Application of Silicon Nanowire Field Effect Transistor (SiNW-FET) Biosensor with High Sensitivity.

As a new type of one-dimensional semiconductor nanometer material, silicon nanowires (SiNWs) possess good application prospects in the field of biomedical sensing. SiNWs have excellent electronic properties for improving the detection sensitivity of biosensors. The combination of SiNWs and field effect transistors (FETs) formed one special biosensor with high sensitivity and target selectivity in real-time and label-free. Recently, SiNW-FETs have received more attention in fields of biomedical detection. Here, we give a critical review of the progress of SiNW-FETs, in particular, about the reversible surface modification methods. Moreover, we summarized the applications of SiNW-FETs in DNA, protein, and microbial detection. We also discuss the related working principle and technical approaches. Our review provides an extensive discussion for studying the challenges in the future development of SiNW-FETs.

Application of Simultaneous 18 F-FDG PET With Monoexponential, Biexponential, and Stretched Exponential Model-Based Diffusion-Weighted MR Imaging in Assessing the Proliferation Status of Lung Adenocarcinoma.

BACKGROUND: Ki-67 proliferation index (PI) is important for providing information on tumor behavior, treatment response, and prognosis. Integrated positron emission tomography/magnetic resonance (PET/MR) may have the potential to assess Ki-67 PI in patients with lung adenocarcinoma. PURPOSE: To explore the value of simultaneous 18 F-fluorodeoxyglucose (18 F-FDG) PET/MR-derived parameters in assessing the proliferation status of lung adenocarcinoma and to determine the best combination of parameters. STUDY TYPE: Prospective. POPULATION: Seventy-eight patients with lung adenocarcinoma and with Ki-67 PI. FIELD STRENGTH/SEQUENCE: 3.0 T, simultaneous PET/MRI including diffusion-weighted imaging (DWI) and 18 F-FDG PET. ASSESSMENT: DWI-derived parameters, namely, apparent diffusion coefficient (ADC), true diffusion coefficient (D), pseudo diffusion coefficient (D*), perfusion fraction (f), diffusion heterogeneity index (α), and distributed diffusion coefficient (DDC); and PET-derived parameters, namely, maximum standardized uptake value (SUVmax ), metabolic tumor volume (MTV), and total lesion glycolytic volume (TLG), were calculated and compared between the high (>25%) and low (≤25%) Ki-67 PI groups. The correlations between PET-derived parameters and DWI-derived parameters were analyzed. STATISTICAL TESTS: Student's t-test, Mann-Whitney U test, chi-square test, and receiver operating characteristic (ROC) curves. A P-value <0.05 was considered statistically significant. RESULTS: The SUVmax , MTV, TLG, ADC, D, and DDC values were significantly different between the high (N = 35) and low Ki-67 PI groups (N = 43). D, SUVmax , and MTV independently predicted the Ki-67 PI status. The combination of D, SUVmax , and MTV had the largest area under the ROC curve (AUC = 0.900), which was significantly larger than the AUC alone of DDC (AUC = 0.725), SUVmax (AUC = 0.815), MTV (AUC = 0.774), or TLG (AUC = 0.783). The perfusion fraction did not correlate with SUVmax , MTV, or TLG (r = -0.03, -0.11, and -0.04, respectively; P = 0.786, 0.348, and 0.733). DATA CONCLUSION: The combination of D, SUVmax , and MTV may predict Ki-67 PI status. No correlation was observed between perfusion parameters and metabolic parameters. LEVEL OF EVIDENCE: 1 TECHNICAL EFFICACY: Stage 2.

Research on exercise fatigue estimation method of Pilates rehabilitation based on ECG and sEMG feature fusion.

