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Baicalin is one of the most abundant flavonoids found in the dried roots of Scutellaria baicalensis Georgi (SBG) belonging to the genus Scutellaria . While baicalin is demonstrated to have anti-inflammatory, antiviral, antitumor, antibacterial, anticonvulsant, antioxidant, hepatoprotective, and neuroprotective effects, its low hydrophilicity and lipophilicity limit the bioavailability and pharmacological functions. Therefore, an in-depth study of baicalin's bioavailability and pharmacokinetics contributes to laying the theoretical foundation for applied research in disease treatment. In this view, the physicochemical properties and anti-inflammatory activity of baicalin are summarized in terms of bioavailability, drug interaction, and inflammatory conditions.

Antibiotic resistance of bacteria and persistent inflammation are critical challenges in treating bacteria infected wounds. Thus, it is urgent to develop versatile wound dressings that possess high-efficiency antibacterial performance and inflammation regulation. Herein, we have successfully constructed a hydrogel wound dressing consisting of the bimetallic metal-organic framework (MOF) loaded with glucose oxidase (GOx), termed as MOF(Fe-Cu)/GOx-polyacrylamide (PAM) gel. Hydrogel dressings can provide an efficient cascade-catalyzed system to accelerate wound healing via synergistic antibacterial and inflammatory modulation. Importantly, the catalytic property of the bimetallic MOF(Fe-Cu) is about five times that of the monometallic MOF(Fe). Based on such a cascade-catalyzed system, the abundant gluconic acid and H 2 O 2 can be continuously produced by decomposing glucose via GOx. Such gluconic acid can notably improve the peroxidase performance of MOF(Fe-Cu), which can further efficiently decompose H 2 O 2 to achieve the antibacterial. Meanwhile, MOF (Fe Cu)/GOx PAM gel can induce macrophages to change into an M2 phenotype, which can accelerate the transformation of the wound microenvironment to a remodeling state and then accelerate angiogenesis and neurogenesis. This work provides multifunctional bioactive materials for accelerating wound healing and will have great potential in clinical applications. STATEMENT OF SIGNIFICANCE: Antibiotic resistance and persistent inflammation are still the critical reasons for the slow healing of bacteria infected wounds. Herein, we prepared a hydrogel wound dressing composed of bimetallic metal organic framework (MOF) loaded with glucose oxidase (GOx). The catalytic activity of the bimetallic MOF(Fe-Cu) is significantly enhanced due to doping of copper, which makes it possess outstanding antibacterial ability based on cascade catalysis. Such dressing can promote the remodeling of inflammatory immunity by regulating macrophage polarization to suppress over-reactive inflammation, further accelerating the healing of bacteria-infected wounds. This study provides an innovative and effective way to accelerate the healing of bacteria infected wound by combining bacteria killing and inflammation modulation., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.)

Generally, axons located at the central end of the nerve system will sprout after injury. Once these sprouts cannot reach the distal end of the severed nerve, they will form a traumatic neuroma. Traumatic neuromas bring a series of complex symptoms to patients, such as neuropathic pain, skin abnormalities, skeletal abnormalities, hearing loss, and visceral damage. To date, the most promising and practical clinical treatments are drug induction and surgery, but both have their limitations. Therefore, it will be the mainstream trend to explore new methods to prevent and treat traumatic neuroma by regulating and remodeling the microenvironment of nerve injury. This work first summarized the pathogenesis of traumatic neuroma. Additionally, the standard methods of prevention and treatment on traumatic neuroma were analyzed. We focused on three essential parts of advanced functional biomaterial therapy, stem cell therapy, and human-computer interface therapy to provide the availability and value of preventing and treating a traumatic neuroma. Finally, the revolutionary development of the prevention and treatment on traumatic neuroma has been prospected. How to transform the existing advanced functional materials, stem cells, and artificial intelligence robots into clinical practical technical means as soon as possible for high-quality nerve repair and prevention of neuroma was further discussed., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Zhou, Huo, Zhang, Han, Wen and Zhang.)

