Dual growth factor methacrylic alginate microgels combined with chitosan-based conduits facilitate peripheral nerve repair.

Treating severe peripheral nerve injuries is difficult. Nerve repair with conduit small gap tubulization is a treatment option but still needs to be improved. This study aimed to assess the use of microgels containing growth factors, along with chitosan-based conduits, for repairing nerves. Using the water-oil emulsion technique, microgels of methacrylic alginate (AlgMA) that contained vascular endothelial growth factor (VEGF) and brain-derived neurotrophic factor (BDNF) were prepared. The effects on rat Schwann cells (RSC96) and human umbilical vein endothelial cells (HUVECs) were evaluated. Chitosan-based conduits were fabricated and used in conjunction with microgels containing two growth factors to treat complete neurotmesis in rats. The results showed that the utilization of dual growth factor microgels improved the migration and decreased the apoptosis of RSC96 cells while promoting the growth and formation of tubes in HUVECs. The utilization of dual growth factor microgels and chitosan-based conduits resulted in notable advancements in the regeneration and myelination of nerve fibers, recovery of neurons, alleviation of muscle atrophy and recovery of neuromotor function and nerve conduction. In conclusion, the use of dual growth factor AlgMA microgels in combination with chitosan-based conduits has the potential to significantly improve the effectiveness of nerve repair.

Jujube Witches' Broom Phytoplasma Effector Zaofeng3, a Homologous Effector of SAP54, Induces Abnormal Floral Organ Development and Shoot Proliferation.

Plant-pathogenic phytoplasmas secrete specific virulence proteins into a host plant to modulate plant function for their own benefit. Identification of phytoplasmal effectors is a key step toward clarifying the pathogenic mechanisms of phytoplasma. In this study, Zaofeng3, also known as secreted jujube witches' broom phytoplasma protein 3 (SJP3), was a homologous effector of SAP54 and induced a variety of abnormal phenotypes, such as phyllody, malformed floral organs, witches' broom, and dwarfism in Arabidopsis thaliana. Zaofeng3 can also induce small leaves, dwarfism, and witches' broom in Ziziphus jujuba. Further experiments showed that the three complete α-helix domains predicted in Zaofeng3 were essential for induction of disease symptoms in jujube. Yeast two-hybrid library screening showed that Zaofeng3 mainly interacts with proteins involved in flower morphogenesis and shoot proliferation. Bimolecular fluorescence complementation assays confirmed that Zaofeng3 interacted with these proteins in the whole cell. Overexpression of zaofeng3 in jujube shoot significantly altered the expression patterns of ZjMADS19, ZjMADS47, ZjMADS48, ZjMADS77, and ZjTCP7, suggesting that overexpressing zaofeng3 might induce floral organ malformation and witches' broom by altering the expression of the transcriptional factors involved in jujube morphogenesis.

Neutrophil peptide 1 accelerates the clearance of degenerative axons during Wallerian degeneration by activating macrophages after peripheral nerve crush injury.

JOURNAL/nrgr/04.03/01300535-202408000-00036/figure1/v/2023-12-16T180322Z/r/image-tiff Macrophages play an important role in peripheral nerve regeneration, but the specific mechanism of regeneration is still unclear. Our preliminary findings indicated that neutrophil peptide 1 is an innate immune peptide closely involved in peripheral nerve regeneration. However, the mechanism by which neutrophil peptide 1 enhances nerve regeneration remains unclear. This study was designed to investigate the relationship between neutrophil peptide 1 and macrophages in vivo and in vitro in peripheral nerve crush injury. The functions of RAW 264.7 cells were elucidated by Cell Counting Kit-8 assay, flow cytometry, migration assays, phagocytosis assays, immunohistochemistry and enzyme-linked immunosorbent assay. Axonal debris phagocytosis was observed using the CUBIC (Clear, Unobstructed Brain/Body Imaging Cocktails and Computational analysis) optical clearing technique during Wallerian degeneration. Macrophage inflammatory factor expression in different polarization states was detected using a protein chip. The results showed that neutrophil peptide 1 promoted the proliferation, migration and phagocytosis of macrophages, and CD206 expression on the surface of macrophages, indicating M2 polarization. The axonal debris clearance rate during Wallerian degeneration was enhanced after neutrophil peptide 1 intervention. Neutrophil peptide 1 also downregulated inflammatory factors interleukin-1α, -6, -12, and tumor necrosis factor-α in vivo and in vitro. Thus, the results suggest that neutrophil peptide 1 activates macrophages and accelerates Wallerian degeneration, which may be one mechanism by which neutrophil peptide 1 enhances peripheral nerve regeneration.