PURPOSE: Surface electromyography (sEMG) is vulnerable to environmental interference, low recognition rate and poor stability. Electrocardiogram (ECG) signals with rich information were introduced into sEMG to improve the recognition rate of fatigue assessment in the process of rehabilitation. METHODS: Twenty subjects performed 150 min of Pilates rehabilitation exercise. Twenty subjects performed 150 min of Pilates rehabilitation exercise. ECG and sEMG signals were collected at the same time. Aftering necessary preprocessing, the classification model of improved particle swarm optimization support vector machine base on sEMG and ECG data fusion was established to identify three different fatigue states (Relaxed, Transition, Tired). The model effects of different classification algorithms (BPNN, KNN, LDA) and different fused data types were compared. RESULTS: IPSO-SVM had obvious advantages in the classification effect of sEMG and ECG signals, the average recognition rate was 87.83%. The recognition rates of sEMG and ECG fusion feature classification models were 94.25%, 92.25%, 94.25%. The recognition accuracy and model performance was significantly improved. CONCLUSION: The sEMG and ECG signal after feature fusion form a complementary mechanism. At the same time, IPOS-SVM can accurately detect the fatigue state in the process of Pilates rehabilitation. On the same model, the recognition effect of fusion of sEMG and ECG(Relaxed: 98.75%, Transition:92.25%, Tired:94.25%) is better than that of only using sEMG signal or ECGsignal. This study establishes technical support for establishing relevant man-machine devices and improving the safety of Pilates rehabilitation.

Activation of MC1R with BMS-470539 attenuates neuroinflammation via cAMP/PKA/Nurr1 pathway after neonatal hypoxic-ischemic brain injury in rats.

BACKGROUND: Microglia-mediated neuroinflammation plays a crucial role in the pathogenesis of hypoxic-ischemic (HI)-induced brain injury. Activation of melanocortin-1 receptor (MC1R) has been shown to exert anti-inflammatory and neuroprotective effects in several neurological diseases. In the present study, we have explored the role of MC1R activation on neuroinflammation and the potential underlying mechanisms after neonatal hypoxic-ischemic brain injury in rats. METHODS: A total of 169 post-natal day 10 unsexed rat pups were used. HI was induced by right common carotid artery ligation followed by 2.5 h of hypoxia. BMS-470539, a specific selective MC1R agonist, was administered intranasally at 1 h after HI induction. To elucidate the potential underlying mechanism, MC1R CRISPR KO plasmid or Nurr1 CRISPR KO plasmid was administered via intracerebroventricular injection at 48 h before HI induction. Percent brain infarct area, short- and long-term neurobehavioral tests, Nissl staining, immunofluorescence staining, and Western blot were conducted. RESULTS: The expression levels of MC1R and Nurr1 increased over time post-HI. MC1R and Nurr1 were expressed on microglia at 48 h post-HI. Activation of MC1R with BMS-470539 significantly reduced the percent infarct area, brain atrophy, and inflammation, and improved short- and long-term neurological deficits at 48 h and 28 days post-HI. MC1R activation increased the expression of CD206 (a microglial M2 marker) and reduced the expression of MPO. Moreover, activation of MC1R with BMS-470539 significantly increased the expression levels of MC1R, cAMP, p-PKA, and Nurr1, while downregulating the expression of pro-inflammatory cytokines (TNFα, IL-6, and IL-1ß) at 48 h post-HI. However, knockout of MC1R or Nurr1 by specific CRISPR reversed the neuroprotective effects of MC1R activation post-HI. CONCLUSIONS: Our study demonstrated that activation of MC1R with BMS-470539 attenuated neuroinflammation, and improved neurological deficits after neonatal hypoxic-ischemic brain injury in rats. Such anti-inflammatory and neuroprotective effects were mediated, at least in part, via the cAMP/PKA/Nurr1 signaling pathway. Therefore, MC1R activation might be a promising therapeutic target for infants with hypoxic-ischemic encephalopathy (HIE).

CdS Reinforced with CoSX /NiCo-LDH Core-shell Co-catalyst Demonstrate High Photocatalytic Hydrogen Evolution and Durability in Anhydrous Ethanol.

