Fe-doped carbon dots: a novel biocompatible nanoplatform for multi-level cancer therapy.

BACKGROUND: Tumor treatment still remains a clinical challenge, requiring the development of biocompatible and efficient anti-tumor nanodrugs. Carbon dots (CDs) has become promising nanomedicines for cancer therapy due to its low cytotoxicity and easy customization. RESULTS: Herein, we introduced a novel type of "green" nanodrug for multi-level cancer therapy utilizing Fe-doped carbon dots (Fe-CDs) derived from iron nutrient supplement. With no requirement for target moieties or external stimuli, the sole intravenous administration of Fe-CDs demonstrated unexpected anti-tumor activity, completely suppressing tumor growth in mice. Continuous administration of Fe-CDs for several weeks showed no toxic effects in vivo, highlighting its exceptional biocompatibility. The as-synthesized Fe-CDs could selectively induce tumor cells apoptosis by BAX/Caspase 9/Caspase 3/PARP signal pathways and activate antitumoral macrophages by inhibiting the IL-10/Arg-1 axis, contributing to its significant tumor immunotherapy effect. Additionally, the epithelial-mesenchymal transition (EMT) process was inhibited under the treatment of Fe-CDs by MAPK/Snail pathways, indicating the capacity of Fe-CDs to inhibit tumor recurrence and metastasis. CONCLUSIONS: A three-level tumor treatment strategy from direct killing to activating immunity to inhibiting metastasis was achieved based on "green" Fe-CDs. Our findings reveal the broad clinical potential of Fe-CDs as a novel candidate for anti-tumor nanodrugs and nanoplatform.

SPIONs mediated magnetic actuation promotes nerve regeneration by inducing and maintaining repair-supportive phenotypes in Schwann cells.

BACKGROUND: Schwann cells, the glial cells in the peripheral nervous system, are highly plastic. In response to nerve injury, Schwann cells are reprogrammed to a series of specialized repair-promoting phenotypes, known as repair Schwann cells, which play a pivotal role in nerve regeneration. However, repair Schwann cells represent a transient and unstable cell state, and these cells progressively lose their repair phenotypes and repair-supportive capacity; the transience of this state is one of the key reasons for regeneration failure in humans. Therefore, the ability to control the phenotypic stability of repair Schwann cells is of great practical importance as well as biological interest. RESULTS: We designed and prepared a type of fluorescent-magnetic bifunctional superparamagnetic iron oxide nanoparticles (SPIONs). In the present study, we established rat sciatic nerve injury models, then applied SPIONs to Schwann cells and established an effective SPION-mediated magnetic actuation system targeting the sciatic nerves. Our results demonstrate that magnetic actuation mediated by SPIONs can induce and maintain repair-supportive phenotypes of Schwann cells, thereby promoting regeneration and functional recovery of the sciatic nerve after crush injury. CONCLUSIONS: Our research indicate that Schwann cells can sense these external, magnetically driven mechanical forces and transduce them to intracellular biochemical signals that promote nerve regeneration by inducing and maintaining the repair phenotypes of Schwann cells. We hope that this study will provide a new therapeutic strategy to promote the regeneration and repair of injured peripheral nerves.

Molecular Etiology in Thumb Polydactyly in Mutated GLI3 Mouse Gene.

Sporadic thumb polydactyly with nonfamily inheritance is the most common in clinical work. This study focused on characterization of GLI3 gene function. We constructed the plasmid with p.m948i point mutation of GLI3 and transfected it into mouse embryonic fibroblasts (MEFs) to study the effects and potential mechanism of the mutant gene. The RNA of GLI3 mutant cells was extracted and analyzed by transcriptome sequencing and bioinformatics. Finally, we constructed cbx3 overexpression plasmid, designed siRNA for gene silencing, and transfected it into the MEFs. Cell proliferation and invasion ability of the MEFs were examined. The results showed that there were 2,452 differential expression genes in the MEFs transfected with GLI3 mutant plasmid compared with wild-type MEFs. The results of differential expression analysis showed that the cbx3 gene was significantly up-regulated. Overexpression of cbx3 in MEFs promoted cell proliferation and invasion, while siRNA knockdown of cbx3 expression reduced proliferation and invasion. GLI3 gene mutation in MEFs resulted in cbx3 up-regulation and promoted MEF proliferation and invasion. This study further clarified the potential function of GLI3 in limb development, established a new relationship between gene mutation and polydactyly, and preliminarily clarified the possible signal pathway, all of which have laid a foundation for further study on the etiology of polydactyl.

