Highly oriented hydrogels for tissue regeneration: design strategies, cellular mechanisms, and biomedical applications.

Many human tissues exhibit a highly oriented architecture that confers them with distinct mechanical properties, enabling adaptation to diverse and challenging environments. Hydrogels, with their water-rich "soft and wet" structure, have emerged as promising biomimetic materials in tissue engineering for repairing and replacing damaged tissues and organs. Highly oriented hydrogels can especially emulate the structural orientation found in human tissue, exhibiting unique physiological functions and properties absent in traditional homogeneous isotropic hydrogels. The design and preparation of highly oriented hydrogels involve strategies like including hydrogels with highly oriented nanofillers, polymer-chain networks, void channels, and microfabricated structures. Understanding the specific mechanism of action of how these highly oriented hydrogels affect cell behavior and their biological applications for repairing highly oriented tissues such as the cornea, skin, skeletal muscle, tendon, ligament, cartilage, bone, blood vessels, heart, etc., requires further exploration and generalization. Therefore, this review aims to fill that gap by focusing on the design strategy of highly oriented hydrogels and their application in the field of tissue engineering. Furthermore, we provide a detailed discussion on the application of highly oriented hydrogels in various tissues and organs and the mechanisms through which highly oriented structures influence cell behavior.

Biomedical applications of stimuli-responsive "smart" interpenetrating polymer network hydrogels.

In recent years, owing to the ongoing advancements in polymer materials, hydrogels have found increasing applications in the biomedical domain, notably in the realm of stimuli-responsive "smart" hydrogels. Nonetheless, conventional single-network stimuli-responsive "smart" hydrogels frequently exhibit deficiencies, including low mechanical strength, limited biocompatibility, and extended response times. In response, researchers have addressed these challenges by introducing a second network to create stimuli-responsive "smart" Interpenetrating Polymer Network (IPN) hydrogels. The mechanical strength of the material can be significantly improved due to the topological entanglement and physical interactions within the interpenetrating structure. Simultaneously, combining different network structures enhances the biocompatibility and stimulus responsiveness of the gel, endowing it with unique properties such as cell adhesion, conductivity, hemostasis/antioxidation, and color-changing capabilities. This article primarily aims to elucidate the stimulus-inducing factors in stimuli-responsive "smart" IPN hydrogels, the impact of the gels on cell behaviors and their biomedical application range. Additionally, we also offer an in-depth exposition of their categorization, mechanisms, performance characteristics, and related aspects. This review furnishes a comprehensive assessment and outlook for the advancement of stimuli-responsive "smart" IPN hydrogels within the biomedical arena. We believe that, as the biomedical field increasingly demands novel materials featuring improved mechanical properties, robust biocompatibility, and heightened stimulus responsiveness, stimuli-responsive "smart" IPN hydrogels will hold substantial promise for wide-ranging applications in this domain.

YTHDF2-mediated circYAP1 drives immune escape and cancer progression through activating YAP1/TCF4-PD-L1 axis.

Immune escape is identified as one of the reasons for the poor prognosis of colorectal cancer (CRC) patients. Circular RNAs are considered to promote tumor progression by mediating tumor immune escape. We discovered that higher expression of circYAP1 was associated with a worse prognosis of CRC patients. Functional experiments in vitro and in vivo showed that circYAP1 upregulation inhibited the cytotoxicity of CD8+ T cells by upregulating programmed death ligand-1 (PD-L1). Mechanistically, we found that circYAP1 directly binds to the YAP1 protein to prevent its phosphorylation, enhancing proportion of YAP1 protein in the nucleus, and that YAP1 interacts with TCF4 to target the PD-L1 promoter and initiate PD-L1 transcription in CRC cells. Taken together, circYAP1 promotes CRC immune escape and tumor progression by activating the YAP1/TCF4-PD-L1 axis and may provide a new strategy for combination immunotherapy of CRC patients.

