Xiaoqinglong decoction mitigates nasal inflammation and modulates gut microbiota in allergic rhinitis mice.

Introduction: Allergic rhinitis (AR) is a respiratory immune system disorder characterized by dysregulation of immune responses. Within the context of AR, gut microbiota and its metabolites have been identified as contributors to immune modulation. These microorganisms intricately connect the respiratory and gut immune systems, forming what is commonly referred to as the gut-lung axis. Xiaoqinglong Decoction (XQLD), a traditional Chinese herbal remedy, is widely utilized in traditional Chinese medicine for the clinical treatment of AR. In this study, it is hypothesized that the restoration of symbiotic microbiota balance within the gut-lung axis plays a pivotal role in supporting the superior long-term efficacy of XQLD in AR therapy. Therefore, the primary objective of this research is to investigate the impact of XQLD on the composition and functionality of the gut microbiota in a murine model of AR. Methods: An ovalbumin-sensitized mouse model to simulate AR was utilized, the improvement of AR symptoms after medication was investigated, and high-throughput sequencing was employed to analyze the gut microbiota composition. Results: XQLD exhibited substantial therapeutic effects in AR mice, notably characterized by a significant reduction in allergic inflammatory responses, considerable alleviation of nasal symptoms, and the restoration of normal nasal function. Additionally, following XQLD treatment, the disrupted gut microbiota in AR mice displayed a tendency toward restoration, showing significant differences compared to the Western medicine (loratadine) group. Discussion: This results revealed that XQLD may enhance AR allergic inflammatory responses through the regulation of intestinal microbiota dysbiosis in mice, thus influencing the dynamics of the gut-lung axis. The proposal of this mechanism provides a foundation for future research in this area.

Multiscale Heterogeneities-Based Piezoresistive Interfaces with Ultralow Detection Limitation and Adaptively Switchable Pressure Detectability.

Mechanical compliance and electrical enhancement are crucial for pressure sensors to promote performances when perceiving external stimuli. Here we propose a bioinspired multiscale heterogeneity-based interface to adaptively regulate its structure layout and switch to desirable piezoresistive behaviors with ultralow detection limitation. In such a multiscale heterogeneities system, the micro-/nanoscale spiny Ag-MnO2 heterostructure contributes to an ultralow detection limitation of 0.008 Pa and can perceive minor pressure increments under preloads with high resolution (0.0083%). The macroscale heterogeneous orientation of the cellular backbone enables anisotropic deformation, allowing the sensor to switch to rational sensitivity and working range (e.g., 580 kPa-1 for 0-20 kPa/54 kPa-1 for 60-140 kPa) as required. The sensor's stepwise activation progresses from the micro-/nanoscale heterostructure to the macroscale heterogeneous orientation, which can adaptively match diverse sensing tasks in complex applications scenarios. This multiscale heterogeneous and switchable design holds immense potential in the development of intelligent electromechanical devices, including wearable sensors, soft robotics, and smart actuators.

Hydrogel-Functionalized Bandages with Janus Wettability for Efficient Unidirectional Drug Delivery and Wound Care.

Chronic wounds have imposed a severe physical and economic burden on the global healthcare system, which are usually treated by the delivery of drugs or bioactive molecules to the wound bed through wound dressings. In this work, we have demonstrated a hydrogel-functionalized bandage with Janus wettability in a bilayer structure to achieve unidirectional drug delivery and multifunctional wound care. The Janus patterned bandage with porous gradient wetting channels on the upper layer is responsible for the unidirectional transport of the drug from the outside to the wound bed (up to 90% drug transport efficiency) while preventing drug diffusion in unwanted directions (<8%). The hydrogel composed of chitosan quaternary ammonium salt (HACC), poly(vinyl alcohol) (PVA), and poly(acrylic acid) (PAA) at the bottom layer further functionalized such a bandage with biocompatibility, excellent antibacterial properties, and hemostatic ability to promote wound healing. Especially, the hydrogel-functionalized bandage with Janus wettability exhibits excellent mechanical flexibility (∼198% strain), which can comply well with skin deformation (stretching, bending, or twisting) and maintain unidirectional drug delivery behavior without any leakage. The in vivo full-thickness skin wound model confirms that the hydrogel-functionalized bandage can significantly facilitate epithelialization and collagen deposition and improve drug delivery efficiency, thus promoting wound closure and healing (the wound healing ratio was 98.10% at day 15). Such a synergistic strategy of unidirectional drug delivery and multifunctional wound care provides a more efficient, economical, and direct method to promote wound healing, which could be used as a potential high-performance wound dressing for clinical application.

