Unveiling the mechanism of photothermal therapy in acne man-agement: targeting sebaceous gland ferroptosis via umbilical cord mesenchymal stem cell membrane-encapsulated Au-Ag-PDA.

Background: Branched gold and silver nanoparticles coated with polydopamine (Au-Ag-PDA) demonstrate high photothermal conversion efficiency. Utilizing umbilical cord mesenchymal stem cell membranes (MSCM) as an effective drug delivery system, our preliminary studies investigated the suppression of sebum secretion in sebaceous glands using MSCM-coated Au-Ag-PDA nano-particles (Au-Ag-PDA@MSCM) combined with 808 nm laser irradiation, showing potential for dermatological applications in acne treatment. Methods: This study employs proteomic analysis, complemented by subsequent techniques such as Western blotting (WB), small interfering RNA (siRNA), and transmission electron microscopy, to further investigate the differential mechanisms by which Au-Ag-PDA and Au-Ag-PDA@MSCM-mediated photothermal therapy (PTT) suppress sebum secretion. Results: Our proteomic analysis indicated mitochondrial respiratory chain damage in sebaceous gland tissues post-PTT, with further validation revealing ferroptosis in sebaceous cells and tissues. Acyl-CoA Synthetase Long-Chain Family Member 4 (Acsl4) has been identified as a critical target, with Au-Ag-PDA@MSCM demonstrating enhanced ferroptotic effects. Conclusion: These findings significantly advance our understanding of how PTT mediated by Au-Ag-PDA@MSCM nanoparticles reduces sebum secretion and underscore the pivotal role of MSCM in inducing ferroptosis in sebaceous glands, thus providing a robust theoretical foundation for employing PTT via specific molecular pathways in acne treatment.

Preliminary outcomes of endovascular treatment of moyamoya disease.

PURPOSE: This study aimed to investigate the effectiveness and safety of endovascular revascularisation of intracranial artery occlusion and stenosis in moyamoya disease using stent angioplasty. MATERIALS AND METHODS: We recruited 12 patients (8 women and 4 men) with occlusion and stenosis of intracranial arteries in the context of moyamoya disease who underwent endovascular stent angioplasty. Clinical data, baseline conditions, lesion location, treatment outcomes, periprocedural complications, and follow-up outcomes were analysed. RESULTS: The occlusion was located at the M1 segment of the middle cerebral artery in 8 patients, at both the M1 and A2 segments in one patient, and at the C7 segment of the internal carotid artery in 3. Thirteen stents were deployed at the occlusion site, including the low-profile visualized intraluminal support (LVIS) device in 8 patients, an LVIS device and a Solitaire AB stent in one, and a Leo stent in 3, with a success rate of 100% and no intraprocedural complications. Plain CT imaging after stenting revealed leakage of contrast agent, which disappeared on the second day, resulting in no clinical symptoms or neurological sequelae. Follow-up angiography studies were performed in all patients for 6-12 months (mean, 8.8). Slight asymptomatic in-stent stenosis was observed in 2 patients (16.7%), and no neurological deficits were observed in the other patients. All preoperative ischaemic symptoms completely disappeared at follow-up. CONCLUSION: Stent angioplasty is a safe and effective treatment for occlusion and stenosis of intracranial arteries in moyamoya disease.

Final-year nursing students' perceptions of humanistic education in nursing: a cross-sectional descriptive study.

BACKGROUND: Humanistic education is an important part of nursing education. Final-year nursing students' perceptions of nursing humanistic education are under-investigated. This study aimed to examined final-year nursing students' perceptions of nursing humanistic education in both school and hospital. METHODS: This was a cross-sectional descriptive study conducted from May to June 2022 among 107 final-year nursing students with a self-designed questionnaire. RESULTS: Final-year nursing students recognized the importance of humanistic education, scoring above 4.0 on a 1-5 scale, while their initiative to enhance humanistic qualities was relatively low. Students' satisfaction with the number of humanities courses offered was only 3.7 ± 0.862. Moreover, 62.6% of students believed there was a need to enhance humanistic environmental development including corridor culture. The "monotonous teaching format" (63.6%) and "teaching methods" (64.5%) have emerged as focal points that students identified as needing attention and improvement. CONCLUSIONS: In the future, nursing humanistic education can be enhanced by increasing the proportion of humanities, improving teaching methods, stimulating students' learning motivation, and strengthening the construction of humanistic environment.

