Dynamic interplay of metal and metal oxide nanoparticles with plants: Influencing factors, action mechanisms, and assessment of stimulatory and inhibitory effects.

Nanoparticles (NPs) of metals and metal oxides have received increasing attention regarding their characteristic behavior in plant systems. The fate and transport of metal NPs and metal oxide NPs in plants is of emerging concern for researchers because they ultimately become part of the food chain. The widespread use of metal-based NPs (MBNPs) in plants has revealed their beneficial and harmful effects. This review addresses the main factors affecting the uptake, translocation, absorption, bioavailability, toxicity, and accumulation of MBNPs in different plant species. It appraises the mechanism of nanoparticle-plant interaction in detail and provides understanding of the estimation strategies for the associated pros and cons with this interplay. Critical parameters of NPs include, but are not limited to, particle size and shape, surface chemistry, surface charge, concentration, solubility, and exposure route. On exposure to MBNPs, the molecular, physiological, and biochemical reactions of plants have been assessed. We have filled knowledge gaps and answered research questions regarding the positive and negative effects of metal and metal oxide NPs on seed germination, callus induction, growth and yield of plant, nutritional content, antioxidants, and enzymes. Besides, the phytotoxicity, cytotoxicity, genotoxicity, and detoxification studies of MBNPs in plants have been outlined. Furthermore, the recent developments and future perspectives of the two-way traffic of interplay of MBNPs and plants have been provided in this comprehensive review.

Early pigment spot segmentation and classification from iris cellular image analysis with explainable deep learning and multiclass support vector machine.

Globally, retinal disorders impact thousands of individuals. Early diagnosis and treatment of these anomalies might halt their development and prevent many people from developing preventable blindness. Iris spot segmentation is critical due to acquiring iris cellular images that suffer from the off-angle iris, noise, and specular reflection. Most currently used iris segmentation techniques are based on edge data and noncellular images. The size of the pigment patches on the surface of the iris increases with eye syndrome. In addition, iris images taken in uncooperative settings frequently have negative noise, making it difficult to segment them precisely. The traditional diagnosis processes are costly and time consuming since they require highly qualified personnel and have strict environments. This paper presents an explainable deep learning model integrated with a multiclass support vector machine to analyze iris cellular images for early pigment spot segmentation and classification. Three benchmark datasets MILE, UPOL, and Eyes SUB were used in the experiments to test the proposed methodology. The experimental results are compared on standard metrics, demonstrating that the proposed model outperformed the methods reported in the literature regarding classification errors. Additionally, it is observed that the proposed parameters are highly effective in locating the micro pigment spots on the iris surfaces.

Synthesis, biomedical applications, and toxicity of CuO nanoparticles.

Versatile nature of copper oxide nanoparticles (CuO NPs) has made them an imperative nanomaterial being employed in nanomedicine. Various physical, chemical, and biological methodologies are in use for the preparation of CuO NPs. The physicochemical and biological properties of CuO NPs are primarily affected by their method of fabrication; therefore, selectivity of a synthetic technique is immensely important that makes these NPs appropriate for a specific biomedical application. The deliberate use of CuO NPs in biomedicine questions their biocompatible nature. For this reason, the present review has been designed to focus on the approaches employed for the synthesis of CuO NPs; their biomedical applications highlighting antimicrobial, anticancer, and antioxidant studies; and most importantly, the in vitro and in vivo toxicity associated with these NPs. This comprehensive overview of CuO NPs is unique and novel as it emphasizes on biomedical applications of CuO NPs along with its toxicological assessments which would be useful in providing core knowledge to researchers working in these domains for planning and conducting futuristic studies. KEY POINTS: • The recent methods for fabrication of CuO nanoparticles have been discussed with emphasis on green synthesis methods for different biomedical approaches. • Antibacterial, antioxidant, anticancer, antiparasitic, antidiabetic, and antiviral properties of CuO nanoparticles have been explained. • In vitro and in vivo toxicological studies of CuO nanoparticles exploited along with their respective mechanisms.

