarker cardiac troponin I for acute myocardial infarction (AMI). The immunochip adopted an innovative design, using perforated hollow glass microspheres (HGMS) as carriers, with antibodies immobilized on the inner surface of the HGMS, thereby achieving ultra-low sample consumption. The performance of the immunochip was improved by fiber laser, including spectral width compression to 0.019 nm, optical signal-to-noise ratio amplification to 63.17 dB, and an enhancement in the limit of detection to 5 pg/mL. Moreover, this immunochip can provide results within 15 min, making it highly suitable for early AMI risk management. Compared to the standard electrochemiluminescence detection method, although some differences exist in the results of the immunochip due to the principle of detection and differences in antibody affinity, its positive reference value can be calculated as 0.0754 ng/mL, with a successful recognition rate of 88% for positive patients. The immunosensor is integrated on a polydimethylsiloxane substrate, with a compact size suitable for use in point-of-care devices and AMI self-screening, as well as rapid disease screening and microanalysis of various biomarkers, offering new possibilities for applications in these fields.

Epigallocatechin-3-gallate inhibits homocysteine-induced apoptosis of endothelial cells by demethylation of the DDAH2 gene.

Our previous study showed that hypermethylation of dimethylarginine dimethylaminohydrolase 2 contributes to homocysteine-induced apoptosis of human umbilical vein endothelial cells. Epigallocatechin-3-gallate is a green tea-derived phenol which has been proved beneficial on atherosclerosis. It was demonstrated that epigallocatechin-3-gallate inhibits DNA methyltransferase activity and reactivates methylation-silenced genes in cancer cells. The aim of this study was to address whether epigallocatechin-3-gallate could induce DNA demethylation of the dimethylarginine dimethylaminohydrolase 2 gene, contributing to prevent endothelial cells from apoptosis induced by homocysteine. Human umbilical vein endothelial cells (ATCC, CRL-2480) were treated with homocysteine (1 mM) for 48 hours with or without epigallocatechin-3-gallate (20 µM) or 5-Aza (DNA methyltransferase inhibitor, 5 µM). Apoptosis rate of human umbilical vein endothelial cells was assayed by flow cytometry with an annexin V-FITC apoptosis detection kit. The mRNA and protein expression level of dimethylarginine dimethylaminohydrolase 2 and DNA methyltransferase 1 were detected by real-time PCR and Western blot, respectively. DNA methylation level of dimethylarginine dimethylaminohydrolase 2 was assayed by methylation specific PCR. The binding level of DNA methyltransferase 1 in the promoter of dimethylarginine dimethylaminohydrolase 2 was determined by chromatin immunoprecipitation-quantitative real-time PCR. It was shown that the apoptosis rate was decreased significantly in human umbilical vein endothelial cells treated with homocysteine compared with the control. Furthermore, the mRNA and protein level of dimethylarginine dimethylaminohydrolase 2 were downregulated, the dimethylarginine dimethylaminohydrolase 2 gene promoter was hypermethylated, and the DNA methyltransferase 1 mRNA and protein level were increased in human umbilical vein endothelial cells treated with homocysteine. Chromatin immunoprecipitation-quantitative real-time PCR revealed that homocysteine-induced binding of DNA methyltransferase 1 to the dimethylarginine dimethylaminohydrolase 2 promoter was increased. Pretreatment with epigallocatechin-3-gallate or 5-Aza inhibited such effects of homocysteine. In conclusion, epigallocatechin-3-gallate exerted protective effects on homocysteine-induced apoptosis in human umbilical vein endothelial cells by inhibiting promoter hypermethylation of the dimethylarginine dimethylaminohydrolase 2 gene and inducing dimethylarginine dimethylaminohydrolase 2 expression. These effects may be due to the decreased DNA methyltransferase 1 expression and binding of DNA methyltransferase 1 to the dimethylarginine dimethylaminohydrolase 2 promoter induced by epigallocatechin-3-gallate. This research suggests that modulating the epigenetic processes might be a novel plausible way for treatment of atherosclerosis.

[Endothelial progenitor cells: the new target of anti-atherosclerosis drugs].

Endothelial progenitor cells (EPCs) are a kind of progenitor cells with high potential of proliferation, which exist in the bone marrow, umbilical cord blood, and peripheral blood. Under certain conditions, EPCs can differentiate into mature vascular endothelial cells. Many studies have shown that EPCs could delay the onset and development of atherosclerosis by promoting the repair of the endothelium and neovascularization. EPCs have also been considered to be a biological marker for cardiovascular diseases. Recent investigations demonstrate that EPCs can mediate the effect of some anti-atherosclerosis drugs. This paper reviews the role of EPCs in atherosclerosis and the influence of drugs on EPC function. The feasibility and the problem of using EPCs as a treatment strategy are also discussed.

High-strength and functional nanocellulose filaments made by direct wet spinning from low concentration suspensions.