QSAR Study, Molecular Docking and Molecular Dynamic Simulation of Aurora Kinase Inhibitors Derived from Imidazo[4,5-b]pyridine Derivatives.

Cancer is a serious threat to human life and social development and the use of scientific methods for cancer prevention and control is necessary. In this study, HQSAR, CoMFA, CoMSIA and TopomerCoMFA methods are used to establish models of 65 imidazo[4,5-b]pyridine derivatives to explore the quantitative structure-activity relationship between their anticancer activities and molecular conformations. The results show that the cross-validation coefficients q2 of HQSAR, CoMFA, CoMSIA and TopomerCoMFA are 0.892, 0.866, 0.877 and 0.905, respectively. The non-cross-validation coefficients r2 are 0.948, 0.983, 0.995 and 0.971, respectively. The externally validated complex correlation coefficients r2pred of external validation are 0.814, 0.829, 0.758 and 0.855, respectively. The PLS analysis verifies that the QSAR models have the highest prediction ability and stability. Based on these statistics, virtual screening based on R group is performed using the ZINC database by the Topomer search technology. Finally, 10 new compounds with higher activity are designed with the screened new fragments. In order to explore the binding modes and targets between ligands and protein receptors, these newly designed compounds are conjugated with macromolecular protein (PDB ID: 1MQ4) by molecular docking technology. Furthermore, to study the nature of the newly designed compound in dynamic states and the stability of the protein-ligand complex, molecular dynamics simulation is carried out for N3, N4, N5 and N7 docked with 1MQ4 protease structure for 50 ns. A free energy landscape is computed to search for the most stable conformation. These results prove the efficient and stability of the newly designed compounds. Finally, ADMET is used to predict the pharmacology and toxicity of the 10 designed drug molecules.

Arterial spin labeling combined with T1 mapping for assessment of kidney function and histopathology in patients with long-term renal transplant survival after kidney transplantation.

Background: The long-term survival of kidney transplants is often influenced by various factors, among which renal allograft rejection is the most notable factor. A noninvasive and reliable imaging biomarker correlating with kidney function and histopathology would facilitate longitudinal long-term follow-up of renal allografts. The aim of the study is to investigate the value of arterial spin labeling (ASL) combined with T1 mapping for assessing kidney function in patients with long-term renal transplant survival, and to establish radiological and histopathologic correlations between the magnetic resonance imaging (MRI) measurements and kidney allograft biopsy findings. Methods: Kidney transplant recipients who were admitted to the Department of Urology in First Affiliated Hospital of Soochow University between January and December 2022 were prospectively consecutively recruited [group A, estimated glomerular filtration rate (eGFR) ≥60 mL/min/1.73 m2; group B, 30≤ eGFR <60 mL/min/1.73 m2; group C, eGFR <30 mL/min/1.73 m2], and part of them underwent biopsies. All patients underwent ASL and T1 mapping. MRI parameters were calculated and analyzed. Results: A total of 63 patients (Group A, 30 cases; Group B, 20 cases; and Group C, 13 cases) were included in this cross-sectional study. Cortical T1 increased, whereas renal blood flow (RBF) and ΔT1 [100% × (cortical T1 - medullary T1)/cortical T1] decreased with the decrease of eGFR. The RBF, cortical T1, and ΔT1 values were moderately correlated with eGFR (r=0.569, -0.573, and 0.672, respectively). The MRI parameters were moderately correlated with Banff scores, which determined renal allograft rejection and chronicity. The area under the curve (AUC) for the discrimination of groups A versus B and groups A versus C were 0.740 [95% confidence interval (CI): 0.597-0.854, P=0.004] and 0.923 (95% CI: 0.800-0.982, P<0.001), respectively, using ASL; 0.873 (95% CI: 0.749-0.950, P<0.001) and 0.926 (95% CI: 0.803-0.983, P<0.001), respectively, using T1 mapping; and 0.892 (95% CI: 0.771-0.962, P<0.001) and 0.956 (95% CI: 0.846-0.995, P<0.001), respectively, using multi-parameter MRI. The AUC for discrimination between groups B and C was 0.729 (95% CI: 0.546-0.868, P=0.02) using ASL. Conclusions: The RBF, cortical T1, and ΔT1 can serve as new imaging biomarkers of kidney function and histopathological microstructure.