There are many problems and challenges related to the treatment of highly prevalent oral mucosal diseases and oral drug delivery because of a large amount of saliva present in the oral cavity, the accompanying oral movements, and unconscious swallowing in the mouth. Therefore, an ideal oral dressing should possess stable adhesion and superior tough strength in the oral cavity. However, this fundamental requirement greatly limits the use of synthetic adhesive dressings for oral dressings. Here, we developed a mussel-inspired Janus gelatin-polydopamine-nano-clay (GPC) hydrogel with controlled adhesion and toughness through the synergistic physical and chemical interaction of gelatin (Gel), nano-clay, and dopamine (DA). The hydrogel not only exhibits strong wet adhesion force (63 kPa) but also has high toughness (1026 ± 100 J m -3 ). Interfacial adhesion of hydrogels is achieved by modulating the interaction of catechol groups of the hydrogel with specific functional groups (e.g., NH 2 , SH, OH, and COOH) on the tissue surface. The matrix dissipation of the hydrogel is regulated by physical crosslinking of gelatin, chemical crosslinking of gelatin with polydopamine (Michael addition and Schiff base formation), and nano-clay-induced constraint of the molecular chain. In addition, the GPC hydrogel shows high cell affinity and favors cell adhesion and proliferation. The hydrogel's instant and strong mucoadhesive properties provide a long-lasting therapeutic effect of the drug, thereby enhancing the healing of oral ulcers. Therefore, mussel-inspired wet-adhesion Janus GPC hydrogels can be used as a platform for mucosal dressing and drug delivery systems. STATEMENT OF SIGNIFICANCE: It is a great challenge to treat oral mucosal diseases due to the large amount of saliva present in the oral cavity, the accompanying oral movements, unconscious swallowing, and flushing of drugs in the mouth. To overcome the significant limitations of clinical bioadhesives, such as weakness, toxicity, and poor usage, in the present study, we developed a simple method through the synergistic effects of gelatin, polydopamine, and nano-clay to prepare an optimal mucosal dressing (Janus GPC) that integrates Janus, adhesion, toughness, and drug release property. It fits effectively in the mouth, resists saliva flushing and oral movements, provides oral drug delivery, and reduces patient discomfort. The Janus GPC adhesive hydrogels have great commercial potential to support further the development of innovative therapies for oral mucosal diseases., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022. Published by Elsevier Ltd.)

Currently, the clinic's treatment of acute/chronic wounds is still unsatisfactory due to the lack of functional and appropriate wound dressings. Intelligent and multifunctional dressings are considered the most advanced wound treatment modalities. It is essential to design and develop wound dressings with required functions according to the wound microenvironment in the clinical treatment. This work summarizes microenvironment characteristics of various common wounds, such as acute wound, diabetic wound, burns wound, scalded wound, mucosal wound, and ulcers wound. Furthermore, the factors of transformation from acute wounds to chronic wounds were analyzed. Then we focused on summarizing how researchers fully and thoroughly combined the complex microenvironment with modern advanced technology to ensure the usability and value of the dressing, such as photothermal-sensitive dressings, microenvironment dressing (pH-sensitive dressings, ROS-sensitive dressings, and osmotic pressure dressings), hemostatic dressing, guiding tissue regeneration dressing, microneedle dressings, and 3D/4D printing dressings. Finally, the revolutionary development of wound dressings and how to transform the existing advanced functional dressings into clinical needs as soon as possible have carried out a reasonable and meaningful outlook.

