Atovaquone enhances antitumor efficacy of TCR-T therapy by augmentation of ROS-induced ferroptosis in hepatocellular carcinoma.

T-cell receptor (TCR) engineered T-cell therapy has recently emerged as a promising adoptive immunotherapy approach for tumor treatment, yet hindered by tumor immune evasion resulting in poor therapeutic efficacy. The introduction of ferroptosis-targeted inducers offers a potential solution, as they empower T cells to induce ferroptosis and exert influence over the tumor microenvironment. Atovaquone (ATO) stands as a prospective pharmaceutical candidate with the potential to target ferroptosis, effectively provoking an excessive generation and accumulation of reactive oxygen species (ROS). In this study, we evaluated the effectiveness of a combination therapy comprising ATO and TCR-T cells against hepatocellular carcinoma (HCC), both in vitro and in vivo. The results of lactate dehydrogenase and cytokine assays demonstrated that ATO enhanced cytotoxicity mediated by AFP-specific TCR-T cells and promoted the release of IFN-γ in vitro. Additionally, in an established HCC xenograft mouse model, the combined therapy with low-dose ATO and TCR-T cells exhibited heightened efficacy in suppressing tumor growth, with no apparent adverse effects, comparable to the results achieved through monotherapy. The RNA-seq data unveiled a significant activation of the ferroptosis-related pathway in the combination therapy group in comparison to the TCR-T cells group. Mechanistically, the synergy between ATO and TCR-T cells augmented the release of IFN-γ by TCR-T cells, while concurrently elevating the intracellular and mitochondrial levels of ROS, expanding the labile iron pool, and impairing the integrity of the mitochondrial membrane in HepG2 cells. This multifaceted interaction culminated in the potentiation of ferroptosis within the tumor, primarily induced by an excess of ROS. In summary, the co-administration of ATO and TCR-T cells in HCC exhibited heightened vulnerability to ferroptosis. This heightened susceptibility led to the inhibition of tumor growth and the stimulation of an anti-tumor immune response. These findings suggest that repurposing atovaquone for adoptive cell therapy combination therapy holds the potential to enhance treatment outcomes in HCC.

A high concentrate diet inhibits forkhead box protein A2 expression, and induces oxidative stress, mitochondrial dysfunction and mitochondrial unfolded protein response in the liver of dairy cows.

High-concentrate diet induce subacute ruminal acidosis (SARA) and cause liver damage in ruminants. It has been reported that forkhead box protein A2 (FOXA2) can enhance mitochondrial membrane potential but its function in mitochondrial dysfunction induced by high concentrate diets is still unknown. Therefore, the aim of this study was to elucidate the effect of high-concentrate (HC) diet on hepatic FOXA2 expression, mitochondrial unfolded protein response (UPRmt), mitochondrial dysfunction and oxidative stress. A total of 12 healthy mid-lactation Holstein cows were selected and randomized into 2 groups: the low concentrate (LC) diet group (concentrate:forage = 4:6) and HC diet group (concentrate:forage = 6:4). The trial lasted 21 d. The rumen fluid, blood and liver tissue were collected at the end of the experiment. The results showed that the rumen fluid pH level was reduced in the HC group and the pH was lower than 5.6 for more than 4 h/d, indicating that feeding HC diets successfully induced SARA in dairy cows. Both FOXA2 mRNA and protein abundance were significantly reduced in the liver of the HC group compared with the LC group. The activity of antioxidant enzymes (CAT, G6PDH, T-SOD, Cu/Zn SOD, Mn SOD) and mtDNA copy number in the liver tissue of the HC group decreased, while the level of H2O2 significantly increased, this increase was accompanied by a decrease in oxidative phosphorylation (OXPHOS). The balance of mitochondrial division and fusion was disrupted in the HC group, as evidenced by the decreased mRNA level of OPA1, MFN1, and MFN2 and increased mRNA level of Drp1, Fis1, and MFF. At the same time, HC diet downregulated the expression level of SIRT1, SIRT3, PGC-1α, TFAM, and Nrf 1 to inhibit mitochondrial biogenesis. The HC group induced UPRmt in liver tissue by upregulating the mRNA and protein levels of CLPP, LONP1, CHOP, Hsp10, and Hsp60. In addition, HC diet could increase the protein abundance of Bax, CytoC, Caspase 3 and Cleaved-Caspase 3, while decrease the protein abundance of Bcl-2 and the Bcl-2/Bax ratio. Overall, our study suggests that the decreased expression of FOXA2 may be related to UPRmt, mitochondrial dysfunction, oxidative stress, and apoptosis in the liver of dairy cows fed a high concentrate diet.