MR Spectroscopy Assessment of Daily Variations of GABA Levels within the Parietal Lobe and Anterior Cingulate Gyrus Regions of Healthy Young Adults.

BACKGROUND: The changes that occur in the gamma-aminobutyric acid (GABA) levels within specific brain regions throughout the day are less clear. PURPOSE: To evaluate the daily fluctuations of GABA levels within the parietal lobe (PL) and anterior cingulate gyrus (ACC) regions and explore their association with melatonin (MT) levels, heart rate (HR), and blood pressure. STUDY TYPE: Prospective. SUBJECTS: 26 healthy young adults (15 males and 11 females aged 22-27 years). FIELD STRENGTH/SEQUENCE: 3.0T, T1-weighted imaging, Mescher-Garwood point resolved spectroscopy (MEGA-PRESS) sequence. ASSESSMENT: The acquired GABA signal contained the overlapping signals of macromolecules and homocarnosine, hence expressed as GABA+. The creatine (Cr) signal was applied as an endogenous reference. The GABA+, GABA+/Cr were measured at six different time points (1:00, 5:00, 9:00, 13:00, 17:00, and 21:00 hours) using MEGA-PRESS. The blood pressure, HR and sputum MT levels, were also acquired. STATISTICAL TESTS: The one-way repeated-measures analysis of variance (ANOVA) was used to evaluate the GABA, blood pressure, HR, and MT levels throughout the day. A general linear model was used to find the correlation between GABA and blood pressure, HR, and MT. P < 0.05 was statistically significant. RESULTS: Significant variations in GABA+/Cr and GABA+ levels were observed throughout the day within the PL region. The lowest levels were recorded at 9:00 hour (GABA+/Cr: 0.100 ± 0.003，GABA+:1.877 ± 0.051 i.u) and the highest levels were recorded at 21:00 hour (GABA+/Cr: 0.115 ± 0.003, GABA+:2.122 ± 0.052 i.u). The MT levels were positively correlated with GABA+/Cr (r = 0.301) and GABA+ (r = 0.312) within the ACC region. DATA CONCLUSION: GABA+/Cr and GABA+ in ACC are positively correlated with MT. GABA levels in the PL have diurnal differences. These findings may indicate that the body's GABA level change in response to the light-dark cycle. LEVEL OF EVIDENCE: 1 TECHNICAL EFFICACY: Stage 2.

Efficacy of acupuncture therapy for spastic paralysis in post-stroke patients: a systematic review and meta-analysis.

BACKGROUND: Despite the potentially good efficacy of acupuncture therapy in the management of post-stroke spastic paralysis demonstrated in previous studies, further verification through meta-analysis can be conducive to eliminating the inconclusive of treatment outcomes in prior findings. This systematic review and meta-analysis were thus performed to comprehensively investigate the effects of acupuncture on the daily living abilities, upper and lower limb motor function, and related functional indices of post-stroke patients with spastic paralysis. METHODS: We conducted a computer search to collect data from PubMed, PEDro, Clinical SportDiscus, and Scopus. The inclusion criteria followed the Population-Intervention-Comparison-Outcome (PICO) principle. Literature screening, data extraction, and quality assessment of the research articles were performed by two independent investigators. Standard mean difference and 95% confidence intervals of the data were analyzed using either a random-effects model or a fixed-effects model. RESULTS: Acupuncture therapy appeared to be effective in mitigating the limb pain of post-stroke patients with spastic paralysis (RR = -0.04, 95% CI: -0.26, 0.17), ameliorating their daily life ability (RR = 4.66, 95% CI: -0.74, 10.05), and improving their hand function (RR = 0.65, 95% CI: 0.40, 0.90) and lower limb function (RR = 0.35, 95% CI: 0.09, 0.62). CONCLUSION: Acupuncture therapy provides more pronounced improvement in the daily life ability and limb motor function of post-stroke patients with spastic paralysis than conventional treatment regimens. Thus, acupuncture therapy can be a viable treatment option for the management of spastic paralysis following stroke.