Chitosan-Based Conduits with Different Inner Diameters at both Ends Combined with Modified Formula Radix Hedysari Promote Nerve Transposition Repair.

BACKGROUND: Severe peripheral nerve injuries, such as deficits over long distances or proximal nerve trunk injuries, pose complex reconstruction challenges that often result in unfavorable outcomes. An innovative approach to repairing severe peripheral nerve damage involves using conduit suturing for nerve transposition repair. Cylindrical nerve guides are typically unsuitable for nerve transposition repair. Moreover, postsurgical adjuvant treatment is essential to promote the development of axonal lateral sprouts, proximal growth, and the restoration of neurostructure and function. The purpose of this research is to assess the impact of chitosan-based conduits with varying inner diameters on nerve transposition repair when combined with modified formula Radix Hedysari (MFRH). METHODS: Using chitosan, we created conduits with varying inner diameters on both ends. These conduits were then utilized to repair the distal common peroneal and tibial nerves in SD rats using the proximal common peroneal nerve. Subsequently, MFRH was employed as a supplementary treatment. The assessment of the repair's effectiveness took place 16 weeks postsurgery, utilizing a range of techniques, including the neurological nerve function index, neuroelectrophysiological measurements, muscle wet weight, and examination of nerve and muscle histology. RESULTS: The outcomes of our study showed that following 16 weeks of postoperative treatment, MFRH had a significant positive impact on the recovery of neuromotor and nerve conduction abilities. Moreover, there was a significant increase in the ratio of wet weight of muscles, cross-sectional area of muscle fibers, quantity and structure of regenerated myelinated nerve fibers, and the count of neurons. CONCLUSIONS: A combination of chitosan-based chitin conduits possessing different inner diameters and MFRH can considerably promote the regeneration and functional recovery of damaged nerves, which in turn enhances nerve transposition repair efficacy.

Chitin Conduits with Different Inner Diameters at Both Ends Combined with Dual Growth Factor Hydrogels Promote Nerve Transposition Repair in Rats.

Severe peripheral nerve injuries, such as deficits over long distances or proximal nerve trunk injuries, pose complex reconstruction challenges that often result in unfavorable outcomes. Innovative techniques, such as nerve transposition repair with conduit suturing, can be employed to successfully treat severe peripheral nerve damage. However, cylindrical nerve guides are typically unsuitable for nerve transposition repair. Furthermore, angiogenic and neurotrophic factors are necessary to stimulate the emergence of axonal lateral sprouts, proximal growth, and the rehabilitation of neuron structures and functions. In the current study, we used chitosan to make chitin conduits with different inner diameters at both ends, combined with gelatin methacrylate hydrogels that can continuously release dual growth factors, namely, the vascular endothelial growth factor (VEGF) and the nerve growth factor (NGF), and evaluated its impact on nerve transposition repair in rats. At 16 weeks after the operation, our findings showed that the conduit combined with the dual growth factor hydrogel significantly improved the restoration of both motor and conduction functions of the nerve. In addition, histological analysis showed significant recovery of nerve fibers, target muscles, and neurons. In conclusion, the combination of chitin conduits with different inner diameters and dual growth factor hydrogels can significantly improve the effect of nerve transposition repair, which has important potential clinical value.

Ce-Doped Three-Dimensional Ni/Fe LDH Composite as a Sulfur Host for Lithium-Sulfur Batteries.

Lithium-sulfur batteries (LSBs) have become the most promising choice in the new generation of energy storage/conversion equipment due to their high theoretical capacity of 1675 mAh g-1 and theoretical energy density of 2600 Wh kg-1. Nevertheless, the continuous shuttling of lithium polysulfides (LiPSs) restricts the commercial application of LSBs. The appearance of layered double hydroxides (LDH) plays a certain role in the anchoring of LiPSs, but its unsatisfactory electronic conductivity and poor active sites hinder its realization as a sulfur host for high-performance LSBs. In this paper, metal organic framework-derived and Ce ion-doped LDH (Ce-Ni/Fe LDH) with a hollow capsule configuration is designed rationally. The hollow structure of Ce-Ni/Fe LDH contains a sufficient amount of sulfur. Fe, Ni, and Ce metal ions effectively trap LiPSs; speed up the conversion of LiPSs; and firmly anchor LiPSs, thus effectively inhibiting the shuttle of LiPSs. The electrochemical testing results demonstrate that a lithium-sulfur battery with capsule-type S@Ce-Ni/Fe LDH delivers the initial discharge capacities of 1207 mAh g-1 at 0.1 C and 1056 mAh g-1 at 0.2 C, respectively. Even at 1 C, a lithium-sulfur battery with S@Ce-Ni/Fe LDH can also cycle 1000 times. This work provides new ideas to enhance the electrochemical properties of LSBs by constructing a hollow capsule configuration.