Ferroptosis in Osteocytes as a Target for Protection Against Postmenopausal Osteoporosis.

Ferroptosis is a necrotic form of iron-dependent regulatory cell death. Estrogen withdrawal can interfere with iron metabolism, which is responsible for the pathogenesis of postmenopausal osteoporosis (PMOP). Here, it is demonstrated that estrogen withdrawal induces iron accumulation in the skeleton and the ferroptosis of osteocytes, leading to reduced bone mineral density. Furthermore, the facilitatory effect of ferroptosis of osteocytes is verified in the occurrence and development of postmenopausal osteoporosis is associated with over activated osteoclastogenesis using a direct osteocyte/osteoclast coculture system and glutathione peroxidase 4 (GPX4) knockout ovariectomized mice. In addition, the nuclear factor erythroid derived 2-related factor-2 (Nrf2) signaling pathway is confirmed to be a crucial factor in the ferroptosis of osteocytic cells. Nrf2 regulates the expression of nuclear factor kappa-B ligand (RANKL) by regulating the DNA methylation level of the RANKL promoter mediated by DNA methyltransferase 3a (Dnmt3a), which is as an important mechanism in osteocytic ferroptosis-mediated osteoclastogenesis. Taken together, this data suggests that osteocytic ferroptosis is involved in PMOP and can be targeted to tune bone homeostasis.

[Metabolomics of nasal lavage fluid in patients with allergic rhinitis treated by Xiaoqinglong Decoction].

This study used nasal lavage fluid for metabolomics to explore its feasibility, and applied it to the clinical metabolomics study of Xiaoqinglong Decoction in the treatment of allergic rhinitis(AR), aiming to investigate the molecular mechanism of Xiaoqing-long Decoction in the treatment of AR through differential changes in local nasal metabolism. AR patients were selected as the research subjects, and nasal lavage fluid was collected as the sample. Metabolomics analysis using liquid chromatography-mass spectrometry was performed on normal group, AR group, and Xiaoqinglong Decoction group. The differences in metabolic profiles among the groups were compared using principal component analysis and partial least squares discriminant analysis, and differential metabolites were identified and subjected to corresponding metabolic pathway analysis. The results showed that Xiaoqinglong Decoction significantly improved the symptoms of AR patients. The metabolomics analysis revealed 20 differential metabolites between AR group and Xiaoqinglong Decoction group. The core metabolite with a trending return in comparison to normal group was trimethyladipic acid. The metabolites were involved in multiple pathways, including ß-alanine metabolism, glutathione metabolism, and phenylalanine, tyrosine, and tryptophan biosynthesis. The feasibility of applying nasal lavage fluid in nasal metabolomics was preliminarily demonstrated. Differential metabolites and enriched pathways in the treatment of AR patients with Xiaoqinglong Decoction were identified, indicating that it may improve rhinitis symptoms through the regulation of various metabolites, including antioxidant effects and correction of Th1/Th2 imbalance.

Premetastatic Niche Mimicking Bone-On-A-Chip: A Microfluidic Platform to Study Bone Metastasis in Cancer Patients.