A Survey on the Current Status of Adult External Ventricular Drainage Care: Exploring Content Framework and the Need for Group Standards.

Background: External ventricular drainage (EVD), a widely used clinical procedure, faces slow translation of knowledge into practice due to practical barriers. The scarcity of high-quality data in the past EVD management and neurocritical care research compounds the challenge. Objective: This study aims to investigate the current status of adult external ventricular drainage care among neurosurgical nurses, delineate nursing priorities and challenges, and explore the necessity for establishing standardized guidelines for external ventricular drainage care. Methods: We conducted a systematic literature search to identify existing clinical guidelines, systematic reviews, evidence summaries, and expert consensus on adult external ventricular drainage care. We developed an electronic questionnaire titled "Survey on the Current Status of Adult External Ventricular Drainage Care" based on our search results. We distributed it to certified registered neurosurgical nurses working in the top 20 neurosurgery hospitals, per the 2022 Fudan Hospital Ranking published by the Institute of Hospital Management at Fudan University. Results: Effective control of drainage speed and total volume is a crucial aspect of nursing care. Existing guidelines primarily emphasize infection prevention in the context of complication care. However, it was observed that nursing staff exhibited limited knowledge concerning the total volume (58.7%) and rate of cerebrospinal fluid drainage (50.8%), as well as the management of complications (56.7%). Factors influencing the extent of nursing knowledge related to external ventricular drainage care include levels of education (P = .022), professional titles (P = .004), department assignments (P < .001), and the completion of relevant training (P = .01). Conclusions: Establishing standardized guidelines for external ventricular drainage care is imperative to bridge the gap between existing evidence and clinical practice.

The Use of Diffusion Tensor Imaging in the Identification of Acute Rejection and Chronic Allograft Nephropathy After Renal Transplantation.

BACKGROUND: Identifying the cause of renal allograft dysfunction is important for the clinical management of kidney transplant recipients. PURPOSE: To evaluate the diagnostic efficiency of diffusion tensor imaging (DTI) for identifying allografts with acute rejection (AR) and chronic allograft nephropathy (CAN). STUDY TYPE: Prospective. SUBJECTS: Seventy-seven renal transplant patients (aged 42.5 ± 9.5 years), including 29 patients with well-functioning stable allografts (Control group), 25 patients diagnosed with acute rejection (AR group), and 23 patients diagnosed with chronic allograft nephropathy (CAN group). FIELD STRENGTH/SEQUENCE: 1.5 T/T2-weighted imaging and DTI. ASSESSMENT: The serum creatinine, proteinuria, pathologic results, and fractional anisotropy (FA) values were obtained and compared among the three groups. STATISTICAL TEST: One-way analysis of variance; correlation analysis; independent-sample t-test; intraclass correlation coefficients and receiver operating characteristic curves. Statistical significance was set to a P-value <0.05. RESULTS: The AR and CAN groups presented with significantly elevated serum creatinine as compared with the Control group (191.8 ± 181.0 and 163.1 ± 115.8 µmol/L vs. 82.3 ± 20.9 µmol/L). FA decreased in AR group (cortical/medullary: 0.13 ± 0.02/0.31 ± 0.07) and CAN group (cortical/medullary: 0.11 ± 0.02/0.27 ± 0.06), compared with the Control group (cortical/medullary: 0.15 ± 0.02/0.35 ± 0.05). Cortical FA in the AR group was higher than in the CAN group. The area under the curve (AUC) for identifying AR from normal allografts was 0.756 and 0.744 by cortical FA and medullary FA, respectively. The AUC of cortical FA and medullary FA for differentiating CAN from normal allografts was 0.907 and 0.830, respectively. The AUC of cortical FA and medullary FA for distinguishing AR and CAN from normal allografts was 0.828 and 0.785, respectively. Cortical FA was able to distinguish between AR and CAN with an AUC of 0.728. DATA CONCLUSION: DTI was able to detect patients with dysfunctional allografts. Cortical FA can further distinguish between AR and CAN. EVIDENCE LEVEL: 2 TECHNICAL EFFICACY: Stage 2.

Allyl-isothiocyanate against colorectal cancer via the mutual dependent regulation of p21 and Nrf2.