Engineering strategies and optimized delivery of exosomes for theranostic application in nerve tissue.

Severe injuries or diseases affecting the peripheral and central nervous systems can result in impaired organ function and permanent paralysis. Conventional interventions, such as drug administration and cell-based therapy, exhibit limited effectiveness due to their inability to preserve post-implantation cell survival and impede the deterioration of adjacent tissues. Exosomes have recently emerged as powerful tools for tissue repair owing to their proteins and nucleic acids, as well as their unique phospholipid properties, which facilitate targeted delivery to recipient cells. Engineering exosomes, obtained by manipulating the parental cells or directly functionalizing exosomes, play critical roles in enhancing regenerative repair, reducing inflammation, and maintaining physiological homeostasis. Furthermore, exosomes have been shown to restore neurological function when used in combination with biomaterials. This paper primarily focuses on the engineering strategies and delivery routes of exosomes related to neural research and emphasizes the theranostic application of optimized exosomes in peripheral nerve, traumatic spinal cord, and brain injuries. Finally, the prospects of exosomes development and their combination with other approaches will be discussed to enhance our knowledge on their theranostic effectiveness in neurological diseases.

Ameliorative Effects of Extracellular Vesicles Derived from Mesenchymal Stem Cells on Apoptosis and Differentiation of Osteoblasts Treated with CoCl2.

Severe osteoporotic fracture occurring in sites with inadequate blood supply can cause irreversible damage to cells, particularly osteoblasts, with current drug and surgical interventions exhibiting limitations for elderly individuals. As participants mediating intercellular communication, extracellular vesicles (EVs) are rarely reported to play functional roles in osteoblasts under hypoxia. Our study mainly investigated the effects of bone marrow mesenchymal stem cells-derived EVs (BMSCs-EVs) on apoptosis and differentiation of osteoblasts treated with CoCl2. Primary rat BMSCs and osteoblasts were extracted as required for the following experiments. Cell counting kit 8 assay was used to explore the concentration of CoCl2 for treating osteoblasts, and we found that 100 µM CoCl2 was appropriate to treat osteoblasts for 48 hours. The analysis of flow cytometer showed that CoCl2-treated osteoblasts apoptosis can be ameliorated when cocultured with BMSCs-EVs. Further findings revealed that reactive oxygen species (ROS) was related to CoCl2-induced apoptosis. In addition, our results demonstrated that EVs exerted an important role in increasing expression levels of ALP, BMP-2, OCN, and OSTERIX under hypoxia. Similarly, the functional effects of BMSCs-EVs were observed on the osteoblasts mineralization. In summary, these findings provide insight that BMSCs-EVs might decrease the effect of CoCl2-induced apoptosis through inhibiting ROS, and promote osteogenic differentiation under hypoxia.

Coordinated Immobilization and Rapid Conversion of Polysulfide Enabled by a Hollow Metal Oxide/Sulfide/Nitrogen-Doped Carbon Heterostructure for Long-Cycle-Life Lithium-Sulfur Batteries.

Lithium-sulfur batteries (LSBs) are recognized as the prospective candidate in next-generation energy storage devices due to their gratifying theoretical energy density. Nonetheless, they still face the challenges of the practical application including low utilization of sulfur and poor cycling life derived from shuttle effect of lithium polysulfides (LiPSs). Herein, a hollow polyhedron with heterogeneous CoO/Co9 S8 /nitrogen-doped carbon (CoO/Co9 S8 /NC) is obtained through employing zeolitic imidazolate framework as precursor. The heterogeneous CoO/Co9 S8 /NC balances the redox kinetics of Co9 S8 with chemical adsorption of CoO toward LiPSs, effectively inhibiting the shuttle of LiPSs. The mechanisms are verified by both experiment and density functional theory calculation. Meanwhile, the hollow structure acts as a sulfur storage chamber, which mitigates the volumetric expansion of sulfur and maximizes the utilization of sulfur. Benefiting from the above advantages, lithium-sulfur battery with S-CoO/Co9 S8 /NC achieves a high initial discharge capacity (1470 mAh g-1 ) at 0.1 C and long cycle life (ultralow capacity attenuation of 0.033% per cycle after 1000 cycles at 1 C). Even under high sulfur loading of 3.0 mg cm-2 , lithium-sulfur battery still shows the satisfactory electrochemical performance. This work may provide an idea to elevate the electrochemical performance of LSBs by constructing a hollow metal oxide/sulfide/nitrogen-doped carbon heterogeneous structure.