Synergistic Boosting Capture Ability of Thiophene Sulfur with a Novel Dual-Amino-Functionalized MOF-on-MOF Adsorbent.

A single metal-organic framework (MOF) exhibits some drawbacks in deep adsorptive desulfurization such as insufficient functional active sites, water instability, low surface area, etc. Herein, a dual-amino-functionalized (ZIF-8-NH2)-PVP-(Cu-BTC-NH2) core-shell dual MOF adsorbent was first synthesized by the hydrothermal growth method. The adsorption performance of thiophene sulfur (ThS) is systematically investigated and evaluated at mild temperatures through batch tests. The (ZIF-8-NH2)-PVP-(Cu-BTC-NH2) exhibits good adsorption ability toward ThS, which is attributed to the associative effects of dual MOFs with structure features such as hydrogen bond, open metal active sites, suitable pore sizes and π-π conjugation, etc. Meanwhile, the (ZIF-8-NH2)-PVP-(Cu-BTC-NH2) embedded 25 wt % water still remains crystal intact and good adsorption desulfurization performance, which is attributed to the NH2- functional groups. After five recycles, more than 90% ThS uptake onto (ZIF-8-NH2)-PVP-(Cu-BTC-NH2) could be recovered, exhibiting good reuse performance. This study presents a new strategy for grafting MOF-on-MOF with specific functional groups to improve the abilities of desulfurization and water resistance.

Clinical Practice Report of Contrast-Enhanced Ultrasound in Renal Artery Disease.

OBJECTIVES: To evaluate the diagnostic performance of renal artery contrast-enhanced ultrasound (CEUS) with modified inspection section and summarize subsequent changes in imaging assessment of renal artery disease. METHODS: A total of 1015 patients underwent renal artery CEUS were included in the study. Among them, 79 patients (156 renal arteries) suspected with renal artery stenosis (RAS) underwent digital subtraction angiography (DSA) subsequently. DSA was used as the gold standard to evaluate the diagnostic performance of CEUS in detecting RAS (≥30%) and severe stenosis (≥70%), as well as the diagnostic accuracy of classification of stenosis degree. Besides, 127 of the 1015 patients underwent other imaging examinations such as computed tomography angiography (CTA) or magnetic resonance angiography (MRA) after CEUS and annual proportion of these imaging examinations was assessed. RESULTS: The sensitivity, specificity, accuracy, positive predictive value (PPV) and negative predictive value (NPV) of CEUS for detecting RAS (≥30%) was 96.4%, 88.6%, 94.2%, 95.6% and 90.7%, respectively and the kappa value was .857 (P < .01). CEUS had a good performance in distinguishing severe stenosis (≥70%) with a sensitivity of 91.1%, specificity of 95.5%, accuracy of 92.9%, PPV of 96.5%, NPV of 88.7% and the kappa value was 0.857(P < .01). There was no significant difference between CEUS and DSA in detecting stenosis (P = 1.0) and severe stenosis (P = .227). The diagnostic accuracy of CEUS in grading RAS was 85.3% and the kappa value was 0.753 (P < .01). Besides, the annual proportion of other imaging examinations decreased for 4 consecutive years. CONCLUSIONS: CEUS is a non-invasive, safe and valuable technique for the assessment of renal artery disease and worthy of promotion.

Proteasome-associated autoinflammatory syndrome 2 in a neonate.