Allyl-isothiocyanate (AITC) is a common Isothiocyanates (ITC) and its chemo-preventive and anti-tumor effects are believed to be related to the activation of NF-E2 p45-related Factor 2 (Nrf2). However, its anti-tumor effects on colorectal cancer (CRC) are not well elucidated. Here, we investigated the therapeutic in vitro and/or in vivo effects and mechanisms of action (MOA) for AITC on CRC cell line HCT116 (human) and MC38 (mouse). AITC treatment in a low concentration range (1 mg/kg in vivo) significantly inhibited the tumor cell growth and increased the expression of p21 and Nrf2. The AITC-mediated induction of p21 was dependent on Nrf2 but independent on p53 in vitro and in vivo at low dose. In contrast, the high dose of AITC (5 mg/kg in vivo) failed to increase substantial levels of p21/MdmX, and impaired the total antioxidant capacity of tumors and subsequent anti-tumor effect in vivo. These results suggest that an optimal dose of AITC is important and required for the proper Nrf2 activation and its anti-CRC effects and thus, providing insights into the potential applications of AITC for the prevention and treatment of CRC.

Urban Flooding Prediction Method Based on the Combination of LSTM Neural Network and Numerical Model.

At present, urban flood risk analysis and forecasting and early warning mainly use numerical models for simulation and analysis, which are more accurate and can reflect urban flood risk well. However, the calculation speed of numerical models is slow and it is difficult to meet the needs of daily flood control and emergency. How to use artificial intelligence technology to quickly predict urban flooding is a key concern and a problem that needs to be solved. Therefore, this paper combines a numerical model with good computational accuracy and an LSTM artificial neural network model with high computational efficiency to propose a new method for fast prediction of urban flooding risk. The method uses the simulation results of the numerical model of urban flooding as the data driver to construct the LSTM neural network prediction model of each waterlogging point. The results show that the method has a high prediction accuracy and fast calculation speed, which can meet the needs of daily flood control and emergency response, and provides a new idea for the application of artificial intelligence technology in the direction of flood prevention and mitigation.

A2aR inhibits fibrosis and the EMT process in silicosis by regulating Wnt/ß-catenin pathway.

Silicosis, a disease characterized by diffuse fibrosis of the lung tissue, is caused by long-term inhalation of free silica (SiO2) dust in the occupational environment and is currently the most serious occupational diseases of pneumoconiosis. Several studies have suggested that alveolar type Ⅱ epithelial cells (AEC Ⅱ) undergo epithelial-mesenchymal transition (EMT) as one of the crucial components of silicosis in lung fibroblasts. A2aR can play a critical regulatory role in fibrosis-related diseases by modulating the Wnt/ß-catenin pathway, but its function in the EMT process of silicosis has not been explained. In this study, an EMT model of A549 cells was established. The results revealed that A2aR expression is reduced in the EMT model. Furthermore, activation of A2aR or suppression of the Wnt/ß-catenin pathway reversed the EMT process, while the opposite result was obtained by inhibiting A2aR. In addition, activation of A2aR in a mouse silicosis model inhibited the Wnt/ß-catenin pathway and ameliorated the extent of silica-induced lung fibrosis in mice. To sum up, we uncovered that A2aR inhibits fibrosis and the EMT process in silicosis by regulating the Wnt/ß-catenin pathway. Our study can provide an experimental basis for elucidating the role of A2aR in the development of silicosis and offer new ideas for further exploration of interventions for silicosis.

MALAT1-miR-30c-5p-CTGF/ATG5 axis regulates silica-induced experimental silicosis by mediating EMT in alveolar epithelial cells.