Primary cancer modulates the bone microenvironment to sow the seeds of dormancy and metastasis in tumor cells, leading to multiple organ metastasis and death. In this study, 3D printing and bone-on-a-chip (BOC) are combined to develop a BOC platform that mimics the pre-metastatic niches (PMNs) and facilitates elucidation of the interactions between bone-resident cells and metastatic tumor cells under the influence of primary cancer. Photocrosslinkable gelatin methacrylate (GelMA) is used as a 3D culturing hydrogel to encapsulate cells, and circulate tumor culture medium (CM) adjacent to the hydrogel to verify the critical role of mesenchymal stem cells (MSCs) and osteoclasts (RAW264.7s). Three niches: the dormancy niche, the perivascular niche, and the "vicious cycle" niche, are devised to recapitulate bone metastasis in one chip with high cell viability and excellent nutrient exchange. With respect to tumor dormancy and reactivation, the invadopodia formation of A549 lung cancer cells in communication with MSCs and RAW264.7 via the cortactin pathway is researched. As a proof of concept, the functionality and practicality of the platform are demonstrated by analyzing the invadopodia formation and the influence of various cells, and the establishment of the dynamic niches paves the way to understanding PMN formation and related drug discovery.

Xiao-qing-long-tang ameliorates OVA-induced allergic rhinitis by inhibiting ILC2s through the IL-33/ST2 and JAK/STAT pathways.

BACKGROUND: Allergic rhinitis (AR) is a chronic inflammatory disease of the nasal mucosa that is mediated by immunoglobulin E (IgE). Xiao-qing-long-tang (XQLT) is a traditional Chinese medicine compound that is widely used to treat respiratory diseases such as AR. However, the underlying mechanism of the effect of XQLT on AR remains unclear. PURPOSE: To elucidate the effect of XQLT on ovalbumin (OVA)-induced AR and the mechanisms of action. METHODS: The therapeutic efficacy of XQLT was evaluated in a well-established OVA-induced AR mouse model. Nasal symptoms were analyzed, type 2 cytokines and OVA-sIgE levels were measured, nasal mucosa tissues were collected for histological analysis, and the changes of Group 2 innate lymphoid cells (ILC2s) and the IL-33/ST2 and JAK/STAT signaling pathways in the nasal mucosa were observed. RESULTS: XQLT significantly alleviated the nasal symptoms and histological damage to the nasal mucosa in AR mice, and reduced the levels of type 2 cytokines and OVA-sIgE. In addition, after XQLT treatment, the numbers of ILC2s in the nasal mucosa of AR mice were reduced, and the mRNA levels of the transcription factors GATA3 and ROR-α were decreased. Moreover, IL-33/ST2 signaling pathway was inhibited. The costimulatory cytokine associated JAK/STAT signaling pathway was also inhibited in ILC2s. CONCLUSION: Our study demonstrated that XQLT regulated ILC2s through the IL-33/ST2 and JAK/STAT pathways to ameliorate type 2 inflammation in OVA-induced AR. These findings suggest that XQLT might be used to treat AR.

Diagnosis and Treatment Strategy of Nasogenic Olfactory Dysfunction.

Since the global outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a symptom of the onset of SARS-CoV-2, olfactory dysfunction (OD), has attracted tremendous attention. OD is not only a negative factor for quality of life but also an independent hazard and early biomarker for various diseases, such as Parkinson's and Huntington's diseases. Therefore, early identification and treatment of OD in patients are critical. Many etiological factors are responsible for OD based on current opinions. Sniffin'Sticks are recommended to identify the initial position (central or peripheral) for OD when treating patients clinically. It is worth emphasizing that the olfactory region in nasal cavity is recognized as the primary and critical olfactory receptor. Many nasal diseases, such as those with traumatic, obstructive and inflammatory causes, can lead to OD. The key question is no refined diagnosis or treatment strategy for nasogenic OD currently. This study summarizes the differences in medical history, symptoms, auxiliary examination, treatment and prognosis of different types of nasogenic OD by analyzing the current studies. We propose using olfactory training after 4-6 weeks of initial treatment for nasogenic OD patients with no significant improvement in olfaction. We hope that our research can provide valuable clinical guidance by systematically summarizing the clinical characteristics of nasogenic OD.