IL1R2 polymorphisms and their interaction are associated with osteoporosis susceptibility in the Chinese Han population.

AIMS: Interleukin 1 (IL-1) inhibitory receptor type 2 (IL1R2) serves as a negative regulator of IL-1 signalling and is involved in the pathogenesis of osteoporosis. This study aimed to determine the correlation between IL1R2 polymorphism and osteoporosis susceptibility in the Chinese Han population. METHODS: We recruited 594 osteoporosis patients and 599 healthy controls. Six single nucleotide polymorphisms (SNPs) in IL1R2 were selected for genotyping using the Agena MassARRAY platform. The odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using logistic regression analysis with adjustment for age and sex. Linkage disequilibrium analysis was plotted using Haploview v4.2. Multifactor dimension reduction (MDR) was performed to estimate the SNP-SNP interactions of IL1R2 variants. RESULTS: Rs11674595 (OR = 1.86, p = 0.020), rs2072472 (OR = 1.26, p = 0.019) and rs4851527 (OR = 0.78, p = 0.007) were related to the risk of osteoporosis. Moreover, the contribution of IL1R2 polymorphisms to osteoporosis risk was associated with age, sex and body mass index. We found the relationships of Trs11674595 Ars4851527 (OR = 0.80, p = 0.015), Crs11674595 Grs4851527 (OR = 1.22, p = 0.043) and Ars3218977 Grs2072472 (OR = 1.25, p = 0.022) haplotypes to osteoporosis occurrence, and a potential accumulated effect of IL1R2 SNPs (testing accuracy = 0.5783 and cross validation consistency = 10/10) on osteoporosis susceptibility. CONCLUSION: IL1R2 polymorphisms (rs11674595, rs4851527, rs2072472 and rs3218977) may contribute to osteoporosis risk in the Chinese Han population. Our findings may increase our understanding of the effects of IL1R2 polymorphisms on the predisposition to osteoporosis.

Growth and elongation of axons through mechanical tension mediated by fluorescent-magnetic bifunctional Fe3O4·Rhodamine 6G@PDA superparticles.

BACKGROUND: The primary strategy to repair peripheral nerve injuries is to bridge the lesions by promoting axon regeneration. Thus, the ability to direct and manipulate neuronal cell axon regeneration has been one of the top priorities in the field of neuroscience. A recent innovative approach for remotely guiding neuronal regeneration is to incorporate magnetic nanoparticles (MNPs) into cells and transfer the resulting MNP-loaded cells into a magnetically sensitive environment to respond to an external magnetic field. To realize this intention, the synthesis and preparation of ideal MNPs is an important challenge to overcome. RESULTS: In this study, we designed and prepared novel fluorescent-magnetic bifunctional Fe3O4·Rhodamine 6G@polydopamine superparticles (FMSPs) as neural regeneration therapeutics. With the help of their excellent biocompatibility and ability to interact with neural cells, our in-house fabricated FMSPs can be endocytosed into cells, transported along the axons, and then aggregated in the growth cones. As a result, the mechanical forces generated by FMSPs can promote the growth and elongation of axons and stimulate gene expression associated with neuron growth under external magnetic fields. CONCLUSIONS: Our work demonstrates that FMSPs can be used as a novel stimulator to promote noninvasive neural regeneration through cell magnetic actuation.

Vascularized Capitate Transposition for the Treatment of Stage IIIB Kienböck Disease.