Reduced graphene oxide-embedded nerve conduits loaded with bone marrow mesenchymal stem cell-derived extracellular vesicles promote peripheral nerve regeneration.

We previously combined reduced graphene oxide (rGO) with gelatin-methacryloyl (GelMA) and polycaprolactone (PCL) to create an rGO-GelMA-PCL nerve conduit and found that the conductivity and biocompatibility were improved. However, the rGO-GelMA-PCL nerve conduits differed greatly from autologous nerve transplants in their ability to promote the regeneration of injured peripheral nerves and axonal sprouting. Extracellular vesicles derived from bone marrow mesenchymal stem cells (BMSCs) can be loaded into rGO-GelMA-PCL nerve conduits for repair of rat sciatic nerve injury because they can promote angiogenesis at the injured site. In this study, 12 weeks after surgery, sciatic nerve function was measured by electrophysiology and sciatic nerve function index, and myelin sheath and axon regeneration were observed by electron microscopy, immunohistochemistry, and immunofluorescence. The regeneration of microvessel was observed by immunofluorescence. Our results showed that rGO-GelMA-PCL nerve conduits loaded with BMSC-derived extracellular vesicles were superior to rGO-GelMA-PCL conduits alone in their ability to increase the number of newly formed vessels and axonal sprouts at the injury site as well as the recovery of neurological function. These findings indicate that rGO-GelMA-PCL nerve conduits loaded with BMSC-derived extracellular vesicles can promote peripheral nerve regeneration and neurological function recovery, and provide a new direction for the curation of peripheral nerve defect in the clinic.

Sustained release of exosomes loaded into polydopamine-modified chitin conduits promotes peripheral nerve regeneration in rats.

Exosomes derived from mesenchymal stem cells are of therapeutic interest because of their important role in intracellular communication and biological regulation. On the basis of previously studied nerve conduits, we designed a polydopamine-modified chitin conduit loaded with mesenchymal stem cell-derived exosomes that release the exosomes in a sustained and stable manner. In vitro experiments revealed that rat mesenchymal stem cell-derived exosomes enhanced Schwann cell proliferation and secretion of neurotrophic and growth factors, increased the expression of Jun and Sox2 genes, decreased the expression of Mbp and Krox20 genes in Schwann cells, and reprogrammed Schwann cells to a repair phenotype. Furthermore, mesenchymal stem cell-derived exosomes promoted neurite growth of dorsal root ganglia. The polydopamine-modified chitin conduits loaded with mesenchymal stem cell-derived exosomes were used to bridge 2 mm rat sciatic nerve defects. Sustained release of exosomes greatly accelerated nerve healing and improved nerve function. These findings confirm that sustained release of mesenchymal stem cell-derived exosomes loaded into polydopamine-modified chitin conduits promotes the functional recovery of injured peripheral nerves.

Potential Effects of Exosomes and their MicroRNA Carrier on Osteoporosis.

Osteoporosis is a common localized or systemic skeletal illness in the clinic, characterized by bone production weakness and increased bone resorption, resulting in a reduction in bone mineral density (BMD), and affecting mostly postmenopausal women. The risk of osteoporosis or even osteoporotic fracture increases as age increases, putting more pressure on society and families. Although anti-osteoporosis drugs have been developed, some side effects are still observed in the treatment group. Hence the need for more reasonable therapeutic strategies. Exosomes are nanosized extracellular vesicles (EVs) secreted virtually by all types of cells in vivo, which play an important role in intercellular communication. Compared with conventional drugs and stem cells transplantation therapy, exosomes have apparent advantages of lower toxicity and immunogenicity. Exosomes contain many functional molecules, such as proteins, lipids, mRNAs, microRNAs (miRNAs), which can be transferred into recipient cells to regulate a series of signaling pathways and influence physiological and pathological behavior. In this review, we briefly summarize the current knowledge of exosomes and the therapeutic potential of exosomal miRNAs derived from mesenchymal stem cells (MSCs), osteoblasts, osteoclasts, and macrophages in osteoporosis. Finally, a prospect of new treatment strategies for osteoporosis using new biomaterial scaffolds combined with exosomes is also given.

