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A unique subpopulation of mesenchymal stem cells (MSCs) has been isolated and characterized from human gingival tissues (GMSCs). Similar to MSCs derived from other sources of tissues, e.g. bone marrow, adipose or umbilical cord, GMSCs also possess multipotent differentiation capacities and potent immunomodulatory effects on both innate and adaptive immune cells through the secretion of various types of bioactive factors with immunosuppressive and anti-inflammatory functions. Uniquely, GMSCs are highly proliferative and have the propensity to differentiate into neural cell lineages due to the neural crest-origin. These properties have endowed GMSCs with potent regenerative and therapeutic potentials in various preclinical models of human disorders, particularly, some inflammatory and autoimmune diseases, skin diseases, oral and maxillofacial disorders, and peripheral nerve injuries. All types of cells release extracellular vesicles (EVs), including exosomes, that play critical roles in cell-cell communication through their cargos containing a variety of bioactive molecules, such as proteins, nucleic acids, and lipids. Like EVs released by other sources of MSCs, GMSC-derived EVs have been shown to possess similar biological functions and therapeutic effects on several preclinical diseases models as GMSCs, thus representing a promising cell-free platform for regenerative therapy. Taken together, due to the easily accessibility and less morbidity of harvesting gingival tissues as well as the potent immunomodulatory and anti-inflammatory functions, GMSCs represent a unique source of MSCs of a neural crest-origin for potential application in tissue engineering and regenerative therapy.

Flavonoids are major active small-molecule compounds in bamboo leaves, which can be easily obtained from the bamboo leaves extraction residues (BLER) after the polysaccharides extraction. Six macroporous resins with different properties were screened to prepare and enrich isoorientin (IOR), orientin (OR), vitexin (VI), and isovitexin (IVI) from BLER, and the XAD-7HP resin with the best adsorption and desorption performance was selected for further evaluation. Based on the static adsorption experiments, the experimental results showed that the adsorption isotherm fitted well with the Langmuir isotherm model, and the adsorption process was better explained by the pseudo-second-order kinetic model. After the dynamic trial of resin column chromatography, 20 bed volume (BV) of upload sample and 60% ethanol as eluting solvent was used in a lab scale-up separation, and the results demonstrated that the content of four flavonoids could be increased by 4.5-fold, with recoveries between 72.86 and 88.21%. In addition, chlorogenic acid (CA) with purity of 95.1% was obtained in water-eluted parts during dynamic resin separation and further purified by high-speed countercurrent chromatography (HSCCC). In conclusion, this rapid and efficient method can provide a reference to utilize BLER to produce high-value-added food and pharmaceutical products.

Photodynamic nanodrugs (PDNS) have demonstrated significant advantages in enhancing therapeutic outcomes while reducing systemic toxicity, achieved primarily through optimized photosensitizer solubility, targeted biodistribution, and site-specific accumulation. This review systematically examines recent progress and future directions of PDNS development, encompassing fundamental research to clinical translation. Specifically, it analyzes the composition, mechanisms of action, inherent advantages, clinical applications, as well as the challenges faced in this domain. The introduction of nanocarriers has circumvented the limitations of the core photosensitizers, substantially enhancing the efficacy and safety of PDNS via targeted delivery and synergistic therapy. Moreover, the integration of stimuli-responsive and multifunctional nanoplatforms has further improved the spatiotemporal control of reactive oxygen species (ROS) generation, thereby minimizing off-target effects. In addition, the combination of PDNS with immunotherapy has exhibited synergistic effects, underscoring the potential of this integrated approach. PDNS has made remarkable progress in cancer treatment through receptor-mediated endocytosis, self-assembly, and precise targeting. Beyond cancer treatment, PDNS holds considerable promise in treating a diverse array of non-oncological diseases, such as acne, psoriasis, dry eye disease, and cardiovascular disorders, et al. In this regard, PDNS has emerged as a pivotal component within the realm of personalized medicine. Despite these notable advancements, challenges persist in optimizing drug delivery and achieving efficient clinical translation. Looking ahead, future perspectives encompass the development of highly efficient photosensitizers and ensuring accurate nanocarrier delivery, which will undoubtedly facilitate the progress of PDNS in the clinical application field.