PURPOSE: The treatment of Kienböck disease (KD) continues to be controversial. In this study, we report the long-term follow-up outcomes of patients who were diagnosed with stage IIIB KD treated with vascularized capitate transposition. METHODS: A total of 16 patients were retrospectively reviewed. Baseline clinical information was extracted from medical records, and wrist function was clinically evaluated, including x-ray images. RESULTS: At the final follow-up, wrist pain was severe in 0 patients, moderate in 2 patients, mild in 5 patients, and absent in 9 patients. The mean postoperative active flexion and extension of the affected wrist was significantly improved after surgery compared with before surgery. The postoperative and preoperative mean grip strength was 35 kg and 27 kg, respectively. The Disabilities of the Arm, Shoulder, and Hand score was significantly improved after surgery compared with before surgery. CONCLUSIONS: Vascularized capitate transposition for the treatment of Lichtman stage IIIB KD is feasible and associated with improvements in wrist function and pain. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic IV.

Visualized identification of the maximal surgical delay effect in a rat flap model.

Currently, experimental evidence suggests that the surgical delay can increase flap survival area, but its effect may decrease if the optimal delay period is missed. The aim of this study is to establish a sensitive and objective modality based on the visualized and individualized infrared thermography for identifying the maximal surgical delay effect. A rectangular three-angiosome flap was designed on the unilateral dorsum of the rat. Ninety-six rats were randomly divided into six groups according to the various delay time. Both the relative temperature and the relative temperature ratio were measured by the infrared thermography. Arterial density, number of vessels >0.1 mm in diameter, microvessel density, VEGF concentration, and flap viability were measured. Receiving operating characteristic curve with the highest Youden-Index was used to detect and identify an optimal cutoff point of the relative temperature ratio in the maximal surgical delay effect. The criteria for identifying the flap maximum delay effect based on the infrared thermography included the surface of the postdelayed flaps presented white color (higher temperature) instead of the red and white pattern of the normal skin and the optimal cutoff point of the relative temperature ratio was ≥1.17 with a sensitivity of 84.6% and a specificity of 77.3%. Instead, the sensitivity and specificity of the conventional method based on the delay time were 38.5 and 90.9%, respectively. Infrared thermal imaging can accurately identify the maximum delay effect when combined with the relative temperature ratio.

Surgical site infection following elective orthopaedic surgeries in geriatric patients: Incidence and associated risk factors.

The purposes of this study were to investigate the incidence of surgical site infection (SSI) following geriatric elective orthopaedic surgeries and identify the associated risk factors This was a retrospective two-institution study. Between January 2014 and September 2017, patients aged 60 years or older undergoing elective orthopaedic surgeries were included for data collection and analysis. SSI was identified through the review of patients' medical records for the index surgery and through the readmission diagnosis of SSI. Patients' demographics, characteristics of disease, surgery-related variables, and laboratory examination indexes were inquired and documented. Univariate and multivariate logistic analyses were performed to determine independent risk factors for SSI. There were 4818 patients undergoing elective orthopaedic surgeries, and within postoperative 1 year, 74 patients were identified to develop SSIs; therefore, the overall incidence of SSI was 3.64%, with 0.4% for deep and 1.1% for superficial infection. Staphylococcus aureus (25/47, 53.2%) and coagulase-negative staphylococci (11/47, 23.4%) were the most common causative pathogens; half of S. aureus SSIs were caused by Methicillin-resistant Staphylococcus aureus (MRSA) (12/25, 48.0%). Five risk factors were identified to be independently associated with SSI, including diabetes mellitus (odds ratio [OR], 3.7; 95% confidence interval [95% CI], 1.7-5.6), morbid obesity (OR, 2.6; 95% CI, 1.3-3.9), tobacco smoking (OR, 4.2; 95% CI, 2.1-6.4), surgical duration>75th percentile (OR, 1.9; 95% CI, 1.0-2.9), and ALB < 35.0 g/L (OR, 2.3; 95% CI, 1.3-3.4). We recommend the optimisation of modifiable risk factors such as morbid obesity, tobacco smoking, and lower serum albumin level prior to surgeries to reduce the risk of SSI.