Dosimetric impacts of cone-beam computed tomography (CBCT)-based anatomic changes in intensity-modulated radiotherapy for cervical cancer.

Background: To evaluate the effects of dose to tumors and organs at risk (OARs) on inter-fractional anatomic changes. Methods: We evaluated nine patients with cervical cancer treated with intensity-modulated radiotherapy (IMRT) (45 Gy in 25 fractions) using kV cone-beam computed tomography (CBCT) image guidance once or twice a week before treatment. For each patient, the original plan on the computed tomography (CT) image was copied to merged images, and then the fractional doses were calculated. Subsequently, deformable accumulated doses were obtained by summing the fractional absolute doses into a single dose in MIM Maestro software. The volume changes in the target and OARs were compared between the original CT and merged CBCT images, and the differences in the fractional and accumulated doses were also evaluated. Results: Sixty-nine merged CBCT images were obtained and analyzed in this study. For the target areas, the volume changes in the clinical target volume (CTV) and planning target volume (PTV) reached -18.05% and -24.11% at most, respectively. The fractional D2% of the CTV and PTV was generally higher than the original plans, and the accumulated deviations were 2.27%±0.82% (P<0.01) and 2.42%±1.28% (P<0.01), respectively. The fractional D98% of the PTV was underdosed up to 18.28% for 78% of patients, and the accumulated deviations were -2.06% to -17.29% (P<0.05). For the OARs, the bladder volume changes were the most dramatic, reducing up to 93.60%. The fractional Dmean and D2cc of the bladder were generally higher than the original plans, and there were significant differences in their accumulated values (P<0.05). There was no obvious trend of rectal volume change with -69.65% to 74.20%. The rectum Dmean and D2cc of the accumulated were not significantly different from the planned dose (P>0.05). Conclusions: For patients with cervical cancer, the changes in bladder and rectal volume were greater than in the target volume. Although the volume changes in the bladder and rectum had no significant effect on D98% of the CTV and PTV, they had a significant effect on their own D2cc and the D2% of the CTV and PTV. More attention should be paid to the volume changes in the bladder and rectum in clinical work.

An injectable and biodegradable nano-photothermal DNA hydrogel enhances penetration and efficacy of tumor therapy.

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.

Association of Epstein-Barr virus infection with peripheral immune parameters and clinical outcome in advanced nasopharyngeal carcinoma.

The purpose of this study was to investigate the association of Epstein-Barr virus (EBV) with peripheral blood immune cell counts and clinical outcomes in advanced nasopharyngeal carcinoma (NPC) patients. In a retrospective design, 146 patients with NPC at stage IV were enrolled in this study. The association of EBV status with peripheral blood immune cell counts, distant metastases, and long-term survival in patients with advanced NPC were determined. Eighty-seven (59.6%) of all patients were positive for EBV. Compared with patients with normal NK cell count, patients with lower NK cell count showed a significantly lower EBV viral load (median: 614.0 vs. 2190.0 copies/mL, P = 0.024). EBV-positive patients showed a significantly higher incidence of liver metastasis than EBV-negative patients (32.6% vs. 23.7%, P = 0.021). Multi-variant regression analysis showed that EBV infection was independently associated with liver metastasis (OR: 2.33, P = 0.043). EBV positive patients showed a significantly worse PFS (P = 0.001) and OS (P = 0.001) than EBV negative patients. Multivariate Cox regression analysis revealed that EBV infection was independently associated with a worse PFS (HR: 1.94, P = 0.003), and OS (HR: 2.12, P = 0.014) in advanced NPC. In conclusion, EBV infection is associated with a high risk of liver metastasis and is also an independent negative predictor for PFS and OS in patients with advanced NPC. EBV infection is associated with lower CD8% and higher NK%, while lower NK cell count is associated with lower EBV viral load.

Reduced graphene oxide-GelMA-PCL hybrid nanofibers for peripheral nerve regeneration.