Recent advances in lipid nanovesicles for targeted treatment of spinal cord injury.

The effective regeneration and functional restoration of damaged spinal cord tissue have been a long-standing concern in regenerative medicine. Treatment of spinal cord injury (SCI) is challenging due to the obstruction of the blood-spinal cord barrier (BSCB), the lack of targeting of drugs, and the complex pathophysiology of injury sites. Lipid nanovesicles, including cell-derived nanovesicles and synthetic lipid nanovesicles, are highly biocompatible and can penetrate BSCB, and are therefore effective delivery systems for targeted treatment of SCI. We summarize the progress of lipid nanovesicles for the targeted treatment of SCI, discuss their advantages and challenges, and provide a perspective on the application of lipid nanovesicles for SCI treatment. Although most of the lipid nanovesicle-based therapy of SCI is still in preclinical studies, this low immunogenicity, low toxicity, and highly engineerable nanovesicles will hold great promise for future spinal cord injury treatments.

Robust α-Fe2O3@TiO2 Core-Shell Structures With Tunable Buffer Chambers for High-Performance Lithium Storage.

α-Fe2O3 has high potential energy storage capacity and can serve as a green and low-cost anode material for lithium-ion batteries. However, α-Fe2O3 suffers large volume expansion and pulverization. Based on DFT calculations, TiO2 can effectively maintain the integrity of the crystal structure during the discharge/charge process. Well-defined cubic α-Fe2O3 is coated with a TiO2 layer using the hydrothermal method with the assistance of oxalic acid surface treatment, and then α-Fe2O3@TiO2 with tunable buffer chambers is obtained by altering the hydrochloric acid etching time. With the joint efforts of the buffer chamber and the robust structure of the TiO2 layer, α-Fe2O3@TiO2 alleviates the expansion of α-Fe2O3 during the discharge/charge process. The optimized sample (FT-1h) achieves good cycling performance. The reversible specific capacity remains at 893.7 mA h g-1, and the Coulombic efficiency still reaches up to 98.47% after 150 cycles at a current density of 100 mA g-1. Furthermore, the reversible specific capacity can return to 555.5 mA h g-1 at 100 mA g-1 after cycling at a high current density. Hence, the buffer chamber and the robust TiO2 layer can effectively improve the cycling stability and rate performance of α-Fe2O3.

Towards producing high-quality lignin-based carbon fibers: A review of crucial factors affecting lignin properties and conversion techniques.

The production of low-cost and high-quality carbon fibers (CFs) from biorenewable lignin precursors has been of worldwide interest for decades. Although numerous works have been reported and the proposed "1.72 GPa/172 GPa" target set by the Department of Energy (DOE) has been closely met in a few studies, most lignin-based CFs (LCFs) have poor strength properties compared to industrial PAN (polyacrylonitrile)-based CFs. The production of LCFs involves several steps, and the final quality of LCFs is governed by both lignin's properties and the manufacturing processes. Therefore, understanding the key factors of producing high quality LCF is of high importance. In this review, we firstly outlined several lignin's properties (e.g., impurities, thermal properties, molecular structure) that may play important role in determining its processability and suitability as carbon fiber precursor. Secondly, conversion strategies include spinning, stabilization and carbonization, and corresponding parameters influencing the final quality of LCF are comprehensively analyzed. Last, additional characterization methods are proposed as a means to facilitate analyzing of lignin and LCF. This review attempts to provide insights towards high-quality LCF production from both material and manufacturing aspects.

Lignin-derived 3D porous graphene on carbon cloth for flexible supercapacitors.