Gingival mesenchymal stem cell-derived exosomes are immunosuppressive in preventing collagen-induced arthritis.

Due to the unsatisfied effects of clinical drugs used in rheumatoid arthritis (RA), investigators shifted their focus on the biotherapy. Although human gingival mesenchymal stem cells (GMSC) have the potential to be used in treating RA, GMSC-based therapy has some inevitable side effects such as immunogenicity and tumorigenicity. As one of the most important paracrine mediators, GMSC-derived exosomes (GMSC-Exo) exhibit therapeutic effects via immunomodulation in a variety of disease models, bypassing potential shortcomings of the direct use of MSCs. Furthermore, exosomes are not sensitive to freezing and thawing, and can be readily available for use. GMSC-Exo has been reported to promote tissue regeneration and wound healing, but have not been reported to be effective against autoimmune diseases. We herein compare the immunomodulatory functions of GMSC-Exo and GMSC in collagen-induced arthritis (CIA) model and in vitro CD4+ T-cell co-culture model. The results show that GMSC-Exo has the same or stronger effects compared with GMSC in inhibiting IL-17A and promoting IL-10, reducing incidences and bone erosion of arthritis, via inhibiting IL-17RA-Act1-TRAF6-NF-κB signal pathway. Our results suggest that GMSC-Exo has many advantages in treating CIA, and may offer a promising new cell-free therapy strategy for RA and other autoimmune diseases.

Influence of calcium and magnesium elimination on plant biomass and secondary metabolites of Stevia rebaudiana Bertoni.

This study reports the increment in the secondary metabolites in Stevia rebaudiana plant after exposure to the elimination of Ca and Mg from Murashige and Skoog culture medium. The effect of nutrient stress on regenerants of S. rebaudiana is measured, which reveals significantly enhanced growth parameters, steviol glycosides (SGs) content, and nonenzymatic antioxidants; total phenolic content, total flavonoid content, total antioxidant capacity, total reducing power, and DPPH-free radical scavenging activity as compared with the control treatment. However, significantly highest amounts are obtained in a medium with only Ca deficiency. The amount of rebaudioside A (Reb A) and stevioside (ST) obtained in the case of Ca-deficient medium is 4.08 and 0.69%, respectively. It is followed by the results obtained from both Ca- and Mg-deprived medium [Reb A (3.23%) and ST (0.52%)] and the lowest values are obtained from medium lacking Mg only [Reb A (2.60%) and ST (0.40%)]. The most probable adaptation mechanism might be the production of reactive oxygen species by nutrients' stress, which results in secondary metabolites production as defensive moieties to overcome stress situation. This effective protocol needs to be refined to apply on an industrial scale in bioreactors for increasing quantities of commercially important pharmaceutical compounds.

Co-exposure of polystyrene microplastics and iron aggravates cognitive decline in aging mice via ferroptosis induction.

The objective of this study was to investigate the effects of co-exposure of iron and microplastics (MPs) on the cognitive function of aged humans and animals. It was already known that individual iron or MPs exposure can initiate potential neurotoxicity. However, the combined effect of MPs and iron remained to be elucidated. In this study, the toxicity of iron, MPs, co-treatment of MPs & iron, and the underlying mechanisms were evaluated in vivo. Our findings suggest that 5 µm MPs could enter the aging mice brain and accumulate in cortex and hippocampus. In addition, MPs and iron have a good binding ability, therefore, co-exposure of MPs & iron cause significant iron overload and cognitive deficits as compared to control and individual treatments of iron and MPs. Moreover, the lipid peroxidation and inflammation, which are involved in ferroptosis, get significantly elevated by co-exposure of iron and MPs. Taken together, our results provide compelling evidence that co-exposure of iron and MPs could aggravate the cognitive impairment via disturbing brain iron homeostasis and inducing ferroptosis in cognitive-related brain areas, what's more, the results warn that MPs may act as vectors of pollutants (mostly heavy metals) increasing the health burden on body.