At present, inefficient charge separation of single photocatalyst impedes the development of photocatalytic hydrogen evolution. In this work, the CoSX /NiCo-LDH core-shell co-catalyst was cleverly designed, which exhibit high activity and high stability of hydrogen evolution in anhydrous ethanol system when coupled with CdS. Under visible light (λ≥420 nm) irradiation, the 3 %Co/NiCo/CdS composite photocatalyst exhibits a surprisingly high photocatalytic hydrogen evolution rate of 20.67 mmol g-1 h-1 , which is 59 times than that of the original CdS. Continuous light for 20 h still showed good cycle stability. In addition, the 3 %Co/NiCo/CdS composite catalyst also shows good hydrogen evolution performance under the Na2 S/Na2 SO3 and lactic acid system. The fluorescence (PL), ultraviolet-visible diffuse reflectance (UV-vis) and photoelectrochemical tests show that the coupling of CdS and CoSX /NiCo-LDH not only accelerates the effective transfer of charges, but also greatly increases the absorption range of CdS to visible light. Therefore, the hydrogen evolution activity of the composite photocatalyst has been significantly improved. This work will provide new insights for the construction of new co-catalysts and the development of composite catalysts for hydrogen evolution in multiple systems.

A Nanoparticle Delivery of Plasmid Encoding Hepatocyte Growth Factor for Gene Therapy of Silicosis in Mice.

PURPOSE: Silicosis is a serious occupational disease that is characterized by pulmonary infiltrates and fibrosis and is often refractory to current treatments. New therapeutic strategies for silicosis are needed. Hepatocyte growth factor (HGF) is a latent anti-inflammatory and anti-fibrotic growth factor. METHODS: We prepared a polyethyleneimine-polyethylene glycol/pHGF/hyaluronic acid (PEG-PEI/pHGF/HA) nanomaterials loaded with plasmid DNA encoding HGF gene to increase its transfection efficiency. The characterization, including DNA entrapment efficiency, morphology, particle size, and zeta-potential of PEG-PEI/pHGF/HA was studied. And a PEG-PEI/pHGF/HA (N/P=30:1) nanoparticle with low toxicity and high transfection efficiency was used in treatment for silicosis in mice. RESULTS: The results showed that the human HGF expression in the lungs of the mice was increased, and the inflammatory cell infiltration and fibrous collagen deposition was significantly reduced. CONCLUSION: Therefore, PEG-PEI/pHGF/HA nanoparticle warrant further investigation and may be a potential therapeutic strategy for silicosis.

[Research Progress on Electrochemical Biosensors for Breast Cancer Detection Based on Nanomaterials].

Breast cancer is one of the most serious diseases threatening women's life and health in the world, and the mortality rate is the second in the world. With the progress of nanotechnology and the advantages of nanomaterials in the field of electrochemistry and biosensor, various nanomaterials have been applied in electrochemical biosensors. This makes the electrochemical nano-biosensor in the field of rapid detection of breast cancer has been widely concerned and studied. This paper introduces the important components of electrochemical nano-biosensor for breast cancer detection and the research progress of each component in breast cancer detection, as well as the performance of electrochemical nano biosensor in breast cancer detection and the prospect of its application.

Hollow and porous nickel sulfide nanocubes prepared from a metal-organic framework as an efficient enzyme mimic for colorimetric detection of hydrogen peroxide.

Hollow, porous NiS nanocubes were prepared by a hydrothermal method starting from Ni-Co Prussian blue analogue nanocubes as the template. The morphology and structure of the NiS nanocubes were tuned by adjustment of the ion-exchange rate and the degree of chemical etching, and they were characterized by scanning electron microscopy, energy-dispersive X-ray spectroscopy, transmission electron microscopy, X-ray diffraction, and nitrogen sorption measurements. The NiS nanocubes are shown to act as a peroxidase mimic that can catalyze the oxidization of 3,3',5,5'-tetramethylbenzidine by hydrogen peroxide (H2O2), producing a visible color change, for which the absorbance is best measured at 652 nm. The outstanding activity may result from the unique structure of the NiS nanocubes. The catalytic oxidation follows Michaelis-Menten kinetics and shows a ping-pong mechanism of enzyme action. The findings were used to develop a rapid, sensitive, and selective colorimetric H2O2 assay with a response that is linear in the 4-40 µM range with a detection limit of 1.72 µM (signal-to-noise ratio of 3). Graphical abstarct ᅟ.

Erratum: Li, D.; Scarano, S.; Lisi, S.; Palladino, P.;Minunni, M. Real-Time Tau Protein Detection bySandwich-Based Piezoelectric Biosensing: ExploringTubulin as a Mass Enhancer. Sensors 2018, 18, 946.

The authors wish to make the following erratum to this paper [...].

Primary central nervous system extranodal nasal-type natural killer/T-cell lymphoma with CD20 expression.