Smart Janus fabrics for one-way sweat sampling and skin-friendly colorimetric detection.

Functionalized textiles with biofluid management capability have attracted tremendous attention in recent years due to their significant roles in health monitoring and dehydration prevention. Here we propose a one-way colorimetric sweat sampling and sensing system based on a Janus fabric using interfacial modification techniques. The opposite wettability of Janus fabric enables sweat to be quickly moved from the skin surface to the hydrophilic side and colorimetric patches. The unidirectional sweat-wicking performance of Janus fabric not only facilitates adequate sweat sampling but also inhibits the backflow of hydrated colorimetric regent from the assay patch toward the skin, eliminating potential epidermal contaminations. On this basis, visual and portable detection of sweat biomarkers including chloride, pH, and urea is also achieved. The results show that the true concentrations of chloride, pH, and urea in sweat are ∼10 mM, ∼7.2, and ∼10 mM, respectively. The detection limits of chloride and urea are 1.06 mM and 3.05 mM. This work bridges the gap between sweat sampling and a friendly epidermal microenvironment, providing a promising way for multifunctional textiles.

HDAC Downregulation of Xiaoqinglong Decoction in the Treatment of Allergic Rhinitis.

INTRODUCTION: As one of the most common allergic diseases, allergic rhinitis (AR) has attracted wide attention all over the world. More appropriate treatment of AR should be explored thoroughly. In recent years, traditional Chinese medicine has attracted more attention in AR treatment. As a classical Chinese medicine prescription, Xiaoqinglong decoction (XQLD) has been commonly used in treating AR. Even though its therapeutic effect on AR has been clinically confirmed, more molecular mechanism remains to be further investigated. Our research aimed to investigate the therapeutic mechanism of XQLD for AR management. METHODS: The study was evaluated in an ovalbumin sensitized mouse model and liquid chromatography-mass spectrometry was adopted to test the stability of XQLD's effective components. RESULTS: The results confirmed the stability and safety of the effective components of XQLD. XQLD significantly downregulated the expression of HDACs (HDAC1, HDAC3, and HDAC4) and Th2 inflammatory factors (IL4, IL5, and IL13) in AR mice. XQLD and the HDAC inhibitor JNJ-26481585 promoted the expression of epithelial tight junction proteins (claudin-1 and ZO-1) and decreased the expression of mucins (Muc5ac and Muc5b) in the nasal mucosa of AR mice. CONCLUSIONS: In conclusion, our findings present the beneficial effects of XQLD on AR and recovery of the nasal epithelium. We also identify the decreased HDAC as a potential target of XQLD for AR treatment. This study provides an important experimental proof for elucidating the therapeutic mechanism of XQLD.

Injectable immunomodulation-based porous chitosan microspheres/HPCH hydrogel composites as a controlled drug delivery system for osteochondral regeneration.

The inappropriate regenerated fibrous cartilage and subchondral bone of the injured chondral defect ultimately cause degeneration of the regenerated cartilage, which eventually leads to the failure of cartilage repair. In this study, we developed a macrophage-modulated and injectable 'building block' drug delivery system comprised of porous chitosan (CS) microspheres and hydroxypropyl chitin (HPCH) hydrogel, where the dimethyloxallyl glycine (DMOG) was encapsulated in the thermosensitive HPCH hydrogel (HD) while kartogenin (KGN) was conjugated on the porous CS microspheres (CSK-PMS). The developed HD/CSK-PMS composite scaffold effectively modulated the microenvironment at the defect site, achieved local macrophage M2 polarization and promoted cartilage regeneration. The fast-degradable HD favored hyaline cartilage regeneration, while the highly stable CSK-PMS supported the endochondral ossification and regenerated the subchondral bone. In vitro and in vivo evaluations revealed that the newly developed HD/CSK-PMS as a controlled drug delivery system could effectively create M2 macrophage microenvironment and orchestrate osteochondral (OC) regeneration. These findings indicate the importance of the immune microenvironment and subchondral bone for high-quality cartilage repair, and thus the immunomodulation-based hydrogel/PMS composite system could be a promising candidate for OC regeneration.