By combining an electron-rich triazatruxene unit (TAT) to an electron-deficient zinc porphyrin fluorophore (ZnPor) via an ethynyl bridge, a new two-photon fluorescent viscosity rotor (TAT-ZnPor) with typical donor-π-acceptor (D-π-A) electronic configuration was developed for the ratiometric two-photon fluorescent detection of intracellular viscosity. The TAT-ZnPor dyad exhibited highly improved fluorescence quantum yield ( Φ em = 0.40) and two-photon absorption cross-section ( δ TPA = 811 GM) in comparison to the individual components. In the methanol/glycerol system, TAT-ZnPor showed sensitive fluorescence responses toward the change of viscosity. Upon elevating the viscosity from 0.59 to 947 cp, the blue emission band around 410 nm gradually enhanced, while the red band at 647 nm concomitantly quenched, leading to a remarkable intensity ratio ( I 410 / I 647 ) change from 0.70 to 81 (116-fold). TAT-ZnPor also displayed good cell imaging performance under one- and two-photon excitation, and strong mitochondria targeting ability in living cells, thus was successfully applied in detecting the change of mitochondrial viscosity during the nystatin-induced degeneration.

Peripheral nerve injury (PNI) is one of the common clinical injuries which needs to be addressed. Previous studies demonstrated the effectiveness of using biodegradable chitin (CT) conduits small gap tubulization technology as a substitute for traditional epineurial neurorrhaphy. Aiming to improve the effectiveness of CT conduits in repairing PNI, we modified their surface with a DNA-peptide coating. The coating consisted of single strand DNA (ssDNA) and its complementary DNA'-peptide mimics. First, we immobilize ssDNA (DNA1 + 2) on CT conduits by carbodiimide hydrochloride/N-hydroxysuccinimide (EDC/NHS) method to construct CT/DNA conduits. EDC/NHS was used to activate carboxyl groups of modified ssDNA for direct reaction with primary amines on the CT via amide bond formation. Then, DNA1'-BDNF + DNA2'-VEGF mimic peptide (RGI + KLT) were bonded to CT/DNA conduits by complementary base pairing principle at room temperature to form CT/RGI + KLT conduits. When the surrounding environment rose to a certain point (37 °C), the CT/RGI + KLT conduits achieved sustainable release of DNA'-peptide. In vitro , the CT conduits modified with the DNA-peptide coating promoted the proliferation and secretion of Schwann cells by maintaining their repair state. It also promoted the proliferation of human umbilical vein vessel endothelial cells and axon outgrowth of dorsal root ganglion explants. In vivo , CT/RGI + KLT conduits promoted regeneration of injured nerves and functional recovery of target muscles, which was facilitated by the synergistic contribution of angiogenesis and neurogenesis. Our research brings DNA and DNA-peptide hybrids into the realm of tissue engineering to repair PNI., (© 2021 IOP Publishing Ltd.)

Peripheral nerve injury (PNI) remains an unresolved challenge in the medicine area. With the development of biomaterial science and tissue engineering, a variety of nerve conduits were widely applied for repairing long defect PNI. DNA materials are developing rapidly due to their multiple advantages. In the present study, we aim to combine a DNA hydrogel, vascular endothelial growth factor (VEGF) and nerve growth factor (NGF) to construct a new type of delivery system, which could achieve a biphasic release profile of VEGF and NGF by taking advantage of the different degradation rates between X- and T-type DNA. In vitro results showed that the DNA gel + VEGF/NGF system could promote proliferation, migration and myelination of Rat Schwann cells (RSC) while maintaining cell viability. In vivo results indicated a better effect of DNA gel + VEGF/NGF on promoting repair of long defect PNI than the hollow chitin conduits (CT), DNA gel or VEGF/NGF group. The new technology invention holds promising clinical application prospects for repairing PNI and may be used broadly after step-by-step improvement.

