Synthetic lethal CRISPR screen identifies a cancer cell-intrinsic role of PD-L1 in regulation of vulnerability to ferroptosis.

Despite the success of programmed cell death 1 (PD-1)/programmed death ligand 1 (PD-L1) inhibition in tumor therapy, many patients do not benefit. This failure may be attributed to the intrinsic functions of PD-L1. We perform a genome-wide CRISPR synthetic lethality screen to systematically explore the intrinsic functions of PD-L1 in head and neck squamous cell carcinoma (HNSCC) cells, identifying ferroptosis-related genes as essential for the viability of PD-L1-deficient cells. Genetic and pharmacological induction of ferroptosis accelerates cell death in PD-L1 knockout cells, which are also more susceptible to immunogenic ferroptosis. Mechanistically, nuclear PD-L1 transcriptionally activates SOD2 to maintain redox homeostasis. Lower reactive oxygen species (ROS) and ferroptosis are observed in patients with HNSCC who have higher PD-L1 expression. Our study illustrates that PD-L1 confers ferroptosis resistance in HNSCC cells by activating the SOD2-mediated antioxidant pathway, suggesting that targeting the intrinsic functions of PD-L1 could enhance therapeutic efficacy.

Solvent Effects on the Phenolic Compounds and Antioxidant Activity Associated with Camellia polyodonta Flower Extracts.

Camellia polyodonta flowers contain limited information available regarding the composition of their bioactive compounds and activity. The objective of this study was to identify phenolic compounds and investigate the effect of different solvents (ethanol and methanol) on the phenolic content and antioxidant activity in C. polyodonta flowers. The analysis using UPLC-Q-TOF-MS/MS revealed the presence of 105 phytochemicals and the most common compounds were flavonols, procyanidins, and ellagitannins. Interestingly, flavonol triglycosides were identified for the first time in these flowers. The study demonstrated that the concentration of the solvent had a significant impact on the total phenolic compound (TPC), total flavonoid compound (TFC), and total proanthocyanidin content (TPAC). The TPC, TFC, and TPAC showed a remarkable increase with the increasing concentration of the solvent, reaching their maximum levels (138.23 mg GAE/g DW, 421.62 mg RE/g DW, 60.77 mg PB2E/g DW) at 70% ethanol. However, the total anthocyanin content reached its maximum at low concentrations (0.49 mg CGE/g DW). Similar trends were observed in the antioxidant activity, as measured by the DPPH· assay (DPPH radical scavenging activity), ABTS·+ assay (ABTS radical cation scavenging activity), and FRAP assay (Ferric reducing antioxidant power). The maximum antioxidant activity was observed at 100% solvents and 70% methanol. Among the 14 individual phenolic compounds, 70% methanol yielded the highest content for 8 (cyanidin-3-O-glucoside, procyanidin B2, procyanidin B4, epicatechin, rutin, kaempferol-3-O-rutinoside, astragaline and quercitrin) out of the 14 compounds. Additionally, it was found that epicatechin was the most abundant phenolic compound, accounting for approximately 20339.37 µg/g DW. Based on these findings, it can be concluded that 70% methanol is the most effective solvent for extracting polyphenols from C. polyodonta flowers. These results provided chemical information and potential antioxidant value for further research in C. polyodonta flowers.

A study on non-vibration-exposed organs correlated indices as diagnostic biomarkers of hand-arm vibration syndrome.

OBJECTIVES: Explore the feasibility of using non-vibration-exposed organ-related indices as vibration-induced white finger (VWF) diagnostic biomarkers. METHODS: Individuals were selected from a factory in China using the judgment sampling method. They were divided into control (con), non-VWF, and VWF groups according to the presence/absence of exposure to hand-transmitted vibration and VWF. Blood samples were collected for ELISA tests. RESULTS: Analysis of receiver operating characteristic (ROC) curves was done on six indicators to assess their diagnostic sensitivity for VWF. Area under the ROC curve (AUC) for insulin was 0.909 and was 0.923 for aspartate aminotransferase. CONCLUSIONS: Insulin and aspartate aminotransferase could be used as indices for the diagnosis of hand-arm vibration syndrome.

Construction of Fe Nanoparticles Interfacial Layer on Micron Al Surface: Boosting the Efficient Energy Release of High-Energy DAP-4 as a Gradient Catalyst.