Significance of Capping Agents of Colloidal Nanoparticles from the Perspective of Drug and Gene Delivery, Bioimaging, and Biosensing: An Insight.

The over-growth and coagulation of nanoparticles is prevented using capping agents by the production of stearic effect that plays a pivotal role in stabilizing the interface. This strategy of coating the nanoparticles' surface with capping agents is an emerging trend in assembling multipurpose nanoparticles that is beneficial for improving their physicochemical and biological behavior. The enhancement of reactivity and negligible toxicity is the outcome. In this review article, an attempt has been made to introduce the significance of different capping agents in the preparation of nanoparticles. Most importantly, we have highlighted the recent progress, existing roadblocks, and upcoming opportunities of using surface modified nanoparticles in nanomedicine from the drug and gene delivery, bioimaging, and biosensing perspectives.

Role of capping agents in the application of nanoparticles in biomedicine and environmental remediation: recent trends and future prospects.

Capping agents are of utmost importance as stabilizers that inhibit the over-growth of nanoparticles and prevent their aggregation/coagulation in colloidal synthesis. The capping ligands stabilize the interface where nanoparticles interact with their medium of preparation. Specific structural features of nanoparticles are attributed to capping on their surface. These stabilizing agents play a key role in altering the biological activities and environmental perspective. Stearic effects of capping agents adsorbed on the surface of nanoparticles are responsible for such changing physico-chemical and biological characteristics. Firstly, this novel review article introduces few frequently used capping agents in the fabrication of nanoparticles. Next, recent advancements in biomedicine and environmental remediation approaches of capped nanoparticles have been elaborated. Lastly, future directions of the huge impact of capping agents on the biological environment have been summarized.

Engineered ZnO and CuO Nanoparticles Ameliorate Morphological and Biochemical Response in Tissue Culture Regenerants of Candyleaf (Stevia rebaudiana).

Sustainable production of secondary metabolites in medicinal plants by artificial culturing on the industrial scale has gained worldwide importance. Engineered nanoparticles (ENPs) play a pivotal role in the elicitation of compounds of medicinal value. This investigation explores the influence of ZnO and CuO ENPs on in vitro roots formation, non-enzymatic antioxidant activities, and production of steviol glycosides (SGs) in regenerants of Candyleaf, Stevia rebaudiana. ENPs were applied in 0, 2, 20, 200, and 2000 mg/L of concentration in the MS medium containing plant shoots. The percentage of rooting induced was 91% and 94% by applying ZnO ENPs (2 mg/L) and CuO ENPs (20 mg/L), respectively. Moreover, at 2 mg/L of ZnO and 20 mg/L of CuO ENPs, the high performance liquid chromatography studies determined the significantly greatest content of SGs; rebaudioside A (4.42 and 4.44) and stevioside (1.28 and 1.96). Phytochemical studies including total flavonoid content, total phenolic content, and 2,2-diphenyl-1-picryl hydrazyl-free radical scavenging activity were calculated highest by the regenerants grown in 2 mg/L of ZnO and 20 mg/L of CuO ENPs dosage. Both ZnO and CuO ENPs at 200 mg/L and 2000 mg/L of concentration induced adverse effects on plant biomass, antioxidant activities, and SGs content up to 1.22 and 1.77 for rebaudioside A and 0.21 and 0.25 for stevioside. Hence, the biochemical and morphophysiological responses of Candyleaf were elicited as a defense against ZnO and CuO ENPs applied under threshold limit. This artificial biotechnological technique holds great promise for continued production of natural antioxidants on commercial scale and our study has further strengthened this impact.

Modulation of callus growth and secondary metabolites in different Thymus species and Zataria multiflora micropropagated under ZnO nanoparticles stress.