Reconstruction of a Complex Foot Injury With Free Remodeled Fibular Osteocutaneous Flap: A Case Report and Literature Review.

Management of complex foot injuries, which involve open fractures and severe trauma to soft tissues, represent a challenge to orthopedic clinicians. In the present case report, we treated a complex foot injury with a remodeled fibular osteocutaneous free flap to reconstruct the anterior and lateral areas of the foot. The flap survived completely. At the 9-month follow-up examination, bony union of the graft bone was identified by radiographic examination. The reconstructed foot could bear body weight, and the patient could maintain a bipedal gait without discomfort. The remodeled fibular osteocutaneous free flap provides an option for functional reconstruction of foot defects.

Internal fixation with Kirschner wires is as efficient as rigid screw fixation in scaphoid fracture: long-term functional outcome.

This study aimed to compare the long-term efficacy of Kirschner wires and Herbert screw internal fixation in scaphoid fracture. A retrospective chart with radiographic review and functional follow-up was conducted for patients with the scaphoid fracture. 65 patients (40 for K-wire fixation and 25 for Herbert screw) were enrolled. The nonunion rate for K-wire fixation and screw method were indifferent comprehensively and for iliac graft subgroup. Less bone necrosis was found with K-wire fixation (2.5% vs 16%, P=0.049). There's no difference between groups in Mayo scores, post-operation pain and grid strength. Patients with K-wire fixation have larger range of motion on radial/ulnar deviation (35.25±11.32 vs 28.00±8.66, P=0.007). The results support the use of Kirschner wires in the treatment of scaphoid fractures. Advantages such as high union rates and good function recovery of wrist could be expected from minimal invasion, multi-axial stable fixation.

Comparison of perioperative complications of pedicled island flap in reconstruction of extremities.

PURPOSE: The aim of this study was to analyze the differences in perioperative complications for pedicled island flaps in the reconstruction of extremities and to identify the factors contributing to pedicled island flap necrosis. Furthermore, the flap indications based on these outcomes are summarized. METHODS: Based on the inclusion criteria, 228 skin flaps were included in this study. Univariate and multivariate analyses were used to identify the risk factors for pedicled island flap necrosis. Differences in perioperative complications between upper and lower extremities were analyzed using the chi-square test or Fisher's exact test. RESULTS: The average age of the patients was 38 years. The overall complication rate was 21.93%, including partial flap necrosis (10.09%) and total flap necrosis (5.70%). The overall complication rate and flap necrosis rate in upper extremity reconstruction were significantly lower than the rates in lower extremity reconstruction. Flap area and postoperative wound infection were statistically significant risk factors for pedicled island flap necrosis in extremity reconstruction. Preoperative contamination of the wound bed was a statistically significant risk factor for postoperative wound infection. CONCLUSIONS: The flap area and postoperative wound infection were both independent risk factors for pedicled island flap necrosis in extremity reconstruction. The causes contributing to the differences in perioperative complications between upper and lower extremities reconstruction included preoperative contamination of the wound bed, postoperative wound infection, and the flap area but were also related to anatomical factors of the skin flap. Pedicled island flaps are more suitable for small- and medium-sized soft tissue defects.

Clinical Application and the Free Posterior Thigh Perforator Flap.