Continuous filaments obtained through the wet spinning of nanocellulose have promising mechanical properties with sustainable features. To guarantee proper spinnability for wet spinning, freshly made cellulose nanofibril (CNF) suspension needs to be concentrated to have a concentration above 1 wt%, resulting in energy- and time-consuming, and inferior mechanical properties of the final filaments owing to decreasing the CNF alignment against shear flows. In this study, a CNF spinning suspension at a low concentration (0.4 wt%) can be used right after the fibrillation process without further treatments. The effects of the concentration and re-concentrating process are studied by carefully characterizing the rheological behavior and filament solidification processes, which provides more fundamental understandings on the spinnability and CNF network formation of such colloidal CNF suspensions. Combined with a post stretching process, the final dried CNF filaments have superior mechanical properties with Young's modulus and tensile strength of 35 GPa and 567 MPa, surpassing most literature data. Moreover, different functional particles can be easily incorporated to prepare functional filaments. With facile preparation and superior properties, these CNF filaments may be suitable for advanced composite filler and special textile applications.

Nanocellulose-Based Hollow Fibers for Advanced Water and Moisture Management.

Natural plant fibers such as cotton have favorable performance in water and moisture management; however, they suffer from inferior processing ability due to limited diameter and length, as well as natural defects. Although commercially available regenerated cellulose fibers such as lyocell fibers can have tunable structures, they rely on the complete dissolution of cellulose molecules, including the highly crystalline parts, leading to inferior mechanical properties. Through a specially designed coaxial wet-spinning process, we prepare a type of hollow fiber using only cellulose nanofibrils (CNFs) as building blocks. It mimics cotton fibers with a lumen structure but with a tunable diameter and a long length. Moreover, such hollow fibers have superior mechanical properties with a Young's modulus of 24.7 GPa and tensile strength of 341 MPa, surpassing lyocell fibers and most wet-spun CNF-based fibers. Importantly, they have 10 times higher wicking ability, wetting rate, drying rate, and maximum wetting ratio compared to lyocell fibers. Together with a superior long-term performance after 500 rounds of wetting-drying tests, such CNF-based hollow fibers are sustainable choices for advanced textile applications. And this study provides a greater understanding of nanoscale building blocks and their assembled macromaterials, which may help to reveal the magic hierarchical design of natural materials, in this case, plant fibers.

Prefab Hollow Glass Microsphere-Based Immunosensor with Liquid Crystal Sensitization for Acute Myocardial Infarction Biomarker Detection.

Quantitative detection of cardiac troponin biomarkers in blood is an important method for clinical diagnosis of acute myocardial infarction (AMI). In this work, a whispering gallery mode (WGM) microcavity immunosensor based on a prefab hollow glass microsphere (HGMS) with liquid crystal (LC) sensitization was proposed and experimentally demonstrated for label-free cardiac troponin I-C (cTnI-C) complex detection. The proposed fiber-optic immunosensor has a simple structure; the tiny modified HGMS serves as the key sensing element and the microsample reservoir simultaneously. A sensitive LC layer with cTnI-C recognition ability was deposited on the inner wall of the HGMS microcavity. The arrangement of LC molecules is affected by the cTnI-C antigen-antibody binding in the HGMS, and the small change of the surface refractive index caused by the binding can be amplified owing to the birefringence property of LC. Using the annular waveguide of the HGMS, the WGMs were easily excited by the coupling scanning laser with a microfiber, and an all-fiber cTnI-C immunosensor can be achieved by measuring the resonant wavelength shift of the WGM spectrum. Moreover, the dynamic processes of the cTnI-C antigen-antibody binding and unbinding was revealed by monitoring the wavelength shift continuously. The proposed immunosensor with a spherical microcavity can be a cost-effective tool for AMI diagnosis.

Fiber-integrated WGM optofluidic chip enhanced by microwave photonic analyzer for cardiac biomarker detection with ultra-high resolution.

Cardiac troponin I (cTnI) plays an important role in emergency diagnosis of cardiovascular diseases, which exists predominately in the form of cardiac troponin I-C (cTnI-C) complex. We proposed a fiber-integrated optofluidic chip immunosensor with time-delay-dispersion based microwave photonic analyzer (MPA) for cTnI-C detection. The whispering gallery mode (WGM) fiber probe was fabricated by embedding a polydopamine functionalized hollow glass microsphere (HGMS) into the etched capillary-fiber structure, and the WGMs could be excited through the efficient coupling between the thin-wall capillary and the HGMS. The reflective WGM optofluidic chip functioned as a wavelength tuner to construct fiber ring laser cavity, whose laser output wavelength was cTnI-C concentration-dependent. The tiny wavelength variation of sensing laser was converted into a radio-frequency (RF) response, which was retrieved by measuring the change of RF-domain free spectrum range (FSR) in time-delay-dispersion based MPA, and the quantitative detection of cTnI-C complex can be achieved with high resolution. Experimental results show that this immunosensor had a limit of detection (LOD) of 0.59 ng/mL, and a detection resolution of 1.2 fg/mL. The relative resolving power was 102-104-fold higher than that of others optical fiber cTnI biosensors. The proposed fiber-integrated optofluidic chip provides an innovative lab-on-chip diagnostic tool for myocardial damage.