In this work, we reported a new method to fabricate flexible carbon-based supercapacitor electrodes derived from a commercialized and low-cost lignin. The fabrication process skips traditional stabilization/carbonization/activation for lignin-based carbon production. Also, the process reported here was green and facile, with minimum solvent use and no pretreatment required. Characterization of the lignin showed that it has common properties among all types of lignin. The lignin was impregnated on carbon cloth and then subjected to direct laser writing to form the desired electrodes (LLC). The results showed that lignin was successfully bonded to carbon cloth. The LLC has a good porous carbon structure with a high I G/I D ratio of 1.39, and a small interlayer spacing d 002 of 0.3436 nm, which are superior to most of the reported lignin-based carbons. Although not optimized, the fabricated LLC showed good supercapacitance behavior with an areal capacitance of 157.3 mF cm-2 at 0.1 mA cm-2. In addition, the superior flexibility of LLC makes it a promising electrode that can be used more widely in portable devices. Conceptually, this method can be generalized to all types of lignin and can define intriguing new research interests towards lignin applications.

DNA Tetrahedra-Cross-linked Hydrogel Functionalized Paper for Onsite Analysis of DNA Methyltransferase Activity Using a Personal Glucose Meter.

Despite the recent developments on the construction of point-of-care testing (POCT) devices, it is still a big challenge to build portable POCT tools for simple, sensitive, selective, and quantitative determination of disease-related biomarkers. With this in mind, we developed a simple and user-friendly POCT tool for onsite analysis of DNA adenine methyltransferase (Dam) activity by using DNA tetrahedra-based hydrogel to trap glucose-producing enzymes for target recognition and signal transduction. The enzyme-encapsulated DNA hydrogel and the substrate of enzyme were separately modified on papers and then combined onto a commercial glucose test strip for the sensitive evaluation of Dam activity via using a personal glucose meter (PGM) for quantitative signal readout. Taking advantage of the great amount of enzyme entrapped in DNA hydrogel and the high signal amplification ability of enzyme, this POCT tool is capable of highly sensitive and selective determination of Dam activity with a direct detection limit down to 0.001 U/mL, which is superior to that of most previously reported biosensors. Furthermore, this device can also be applied to screen inhibitor and analyze Dam activity in spiked serum samples, indicating the great potential for clinical practice and diagnostic applications. Additionally, all the reactions for Dam assay are performed on paper, which is simple and deliverable to end-users for medical diagnostics at home or in-field.

A direct-write method for preparing a bimetal sulfide/graphene composite as a free-standing electrode for high-performance microsupercapacitors.

It is a great challenge to ideally integrate graphene with its unique two-dimensional (2D) and porous structure into the pseudocapacitive materials. In this paper, a simple technique, i.e. direct-laser-writing (DLW), was developed to fabricate microsupercapacitors (MSCs) with excellent electrochemical performance, marked as Ni-Co-S/laser induced graphene (LIG) that exhibit a high areal specific capacitance of 680 mF cm-2 at the current density of 1 mA cm-2. A symmetric MSC device was assembled using Ni-Co-S/LIG as a positive electrode and active carbon (AC) as the negative electrode, and exhibited a high areal energy density of 56.9 µW h cm-2 at the power density of 800 µW cm-2, and excellent cycling stability maintaining 89.6% of the areal specific capacitance after 8000 cycles. The synergistic effect of bimetallic Ni-Co-S and the LIG with the 2D structure results in the excellent electrochemical performance. This work demonstrates a method to integrate Ni-Co-S pseudocapacitive materials into porous graphene with a direct-laser-writing technique. The produced integrated materials possess high energy density that can be used in MSCs.

Self-Assembled Naphthalimide Conjugated Porphyrin Nanomaterials with D-A Structure for PDT/PTT Synergistic Therapy.