Biospired Janus Silk E-Textiles with Wet-Thermal Comfort for Highly Efficient Biofluid Monitoring.

Functionalized textiles capable of biofluid administration are favorable for enhancing the wet-thermal comfort of the wearer and healthcare performance. Herein, inspired by the Janus wettability of lotus leaf, we propose a skin-comfortable Janus electronic textile (e-textile) based on natural silk materials for managing and analysis of biofluid. Silk materials are chosen and modified as both a textile substrate and a sensing electrode due to its natural biocompatibility. The unidirectional biofluid behavior of such Janus silk substrate facilitates a comfortable skin microenvironment, including weakening the undesired wet adhesion (∼0 mN cm-2) and avoiding excessive heat or cold on the epidermis. We noninvasively analyze multiple targets of human sweat with less required liquid volume (∼5 µL) and a faster (2-3 min) response time based on the silk-based yarn electrode woven into the hydrophilic side of Janus silk. This work bridges the gap between physiological comfort and sensing technology using biomass-derived elements, presenting a new type of smart textiles for wet-thermal management and health monitoring.

Integrated Wound Recognition in Bandages for Intelligent Treatment.

The mismatch between irregular wounds and fixed dressings is an important but long-neglected problem in wound management, which may cause imprecise or incomplete care outcomes. Continuous advances in the internet, Internet of Things, and materials science put forward higher requirements in precise wound treatment. Herein, an integrated wound recognition strategy is demonstrated by extracting digital geometric information of specific irregular wounds. Such online wound image scanning and recognition integrated with offline intelligent material fabrication can greatly reduce incomplete wound closure or potential irritation toward normal tissue around the wound site. As a proof-of-concept, an active matrix of Ag-modified gelatin on bandages demonstrates promising antibacterial properties for practical application. In vivo mouse experiment reveals that wound-customized bands enable precisely fitting in the irregular wound bed, resulting in accelerating wound healing efficiency. Such wound recognitions in a bandage involve multidisciplinary technology including image identification, computer modeling nanomaterial fabrication and modification, presenting a broad potential of personalized wound healthcare for a wide variety of clinical applications.

Droplet array for open-channel high-throughput SERS biosensing.

Open-channel and high throughput are two important aspects of clinical diagnosis, correlation biochemical analysis, cell culture techniques and food safety. Here, we propose the mini-pillar based array for open-channel and high-throughput SERS detection of miRNA. The polydimethylsiloxane (PDMS) mini-pillars are used as a high-throughput platform, which have good anchoring and aggregation effects on microdroplets, greatly reducing the amount of analytical solution and facilitate the homogeneous sample distribution after evaporation. The deposited gold nanorods (Au NRs) on the pillars with optimized diameter served as SERS-active substrate, can greatly improve the sensitivity of SERS signal compared to other planar substrates. On the open-channel biological chip, sensitive, simultaneous, and specific detection of breast cancer marker miRNA-1246 can be performed. In this mini-pillar array SERS system, the limit of detection (LOD) is 10-12 M. The mini-pillar array shows enormous potential for open channel, high-throughput biomolecular detection, providing an opportunity for biomedical point-of-care testing (POCT) and drug screening.

Integrated Smart Janus Textile Bands for Self-Pumping Sweat Sampling and Analysis.