We report a unique case of primary CNS extranodal natural killer/T-cell lymphoma (PCNS ENKTCL) with CD20 expression and the monoclonal rearrangement of Ig heavey chain (IgH) gene. Resection specimens were evaluated using HE-stained sections, immunohistochemistry, in situ hybridization and PCR. Histopathologic examination, immunohistochemistry and molecular studies showed the intermediate-sized lymphoma cells expressing CD2, CD3ε, granzyme B, TIA-1, CD20 and Epstein-Barr virus-encoded RNA, with germline T-cell receptor gene and the monoclonal rearrangement of IgH gene. Clinicopathologic and radiographic evaluation indicated the lesion was of exclusive left cerebellar localization. Thus, PCNS ENKTCL with the CD20 expression was diagnosed. ENKTCL with both CD20-positive expression and the monoclonal rearrangement of IgH gene may be mistaken for B-cell lymphoma; thus, the comprehensive evaluation of histomorphology, more extensive immunoprofiles and molecular studies is essential to reach the correct diagnosis. The rare PCNS ENKTCL shows a highly aggressive nature and a poorer prognosis.

Real-Time Tau Protein Detection by Sandwich-Based Piezoelectric Biosensing: Exploring Tubulin as a Mass Enhancer.

Human tau protein is one of the most advanced and accepted biomarkers for AD and tauopathies diagnosis in general. In this work, a quartz crystal balance (QCM) immunosensor was developed for the detection of human tau protein in buffer and artificial cerebrospinal fluid (aCSF), through both direct and sandwich assays. Starting from a conventional immuno-based sandwich strategy, two monoclonal antibodies recognizing different epitopes of tau protein were used, achieving a detection limit for the direct assay in nanomolar range both in HBES-EP and aCSF. Afterward, for exploring alternative specific receptors as secondary recognition elements for tau protein biosensing, we tested tubulin and compared its behavior to a conventional secondary antibody in the sandwich assay. Tau-tubulin binding has shown an extended working range coupled to a signal improvement in comparison with the conventional secondary antibody-based approach, showing a dose-response trend at lower tau concentration than is usually investigated and closer to the physiological levels in the reference matrix for protein tau biomarker. Our results open up new and encouraging perspectives for the use of tubulin as an alternative receptor for tau protein with interesting features due to the possibility of taking advantage of its polymerization and reversible binding to this key hallmark of Alzheimer's disease.

Pentraxin 3 promotes oxLDL uptake and inhibits cholesterol efflux from macrophage-derived foam cells.

BACKGROUND: The objective of this study was to determine the effects of pentraxin3 (PTX3) on human oxidized low density lipoprotein (oxLDL) uptake and cholesterol efflux from human macrophage foam cells, which may play a critical role in atherogenesis. METHODS: The effects of PTX3 on oxLDL uptake and cholesterol efflux were determined after transfection of human THP-1 macrophages with pSG5hPTX3 or PTX3siRNA plasmids. To evaluate the role of specific signaling pathways, human THP-1 cells were pre-treated with inhibitors of the extracellular signal-regulated protein kinases 1 and 2 (ERK1/2), phosphatidylinositide 3-kinases (PI3-K), and p38 mitogen-activated protein kinase (MAPK) pathways (PD98059, LY294002, and SB203580, respectively), and then exposed to oxLDL for the uptake assay or oxLDL and [(3)H]-cholesterol and apolipoprotein A-I (apoA-I) for the cholesterol efflux assay. RESULTS: PTX3 overexpression not only promoted oxLDL uptake but also significantly reduced cholesterol efflux to apoA-I; it also significantly decreased the expression of peroxisome proliferator-activated receptor-γ (PPARγ), liver X receptor alpha (LXRα) and ATP-binding membrane cassette transporter A-1 (ABCA1), which was increased with PTX3 silencing. Furthermore, PTX3 significantly increased p-ERK1/2 levels in THP-1-derived foam cells, and inhibition of ERK1/2 by PD98059 significantly reduced the oxLDL uptake and promoted the cholesterol efflux induced by PTX3 overexpression. CONCLUSION: Here, we demonstrate that PTX3 affects lipid accumulation in human macrophages, increasing oxLDL uptake and inhibiting cholesterol efflux. That is the underlying possible mechanisms of PTX3 contribution to the progression of atherosclerosis.