Graphene oxide is currently used in peripheral nerve engineering but has certain limitations, such as cytotoxicity and lack of electrical conductivity, both of which are crucial in regulating nerve-associated cell behaviors. In this work, we engineered reduced graphene oxide-GelMA-PCL nanofiber nerve guidance conduits via electrospinning. rGO incorporated into the GelMA/PCL matrix significantly enhanced the electrical conductivity and biocompatibility of the hybrid materials. In addition, hybrid nanofibers with low concentrations of rGO (0.25 and 0.5 wt%) could significantly improve the proliferation of Schwann cells (RSC96). More importantly, rGO/GelMA/PCL hybrid nanofibers could activate the epithelial-mesenchymal transition (EMT)-related gene expression of Schwann cells (RSC96). From the in vivo study, it was observed that rGO/GelMA/PCL nerve guidance conduits could promote both sensory/motor nerve regeneration and functional recovery in rats. Our composite strategy of combining rGO within a biocompatible nanofiber scaffold is simple but effective in improving tissue engineering outcomes. The rGO/GelMA/PCL hybrid nanofibers have great potential in peripheral nerve tissue engineering. They will also provide an experimental basis for the development of further electrical stimulation in peripheral nerve regeneration.

Bilberry anthocyanin extracts enhance anti-PD-L1 efficiency by modulating gut microbiota.

The undesirable low response rate is a major hurdle to garnering the maximum potential of immune checkpoint inhibitors in cancer treatments. Recent advances in exploring the effects of intestinal flora on the medical efficacy of immune checkpoint blockade have shed new light on the application of immune checkpoint inhibitors. Inspired by the prebiotic role of anthocyanin-rich extracts, we propose using bilberry anthocyanin extracts to modulate the composition of gut microbiota and eventually, promote the efficiency of immune checkpoint inhibitors. This study demonstrates the effectiveness of orally administered bilberry anthocyanin extracts in enhancing the anti-tumor efficiency of the PD-L1 antibody in the experimental mouse MC38 tumor model. We observed an increase in the fecal abundance of Clostridia and Lactobacillus johnsonii and improved effective community diversity. These findings reinforce the importance of intestinal flora composition and open up unprecedented opportunities in using natural compounds to enhance the efficacy of immune checkpoint inhibitors.

Clinical Impact of the Bolus in Intensity-Modulated Radiotherapy and Volumetric-Modulated Arc Therapy for Stage I-II Nasal Natural Killer/T-Cell Lymphoma.

INTRODUCTION: To estimate the clinical impact of bolus in intensity-modulated radiotherapy (IMRT) and volumetric-modulated arc therapy (VMAT) for stage I-II nasal natural killer/T-cell lymphoma (NNKTCL), including target quality, organs at risk (OARs) sparing, and tumor control probability (TCP). METHODS: Two different treatment plans were designed in IMRT and VMAT for 10 stage I-II NNKTCL patients. The clinical plans added bolus perfectly contacting the nose skin, similar to common clinical planning design practices. The edited bolus plans resulted from dose recalculation with the edited bolus, which simulated the actual shape of a commercial flat bolus during treatment. All the plans were with no beam passing through the couch avoiding beam attenuation caused by the couch. Differences between both types of plans in target quality, OARs sparing, and TCP were evaluated. RESULTS: Compared with clinical plans, the D98%, D2%, Dmean, and TCP of edited bolus plans with IMRT slightly decreased (p = 0.002, 0.015, 0.000, and 0.000), the homogeneity index increased 8.33% (p = 0.024), and the doses to a small number of OARs slightly changed. Similar results were obtained for VMAT. CONCLUSION: The bolus deformation in practical clinical treatment resulted clinically in tiny changes with respect to the target coverage, OARs sparing, and TCP in both IMRT and VMAT for stage I-II NNKTCL. This implied that the clinical impact of the boluscan be negligible when utilizing it to increase the dose to irregularly shaped tumors in the nasal area.

Conductive conduit small gap tubulization for peripheral nerve repair.

Despite advances in surgical techniques, functional recovery following epineurial neurorrhaphy of transected peripheral nerves often remains quite unsatisfactory. Small gap tubulisation is a promising approach that has shown potential to traditional epineurial neurorrhaphy in the treatment of peripheral nerve injury. Thus, the goal of this study is to evaluate sciatic nerve regeneration after nerve transection, followed by small gap tubulization using a reduced graphene oxide-based conductive conduit. In vitro, the electrically conductive conduit could promote Schwann cell proliferation through PI3K/Akt signaling pathway activation. In vivo, the results of electrophysiological and walking track analysis suggest that the electrically conductive conduit could promote sensory and motor nerve regeneration and functional recovery, which is based on the mechanisms of selective regeneration and multiple-bud regeneration. These promising results illustrate electrically conductive conduit small gap tubulization as an alternative approach for transected peripheral nerve repair.