OBJECTIVE: The posterior thigh region has been neglected as a donor site for free perforator flaps, likely due to difficulties in positioning the patient during surgery. This study describes the clinical application of the posterior thigh perforator flap based on the third perforating artery of the profunda femoris artery (PFA). METHODS: The free posterior thigh perforator flap based on the third perforating artery of the PFA was used for reconstruction of soft tissue defects in nine patients between February 2010 and May 2014. RESULTS: Flap sizes ranged from 12 × 7 cm to 20 × 13 cm. The length of the vascular pedicle averaged 10.28 cm, and the mean diameters of the third perforating artery and venae comitantes were 1.68 and 1.14 mm, respectively. All of the perforators originated from the PFA. Of the 9 free flaps used in 9 patients, 7 flaps survived completely. There were no early complications in these flaps. During the follow-up period, no patient experienced cold intolerance, scar contracture, or scar pain. There were no functional impairments at the donor or recipient sites. CONCLUSIONS: The posterior thigh flap based on the third perforating artery of the PFA is an excellent option for reconstructing soft tissue defects. The anatomical location of the third perforating artery is relatively consistent. The vascular pedicle is relatively longer and has large caliber vessels. The scar at the donor site can be well concealed with low morbidity. The skin color and texture of this flap show satisfactory results.

Neuroinflammation signatures in dorsal root ganglia following chronic constriction injury.

Neuropathic pain (NP) is a common debilitating chronic pain condition with limited effective therapeutics. Further investigating mechanisms underlying NP is therefore of great importance for discovering more promising therapeutic targets. In the current study, we employed high-throughput RNA sequencing to explore transcriptome profiles of mRNAs and microRNAs in the dorsal root ganglia (DRG) following chronic constriction injury (CCI) and also integrated published datasets for comprehensive analysis. First, we established CCI rat model confirmed by behavioral testings, and excavated 467 differentially expressed mRNAs (DEGs) and 16 differentially expressed microRNAs (DEmiRNAs) in the ipsilateral lumbar 4-6 DRG of CCI rats 11 days after surgery. Functional enrichment analysis of 337 upregulated DEGs showed that most of the DEGs were enriched in inflammation- and immune-associated biological processes and signaling pathways. The protein-protein interaction networks were constructed and hub DEGs were screened. Besides hub DEGs, we also identified 113 overlapped DEGs by intersecting our dataset with dataset GSE100122. Subsequently, we predicted potential miRNA-mRNA regulatory pairs using DEmiRNAs and a given set of key DEGs (including hub and overlapped DEGs). By integrative analysis, we found commonly differentially expressed mRNAs and miRNAs following CCI of different time points and different nerve injury types. Highlighted mRNAs include Atf3, Vip, Gal, Npy, Adcyap1, Reg3b, Jun, Cd74, Gadd45a, Tgm1, Csrp3, Sprr1a, Serpina3n, Gap43, Serpinb2 and Vtcn1, while miRNAs include miR-21-5p, miR-34a-5p, miR-200a-3p, miR-130a-5p, miR-216b-5p, miR-217-5p, and miR-541-5p. Additionally, 15 DEGs, including macrophages-specific (Cx3cr1, Arg1, Cd68, Csf1r) and the ones related to macrophages' involvement in NP (Ccl2, Fcgr3a, Bdnf, Ctss, Tyrobp) were verified by qRT-PCR. By functional experiments in future studies, promising therapeutic targets for NP treatment may be identified among these mRNAs and miRNAs.

Peripheral nerve injury repair by electrical stimulation combined with graphene-based scaffolds.

Peripheral nerve injury (PNI) is a common clinical problem, which due to poor recovery often leads to limb dysfunction and sensory abnormalities in patients. Tissue-engineered nerve guidance conduits (NGCs) that are designed and fabricated from different materials are the potential alternative to nerve autografts. However, translation of these NGCs from lab to commercial scale has not been well achieved. Complete functional recovery with the aid of NGCs in PNI becomes a topic of general interest in tissue engineering and regeneration medicine. Electrical stimulation (ES) has been widely used for many years as an effective physical method to promote nerve repair in both pre-clinical and clinical settings. Similarly, ES of conductive and electroactive materials with a broad range of electrical properties has been shown to facilitate the guidance of axons and enhance the regeneration. Graphene and its derivatives possess unique physicochemical and biological properties, which make them a promising outlook for the development of synthetic scaffolds or NGCs for PNI repair, especially in combination with ES. Considering the discussion regarding ES for the treatment of PNI must continue into further detail, herein, we focus on the role of ES in PNI repair and the molecular mechanism behind the ES therapy for PNI, providing a summary of recent advances in context of graphene-based scaffolds (GBSs) in combination with ES. Future perspectives and some challenges faced in developing GBSs are also highlighted with the aim of promoting their clinical applications.