The intelligent wearable sensors promote the transformation of the health care from a traditional hospital-centered model to a personal portable device-centered model. There is an urgent need of real-time, multi-functional, and personalized monitoring of various biochemical target substances and signals based on the intelligent wearable sensors for health monitoring, especially wound healing. Under this background, this review article first reviews the outstanding progress in the development of intelligent, wearable sensors designed for continuous, real-time analysis, and monitoring of sweat, blood, interstitial fluid, tears, wound fluid, etc. Second, this paper reports the advanced status of intelligent wound monitoring sensors designed for wound diagnosis and treatment. The paper highlights some smart sensors to monitor target analytes in various wounds. Finally, this paper makes conservative recommendations regarding future development of intelligent wearable sensors., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The Reviewer A.C declared a shared affiliation with the Author (Z.Z) to the Handling Editor at the time of review., (Copyright © 2021 Cheng, Gu, Zhou, Hao, An, Song, Wu, Zhang, Zhao, Dong and Wen.)

The biological barrier of solid tumors hinders deep penetration of nanomedicine, constraining anticancer treatment. Moreover, the inherent multidrug resistance (MDR) of cancer tissues may further limit the efficacy of anti-tumor nanomedicine. We synthesized highly permeable, photothermal, injectable, and positively charged biodegradable nucleic acid hydrogel (DNA-gel) nanoparticles to deliver cancer drugs. The nanoparticles are derived from photothermal materials containing black phosphorus quantum dots (BPQDs). The intra-tumoral BPQDs improve the sensitivity of tumor cells to photothermal therapy (PTT) and photodynamic treatment (PDT). Tumor cells take up the positively charged and controllable size DNA-gel nanoparticles, facilitating easy penetration and translocation of the particles across and within the cells. Mouse models demonstrated the anti-tumor activity of the DNA gel nanoparticles in vivo. In particular, the DNA gel nanoparticles enhanced clearance of both small and large tumor masses. Just 20 days after treatment, the tumor masses had been cleared. Compared to DOX chemotherapy alone, the DNA-gel treatment also significantly reduced drug resistance and improved the overall survival of mice with orthotopic breast tumors (83.3%, 78 d). Therefore, DNA gel nanoparticles are safe and efficient supplements for cancer therapy.

In the deoxyribonucleic acid (DNA) repair pathways, DNA repair enzymes have great significance for genomic integrity. As one important initiator of the base-excision repair pathway, the aberrant activity of uracil-DNA glycosylase (UDG) is closely associated with many diseases. Herein, we developed a simple distance-based device for visual detection of UDG activity using a load-free DNA hydrogel. The DNA hydrogel consists of polyacrylamide-DNA chains being bridged by a single-stranded DNA crosslinker containing a responsive uracil base site. UDG can recognize and remove the uracil, resulting in the cleavage effect of the DNA crosslinker strand with the assistance of endonuclease IV (Endo IV). Plugging one end of the capillary tube, the DNA hydrogel acting as a filter membrane separator would control molecules to flow into the tube. The integrity of the DNA hydrogel networks is affected by the excision of UDG. Therefore, taking full advantage of membrane filtration of the DNA hydrogel, the activity of UDG can be quantitatively detected via reading the distance of the red indicator solution in the capillary tube. Without any instruments and complicated procedures, this method realizes high sensitivity and specificity for the detection of UDG as low as 0.02 mU/mL and can even measure UDG in complex cell samples. Additionally, this method is simple, universal, and can be used to screen inhibitors, which shows great potential for point-of-care testing, clinical diagnosis, and drug discovery.

A novel, to the best of our knowledge, method to extract optical microring resonators' loss characteristics is proposed and demonstrated using optical frequency domain reflectometry (OFDR). Compared with the traditional optical transmission measurement method, the spatial-resolved backscattering optical signals obtained from the OFDR can clearly show the resonance mode's increased optical path length due to its circulation inside the resonator. By further processing the backscattered optical signals, loaded $Q$-factors of several resonators can be accurately determined. A calculation model is proposed to derive the resonance mode's intrinsic $Q$-factor from OFDR measurements of a series of loaded resonators.