Surgical intervention is a crucial treatment for hepatic cystic echinococcosis. However, the choice between radical and conservative surgery remains controversial. This study aimed to compare the perioperative outcomes and hospitalization costs between radical and conservative surgery for hepatic cystic echinococcosis. A retrospective cohort study was conducted on patients undergoing surgical treatment at the First People's Hospital of Kashi Prefecture from July 1, 2012, to October 1, 2023. Propensity score-matching analysis was utilized to mitigate patient selection bias between the two surgical groups. Of the 434 patients included, 324 underwent conservative surgery and 110 underwent radical surgery. After propensity score-matching, 182 conservative surgery and 102 radical surgery patients were compared. Radical surgery patients experienced longer operative time, higher intraoperative blood loss, increased blood transfusion, and higher costs compared to conservative surgery patients. However, no differences were observed in short-term outcomes, including overall morbidity, death, bile leak, effusion, pulmonary infection, incision infection, intestinal obstruction, ICU stay, abdominal drainage time, and postoperative hospital stays. This study suggests that radical surgery is associated with greater surgical complexity and higher hospitalization costs, while it doesn't offer a significant short-term advantage. Conservative surgery may be a viable option in resource-limited settings or for patients unsuitable for complex procedures. Further research with long-term follow-up is needed to determine the optimal approach.

Background Accumulating evidence demonstrates that the therapeutic effects of stem cells are most likely attributed to their secretome, composed of a myriad of bioactive factors, including small extracellular vesicles (EVs). Due to the potential benefits over cells in term of handling, preservation, stability, and safety, MSC-derived secretome is emerging as a novel cell-free therapeutic for regenerative therapy of various diseases. The purpose of this study is to optimize the xeno-free culture conditions to improve the secretome production by human gingiva-derived mesenchymal stem cells (GMSCs) and test their regenerative potential using an experimental rat model of tongue muscle defect. Methods Next-generation mRNA sequencing was performed to compare the gene expression profiles between GMSCs cultured under the defined xeno-free induction culture conditions (iGMSCs) and their 2D-cultured counterparts under regular serum-free conditions. The conditioned media (CM) from iGMSCs and 2D-GMSCs were harvested and concentrated through ultrafiltration to obtain secretomes. The EVs and soluble protein/peptide factor fractions (SPs) from the concentrated CM/secretome were separated using the 35 nm qEVoriginal size exclusion columns. The EVs were confirmed by Nanoparticle Tracking Analysis (NTA), Western blot, and transmission electron microscopy (TEM). The functional effects of secretomes derived from iGMSCs and 2D-GMSCs on macrophage polarization and skeletal muscle progenitor cells were compared both in vitro and in vivo using a rat tongue defect model. Results Next-generation mRNA sequencing showed profound transcriptomic changes in iGMSCs compared to their 2D counterparts. Further Gene Ontology (GO)-term annotation and Gene Set Enrichment Analysis (GSEA) revealed significant upregulation of a panel of differentially expressed genes (DEGs) related to EVs and secreted cellular components (GO_CCs) and enriched pathways in oxidative phosphorylation, Wnt/β-catenin signaling, Notch signaling, and inflammatory responses in iGMSCs compared to 2D-GMSCs. iGMSC-derived CM/secretome showed a significant enrichment of both EVs and SPs compared to that derived from 2D-GMSCs, as confirmed by Nanoparticle Tracking Analysis (NTA), Western blot, and transmission electron microscopy (TEM). In vitro functional assays revealed a markedly enhanced secretion of IL-10, whilst suppressed LPS-stimulated secretion of TNF-α in macrophages treated with iGMSC-derived CM/secretome in comparison with that from 2D-GMSCs. In addition, iGMSC-derived CM/secretome potently induced the expression of myogenic transcriptional factors in both murine myoblasts and human skeletal muscle progenitors in comparison with 2D-GMSC-derived CM/secretome. Notably, in vivo studies using a rat tongue wound defect model, iGMSC-derived CM/secretome applied topically at the excised wound bed promoted rapid tissue repair/regeneration without fibrosis/scar and shape deformity. Conclusion Secretome derived from GMSCs cultured under optimized xeno-free induction displayed enrichment of EVs and SPs and enhanced pro-myogenic potentials and anti-inflammatory effect on macrophages. These findings have shed light on the potential applications of the optimized iGMSC-derived secretome as cell-free therapeutics for regenerative therapy of tongue wound defects and other muscular diseases. Graphical Abstract