Epithelial-mesenchymal transdifferentiation of alveolar type Ⅱ epithelial cells is a vital source of pulmonary myofibroblasts, and myofibroblasts formation is recognized as an important phase in the pathological process of silicosis. miR-30c-5p has been determined to be relevant in the activation of the epithelial-mesenchymal transition (EMT) in numerous disease processes. However, elucidating the role played by miR-30c-5p in the silicosis-associated EMT process remains a great challenge. In this work, based on the establishment of mouse silicosis and A549 cells EMT models, miR-30c-5p was interfered with in vivo and in vitro models to reveal its effects on EMT and autophagy. Moreover, metastasis-associated lung adenocarcinoma transcript 1 (MALAT1), connective tissue growth factor (CTGF), autophagy-related gene 5 (ATG5), and autophagy were further interfered with in the A549 cells models to uncover the possible molecular mechanism through which miR-30c-5p inhibits silicosis associated EMT. The results demonstrated the targeted binding of miR-30c-5p to CTGF, ATG5, and MALAT1, and showed that miR-30c-5p could prevent EMT in lung epithelial cells by acting on CTGF and ATG5-associated autophagy, thereby inhibiting the silicosis fibrosis process. Furthermore, we also found that lncRNA MALAT1 might competitively absorb miR-30c-5p and affect the EMT of lung epithelial cells. In a word, interfering with miR-30c-5p and its related molecules (MALAT1, CTGF, and ATG5-associated autophagy) may provide a reference point for the application of silicosis intervention-related targets.

A Robust Faster R-CNN Model with Feature Enhancement for Rust Detection of Transmission Line Fitting.

Rust of transmission line fittings is a major hidden risk to transmission safety. Since the fittings located at high altitude are inconvenient to detect and maintain, machine vision techniques have been introduced to realize the intelligent rust detection with the help of unmanned aerial vehicles (UAV). Due to the small size of fittings and disturbance of complex environmental background, however, there are often cases of missing detection and false detection. To improve the detection reliability and robustness, this paper proposes a new robust Faster R-CNN model with feature enhancement mechanism for the rust detection of transmission line fitting. Different from current methods that improve feature representation in front end, this paper adopts an idea of back-end feature enhancement. First, the residual network ResNet-101 is introduced as the backbone network to extract rich discriminative information from the UAV images. Second, a new feature enhancement mechanism is added after the region of interest (ROI) pooling layer. Through calculating the similarity between each region proposal and the others, the feature weights of the region proposals containing target object can be enhanced via the overlaying of the object's representation. The weight of the disturbance terms can then be relatively reduced. Empirical evaluation is conducted on some real-world UAV monitoring images. The comparative results demonstrate the effectiveness of the proposed model in terms of detection precision and recall rate, with the average precision of rust detection 97.07%, indicating that the proposed method can provide an reliable and robust solution for the rust detection.

Potential biocontrol efficiency of Trichoderma species against oomycete pathogens.

Plant health is of utmost importance for optimal agricultural production and sustainability. Unfortunately, biotic and abiotic factors put a major constraint on crop safety and productivity. Plant diseases caused by oomycetes inflict serious damage to various crops. Moreover, the injudicious use of chemical pesticides poses threats related to pesticide resistance development in pathogens and environmental pollution. Biocontrol offers an effective solution for disease control; however, research on biocontrol of oomycete-related diseases is scarce. Thus, this study undertakes the screening of biocontrol resources for the effective management of oomycete-related plant diseases. In this regard, 86 isolates of Trichoderma spp. were assessed against Phytophthora nicotianae, P. capsici, Pythium vexans, P. ultimum, and P. dissotocum through dual culture assay. Furthermore, the antagonistic effect of selected isolates was studied against tobacco black shank disease and damping-off of cucumber seedlings in the greenhouse. The relative control effect of the three antagonistic Trichoderma strains AR-4, Tv-1, and ST4-1 on tobacco black shank was more than 60%, which was not significantly different from 6.88 gl-1 fluopicolide-propamocarb. Whereas, the relative control effect of Trichoderma AR-4 and ST4-1 on damping-off of cucumber seedlings was 80.33% and 82.67%, respectively, which were significantly higher than Trichoderma Tv-1 (35.49%) and fluopicolide-propamocarb (47.82%). According to the morphological and molecular characterization, the fungal strains AR-4, Tv-1, and ST4-1 were identified as Trichoderma koningiopsis, T. asperellum, and T. gamsii, respectively. In conclusion, the strains exhibited a strong antagonistic effect against oomycete pathogens and can be integrated into disease management strategies.

A Method of Calibration for the Distortion of LiDAR Integrating IMU and Odometer.