Light-activated phototherapy, including photothermal and photodynamic therapy, has become a new way for spatiotemporal control and noninvasive treatment of cancer. In this study, two new organic porphyrin molecules (NI-Por and NI-ZnPor) with donor (D)-acceptor (A) structure were designed and synthesized. The donor-acceptor pairs facilitated the intermolecular electron transfer, resulting in the enhancement of near-infrared (NIR) absorbance and nonradiative heat generation. After self-assembling, the nanoparticles were formed with the size around 60 nm. Relative to that of organic molecules, the absorption of NI-Por NPs and NI-ZnPor NPs broadened and red-shifted to the near-infrared region. Moreover, the porphyrin-containing nanoparticles can generate heat and reactive oxygen species (ROS) simultaneously induced by a single laser (635 nm). The intracellular reactive oxygen species production of NI-Por NPs and NI-ZnPor NPs was confirmed using DCFH-DA as an indicator. Furthermore, the localization of NI-Por NP and NI-ZnPor NP in HeLa cells was verified by fluorescence confocal laser microscopy. The photocytoxicity of two nanoparticles against HeLa cells was evaluated through the CCK-8 method. The IC50 of NI-Por NPs and NI-ZnPor NPs upon 635 nm laser irradiation was calculated to be 6.92 µg/mL and 5.86 µg/mL, respectively. Furthermore, the PDT/PTT synergistic effect of NPs under a 635 nm laser was verified through different treatment groups in vitro. All these results demonstrated that the as-prepared porphyrin-based nanoparticles are promising nanoagents for PDT/PTT in clinic.

A Universal Paper-Based Electrochemical Sensor for Zero-Background Assay of Diverse Biomarkers.

This paper describes a universal paper-based electrochemical sensing platform that uses a paper modified with signal molecule-labeled DNA and a screen-printed electrode along with target recognition solutions to achieve the detection of multiple types of biomarkers. These assays rely on the target-induced synthesis of Mg2+-dependent DNAzyme for catalyzing the cleavage of substrate DNA from paper, which have been demonstrated by using microRNA recognition probe for miR-21, a phosphorylated hairpin probe for alkaline phosphatase, and a DNA aptamer for carcinoembryonic antigen assays, respectively. Taking advantages of the high specific target-triggered polymerization/nicking and DNAzyme-catalyzed signal amplification, the present assays enable highly sensitive and selective detection of these targets with zero-background. These assays can also be applied to detect target in spiked serum samples, demonstrating the potential for point-of-care detection of clinical samples.

Cetuximab-conjugated iodine doped carbon dots as a dual fluorescent/CT probe for targeted imaging of lung cancer cells.

Iodine doped carbon quantum dots (I-CQDs) have been synthesized by a facile one-pot hydrothermal method using citric acid and iohexol as precursors. The morphology and chemical structures of I-CQDs are investigated by TEM, XRD, XPS, and FTIR spectroscopy. The as-prepared I-CQDs exhibit excitation-dependent PL behavior with the emission quantum yield of 18%. The presence of iodine ions in I-CQDs is confirmed by XPS spectrum, which endows the composite with CT imaging performance. Thus, they could be used as efficient probes for fluorescence/CT bimodal imaging. To realize a precise diagnosis of tumor lesions, the surface of I-CQDs is conjugated with a targeting molecular (cetuximab) to afford I-CQDs-C225. The MTT assay against three kinds of human cell lines verifies the low cytotoxicity of I-CQDs-C225. The targeting ability of I-CQDs-C225 are evaluated in vitro using HCC827 cells (lung cancer cell line, over-expression of EGFR), H23 (lung cancer cell line, low expression of EGFR) and HLF cells (lung normal cell line, low expression of EGFR) via a confocal laser scanning microscope. The results show that HCC827 cells exhibited strong fluorescence, indicating the cetuximab-conjugated I-CQDs could target specifically the cancer cells with over-expression of EGFR via EGFR mediated endocytosis.

Ultrasensitive Ratiometric Homogeneous Electrochemical MicroRNA Biosensing via Target-Triggered Ru(III) Release and Redox Recycling.