The demand for highly functional chemical gas sensors has surged in response to critical needs such as health monitoring, protection against harmful gases, and assessment of food freshness. Over the past few decades, various chemiresistive gas sensors have been developed, exhibiting considerable sensitivity to a range of gases. However, their performance remains constrained by notable drawbacks, including elevated operating temperatures, inadequate sensitivity, and poor selectivity. In recent years, perovskite materials have garnered substantial attention due to their exceptional chemical and physical properties-such as a high absorption coefficient, low ionic binding energy, tunable bandgap, and high carrier mobility. Concurrently, significant strides have been made in leveraging both organic and inorganic perovskite-based sensors for detecting environmental gases. This review provides a comprehensive overview of the recent advancements in perovskite-based gas sensors, systematically analyzing the field from material design and engineering to device applications. We dissect the critical influence of perovskite crystal structures and micro/nano-architectures on key performance metrics such as sensitivity, selectivity, response/recovery time, and stability. The applications of these materials in detecting a wide array of hazardous gases-including H S, NH , NOx, CO/CO , and various volatile organic compounds (VOCs)-are thoroughly examined, with representative examples and underlying sensing mechanisms discussed in detail. However, the path to commercialization is obstructed by persistent challenges of instability, selectivity, and the severe environmental and health risks of lead. This has catalyzed a major research thrust towards non-toxic, lead-free perovskites. Consequently, the field is pivoting towards lead-free perovskites. This analysis underscores that synergistic innovation in lead-free material science and device engineering is critical to overcoming current barriers, paving the way for the development of robust, high-performance, and commercially viable gas sensors that align with global sustainability goals.

Non-genetic induction of somatic cells into neural crest stem-like cells (NCSCs) is promising for potential cell-based therapies for post-traumatic peripheral nerve regeneration. Here, we report that human gingiva-derived mesenchymal stem cells (GMSCs) could be reproducibly and readily induced into NCSCs via non-genetic approaches. Compared to parental GMSCs, induced NCSC population had increased expression in NCSC-related genes and displayed robust differentiation into neuronal and Schwann-like cells. Knockdown of the expression of Yes-associated protein 1 (YAP1), a critical mechanosensor and mechanotransducer, attenuated the expression of NCSC-related genes; specific blocking of RhoA/ROCK activity and non-muscle myosin II (NM II)-dependent contraction suppressed YAP1 and NCSC-related genes and concurrently abolished neural spheroid formation in NCSCs. Using a rat model of facial nerve defect, implantation of NCSC-laden nerve conduits promoted functional regeneration of the injured nerve. These promising findings demonstrate that induced NCSCs derived from GMSCs represent an easily accessible and promising source of neural stem-like cells for peripheral nerve regeneration.

Regeneration of peripheral nerve injury remains a major clinical challenge. Recently, mesenchymal stem cells (MSCs) have been considered as potential candidates for peripheral nerve regeneration; however, the underlying mechanisms remain elusive. Here, we show that human gingiva‐derived MSCs (GMSCs) could be directly induced into multipotent NPCs (iNPCs) under minimally manipulated conditions without the introduction of exogenous genes. Using a crush‐injury model of rat sciatic nerve, we demonstrate that GMSCs transplanted to the injury site could differentiate into neuronal cells, whereas iNPCs could differentiate into both neuronal and Schwann cells. After crush injury, iNPCs, compared with GMSCs, displayed superior therapeutic effects on axonal regeneration at both the injury site and the distal segment of the injured sciatic nerve. Mechanistically, transplantation of GMSCs, especially iNPCs, significantly attenuated injury‐triggered increase in the expression of c‐Jun, a transcription factor that functions as a major negative regulator of myelination and plays a central role in dedifferentiation/reprogramming of Schwann cells into a progenitor‐like state. Meanwhile, our results also demonstrate that transplantation of GMSCs and iNPCs consistently increased the expression of Krox‐20/EGR2, a transcription factor that governs the expression of myelin proteins and facilitates myelination. Altogether, our findings suggest that transplantation of GMSCs and iNPCs promotes peripheral nerve repair/regeneration, possibly by promoting remyelination of Schwann cells mediated via the regulation of the antagonistic myelination regulators, c‐Jun and Krox‐20/EGR2. Stem Cells Translational Medicine 2017;6:458–470

m-Difluorobenzene is an important structural in many pharmaceutical agents and nature products. However, the conventional method of preparing m-difluorobenzene, which was adopts double diazotization from m-phenylenediamine, is very tricky with potential hazards associated with the strongly exothermic and thermal instability of the diazonium intermediate, and has severe coupled side reactions. Here, we report the continuous-flow methodology, which effectively addresses this series of process challenges by an extra inert solvent flow. The protocol rapidly synthesize m-Difluorobenzene with 85% total yield (the traditional method has 65% total yield). The molar ratio of hydrochloric acid used in the process deduce to 3.6 equivalent (traditional method requires 12 equivalent). Furthermore, the reaction time can be decreased from hours to within 40 s. Above all, the method has potential industrial application value.Graphical abstract