Thymus species are aromatic plants with diverse applications in food industries and medicine. This study was conducted to evaluate the potential effect of ZnO nanoparticles (NPs) on callus proliferation and thymol and carvacrol production in three Thymus species, that is, T. vulgaris, T. daenensis, and T. kotschyanus, and Zataria multiflora. For this purpose, callus induction was performed on Murashige and Skoog (MS) medium containing different plant growth regulators (PGRs). After optimization of callus growth, the effects of different concentrations of ZnO NPs (100 and 150 mg L-1 ) were investigated. MS containing 2 mg L-1 of 2, 4-dichlorophenoxy acetic acid (2,4-D) and 1 mg L-1 of kinetin (Kin) revealed significantly highest fresh weight (0.18 g) of callus in T. kotschyanus. Callus growth rate (0.079 mm day-1 ) was found highest in T. vulgaris under similar conditions. Moreover, highest callus induction (92.50%) was achieved by T. kotschyanus in MS containing 2.5 mg L-1 of 2,4-D. Regarding the highest content of thymol (22.8 mg L-1 ) and carvacrol (0.68 mg L-1 ) evaluated by high-performance liquid chromatography, best results were achieved under 150 mg L-1 of ZnO NPs in T. kotschyanus and T. daenesis, respectively. This is simple and cost-effective method to be applied on industrial level for production of enhanced secondary metabolites content.

Appraisal of Comparative Therapeutic Potential of Undoped and Nitrogen-Doped Titanium Dioxide Nanoparticles.

Nitrogen-doped and undoped titanium dioxide nanoparticles were successfully fabricated by simple chemical method and characterized using x-ray diffraction (XRD), scanning electron microscopy (SEM), energy dispersive x-ray (EDX), and transmission electron microscopy (TEM) techniques. The reduction in crystalline size of TiO2 nanoparticles (from 20-25 nm to 10-15 nm) was observed by TEM after doping with N. Antibacterial, antifungal, antioxidant, antidiabetic, protein kinase inhibition and cytotoxic properties were assessed in vitro to compare the therapeutic potential of both kinds of TiO2 nanoparticles. All biological activities depicted significant enhancement as a result of addition of N as doping agent to TiO2 nanoparticles. Klebsiella pneumoniae has been illuminated to be the most susceptible bacterial strain out of various Gram-positive and Gram-negative isolates of bacteria used in this study. Good fungicidal activity has been revealed against Aspergillus flavus. 38.2% of antidiabetic activity and 80% of cytotoxicity has been elucidated by N-doped TiO2 nanoparticles towards alpha-amylase enzyme and Artemia salina (brine shrimps), respectively. Moreover, notable protein kinase inhibition against Streptomyces and antioxidant effect including reducing power and % inhibition of DPPH has been demonstrated. This investigation unveils the more effective nature of N-doped TiO2 nanoparticles in comparison to undoped TiO2 nanoparticles indicated by various biological tests. Hence, N-doped TiO2 nanoparticles have more potential to be employed in biomedicine for the cure of numerous infections.

Hypoplastic Left Heart Syndrome: An Overview for Primary Care Providers.

Hypoplastic left heart syndrome is one of the most complex congenital heart diseases and requires several cardiac surgeries for survival. The diagnosis is usually established prenatally or shortly after birth. Each stage of surgery poses a unique hemodynamic situation that requires deeper understanding to manage common pediatric problems such as dehydration and respiratory infections. Careful multidisciplinary involvement in the care of these complex patients is improving their outcome; however, morbidity and mortality are still substantial. In this review, we focus on the hemodynamic aspects of various surgical stages that a primary care provider should know to manage these challenging patients.

Wound healing applications of biogenic colloidal silver and gold nanoparticles: recent trends and future prospects.