Extragastrointestinal stromal tumor presenting as a recurrent vulvar mass.

Extragastrointestinal stromal tumors (EGIST) primarily arising from the female genital tract are extremely rare. We report a case of EGIST presenting as a recurrent vulvar mass with genetic analyses. A 59-year-old woman was found to have a 4-cm recurrent mass in the right vulva after 6 months of the first resection. Histological findings showed that the uniform spindle cells formed interlacing bundles, with high cellular density and mild to moderate atypia. Mitotic activity averaged 10 mitoses per 50 high-power fields. Immunohistochemical evaluation revealed that the tumor cells exhibited strong and diffuse staining for CD117, CD34 and DOG1. Ki67 labeling was approximately 15%. Molecular analysis showed an in-frame protein deletion (P551_Q556del) at exon 11 of c-KIT. The tumor was diagnosed as an EGIST. The patient was treated with imatinib, and was healthy at 12-month follow-up. EGIST should be considered in the differential diagnosis of vulvar mesenchymal tumors.

Potential of V-Si72, V-C72, and V-Al36N36 as catalysts for oxygen reduction reaction.

CONTEXT: The capacities of V-Si72, V-C72, and V-Al36N36 nanocages to catalyze the ORR processes have been investigated. The acceptable pathways of ORR processes on V-Si72, V-C72, and V-Al36N36 nanocages have been examined by DSD-PBEPBE-D3/aug-cc-pVDZ, PW91PW91/aug-cc-pVDZ, and COSMO model in the gas phase and water. The ΔGreaction values of reaction steps of ORR pathways on V-Si72, V-C72, and V-Al36N36 nanocages are calculated. The Eadoption and Eformation of V-Si72, V-C72, and V-Al36N36 nanocages are negative values and these nanostructures are stable materials. The H2O has the lowest Eadsorption on V-Si72, V-C72, and V-Al36N36 nanocages. The *OH formation, creation of *OH-OH*, and formation of O* are rate-determining steps of ORR mechanisms. The overpotential values of ORR processes on V-Si72, V-C72, and V-Al36N36 nanocages are 0.41, 0.37, and 0.30 V, respectively. The V-Al36N36 nanocage have lower overpotential for ORR processes than V-Si72 and V-C72 nanocages by DSD-PBEPBE-D3/aug-cc-pVDZ, PW91PW91/aug-cc-pVDZ, and COSMO model in the gas phase and water. The V-Al36N36 nanocage have more negative ∆Greaction for reaction steps of ORR than V-Si72 and V-C72 nanocages. The V-Al36N36 nanocage with lower overpotential is proposed as an effective catalyst for ORR processes via studied pathways. METHODS: The DSD-PBEPBE-D3/aug-cc-pVDZ method has been used to optimize and calculate the frequencies of V-Si72, V-C72, and V-Al36N36 nanocages in GAMESS software. The complexes of O, OH, OOH, and H2O with V-Si72, V-C72, and V-Al36N36 nanocages are optimized and frequencies are determined by the DSD-PBEPBE-D3/aug-cc-pVDZ method. The Gactivation and ∆Greaction of ORR pathways on V-Si72, V-C72, and V-Al36N36 nanocages are calculated by DSD-PBEPBE-D3/aug-cc-pVDZ, PW91PW91/aug-cc-pVDZ, and COSMO model in the gas phase and water.

Research on the recognition model of exercise fatigue based on the fusion of sEMG and ECG signals.

This study significantly enhances the accuracy of exercise state identification in wearable devices through improved denoising techniques for sEMG and ECG signals. By adopting an optimized Variational Mode Decomposition (VMD) method, combined with the Improved Sparrow Search Algorithm and Second Generation Wavelet Transform (ISSA-VMD-SWT), and introducing chaos mapping to strengthen the algorithm's initial population, this approach effectively reduces noise while preserving key fatigue-related features. In tests conducted on data from 32 participants, the method achieved accuracy rates of 93.25%, 95.16%, and 93.05% for identifying "Easy," "Transition," and "Tired" exercise states, respectively, showing significant advantages over traditional denoising techniques. These results indicate that the denoising technology developed in this study represents a significant technological advancement for the application of ECG and sEMG fatigue identification technologies in wearable health monitoring devices.