Proteasome-associated autoinflammatory syndrome-2 (PRAAS2) is characterized by early onset combined immunodeficiency, inflammatory neutrophilic dermatosis, and autoimmunity. We report the case of a premature baby (GA 35+5 weeks) born with disseminated and confluent red papules, diagnosed with PRAAS2. A novel de novo frameshift proteasome maturation protein (POMP) mutation (c.333delT (p.t111fs)) was detected, confirming the diagnosis.

Risk factors for avascular necrosis of the femoral head after developmental hip dislocation reduction surgery and construction of Nomogram prediction model.

BACKGROUND: To analyze the risk factors for the development of avascular necrosis (AVN) of the femoral head after reduction surgery in children with developmental hip dysplasia (DDH), and to establish a prediction nomogram. METHODS: The clinical data of 134 children with DDH (169 hips) treated with closure reduction or open reduction from December 2016 to December 2019 were retrospectively analyzed. Independent risk factors for AVN after DDH reduction being combined with cast external immobilization were determined by univariate analysis and multivariate logistic regression and used to generate nomograms predicting the occurrence of AVN. RESULTS: A total of 169 hip joints in 134 children met the inclusion criteria, with a mean age at surgery of 10.7 ± 4.56 months (range: 4-22 months) and a mean follow-up duration of 38.32 ± 27.00 months (range: 12-94 months). AVN developed in 42 hip joints (24.9%); univariate analysis showed that the International Hip Dysplasia Institute (IHDI) grade, preoperative development of the femoral head ossification nucleus, cartilage acetabular index, femoral head to acetabular Y-shaped cartilage distance, residual acetabular dysplasia, acetabular abduction angle exceeding 60°, and the final follow-up acetabular index (AI) were associated with the development of AVN (P < 0.05). Multivariate logistic regression analysis showed that the preoperative IHDI grade, development of the femoral head ossification nucleus, acetabular abduction angle exceeding 60°, and the final follow-up AI were independent risk factors for AVN development (P < 0.05). Internal validation of the Nomogram prediction model showed a consistency index of 0.833. CONCLUSION: Preoperative IHDI grade, preoperative development of the femoral head ossification nucleus, final AI, and acetabular abduction angle exceeding 60° are risk factors for AVN development. This study successfully constructed a Nomogram prediction model for AVN after casting surgery for DDH that can predict the occurrence of AVN after casting surgery for DDH.

Emotional labour in nursing research: A bibliometric analysis.

AIM: This study aims to conduct a comprehensive bibliometric analysis to explore the trajectory and thematic developments of emotional labour research in nursing. DESIGN: Utilizing descriptive and bibliometric analysis techniques. METHODS: The data analysis and graphical presentation were conducted using the Bibliometrix Package in R software. DATA SOURCES: The Web of Science Core Collection (WoSCC) database was searched on October 20, 2023. RESULTS: From 1992 to 2023, 842 authors published relevant articles, yielding 779 author keywords. There has been a general upward trend in the number of articles published over the past 30 years, with an annual growth rate of 11.71%. Keyword co-occurrence cluster analysis revealed the main focus areas of research on emotional labour antecedents and consequences, regulatory modalities, training and education, as well as research methods and application scenarios. CONCLUSION: Emotional labour significantly influences nursing staff's well-being and patient care outcomes. Effective management and education regarding emotional labour are crucial for enhancing nursing staff performance and patient care quality. Future research should focus on long-term effects, training efficacy, regulatory strategies across clinical settings, and innovative approaches to address current challenges. IMPACT: This study provides valuable insights into the unique trajectory and thematic developments of emotional labour research in nursing. The findings underscore the importance of addressing emotional labour in nursing practice and education to improve patient care outcomes and nursing staff well-being. REPORTING METHOD: Adherence to recognized bibliometric reporting methods, following relevant EQUATOR guidelines. NO PATIENT OR PUBLIC CONTRIBUTION: This study is based solely on existing literature and did not involve patients or the public in its design, conduct, analysis, interpretation, or preparation.

Application of MR images in radiotherapy planning for brain tumor based on deep learning.