Nanotechnology has emerged as a prominent scientific discipline in the technological revolution of this millennium. The scientific community has focused on the green synthesis of metal nanoparticles as compared to physical and chemical methods due to its eco-friendly nature and high efficacy. Medicinal plants have been proven as the paramount source of various phytochemicals that can be used for the biogenic synthesis of colloidal silver and gold nanoparticles as compared to other living organisms, e.g., microbes and fungi. According to various scientific reports, the biogenic nanoparticles have shown promising potential as wound healing agents. However, not a single broad review article was present that demonstrates the wound healing application of biogenic silver and gold nanoparticles. Foreseeing the overall literature published, we for the first time intended to discuss the current trends in wound healing via biogenic silver and gold nanoparticles. Furthermore, light has been shed on the mechanistic aspects of wound healing along with futuristic discussion on the faith of biogenic silver and gold nanoparticles as potential wound healing agents.

Pediatric Quadricuspid Aortic Valve: Morphology, Characteristics, Clinical Outcomes, and Literature Review.

BACKGROUND: Quadricuspid aortic valve (QAV) is an exceedingly rare congenital heart defect (CHD) which has not been well-defined in a pediatric population. METHODS: The Mayo Clinic echocardiography database was retrospectively analyzed to identify patients ≤18 years diagnosed with QAV from January 1990 to December 2023. Patients with truncus arteriosus were excluded. All images were independently reviewed to define morphology of the QAV by using the Hurwitz and Roberts classification. RESULTS: Fourteen patients with QAV were identified with a median age at time of diagnosis being 10.5 years (interquartile range [IQR] 6-14 years). Male-to-female ratio was 3:1. Associated CHDs were present in 50% (n = 7) patients. The most common morphological subtypes of QAV were Type D in 43% (n = 6) and Type B in 29% (n = 4). Aortic regurgitation was the most frequently associated valvular abnormality affecting 86% (n = 12) cases, with greater than moderate regurgitation in only two patients. Aortic valve stenosis was observed in 14% (n = 2) patients. Ascending aortic dilatation was present in 21% (3/14) of the cohort, but only 14% (1/7) of isolated QAV patients. At a mean follow up of 11 ± 6.6 years and a median follow-up age of 22 years (IQR 14-27 years), survival was 100% with no primary interventions on the aortic valve or aorta. However, four patients required surgical interventions for associated CHDs. CONCLUSION: Among children with QAV, almost half of the patients had additional CHD. Aortic regurgitation was the predominant hemodynamic abnormality. Long-term survival was excellent with minimal progression during childhood and adolescence.

Nanotoxicity assessment in plants: an updated overview.

Nanotechnology is rapidly emerging and innovative interdisciplinary field of science. The application of nanomaterials in agricultural biotechnology has been exponentially increased over the years that could be attributed to their uniqueness, versatility, and flexibility. The overuse of nanomaterials makes it crucial to determine their fate and distribution in the in vitro (in cell and tissue cultures) and in vivo (in living species) biological environments by investigating the nano-biointerface. The literature states that the beneficial effects of nanoparticles come along with their adverse effects, subsequently leading to an array of short-term and long-term toxicities. It has been evident that the interplay of nanoparticles with abiotic and biotic communities produces several eco-toxicological effects, and the physiology and biochemistry of crops are greatly influenced by the metabolic alterations taking place at cellular, sub-cellular, and molecular levels. Numerous risk factors affect nanoparticle's accumulation, translocation, and associated cytogenotoxicity. This review article summarizes the contributing factors, possible mechanisms, and risk assessment of hazardous effects of various types of nanoparticles to plant health. The methods for evaluating the plant nanotoxicity parameters have been elaborated. Conclusively, few recommendations are put forward for designing safer, high-quality nanomaterials to protect and maintain environmental safety for smarter agriculture demanded by researchers and industrialists.

Biochemical and phytochemical responses of Ammi visnaga L. (Apiaceae) callus culture elicited by SiO2 and graphene Oxide-SiO2 nanoparticles.