It is widely accepted that a small particle size and rough surface can enhance tumor tissue accumulation and tumor cellular uptake of nanoparticles, respectively. Herein, sub-50 nm urchin-inspired disulfide bond-bridged mesoporous organosilica nanoparticles (UMONs) featured with a spiky surface and glutathione (GSH)-responsive biodegradability were successfully synthesized by a facile one-pot biphasic synthesis strategy for enhanced cellular internalization and tumor accumulation. l-Arginine (LA) is encapsulated into the mesopores of UMONs, whose outer surface is capped with the gatekeeper of ultrasmall gold nanoparticles, i.e., UMONs-LA-Au. On the one hand, the mild acidity-activated uncapping of ultrasmall gold can realize a tumor microenvironment (TME)-responsive release of LA. On the other hand, the unique natural glucose oxidase (GOx)-mimicking catalytic activity of ultrasmall gold can catalyze the decomposition of intratumoral glucose to produce acidic hydrogen peroxide (H 2 O 2 ) and gluconic acid. Remarkably, these products can not only further facilitate the release of LA, but also catalyze the LA-H 2 O 2 reaction for an increased nitric oxide (NO) yield, which realizes synergistic catalysis-enhanced NO gas therapy for tumor eradication. The judiciously fabricated UMONs-LA-Au present a paradigm of TME-responsive nanoplatforms for both enhanced cellular uptake and tumor-specific precision cascaded therapy, which broadens the range of practical biomedical applications and holds a significant promise for the clinical translation of silica-based nanotheranostics.

Lateral flow biosensor (LFB) is one of the most successful and applied commercial detection methods for food safety, drug abuse, and disease. Here, we integrated the ultrasound enrichment as sample preparation with LFB to achieve the ultra-trace protein detection in blood. When the ultrasound field is applied, the interaction between the acoustic field and gold nanoparticles can gather specifically modified gold nanoparticles toward pressure nodes in seconds and enrich target proteins. Such an approach can detect protein with a linear range of 1-20 ng mL -1 and detection limit of 0.58 ng mL -1 in blood within 20 min, which enormously reduces false positive readings caused by interference in real blood samples with complex components. Such a microchip that integrated acoustic enrichment with LFB shows great potential in detecting ultra-trace biomarkers for clinical diagnosis.

This review (with 187 refs.) summarizes the progress that has been made in the design of lateral flow biosensors (LFBs) based on the use of micro- and nano-materials. Following a short introduction into the field, a first section covers features related to the design of LFBs, with subsections on strip-based, cotton thread-based and vertical flow- and syringe-based LFBs. The next chapter summarizes methods for sample pretreatment, from simple method to membrane-based methods, pretreatment by magnetic methods to device-integrated sample preparation. Advances in flow control are treated next, with subsections on cross-flow strategies, delayed and controlled release and various other strategies. Detection conditionst and mathematical modelling are briefly introduced in the following chapter. A further chapter covers methods for reliability improvement, for example by adding other validation lines or adopting different detection methods. Signal readouts are summarized next, with subsections on color-based, luminescent, smartphone-based and SERS-based methods. A concluding section summarizes the current status and addresses challenges in future perspectives. Graphical abstractRecent development and breakthrough points of lateral flow biosensors.

The authors describe a magnetized carbon nanotube (MCNT)-based lateral flow strip biosensor for visual detection of proteins directly in whole blood avoiding complex purification and sample pre-treatments. MCNT were synthesized by coating Fe 3 O 4 nanoparticles on the shortened multiwalled carbon nanotube (CNT) surface via co-precipitation of ferric and ferrous ions within a dispersion of shorten multiwalled CNTs. The antibody-modified MCNTs were used to capture target protein in whole blood; the formed MCNT-antibody-target protein complexes were applied to the lateral flow strip biosensor, in which a capture antibody was immobilized on the test zone of the biosensor. The captured MCNTs on the test zone and control zone were producing characteristic brown/black bands, and this enabled target protein to be visually detected. Quantification was accomplished by reading the intensities of the bands with a portable strip reader. Rabbit IgG was used as a model target to demonstrate the proof-of-concept. After systematic optimizations of assay parameters, the detection limit of the assay in whole blood was determined to be 10 ng mL -1  (S/N = 3) with a linear dynamic range of 10-200 ng mL -1 . This study provides a rapid and low-cost approach for detecting proteins in blood, showing great promise for clinical application and biomedical diagnosis, particularly in limited resource settings., (Copyright © 2017 Elsevier B.V. All rights reserved.)