The high-energy (H2dabco)[NH4(ClO4)3] (DAP-4) with excellent energetic performance attracts wide attention from researchers. The investigation of its interaction with the Aluminum (Al) is of great importance. However, the higher ignition threshold of DAP-4 and the dense oxide layer (Al2O3) of Al severely limit the energy release efficiency of Al/DAP-4. In this study, a new idea to is first proposed to improve and adjust the thermal decomposition and combustion performance of Al/DAP-4 by constructing a highly dispersed iron (Fe) nanoparticle interfacial layer. It acts as a gradient catalyst to promote the thermal decomposition and combustion of DAP-4 and Al, and it also act as an oxygen transport channel to promote the contact and reaction of oxidizing gases with the internal reactive Al powder. It reduces the thermal decomposition temperature of Al@Fe-3/DAP-4 from 386.30 °C (Al/DAP-4) to 349.48 °C and leads to the vigorous combustion. Theoretical calculations show that Fe nanoparticle interfacial layer can facilitate the transport of oxygen through the established oxygen transport channels, and it can also significantly improve the energetic properties of Al@Fe-3/DAP-4 composites. In conclusion, the new approach is proposed to improve the performance of metal fuel/oxidizer composites by constructing interfacial layers, which is expected to promote their practical applications.

Purification of Phenolic Compounds from Camellia polyodonta Flower: Composition Analysis, Antioxidant Property, and Hypolipidemic Activity In Vitro and In Vivo.

Camellia polyodonta flowers are rich sources of phenolics and less attention has been paid to their potential biological activity. This study aims to explore the crude extracts and resulting purified fractions (CPFP-I, II, III, and IV) through compositional analysis and antioxidant and hypolipidemic activities in vitro and in vivo. Among four fractions, CPFP-II contained the highest total phenolic content and flavonoid content, while CPFP-III exhibited the greatest total proanthocyanidin content. Among the 14 phenolic compounds, CPFP-II displayed the highest content of procyanidin B2, B4, and C1, whereas CPFP-III contained the highest amount of 1,2,3,6-tetragalloylglucose. The DPPH, ABTS, and FRAP assessments demonstrated a consistent trend: CPFP-II > CPFP-III > CPFP-I > CPFP-IV. In vivo experiments showed that that all four fractions significantly reduced lipid levels in hyperlipidemic C. elegans (p < 0.05), with CPFP-II exhibiting the most potent effect. Furthermore, CPFP-II effectively bound to bile acids and inhibited the enzymatic activity of pancreatic lipase in vitro. Consequently, CPFP-II should be prioritized as a promising fraction for further exploration and should provide substantial support for the feasibility of the C. polyodonta flower as a natural alternative.

Effect of mPEG-PLGA on Drug Crystallinity and Release of Long-Acting Injection Microspheres: In Vitro and In Vivo Perspectives.

PURPOSE: Traditional progesterone (PRG) injections require long-term administration, leading to poor patient compliance. The emergence of long-acting injectable microspheres extends the release period to several days or even months. However, these microspheres often face challenges such as burst release and incomplete drug release. This study aims to regulate drug release by altering the crystallinity of the drug during the release process from the microspheres. METHODS: This research incorporates methoxy poly(ethylene glycol)-b-poly(lactide-co-glycolide) (mPEG-PLGA) into poly(lactide-co-glycolide) (PLGA) microspheres to enhance their hydrophilicity, thus regulating the release rate and drug morphology during release. This modification aims to address the issues of burst and incomplete release in traditional PLGA microspheres. PRG was used as the model drug. PRG/mPEG-PLGA/PLGA microspheres (PmPPMs) were prepared via an emulsification-solvent evaporation method. Scanning electron microscopy (SEM), powder X-ray diffraction (PXRD), and differential scanning calorimetry (DSC) were employed to investigate the presence of PRG in PmPPMs and its physical state changes during release. RESULTS: The addition of mPEG-PLGA altered the crystallinity of the drug within the microspheres at different release stages. The crystallinity correlated positively with the amount of mPEG-PLGA incorporated; the greater the amount, the faster the drug release from the formulation. The bioavailability and muscular irritation of the long-acting injectable were assessed through pharmacokinetic and muscle irritation studies in Sprague-Dawley (SD) rats. The results indicated that PmPPMs containing mPEG-PLGA achieved low burst release and sustained release over 7 days, with minimal irritation and self-healing within this period. PmPPMs with 5% mPEG-PLGA showed a relative bioavailability (Frel) of 146.88%. IN CONCLUSION: In summary, adding an appropriate amount of mPEG to PLGA microspheres can alter the drug release process and enhance bioavailability.

The PP2A inhibitor LB-100 mitigates lupus nephritis by suppressing tertiary lymphoid structure formation.

Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by multi-organ involvement and autoantibody production. Patients with SLE face a substantial risk of developing lupus nephritis (LN), which imposes a substantial burden on both patients and their families. Protein phosphatase 2A (PP2A) is a widely distributed serine/threonine phosphatase that participates in regulating multiple signaling pathways. Inhibition of PP2A has been implicated in the treatment of various diseases. LB-100, a small molecule inhibitor of PP2A, has demonstrated anti-tumor therapeutic effects and high safety profile in preclinical experiments. However, the role of PP2A and its inhibitor has been insufficiently studied in LN. In this study, we assessed the potential effects of LB-100 in both MRL/lpr mice and R848-induced BALB/c mice. Our findings indicated that LB-100 administration led to reduced spleen enlargement, decreased deposition of immune complexes, ameliorated renal damage, and improved kidney function in both spontaneous and R848-induced lupus mouse models. Importantly, we observed the formation of tertiary lymphoid structures (TLSs) in the kidneys of two distinct lupus mouse models. The levels of signature genes of TLS were elevated in the kidneys of lupus mice, whereas LB-100 mitigated chemokine production and inhibited TLS formation. In addition, we confirmed that inhibition or knockdown of PP2A reduced the production of T cell-related chemokines by renal tubular epithelial cells (RTEC). In summary, our study highlighted the renal protective potential of the PP2A inhibitor LB-100 in two distinct lupus mouse models, suggesting its potential as a novel strategy for treating LN and other autoimmune diseases.