Ammi visnaga L. is an enriched medicinal plant with medicinally important compounds. Two types of nanoparticles (NPs) including silica (SiO2) and graphene oxide bound with SiO2 (GO-SiO2) NPs at different concentrations (0, 15, 25 mg L-1) were used as elicitors to investigate their effects on callus morphology, H2O2 content, total phenolic content (TPC), total flavonoids content (TFC), ferric reducing/antioxidant power (FRAP), and few antioxidant enzymes such as catalase (CAT), guaiacol peroxidase (GPX), superoxide dismutase (SOD), ascorbate peroxidase (APX), and polyphenol oxidase (PPO) in the callus cultures of A. visnaga. The effects of elicitation of both NPs on calli were observed using a scanning electron microscope (SEM). The 15 mg L-1 concentration of GO-SiO2 NPs produced the highest TPC (193.3 mg GAE g-1 FW), CAT (13.1 U mg-1 Protein), GPX (0.0089 U mg-1 Protein), and APX (0.079 U mg-1 Protein). Whereas, the maximum content of H2O2 (0.68 µmol g-1 FW), FRAP (0.0092 µmol mg-1), and TFC (62.27 mg QE g-1 FW) was observed at 25 mg L-1 and 15 mg L-1 of SiO2 NPs, respectively. Conclusively, in the callus culture of A. visnaga, the 15 mg L-1 concentration of GO-SiO2 NPs was the most suitable dosage for enhancing the enzymatic antioxidant activities (CAT, GPX, APX) and TPC, rather than SiO2 NPs.

IAA-decorated CuO nanocarriers significantly improve Chickpea growth by increasing antioxidative activities.

Plant growth regulators tagged on metallic oxide nanoparticles (NPs) may function as nanofertilizers with reduced toxicity of NPs. CuO NPs were synthesized to function as nanocarriers of Indole-3-acetic acid (IAA). Powder X-ray diffraction (XRD) and scanning electron microscopy (SEM) revealed 30.4 nm size of NPs and sheet-like structure, respectively, of CuO-IAA NPs. Fourier-transform infrared spectroscopy (FTIR) confirmed CuO-IAA formation. IAA-decorated CuO NPs enhanced the physiological parameters of Chickpea plants, i.e., root length, shoot length, and biomass compared to naked CuO NPs. The variation in physiological response was due to change of phytochemical contents in plants. Phenolic content increased up to 17.98 and 18.13 µgGAE/mg DW at 20 and 40 mg/L of CuO-IAA NPs, respectively. However, significant decrease in antioxidant enzymes' activity was recorded compared to control. Presence of CuO-IAA NPs increased the reducing potential of plants at higher concentration of NPs, while decrease in total antioxidant response was observed. This study concludes that IAA conjugation to CuO NPs reduces toxicity of NPs. Furthermore, NPs can be explored as nanocarriers for plant modulators and slow release in future studies.

The Intensity and Pattern of Syndecan-1 (CD138) Expression in Normal and Diseased Livers.