To improve the motion distortion caused by LiDAR data at low and medium frame rates when moving, this paper proposes an improved algorithm for scanning matching of estimated velocity that combines an IMU and odometer. First, the information of the IMU and the odometer is fused, and the pose of the LiDAR is obtained using the linear interpolation method. The ICP method is used to scan and match the LiDAR data. The data fused by the IMU and the odometer provide the optimal initial value for the ICP. The estimated speed of the LiDAR is introduced as the termination condition of the ICP method iteration to realize the compensation of the LiDAR data. The experimental comparative analysis shows that the algorithm is better than the ICP algorithm and the VICP algorithm in matching accuracy.

Diallyl trisulfide sensitizes radiation therapy on glioblastoma through directly targeting thioredoxin 1.

Radiotherapy is a standard-of-care treatment approach for glioblastoma (GBM) patients, but therapeutic resistance to radiotherapy remains a major challenge. Here we demonstrate that diallyl trisulfide (DATS) directly conjugates with cysteine (C) 32 and C35 (C32/35) residues of thioredoxin 1 (Trx1) through Michael addition reactions. Due to localizing in activity center of Trx1, the conjugation between DATS and C32/35 results in inhibition of Trx1 activity, therefore disturbing thioredoxin system and leading to accumulated levels of reactive oxygen species (ROS). High levels of Trx1 expression are correlated with poor prognosis of glioma patients. Notably, we reveal that DATS synergistically enhances irradiation (IR)-induced ROS accumulation, apoptosis, DNA damage, as well as inhibition of tumor growth of GBM cells. These findings highlight the potential benefits of DATS in sensitizing radiotherapy of GBM patients.

Mechanism of LncRNA XIST/ miR-101-3p/ZEB1 axis in EMT associated with silicosis.

Silicosis is a systemic disease characterized by diffuse fibrosis of lung tissue. However, its pathogenesis has not been fully elucidated. Previous studies have demonstrated that there is a close relationship between EMT and pulmonary fibrosis. However, LncRNA XIST and miR-101-3p regulate the expression of ZEB1 which is a key transcription factor in the process of EMT through competitive endogenous RNA, thus affecting the process of EMT has not been reported. In this work, an experimental silicosis mouse model and cell model of TGF-ß1 stimulated lung epithelial cells (A549) for 48 h are established to investigate the biological effects of LncRNA XIST/ miR-101-3p/ZEB1 axis in the EMT process. The results reveal that LncRNA XIST and ZEB1 are up-regulated while the miR-101-3p expression is down-regulated in vivo and vitro models. Furthermore, the knockdown of LncRNA XIST prevents the EMT process and the inhibition of miR-101-3p markedly promotes EMT stimulated by TGF-ß1. Moreover, the results also illustrate that LncRNA XIST is mainly localized in the cytoplasm used FISH and possesses binding site with miR-101-3p which was identified as the target of ZEB1 used bioinformatics prediction website and Dual-luciferase reporter assay. The above demonstrated that LncRNA-XIST regulates ZEB1 by directly sponging miR-101-3p. To sum up, we uncovered that the up-regulated LncRNA XIST can modulate miR-101-3p and then up-regulate the expression of ZEB1, thus promoting the EMT process of alveolar epithelial cells in the process of silicosis-related pulmonary fibrosis EMT. Our study provides a new research idea for related targets of silicosis treatment.

Recent Advances in Nanoplatforms for the Treatment of Osteosarcoma.

Osteosarcoma (OS) is the most common primary bone tumor in children and young people. Traditional surgical excision combined with chemotherapy presents many limitations, such as resistance and systemic side effects of chemotherapy drugs, postoperative recurrence, and bone defects. Given these limitations, novel therapeutic modalities for OS treatment using nanometer-sized platform-based chemotherapeutic delivery have emerged as a promising alternative therapy. This form of therapy offers multiple advantages, such as accurate delivery of the drug to the tumor site and repair of limited bone defects after tumor resection. In this review, we briefly summarize nanoplatforms, including liposomes, polymeric nanoparticles, inorganic nanoparticles, nanomicelles, dendrimers, nanocapsules, and exosomes. The essential shortcomings involved in these nanoplatforms, such as poor stability, immunogenicity, insufficient circulation, and drug leakage are also discussed, and related solutions are briefly proposed. Finally, the application prospects of nanoplatforms in the treatment of OS are discussed.