PURPOSE: Explore the function and dose calculation accuracy of MRI images in radiotherapy planning through deep learning methods. METHODS: 131 brain tumor patients undergoing radiotherapy with previous MR and CT images were recruited for this study. A new series of MRI from the aligned MR was firstly registered to CT images strictly using MIM software and then resampled. A deep learning method (U-NET) was used to establish a MRI-to-CT conversion model, for which 105 patient images were used as the training set and 26 patient images were used as the tuning set. Data from additional 8 patients were collected as the test set, and the accuracy of the model was evaluated from a dosimetric standpoint. RESULTS: Comparing the synthetic CT images with the original CT images, the difference in dosimetric parameters D98, D95, D2 and Dmean of PTV in 8 patients was less than 0.5%. The gamma passed rates of PTV and whole body volume were: 1%/1 mm: 93.96%±6.75%, 2%/2 mm: 99.87%±0.30%, 3%/3 mm: 100.00%±0.00%; and 1%/1 mm: 99.14%±0.80%, 2%/2 mm: 99.92%±0.08%, 3%/3 mm: 99.99%±0.01%. CONCLUSION: MR images can be used both in delineation and treatment efficacy evaluation and in dose calculation. Using the deep learning way to convert MR image to CT image is a viable method and can be further used in dose calculation.

Wheat Seed Detection and Counting Method Based on Improved YOLOv8 Model.

Wheat seed detection has important applications in calculating thousand-grain weight and crop breeding. In order to solve the problems of seed accumulation, adhesion, and occlusion that can lead to low counting accuracy, while ensuring fast detection speed with high accuracy, a wheat seed counting method is proposed to provide technical support for the development of the embedded platform of the seed counter. This study proposes a lightweight real-time wheat seed detection model, YOLOv8-HD, based on YOLOv8. Firstly, we introduce the concept of shared convolutional layers to improve the YOLOv8 detection head, reducing the number of parameters and achieving a lightweight design to improve runtime speed. Secondly, we incorporate the Vision Transformer with a Deformable Attention mechanism into the C2f module of the backbone network to enhance the network's feature extraction capability and improve detection accuracy. The results show that in the stacked scenes with impurities (severe seed adhesion), the YOLOv8-HD model achieves an average detection accuracy (mAP) of 77.6%, which is 9.1% higher than YOLOv8. In all scenes, the YOLOv8-HD model achieves an average detection accuracy (mAP) of 99.3%, which is 16.8% higher than YOLOv8. The memory size of the YOLOv8-HD model is 6.35 MB, approximately 4/5 of YOLOv8. The GFLOPs of YOLOv8-HD decrease by 16%. The inference time of YOLOv8-HD is 2.86 ms (on GPU), which is lower than YOLOv8. Finally, we conducted numerous experiments and the results showed that YOLOv8-HD outperforms other mainstream networks in terms of mAP, speed, and model size. Therefore, our YOLOv8-HD can efficiently detect wheat seeds in various scenarios, providing technical support for the development of seed counting instruments.

Specific functions of single pistil S-RNases in S-gene homozygous Pyrus germplasm.

Gametophytic self-incompatibility (SI) is regulated by S-allele recognition; that is, pollen in a style with the same S-genotype will undergo programmed cell death and stop growing so that it is unable to complete double fertilization, ultimately resulting in the SI response. S-RNase is the female determinant of SI in pear (Pyrus). In the Pyrus genome, there are two different S-RNase alleles at the S-locus, which generate two different S-RNase products in the pistil. The extracted S-glycoprotein is actually a protein complex. In this study, artificial self-pollination was conducted at the bud stage to overcome SI in 'Huanghua' (S1S2) pear. Seven plants homozygous for S1-RNase and four homozygous for S2-RNase were selected from the selfed progeny of 'Huanghua' by S-gene molecular identification biotechnology. We investigated the function of single S-RNases isolated from the pistils of S-gene homozygous Pyrus germplasm. The pollen of 'Huanghua' could smoothly pass through the style of the S-gene homozygous germplasm and complete fertilization. S-RNases were extracted from flower styles of different genotypes and used to treat different types of pollen. The S-RNase from 'Huanghua' completely inhibited the growth of S1S2, S1S1, and S2S2 pollen, while the S-RNase from homozygous germplasm allowed some S1S2 pollen and different single genotypes of pollen to continue growing. These results further validate the core events of SI including cytoskeleton depolymerization and programmed cell death. By iTRAQ-based proteomic analysis of style proteins, a total of 13 S-RNase-related proteins were identified. In summary, we have created reliable S-RNase gene homozygous germplasm, which will play a crucial role in further research on SI in pear and in the development of the pear industry.