Wearable sweat sensors have spearheaded the thrust toward personalized health monitoring with continuous, real-time, and molecular-level insight in a noninvasive manner. However, effective sweat sampling still remains a huge challenge. Here, we introduce an intelligent Janus textile band that bridges the gap between self-pumping sweat collection, comfortable epidemic microclimate, and sensitive electrochemical biosensing via an integrated wearable platform. The dominant sweat sampling configuration is a textile with Janus wettability, which is fabricated by electrospinning a hydrophobic polyurethane (PU) nanofiber array onto superhydrophilic gauze. Based on a contact-pumping model, the Janus textile can unidirectionally and thoroughly transport sweat from skin (hydrophobic side) to embedded electrode surface (hydrophilic side) with epidemic comfort. On-body experimentation reveals that the sensitive detection of multiple biomarkers including glucose, lactate, K+, and Na+ is achieved in the pumped sweat. Such smart Janus textile bands can effectively drain epidermal sweat to targeted assay sites via interface modifications, representing a reinforced and controlled biofluids analysis pathway with physiological comfort.

Microdroplet-captured tapes for rapid sampling and SERS detection of food contaminants.

Simple, effective, and rapid detection of chemically relevant hazards is a highly desirable research goal, which can provide early-warning information to improve the patient-care outcomes for public health. Here, we introduce a microdroplet-captured tape toward rapid SERS screening of food contaminants. The dominant sensing unit lies on functionalized microwell in conductive carbon tapes, which is simply prepared by physical punching, magnetron sputtering and electrochemical deposition of Au nanodendrites. The tape-based sensors not only possess highly branched Au nanodendrites in microwell for promoting SERS activity, but also enable anchoring the microdroplets via direct dip-pulling from pristine analytes solutions upon sticky incorporated on a glove. Early-warning SERS detection of food contaminants including Sudan-1, thiram, and thiabendazole from the real samples can be achieved by such simple sampling method. These tape-based sensors with a facile operation module and accessible signal read-out represent an innovative point-of-care testing (POCT) device for forensic, military, consumer protection, environmental monitoring, and food safety applications.

Flexible and Superwettable Bands as a Platform toward Sweat Sampling and Sensing.

Wearable biosensors as a user-friendly measurement platform have become a rapidly growing field of interests due to their possibility in integrating traditional medical diagnostics and healthcare management into miniature lab-on-body analytic devices. This paper demonstrates a flexible and skin-mounted band that combines superhydrophobic-superhydrophilic microarrays with nanodendritic colorimetric biosensors toward in situ sweat sampling and analysis. Particularly, on the superwettable bands, the superhydrophobic background could confine microdroplets into superhydrophilic microwells. On-body investigations further reveal that the secreted sweat is repelled by the superhydrophobic silica coating and precisely collected and sampled onto the superhydrophilic micropatterns with negligible lateral spreading, which provides an independent "vessel" toward cellphone-based sweat biodetection (pH, chloride, glucose and calcium). Such wearable, superwettable band-based biosensors with improved interface controllability could significantly enhance epidemical sweat sampling in well-defined sites, holding a great promise for facile and noninvasive biofluids analysis.

Flexible Superwettable Tapes for On-Site Detection of Heavy Metals.

Bioinspired superwettable micropatterns that combine superhydrophobicity and superhydrophilicity have been proved to exhibit outstanding capacity in controlling and patterning microdroplets and possessed new functionalities and possibilities in emerging sensing applications. Here, we introduce a flexible tape-based superhydrophilic-superhydrophobic tape toward on-site heavy metals monitoring. On such a superwettable tape, capillarity-assisted superhydrophilic microwells allow directly anchoring indicators in fixed locations and sampling into a test zone via simple dip-pull from an origin specimen solution. In contrast, the superhydrophobic substrate could confine the microdroplets in the superhydrophilic microwells for reducing the amount of analytical solution. The tape-based microchip also displays excellent flexibility against stretching, bending, and torquing for expanding wearable and portable sensing devices. Qualitative and quantitative colorimetric assessments of multiplex heavy metal analyses (chromium, copper, and nickel) by the naked eye are also achieved. The superwettable tape-based platforms with a facile operation mode and accessible signal read-out represent unrevealed potential for on-site environmental monitoring.