The authors describe a rapid, low-cost and sensitive approach for the determination of carbohydrate antigen 19-9 (CA 19-9) in whole blood by using magnetized carbon nanotube (MCNT) and lateral flow strip biosensor (LFSB). MCNTs were synthesized by depositing magnetite (Fe 3 O 4 ) nanoparticles on multiwalled carbon nanotube (CNT) via co-precipitation of ferric and ferrous ions within a dispersion of shortened multiwalled CNTs. Antibody against CA 19-9 (Ab 1 ) was covalently immobilized on the MCNTs and were used to capture CA 19-9 in blood. After magnetic separation, the formed MCNT-Ab 1 -CA 19-9 complexes are applied to the LFSB, in which a capture antibody (Ab 2 ) and a secondary antibody (Ab 3 ) are immobilized on the test zone and control zone of the LFSB, respectively. The captured MCNTs on the test zone and control zone are producing characteristic brown bands, and this enables CA 19-9 to be visually detected. Quantitation is accomplished by reading the intensities of the bands with a portable strip reader. Under optimized conditions, the assay has a detection limit as low as 30 U⋅mL -1 of CA19-9 in blood. This is below the cutoff value (37 U mL -1 ) of CA 19-9. The assay duration for blood samples is 35 min. In our perception, the assay represents a rapid and low-cost tool for rapid determination of CA19-9 in blood that holds promise for clinical applications, particularly in limited resource settings.

A pH-responsive free-blockage release system was achieved through controlling the hydrophobic/hydrophilic conversion of mesoporous silica nanopores. This system further presented pulsatile release with changing pH values between 4.0 and 7.0 for several cycles. This free-blockage release system could also release antitumor agents to induce cell death after infecting tumor cells and could have the ability of continuous infection to tumor cells with high drug-delivery efficiency and few side effects., (© 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

A straightforward strategy to stably anchor one or more gold nanoparticles (AuNPs) at both the internal and terminal positions of single-stranded DNA is presented. Discrete DNA-AuNP conjugates are isolated using a noncovalent extension strand strategy, that helps to resolve prepared species by agarose gel electrophoresis (AGE). These are used to assemble well-defined AuNP squares and rectangles. Two complementary bis-AuNP-labeled DNA conjugates are then prepared. One of these places two smaller (5 nm) AuNPs at defined internal positions within a DNA strand, and the other places two larger (13 nm) AuNPs at each of its terminal positions. We show the self-assembly of these bis-AuNP conjugates into a tapered tetrameric gold nanoparticle "antenna" structures of direct relevance to engineered "hot spots" and surface enhanced Raman scattering (SERS) substrates.

Objective: To retrospectively analyze the clinical and imaging features of multi-segmental lumbar intervertebral disc protrusion and its treatment with the limited recessive decompression operation., Methods: Twenty-two patients (14 males and 8 females, aged 49-68 years) were admitted to hospital from March 1999 to March 2004. They suffered from multi-segmental lumbar intervertebral disc protrusion that involved L1-S1 and were treated with the limited recessive decompression operation., Results: The follow-up for 4-21 months showed that 16 of the patients had an excellent outcome, 5 had a good outcome, and 1 had fair outcome. There were no such operative complications as nerve root lesions and putamen lesions., Conclusion: The limited recessive decompression operation is one of the available good treatments for multi-segmental lumbar intervertebral disc protrusion. It solves problems of herniation and stenosis and maintains stability of the spine.