Programmable Interactions of Cellulose Acetate with Octadecyltrichlorosilane-Functionalized SiO2 Nanoparticles.

It is significant to understand the interfacial interactions involved between the cellulose acetate (CA) and dispersed nanomaterials, in which the enhanced interaction improves the mechanical behavior of CA. In this work, the amendments of CA with SiO2 nanoparticles have been found to be endowed by grafting varying concentrations (0, 3, 5, and 6%) of octadecyltrichlorosilane (OTS). Aided by SiO2 colloid probe atomic force microscopy (AFM with a probe diameter of 20 µm), the adhesion force between CA and SiO2 is found to be programmable by tuning OTS concentrations functionalized onto SiO2 surfaces. The adhesion forces of 5% OTS-functionalized SiO2 with CA are the strongest, followed by the ones of 0, 3, and 6% OTS, resulting in a smoother and denser morphology on the film with 5% OTS. The AFM-measured approaching force-distance curves have been further compared to predictions by the extended Derjaguin-Landau-Verwey-Overbeek (XDLVO) theory, in which the XDLVO force is summed as the Liftshitz-van der Waals force (FLW), the electrostatic double-layer force (FEL), and the acid-base interaction force (FAB). FLW and FEL do not change significantly with OTS concentrations functionalized onto SiO2. However, FAB is sensitive to the functionalized OTS concentration onto SiO2 and significantly contributes to the interaction force of the composite films with 5% OTS, promoting the formation of a smooth and dense surface feature with a considerable mechanical performance demonstrated by load-displacement curves from a nanoindenter. This is highly encouraging and suggests that nanomaterials can be incorporated into CA to effectively improve their mechanical compatibility by programming the interaction between the CA matrix and nanomaterials.

An Autonomous Mobile Combination Disinfection System.

To address the common drawbacks of current disinfection robots, which include the potential for secondary environmental pollution, disinfection dead corners, and low efficiency, in this paper, an autonomous mobile combination disinfection system is proposed. The system utilizes ultraviolet (UV) radiation and a low-concentration hydrogen peroxide aerosol to kill pathogens. It comprises three parts: a human-computer interface, a mobile robot, and disinfection equipment. A disinfection process model with continuous and fixed-point modes was established, and the effective disinfection range, speed, and duration were quantitatively calculated. The developed prototype was tested on-site by a professional third-party testing agency. The experimental results demonstrated that the combination disinfection robot achieved a 92.95% disinfection rate of natural airborne bacteria in a room measuring 22 square meters with a height of 2.8 m in just 30 min. The disinfection efficiency is at least 25% higher compared to standalone UV lamp disinfection and also exhibits a noticeable improvement over standalone hydrogen peroxide aerosol disinfection. The system enables the environmentally friendly, rapid, efficient, and all-encompassing disinfection of natural airborne bacteria. Finally, various disinfection solutions and recommendations for different application scenarios and requirements are provided.

Modified Levator Resection Technique for Moderate Congenital Blepharoptosis.