Reduced Graphene Oxide Fibers Combined with Electrical Stimulation Promote Peripheral Nerve Regeneration.

Background: The treatment of long-gap peripheral nerve injury (PNI) is still a substantial clinical problem. Graphene-based scaffolds possess extracellular matrix (ECM) characteristic and can conduct electrical signals, therefore have been investigated for repairing PNI. Combined with electrical stimulation (ES), a well performance should be expected. We aimed to determine the effects of reduced graphene oxide fibers (rGOFs) combined with ES on PNI repair in vivo. Methods: rGOFs were prepared by one-step dimensionally confined hydrothermal strategy (DCH). Surface characteristics, chemical compositions, electrical and mechanical properties of the samples were characterized. The biocompatibility of the rGOFs were systematically explored both in vitro and in vivo. Total of 54 Sprague-Dawley (SD) rats were randomized into 6 experimental groups: a silicone conduit (S), S+ES, S+rGOFs-filled conduit (SGC), SGC+ES, nerve autograft, and sham groups for a 10-mm sciatic defect. Functional and histological recovery of the regenerated sciatic nerve at 12 weeks after surgery in each group of SD rats were evaluated. Results: rGOFs exhibited aligned micro- and nano-channels with excellent mechanical and electrical properties. They are biocompatible in vitro and in vivo. All 6 groups exhibited PNI repair outcomes in view of neurological and morphological recovery. The SGC+ES group achieved similar therapeutic effects as nerve autograft group (P > 0.05), significantly outperformed other treatment groups. Immunohistochemical analysis showed that the expression of proteins related to axonal regeneration and angiogenesis were relatively higher in the SGC+ES. Conclusion: The rGOFs had good biocompatibility combined with excellent electrical and mechanical properties. Combined with ES, the rGOFs provided superior motor nerve recovery for a 10-mm nerve gap in a murine acute transection injury model, indicating its excellent repairing ability. That the similar therapeutic effects as autologous nerve transplantation make us believe this method is a promising way to treat peripheral nerve defects, which is expected to guide clinical practice in the future.

A Co-MOF encapsulated microneedle patch activates hypoxia induction factor-1 to pre-protect transplanted flaps from distal ischemic necrosis.

Avoiding ischemic necrosis after flap transplantation remains a significant clinical challenge. Developing an effective pretreatment method to promote flap survival postoperatively is crucial. Cobalt chloride (CoCl2) can increase cell tolerance to ischemia and hypoxia condition by stimulating hypoxia-inducible factor-1 (HIF-1) expression. However, the considerable toxic effects severely limit the clinical application of CoCl2. In this study, cobalt-based metal-organic frameworks (Co-MOF) encapsulated in a microneedle patch (Co-MOF@MN) was developed to facilitate the transdermal sustained release of Co2+ for rapid, minimally invasive rapid pretreatment of flap transplantation. The MN patch was composed of a fully methanol-based two-component cross-linked polymer formula, with a pyramid structure and high mechanical strength, which satisfied the purpose of penetrating the skin stratum corneum of rat back to achieve subcutaneous vascular area administration. Benefiting from the water-triggered disintegration of Co-MOF and the transdermal delivery via the MN patch, preoperative damage and side effects were effectively mitigated. Moreover, in both the oxygen-glucose deprivation/recovery (OGD/R) cell model and the rat dorsal perforator flap model, Co-MOF@MN activated the HIF-1α pathway and its associated downstream proteins, which reduced reperfusion oxidative damage, improved blood supply in choke areas, and increased flap survival rates post-transplantation. This preprotection strategy, combining MOF nanoparticles and the MN patch, meets the clinical demands for trauma minimization and uniform administration in flap transplantation. STATEMENT OF SIGNIFICANCE: Cobalt chloride (CoCl2) can stimulate the expression of hypoxia-inducible factor (HIF-1) and improve the tolerance of cells to ischemia and hypoxia conditions. However, the toxicity and narrow therapeutic window of CoCl2 severely limit its clinical application. Herein, we explored the role of Co-MOF as a biocompatible nanocage for sustained release of Co2+, showing the protective effect on vascular endothelial cells in the stress model of oxygen-glucose deprivation. To fit the clinical needs of minimal trauma in flap transplantation, a Co-MOF@MN system was developed to achieve local transdermal delivery at the choke area, significantly improving blood supply opening and flap survival rate. This strategy of two-step delivery of Co2+ realized the enhancement of biological functions while ensuring the biosafety.