A new label-free and enzyme-free ratiometric homogeneous electrochemical microRNA biosensing platform was constructed via target-triggered Ru(III) release and redox recycling. To design the effective ratiometric dual-signal strategy, [Ru(NH3)6]3+ (Ru(III)), as one of the electroactive probes, was ingeniously entrapped in the pores of the positively charged mesoporous silica nanoparticle (PMSN), and another electroactive probe, [Fe(CN)6]3- (Fe(III)), was selected to facilitate Ru(III) redox recycling due to its distinctly separated reduction potential and different redox properties. Owing to the liberation of the formed RNA-ssDNA complex from PMSN, the target miRNA triggered the Ru(III) release and was quickly electroreduced to Ru(II), and then, the in-site-generated Ru(II) could be chemically oxidized back to Ru(III) by Fe(III). Thus, with the release of Ru(III) and the consumption of Fe(III), a significant enhancement for the ratio of electroreduction current [Ru(NH3)6]3+ over [Fe(CN)6]3- (IRu(III)/IFe(III)) value was observed, which was dependent on the concentration of the target miRNA. Consequently, a simple, accurate, and ultrasensitive method for the miRNA assay was readily realized. Furthermore, the limit of detection (LOD) of our method was down to 33 aM (S/N = 3), comparable or even superior to other approaches reported in literature. More importantly, it also exhibited excellent analytical performance in the complex biological matrix cell lysates. Therefore, this homogeneous biosensing strategy not only provides an ingenious idea for realizing simple, rapid, reliable, and ultrasensitive bioassays but also has a great potential to be adopted as a powerful tool for precision medicine.

Neuroprotective effects of ganoderma lucidum polysaccharides against oxidative stress-induced neuronal apoptosis.

Ganoderma lucidum polysaccharides have protective effects against apoptosis in neurons exposed to ischemia/reperfusion injury, but the mechanisms are unclear. The goal of this study was to investigate the underlying mechanisms of the effects of ganoderma lucidum polysaccharides against oxidative stress-induced neuronal apoptosis. Hydrogen peroxide (H2O2) was used to induce apoptosis in cultured cerebellar granule cells. In these cells, ganoderma lucidum polysaccharides remarkably suppressed H2O2-induced apoptosis, decreased expression of caspase-3, Bax and Bim and increased that of Bcl-2. These findings suggested that ganoderma lucidum polysaccharides regulate expression of apoptosis-associated proteins, inhibit oxidative stress-induced neuronal apoptosis and, therefore, have significant neuroprotective effects.

Biphasic photoelectrochemical sensing strategy based on in situ formation of CdS quantum dots for highly sensitive detection of acetylcholinesterase activity and inhibition.

Herein, we reported a facile and highly sensitive biphasic photoelectrochemical (PEC) sensing strategy based on enzymatic product-mediated in situ formation of CdS quantum dots (QDs), and assayed the activity and inhibition of acetylcholinesterase (AChE) in its optimal state. Upon the hydrolysis of acetylthiocholine catalyzed by AChE, the product thiocholine stabilizes the in situ formation of CdS QDs in homogenous solution. Due to the electrostatic attraction, the resulting tertiary amino group-functionalized CdS QDs are attached to the surface of the negatively charged indium tin oxide (ITO) electrode, generating significant PEC response upon illumination in the presence of electron donors. By taking full advantage of the in situ formation of CdS QDs in homogenous solution, this strategy is capable of detecting AChE activity and inhibition in its optimal state. A directly measured detection limit of 0.01mU/mL for AChE activity is obtained, which is superior to those obtained by some fluorescence methods. The inhibition of AChE activity by aldicarb is successfully detected, and the corresponding IC50 is determined to be 13µg/L. In addition to high sensitivity and good selectivity, this strategy also exhibits additional advantages of simplicity, low cost and easy operation. To the best of our knowledge, the as-proposed strategy is the first example demonstrating the application of CdS QDs formed in situ for biphasic PEC detection of enzyme activity and inhibition. More significantly, it opens up a new horizon for the development of homogenous PEC sensing platforms, and has great potential in probing many other analytes.