Introduction Heparan sulfate proteoglycans (HSPGs) belong to the syndecan family, and syndecan-1 (CD138) is a heparan sulfate proteoglycan. Syndecan-1 has a potential role in cell-matrix and cell-cell communications as they are present in cell epithelium. Its expression is different in an extensive range of benign, inflammatory, and neoplastic diseases. In routine histopathology, it is used as a marker for plasma cells. However, it is expressed in a large variety of normal and neoplastic epithelia including squamous epithelium and gastric glandular epithelium expressed in other tissues, i.e., the liver. In the liver, variable expression is seen in cirrhosis, hepatitis, and carcinoma. The objective of this study was to investigate the expression of this marker in normal, inflammatory, and neoplastic lesions of the liver. This in turn may help clinicians to select patients who may benefit from anti-CD138 therapy. It is currently used in the diagnosis and management of plasma cell proliferations. Material and methods This is a retrospective study in which we retrieved 53 formalin-fixed paraffin-embedded (FFPE) liver specimen blocks and selected one block from each case by reviewing the hematoxylin and eosin (H&E) slides of each case. Syndecan-1 (CD138), pancytokeratin, and CD68 expression were analyzed immunohistochemically (IHC) to evaluate the percentage and intensity of CD138 expression in various hepatic entities and identify those entities where syndecan-1 can be consistently used to make a definitive diagnosis. Results The expression of pancytokeratin and CD68 was analyzed in hepatocytes and Kupffer cells, respectively. For syndecan-1 (CD138), 15.4% of cases showed basolateral membranous positivity, 44.6% of cases showed complete membranous positivity, and 40% of cases showed no positivity in hepatocytes. Cytokeratin (CK) was positive as expected in hepatocytes, and CD68 was expressed in Kupffer cells. Conclusion CD138 does not appear to be a reliable surrogate marker for liver disease. However, it may be included with other ancillary markers as a predictor of the stage of chronic liver disease and metastatic potential. The response to anti-CD138 therapy needs to be further studied.

Nano-stevia interaction: Past, present, and future.

Nanotechnology has recently been emerged as a transformative technology that offers efficient and sustainable options for nano-bio interface. There has been a considerable interest in exploring the factors affecting elicitation mechanism and nanomaterials have been emerged as strong elicitors in medicinal plants. Stevia rebaudiana is well-known bio-sweetener and the presence of zero calorie, steviol glycosides (SGs) in the leaves of S. rebaudiana have made it a desirable crop to be cultivated on large scale to obtain its higher yield and maximal content of high quality natural sweeteners. Besides, phenolics, flavonoids, and antioxidants are abundant in stevia which contribute to its medicinal importance. Currently, scientists are trying to increase the market value of stevia by the enhancement in production of its bioactive compounds. As such, various in vitro and cell culture strategies have been adopted. In stevia agronanotechnology, nanoparticles behave as elicitors for the triggering of its secondary metabolites, specifically rebaudioside A. This review article discusses the importance of S. rebaudiana and SGs, conventional approaches that have failed to increase the desired yield and quality of stevia, modern approaches that are currently being applied to obtain utmost benefits of SGs, and future needs of advanced technologies for further exploitation of this wonder of nature.

Sequential expression of miR-221-3p and miR-338-3p in Schwann cells as a therapeutic strategy to promote nerve regeneration and functional recovery.

The functional properties of endogenous Schwann cells (SCs) during nerve repair are dynamic. Optimizing the functional properties of SCs at different stages of nerve repair may have therapeutic benefit in improving the repair of damaged nerves. Previous studies showed that miR-221-3p promotes the proliferation and migration of SCs, and miR-338-3p promotes the myelination of SCs. In this study, we established rat models of sciatic nerve injury by bridging the transected sciatic nerve with a silicone tube. We injected a miR-221 lentiviral vector system together with a doxycycline-inducible Tet-On miR-338 lentiviral vector system into the cavity of nerve conduits of nerve stumps to sequentially regulate the biological function of endogenous SCs at different stages of nerve regeneration. We found that the biological function of SCs was sequentially regulated, the diameter and density of myelinated axons were increased, the expression levels of NF200 and myelin basic protein were increased, and the function of injured peripheral nerve was improved using this system. miRNA Target Prediction Database prediction, Nanopore whole transcriptome sequencing, quantitative PCR, and dual luciferase reporter gene assay results predicted and verified Cdkn1b and Nrp1 as target genes of miR-221-3p and miR-338-3p, respectively, and their regulatory effects on SCs were confirmed in vitro. In conclusion, here we established a new method to enhance nerve regeneration through sequential regulation of biological functions of endogenous SCs, which establishes a new concept and model for the treatment of peripheral nerve injury. The findings from this study will provide direct guiding significance for clinical treatment of sciatic nerve injury.