Vascular Adhesion Protein-1 (VAP-1)/Semicarbazide-Sensitive Amine Oxidase (SSAO): A Potential Therapeutic Target for Atherosclerotic Cardiovascular Diseases.

Vascular adhesion protein-1 (VAP-1) is a semicarbazide-sensitive amine oxidase (SSAO), whose enzymatic activity regulates the adhesion/exudation of leukocytes in/from blood vessels. Due to its abundant expressions in vascular systems and prominent roles in inflammations, increasing attentions have been paid to the roles of VAP-1/SSAO in atherosclerosis, a chronic vascular inflammation that eventually drives clinical cardiovascular events. Clinical studies have demonstrated a potential value of soluble VAP-1 (sVAP-1) for the diagnosis and prognosis of cardiovascular diseases. Recent findings revealed that VAP-1 is expressed in atherosclerotic plaques and treatment with VAP-1 inhibitors alleviates the progression of atherosclerosis. This review will focus on the roles of VAP-1/SSAO in the progression of atherosclerotic lesions and therapeutic potentials of VAP-1 inhibitors for cardiovascular diseases.

Inactivation of Semicarbazide-Sensitive Amine Oxidase Stabilizes the Established Atherosclerotic Lesions via Inducing the Phenotypic Switch of Smooth Muscle Cells.

Given that the elevated serum semicarbazide-sensitive amine oxidase (SSAO) activity is associated with the severity of carotid atherosclerosis in clinic, the current study aims to investigate whether SSAO inactivation by semicarbazide is beneficial for established atherosclerotic lesions in LDLr knockout mice on a high-fat/high- cholesterol Western-type diet or after dietary lipid lowering. Despite no impact on plasma total cholesterol levels, the infiltration of circulating monocytes into peripheral tissues, and the size of atherosclerotic lesions, abrogation of SSAO activity resulted in the stabilization of established lesions as evidenced by the increased collagen contents under both conditions. Moreover, SSAO inactivation decreased Ly6Chigh monocytosis and lesion macrophage contents in hypercholesterolemic mice, while no effect was observed in mice after normalization of hypercholesterolemia by dietary lipid lowering. Strikingly, abrogation of SSAO activity significantly increased not only the absolute numbers of smooth muscle cells (SMCs), but also the percent of SMCs with a synthetic phenotype in established lesions of mice regardless of plasma cholesterol levels. Overall, our data indicate that SSAO inactivation in vivo stabilizes the established plaques mainly via inducing the switch of SMCs from a contractile to a synthetic phenotype. Targeting SSAO activity thus may represent a potential treatment for patients with atherosclerosis.

Inactivation of semicarbazide-sensitive amine oxidase induces the phenotypic switch of smooth muscle cells and aggravates the development of atherosclerotic lesions.

BACKGROUND AND AIMS: Clinical studies have demonstrated that serum semicarbazide-sensitive amine oxidase (SSAO) activities positively correlate with the progression of atherosclerosis. The aim of the present study is to investigate the effect of SSAO inactivation on the development of atherosclerosis. METHODS: Female LDLr knockout (KO) mice were given the Western-type diet for 6 and 9 weeks to induce the formation of early and advanced lesions, and semicarbazide (SCZ, 0.125%) was added into the drinking water to inactivate SSAO in vivo. RESULTS: Despite no impact on plasma total cholesterol levels, abrogation of SSAO by SCZ not only resulted in the enlargement of both early (1.5-fold, p = 0.0043) and advanced (1.8-fold, p = 0.0013) atherosclerotic lesions, but also led to reduced/increased lesion contents of macrophages/smooth muscle cells (SMCs) (macrophage: ∼0.74-fold, p = 0.0002(early)/0.0016(advanced); SMC: ∼1.55-fold, p = 0.0003(early)/0.0001(advanced)), respectively. Moreover, SSAO inactivation inhibited the migration of circulating monocytes into peripheral tissues and reduced the amount of circulating Ly6C(high) monocytes (0.7-fold, p = 0.0001), which may account for the reduced macrophage content in lesions. In contrast, the increased number of SMCs in lesions of SCZ-treated mice is attributed to an augmented synthetic vascular SMC phenotype switch as evidenced by the increased proliferation of SMCs and accumulation of collagens in vivo. CONCLUSION: SSAO inactivation by SCZ promotes the phenotypic switch of SMCs and the development of atherosclerosis. The enzymatic activity of SSAO may thus represent a potential target in the prevention and/or treatment of atherosclerosis.