BACKGROUND: For moderate ptosis associated with fair levator function (LF), the levator resection is the most commonly used procedure. However, the levator resection technique still has some disadvantages, such as residual lagophthalmos (RL), undercorrection, conjunctival prolapse, and eyelid contour abnormality. To solve the above problems, our team have made modifications to the levator resection technique in three aspects: releasing the levator muscle sufficiently, preserving the supporting structure of the conjunctiva, and placing multiple suture sites. METHODS: Fifty-seven patients (81 eyes) underwent the modified levator resection technique and were enrolled in the study. Preoperative data collected included age, sex, margin reflex distance 1 (MRD1), and LF. Postoperative data collected included MRD1, RL, patient satisfaction, complications, and length of follow-up. RESULTS: Mean MRD1 significantly increased from 1.45 ± 0.65 mm preoperatively to 3.57 ± 0.51 mm postoperatively. Mean LF significantly increased from 6.49 ± 1.12 mm preoperatively to 9.48 ± 1.39 mm postoperatively. Successful correction was obtained in 77 eyes (95.1%). Mean RL was 1.09 ± 0.57 and 72 eyes (88.9%) showed excellent or good eyelid closure function. Fifty-four patients (94.7%) were completely satisfied with the final result. Complications such as hematoma, infection, conjunctival prolapse, suture exposure, corneal abrasion, and keratitis were not found in any cases during follow-up. CONCLUSION: This modified levator resection technique introduced in this study is effective in correcting moderate congenital blepharoptosis, while minimizing RL, undercorrection, conjunctival prolapse, eyelid contour abnormality by releasing the levator muscle sufficiently, preserving the supporting structure of the conjunctiva, and placing multiple suture sites. LEVEL OF EVIDENCE IV: This journal requires that authors 42 assign a level of evidence to each article. For a full 43 description of these Evidence-Based Medicine ratings, 44 please refer to the Table of Contents or the online 45 Instructions to Authors www.springer.com/00266 .

Effects of oxycodone hydrochloride sustained-release tablets and morphine hydrochloride sustained-release tablets on peripheral blood T cell levels in advanced lung squamous cell carcinoma with moderate to severe cancer pain.

Objective: To investigate the effects of morphine hydrochloride sustained-release tablets and oxycodone hydrochloride sustained-release tablets on T-cell levels in advanced lung squamous cell carcinoma(LUSC) with moderate to severe cancer pain. Methods: A retrospective study was used, ninety-eight patients who were admitted to The First Affiliated Hospital of Hebei North University for treatment of advanced LUSC with moderate to severe cancer pain between January 2021 and December 2021 were randomized into two groups(n=49 each) using the sealed envelope system. The reference group was treated with morphine hydrochloride sustained-release tablets, while the experimental group received oxycodone hydrochloride sustained-release tablets to compare pain relief rates(PRRs), levels of T cells, pain intensity, et al. Blood samples were collected for lymphocyte levels by flow cytometry. Results: The experimental group had significantly higher level than the reference group(P<0.05). Before administration, the two groups did not differ greatly in levels of T-cell subsets or pain scores on the visual analog scale(P>0.05, respectively). At 15 days of administration, the Treg level in the experimental group was higher than in the reference group; T helper 17 and 22 cells were reduced in both groups, and the decrease was more pronounced in the experimental group. At seven and 15 days of administration, the experimental group had a VAS score significantly lower than the reference group(P<0.05). The total adverse reaction rate was significantly lower in the experimental group as compared with the reference group(P<0.05). Conclusions: Oxycodone hydrochloride sustained-release tablets demonstrate desirable efficacy and safety in advanced LUSC with moderate to severe cancer pain by modulating T-cells in the body and improving the PRR.

Modulating oxidative stress counteracts specific antigen-induced regulatory T-cell apoptosis in mice.

Treg are known to have a central role in orchestrating immune responses, but less is known about the destiny of Treg after being activated by specific Ags. This study aimed to investigate the role of superoxide dismutase, an active molecule in the regulation of oxidative stress in the body, in the prevention of Treg apoptosis induced by specific Ags. Ag-specific Tregs were isolated from the DO11.10 mouse intestine. A food allergy mouse model was developed with ovalbumin as the specific Ag and here, we observed that exposure to specific Ag induced Treg apoptosis through converting the precursor of TGF-ß to its mature form inside the Tregs. Oxidative stress was induced in Tregs upon exposure to specific Ags, in which Smad3 bound the latency-associated peptide to induce its degradation, converting the TGF-ß precursor to its mature form, TGF-ß. Suppressing oxidative stress in Tregs alleviated the specific Ag-induced Treg apoptosis in in vitro experiments and suppressed experimental food allergy by preventing the specific Ag-induced Treg apoptosis in the intestine. In conclusion, exposure to specific Ags induces Treg apoptosis and it can be prevented by upregulating superoxide dismutase or suppressing reactive oxidative species in Tregs.