{2-[(2-Amino-cyclo-hex-yl)imino-meth-yl]phenolato}dioxidovanadium(V).

In the title dioxidovanadium complex, [V(C(13)H(17)N(2)O)O(2)], the V(V) atom is in a square-based pyramidal coordination: the basal plane is defined by the phenolate O, imine N and amine N atoms of the tridentate Schiff base ligand, and by one oxide O atom. The apical position is occupied by the other oxide O atom. In the crystal, mol-ecules are connected by N-H⋯O and N-H⋯(O,O) hydrogen bonds, forming a tetra-mer.

The frequency and treatment of dural tears and cerebrospinal fluid leakage in 266 patients with thoracic myelopathy caused by ossification of the ligamentum flavum.

STUDY DESIGN: Retrospective review. OBJECTIVE: To perform a single-institution analysis of incidence, treatment, and clinical outcome in patients with thoracic ossification of the ligamentum flavum (OLF) who experienced dural tears and cerebrospinal fluid (CSF) leakage. SUMMARY OF BACKGROUND DATA: There is a paucity of clinical reports focusing on dural tears and CSF leakage after thoracic OLF surgery. Because dural adhesion and dural ossification are common features of thoracic OLF, the incidence of CSF leakage in OLF patients is high and represents a significant clinical challenge. METHODS: A total of 266 patients with thoracic OLF were admitted to our hospital from 1995 to 2011. Each patient's medical records were reviewed to identify cases of dural tears and CSF leakage. Information on therapeutic strategy used to repair the dural tears and complications related to CSF leakage was extracted. RESULTS: The incidence of dural tears and CSF leakage in OLF patients was 32% (85/266). The incidence of dural ossification was 25.2%. The dural tears were repaired with a range of materials, including gelatin sponge, muscle/fascia, artificial dura, silk suture, and fibrin glue. The intraoperative repair procedure did not resolve CSF leakage in 65 cases, and 16 of those cases experienced complications related to the continued CSF leakage, including CSF pseudocyst, wound dehiscence, and meningitis. Fifty-eight patients with CSF leakage were eventually cured by a series of comprehensive treatments, which included prone position, continuous pressure by sandbag, ultrasound-guided puncture, and aspiration. Only 7 patients required reoperation. CONCLUSION: Dural ossification was the main reason for dural tears. In all, 78 of the 85 patients with CSF leakage or dural tear were successfully cured. The success rate was 91.8%, which indicated that a series of comprehensive treatments was an effective strategy to treat these patients.

Diagnosis and treatment of ossification of the ligamentum flavum associated with dural ossification: clinical article.

OBJECT: In this paper, the authors aimed to summarize the clinical characteristics of ossification of the ligamentum flavum (OLF) associated with dural ossification (DO) and to identify improved methods for preoperative diagnosis. METHODS: Thirty-six patients who had undergone OLF surgery between February 2005 and September 2009 were included in this retrospective study. The patients were divided into 2 groups: one that included patients with intraoperative evidence of DO and a second group that included patients without DO. The clinical features of DO were summarized and the neurological status of the patients was evaluated pre- and postoperatively. RESULTS: The incidence rate of DO associated with OLF was 39% (14/36). The sensitivity and specificity of the tram track sign were found to be 93% and 59%, respectively. Dural ossification was found among 86% of the patients with tuberous type Sato classification. The postoperative neurological status of patients was generally improved relative to that observed prior to surgery, although neurological recovery did not differ between the 2 groups. Cerebrospinal fluid leakage was the main complication, occurring predominantly in the patients with DO, and all leaks resolved in all patients after comprehensive treatments. CONCLUSIONS: The tram track sign and Sato classification were found to be useful for preoperative diagnosis of DO and for determining the surgical procedure to be performed. Dural ossification had no effect on postoperative neurological recovery.