Biodegradable conduit small gap tubulization for peripheral nerve mutilation: a substitute for traditional epineurial neurorrhaphy.

Nerve regeneration and re-innervation are usually difficult after peripheral nerve injury. Epineurium neurorrhaphy to recover the nerve continuity is the traditional choice of peripheral nerve mutilation without nerve defects, whereas the functional recovery remains quite unsatisfactory. Based on previous research in SD rats and Rhesus Monkeys, a multiple centers clinical trial about biodegradable conduit small gap tubulization for peripheral nerve mutilation to substitute traditional epineurial neurorrhaphy was carried out. Herein, the authors reviewed the literature that focused on peripheral nerve injury and possible clinical application, and confirmed the clinical possibilities of biodegradable conduit small gap tubulization to substitute traditional epineurial neurorrhaphy for peripheral nerve mutilation. The biodegradable conduit small gap tubulization to substitute traditional epineurial neurorrhaphy for peripheral nerve mutilation may be a revolutionary innovation in peripheral nerve injury and repair field.

Microfluidic Manipulation for Biomedical Applications in the Central and Peripheral Nervous Systems.

Physical injuries and neurodegenerative diseases often lead to irreversible damage to the organizational structure of the central nervous system (CNS) and peripheral nervous system (PNS), culminating in physiological malfunctions. Investigating these complex and diverse biological processes at the macro and micro levels will help to identify the cellular and molecular mechanisms associated with nerve degeneration and regeneration, thereby providing new options for the development of new therapeutic strategies for the functional recovery of the nervous system. Due to their distinct advantages, modern microfluidic platforms have significant potential for high-throughput cell and organoid cultures in vitro, the synthesis of a variety of tissue engineering scaffolds and drug carriers, and observing the delivery of drugs at the desired speed to the desired location in real time. In this review, we first introduce the types of nerve damage and the repair mechanisms of the CNS and PNS; then, we summarize the development of microfluidic platforms and their application in drug carriers. We also describe a variety of damage models, tissue engineering scaffolds, and drug carriers for nerve injury repair based on the application of microfluidic platforms. Finally, we discuss remaining challenges and future perspectives with regard to the promotion of nerve injury repair based on engineered microfluidic platform technology.

S-Doped carbonized polymer dots inhibit early myocardial fibrosis by regulating mitochondrial function.

Myocardial fibrosis (MF) is a critical pathological lesion in the progression of various acute and chronic cardiovascular diseases. However, there is still a lack of clinically effective drugs and treatments for MF therapies. Herein, for the first time, we developed fluorescent sulfur-doped carbonized polymer dots (S-CPDs) as new nano-antioxidants to reduce the cardiomyocyte damage caused by reactive oxygen species (ROS) in the early stage of fibrotic lesions. In vitro results suggested that the pre-protection of S-CPDs significantly increased the survival rate of H9c2 cells under severe oxidative stress, inhibited the isoproterenol (ISO)-induced hypertrophy of myocardial cells through improving the content of mitochondria related proteins and adenosine triphosphate (ATP) in cells. Moreover, S-CPD administration could effectively decrease cardiac hypertrophy and promote heart function in MF rat models. The rapid internalization, high biocompatibility and fluorescence imaging potential of S-CPDs revealed their promising application prospects in the diagnoses and treatments of cardiovascular diseases.