Monophosphoryl lipid A ameliorates radiation-induced lung injury by promoting the polarization of macrophages to the M1 phenotype.

BACKGROUND: Radiation-induced lung injury (RILI) often occurs during clinical chest radiotherapy and acute irradiation from accidental nuclear leakage. This study explored the role of monophosphoryl lipid A (MPLA) in RILI. MATERIALS AND METHODS: The entire thoracic cavity of C57BL/6N mice was irradiated at 20 Gy with or without pre-intragastric administration of MPLA. HE staining, Masson trichrome staining, and TUNEL assay were used to assess lung tissue injury after treatment. The effect of irradiation on the proliferation of MLE-12 cells was analyzed using the Clonogenic assay. The effect of MPLA on the apoptosis of MLE-12 cells was analyzed using flow cytometry. Expression of γ-H2AX and epithelial-mesenchymal transition (EMT) markers in MLE-12 cells was detected by immunofluorescence and Western blot, respectively. RESULTS: MPLA attenuated early pneumonitis and late pulmonary fibrosis after thoracic irradiation and reversed radiation-induced EMT in C57 mice. MPLA further promoted proliferation and inhibited apoptosis of irradiated MLE-12 cells in vitro. Mechanistically, the radioprotective effect of MPLA was mediated by exosomes secreted by stimulated macrophages. Macrophage-derived exosomes modulated DNA damage in MLE-12 cells after irradiation. MPLA promoted the polarization of RAW 264.7 cells to the M1 phenotype. The exosomes secreted by M1 macrophages suppressed EMT in MLE-12 cells after irradiation. CONCLUSION: MPLA is a novel treatment strategy for RILI. Exosomes derived from macrophages are key to the radioprotective role of MPLA in RILI.

Soluble POSTN is a novel biomarker complementing CA153 and CEA for breast cancer diagnosis and metastasis prediction.

BACKGROUND: Breast cancer (BCa) is the leading cause of cancer deaths among women. Reliable biomarkers for early diagnosis and metastasis prediction are essential to improve the prognosis of BCa. This study aimed to evaluate serum periostin (POSTN) as a novel biomarker complementing CA153 (carbohydrate antigen 153) and CEA (carcinoembryonic antigen) for BCa diagnosis and metastasis prediction. METHODS: To assess the potential of soluble POSTN as a circulating biomarker, 242 participants, including 173 patients with different stages of BCa and 69 healthy individuals, were enrolled in this study. Soluble POSTN, together with CA153 and CEA, were determined in serum by enzyme linked immunosorbent assay (ELISA) or electrochemiluminescence immunoassays. RESULTS: Serum POSTN levels in locoregional BCa patients were significantly higher than that in healthy controls. Receiver operating curve (ROC) analysis revealed that, to distinguish health controls from locoregional BCa, POSTN was observed with the highest AUC (area under curve) (AUCPOSTN = 0.72 [0.65 - 0.79], AUCCA153 = 0.57 [0.49 - 0.64], AUCCEA = 0.62 [0.55 - 0.69]), and both CA153 and CEA were observed with significantly improved AUCs by combination with POSTN (AUCPOSTN + CA153 = 0.74 [0.67 - 0.80], P < 0.001; AUCPOSTN + CEA = 0.77 [0.70 - 0.82], P < 0.001). Moreover, the performances of the POSTN were comparable with that of CA153 in predicting distant metastasis of BCa (AUCPOSTN = 0.78 [0.71 - 0.84], AUCCA153 = 0.82 [0.76 - 0.88]). Kaplan-Meier analysis indicated that elevated serum POSTN was associated with poor overall survival and progression-free survival. CONCLUSIONS: This study suggested that soluble POSTN is a promising potential biomarker for diagnosis and metastasis prediction of BCa.