A Simple Sandwich Electrochemical Immunosensor for Rapid Detection of the Alzheimer's Disease Biomarker Tau Protein.

As a typical biomarker of Alzheimer's disease, rapid and specific detection of tau protein can help improve the early diagnosis and prognosis of the disease. In this study, a simple sandwich electrochemical immunosensor was developed for rapid detection of tau protein. Primary monoclonal antibodies (mAb1) against the middle domain of tau protein (amino acids 189-195) were immobilized on the gold electrode surface through a self-assembled monolayer (SAM) of 3,3'-dithiobis (sulfosuccinimidyl propionate) (DTSSP). Then the tau protein was captured through the specific adsorption between the antigen and the antibody, resulting in a change in the impedance. Secondary monoclonal antibodies (mAb2) against the N-terminal region of tau protein were used for further amplification of the binding reaction between mAb1 and tau protein. A linear correlation between the total change in impedance and the logarithm of tau concentration was found from 2 × 10-6 mg mL-1 to 2 × 10-3 mg mL-1, with a detection limit as low as 1 × 10-6 mg mL-1. No significant interference was observed from human serum albumin. Furthermore, the fabricated sandwich immunosensor successfully detected target tau protein in artificial cerebrospinal fluid (aCSF) samples, indicating good potential for clinical applications in the future.

Unveiling Organic Electrode Materials in Aqueous Zinc-Ion Batteries: From Structural Design to Electrochemical Performance.

Aqueous zinc-ion batteries (AZIBs) are one of the most compelling alternatives of lithium-ion batteries due to their inherent safety and economics viability. In response to the growing demand for green and sustainable energy storage solutions, organic electrodes with the scalability from inexpensive starting materials and potential for biodegradation after use have become a prominent choice for AZIBs. Despite gratifying progresses of organic molecules with electrochemical performance in AZIBs, the research is still in infancy and hampered by certain issues due to the underlying complex electrochemistry. Strategies for designing organic electrode materials for AZIBs with high specific capacity and long cycling life are discussed in detail in this review. Specifically, we put emphasis on the unique electrochemistry of different redox-active structures to provide in-depth understanding of their working mechanisms. In addition, we highlight the importance of molecular size/dimension regarding their profound impact on electrochemical performances. Finally, challenges and perspectives are discussed from the developing point of view for future AZIBs. We hope to provide a valuable evaluation on organic electrode materials for AZIBs in our context and give inspiration for the rational design of high-performance AZIBs.

Forskolin is an effective therapeutic small molecule for the treatment of hypertrophic cardiomyopathy through ADCY6/cAMP/PKA pathway.

Hypertrophic cardiomyopathy (HCM) arises from a pathogenic variant in the gene responsible for encoding the myocardium-associated protein. Forskolin (FSK), a labdane diterpene isolated from Sphingomonas capillaris, exhibits diverse pharmacological effects, including bronchospasm relief, intraocular pressure reduction, and glaucoma treatment. However, whether FSK could regulate HCM and its associated mechanism remains unclear. Here, we discovered that FSK could mitigate cardiac hypertrophy in two HCM mouse models (Myh6R404Q and Tnnt2R109Q) in vivo. Additionally, FSK could prevent norepinephrine (NE)-induced cardiomyocyte hypertrophy in vitro. It reversed cardiac dysfunction, reduced enlarged cell size, and downregulated the expression of hypertrophy-related genes. We further demonstrated that FSK's mechanism in alleviating HCM relied on the activation of ADCY6. In conclusion, our findings demonstrate that FSK alleviates hypertrophic cardiomyopathy by modulating the ADCY6/cAMP/PKA pathway, suggesting that FSK holds promise as a therapeutic agent for HCM.

Local Multiple-site Injections of a Plasmid Encoding Human MnSOD Mitigate Radiation-induced Skin Injury by Inhibiting Ferroptosis.