Boosting the Adsorption Performance of Thiophenic Sulfur Compounds with a Multimetallic Dual Metal-Organic Framework Composite.

Adsorptive desulfurization over metal-organic frameworks (MOFs) remains a challenge in maintaining good performance in the presence of water. Herein, multimetallic Fe/Ni/Cu/Zn-(MIL-88B)-on-(MOF-5) is first achieved through phase-competition-driven growth technology. The adsorption performance of thiophene (Th), benzothiophene (BT), and dibenzothiophene (DBT) in model fuels is systematically investigated at mild temperature and follows the order Fe/Ni/Cu/Zn-(MIL-88B)-on-(MOF-5) > MOF-5 > MIL-88B. Excellent adsorptive activity is mainly ascribed to the associative effects of multimetal active sites, suitable pore sizes and shapes, acid-base interactions, and complexation. Meanwhile, MIL-88B exhibits a "brick-wall" effect and effectively enhances the water stability of Fe/Ni/Cu/Zn-(MIL-88B)-on-(MOF-5) more than does MOF-5. Fe/Ni/Cu/Zn-(MIL-88B)-on-(MOF-5) exhibits superior stability even after being immersed in water for 5 days, maintaining 77, 77, and 81% of the initial DBT, BT, and Th uptake capacities. After five periods of regeneration, more than 90% of the desulfurization capacity of Fe/Ni/Cu/Zn-(MIL-88B)-on-(MOF-5) was recovered. This work provides a new strategy for the synthesis of desirable MOF-on-MOF, promoting its potential application to adsorption desulfurization.

Immobilizing Ionic Liquids onto Functionalized Surfaces for Sensing Volatile Organic Compounds.

Herein, a highly sensitive volatile organic compound (VOC) gas sensor is demonstrated using immobilized ionic liquid (IL), 1-butyl-3-methylimidazolium hexafluorophosphate, onto surfaces functionalized by the quaternary ammonium group -N+R, -COOH, and -NH2, i.e., N+-IL, COOH-IL, and NH2-IL, respectively. These functional groups ensure highly tunable interactions between the IL and surfaces, efficiently modulating the electrical resistance of the immobilized IL upon exposure to acetone and toluene. The immobilized IL to both acetone and toluene displays significant electronic resistance changes at a concentration of 150 ppm, falling in the order NH2-IL > N+-IL > COOH-IL for acetone while COOH-IL > NH2-IL > N+-IL for toluene. A better gaseous sensing ability is achieved in COOH-IL for toluene than acetone, while this does not hold in the case of NH2-IL and N+-IL surfaces because of the completely different ion structuring of the IL at these functionalized surfaces. The accelerated ion mobility in the IL that is immobilized onto functionalized surfaces is also responsible for the strong gaseous sensing response, which is demonstrated further by the atomic force microscopy-measured smaller friction coefficient. This is highly encouraging and suggests that ILs can be immobilized by a network formed by surface functionalization to easily and cheaply detect VOCs at ppm concentrations.

Cascade cyclization for the synthesis of indolo[2,1-α]isoquinoline derivatives via visible-light-induced halogen-atom-transfer (XAT) and hydrogen-atom-transfer (HAT).

A transition metal-free photoredox cascade cyclization is herein reported. In this protocol, sustainable visible light was used as the energy source and organic light-emitting molecule eosin Y served as an efficient photocatalyst. A variety of easily available 2-aryl-N-acryloyl indoles can readily react with alkyl radicals, which are generated from organohalides and tertiary amines via either the halogen-atom-transfer (XAT) or the hydrogen-atom-transfer (HAT) process, furnishing the desired indolo[2,1-α]isoquinoline derivatives in good to moderate yields. This protocol features broad substrate scope and good functional group tolerance under mild conditions.