BACKGROUND: Most patients who undergo radiotherapy develop radiation skin injury, for which effective treatment is urgently needed. MnSOD defends against reactive oxygen species (ROS) damage and may be valuable for treating radiation-induced injury. Here, we (i) investigated the therapeutic and preventive effects of local multiple-site injections of a plasmid, encoding human MnSOD, on radiation-induced skin injury in rats and (ii) explored the mechanism underlying the protective effects of pMnSOD. METHODS: The recombinant plasmid (pMnSOD) was constructed with human cytomegalovirus (CMV) promoter and pUC-ori. The protective effects of pMnSOD against 20-Gy X-ray irradiation were evaluated in human keratinocytes (HaCaT cells) by determining cell viability, ROS levels, and ferroptosisrelated gene expression. In therapeutic treatment, rats received local multiple-site injections of pMnSOD on days 12, 19, and 21 after 40-Gy γ-ray irradiation. In preventive treatment, rats received pMnSOD injections on day -3 pre-irradiation and on day 4 post-irradiation. The skin injuries were evaluated based on the injury score and pathological examination, and ferroptosis-related gene expression was determined. RESULTS: In irradiated HaCaT cells, pMnSOD transfection resulted in an increased SOD2 expression, reduced intracellular ROS levels, and increased cell viability. Moreover, GPX4 and SLC7A11 expression was significantly upregulated, and erastin-induced ferroptosis was inhibited in HaCaT cells. In the therapeutic and prevention treatment experiments, pMnSOD administration produced local SOD protein expression and evidently promoted the healing of radiation-induced skin injury. In the therapeutic treatment experiments, the injury score in the high-dose pMnSOD group was significantly lower than in the PBS group on day 33 post-irradiation (1.50 vs. 2.80, P < 0.05). In the prevention treatment experiments, the skin injury scores were much lower in the pMnSOD administration groups than in the PBS group from day 21 to day 34. GPX4, SLC7A11, and Bcl-2 were upregulated in irradiated skin tissues after pMnSOD treatment, while ACSL4 was downregulated. CONCLUSION: The present study provides evidence that the protective effects of MnSOD in irradiated HaCaT cells may be related to the inhibition of ferroptosis. The multi-site injections of pMnSOD had clear therapeutic and preventive effects on radiation-induced skin injury in rats. pMnSOD may have therapeutic value for the treatment of radiation-induced skin injury.

A recombinant plasmid encoding human hepatocyte growth factor promotes healing of combined radiation-trauma skin injury involved in regulating Nrf2 pathway in mice.

Combined radiation-trauma skin injury represents a severe and intractable condition that urgently requires effective therapeutic interventions. In this context, hepatocyte growth factor (HGF), a multifunctional growth factor with regulating cell survival, angiogenesis, anti-inflammation and antioxidation, may be valuable for the treatment of combined radiation-trauma injury. This study investigated the protective effects of a recombinant plasmid encoding human HGF (pHGF) on irradiated human immortalized keratinocytes (HaCaT) cells in vitro, and its capability to promote the healing of combined radiation-trauma injuries in mice. The pHGF radioprotection on irradiated HaCaT cells in vitro was assessed by cell viability, the expression of Nrf2, Bcl-2 and Bax, as well as the secretion of inflammatory cytokines. In vivo therapeutic treatment, the irradiated mice with full-thickness skin wounds received pHGF local injection. The injuries were appraised based on relative wound area, pathology, immunohistochemical detection, terminal deoxynucleotidyl transferase dUTP nick end labelling assay and cytokine content. The transfection of pHGF increased the cell viability and Nrf2 expression in irradiated HaCaT cells. pHGF also significantly upregulated Bcl-2 expression, decreased the Bax/Bcl-2 ratio and inhibited the expression of interleukin-1ß and tumor necrosis factor-α in irradiated cells. Local pHGF injection in vivo caused high HGF protein expression and noticeable accelerated healing of combined radiation-trauma injury. Moreover, pHGF administration upregulated Nrf2, vascular endothelial growth factor, Bcl-2 expression, downregulated Bax expression and mitigated inflammatory response. In conclusion, the protective effect of pHGF may be related to inhibiting apoptosis and inflammation involving by upregulating Nrf2. Local pHGF injection distinctly promoted the healing of combined radiation-trauma injury and demonstrates potential as a gene therapy intervention for combined radiation-trauma injury in clinic.