Structure-aware diffusion for low-dose CT imaging.

Reducing the radiation dose leads to the x-ray computed tomography (CT) images suffering from heavy noise and artifacts, which inevitably interferes with the subsequent clinic diagnostic and analysis. Leading works have explored diffusion models for low-dose CT imaging to avoid the structure degeneration and blurring effects of previous deep denoising models. However, most of them always begin their generative processes with Gaussian noise, which has little or no structure priors of the clean data distribution, thereby leading to long-time inference and unpleasant reconstruction quality. To alleviate these problems, this paper presents a Structure-Aware Diffusion model (SAD), an end-to-end self-guided learning framework for high-fidelity CT image reconstruction. First, SAD builds a nonlinear diffusion bridge between clean and degraded data distributions, which could directly learn the implicit physical degradation prior from observed measurements. Second, SAD integrates the prompt learning mechanism and implicit neural representation into the diffusion process, where rich and diverse structure representations extracted by degraded inputs are exploited as prompts, which provides global and local structure priors, to guide CT image reconstruction. Finally, we devise an efficient self-guided diffusion architecture using an iterative updated strategy, which further refines structural prompts during each generative step to drive finer image reconstruction. Extensive experiments on AAPM-Mayo and LoDoPaB-CT datasets demonstrate that our SAD could achieve superior performance in terms of noise removal, structure preservation, and blind-dose generalization, with few generative steps, even one step only.

Phosphorus and nitrogen supramolecule for fabricating flame-retardant, transparent and robust polyvinyl alcohol film.

Supramolecular flame retardants have attracted increasing attention recently due to their simple and eco-friendly preparation process. In this study, a novel flame retardant HEPFR was prepared using supramolecular self-assembly technology between piperazine and 1-hydroxy ethylidene-1,1-diphosphonic acid (HEDP). It was introduced into polyvinyl alcohol (PVA) matrix to form PVA/HEPFR composite film. Subsequently, the transparency, mechanical properties, thermal stability, and flame retardancy of PVA/HEPFR films were studied. Due to the hydrogen bonded cross-linked network structure between PVA and HEPFR, the mechanical properties of PVA/HEPFR films have been improved, while maintaining good transparency. With 10 wt% addition of HEPFR, PVA films can reach the VTM-0 level in UL-94 testing. And the limiting oxygen index can be increased from 18.5% of pure PVA to 26.5%. The peak heat release rate was reduced by 61.5%. The flame retardancy and thermal stability of PVA/HEPFR films have been greatly improved. This study provides a "one stone, three birds" strategy for preparing flame-retardant, transparent, and robust PVA film.

Nano-Enhanced Phase Reinforced Magnesium Matrix Composites: A Review of the Matrix, Reinforcement, Interface Design, Properties and Potential Applications.

Magnesium matrix composites are essential lightweight metal matrix composites, following aluminum matrix composites, with outstanding application prospects in automotive, aerospace lightweight and biomedical materials because of their high specific strength, low density and specific stiffness, good casting performance and rich resources. However, the inherent low plasticity and poor fatigue resistance of magnesium hamper its further application to a certain extent. Many researchers have tried many strengthening methods to improve the properties of magnesium alloys, while the relationship between wear resistance and plasticity still needs to be further improved. The nanoparticles added exhibit a good strengthening effect, especially the ceramic nanoparticles. Nanoparticle-reinforced magnesium matrix composites not only exhibit a high impact toughness, but also maintain the high strength and wear resistance of ceramic materials, effectively balancing the restriction between the strength and toughness. Therefore, this work aims to provide a review of the state of the art of research on the matrix, reinforcement, design, properties and potential applications of nano-reinforced phase-reinforced magnesium matrix composites (especially ceramic nanoparticle-reinforced ones). The conventional and potential matrices for the fabrication of magnesium matrix composites are introduced. The classification and influence of ceramic reinforcements are assessed, and the factors influencing interface bonding strength between reinforcements and matrix, regulation and design, performance and application are analyzed. Finally, the scope of future research in this field is discussed.

Association between modifiable lifestyle pattern and periodontitis: a cross-sectional study based on NHANES.

BACKGROUND: Periodontitis can be avoided with a healthy lifestyle. However, studies have only looked at one lifestyle, ignoring the connection between lifestyle patterns and periodontitis. The purpose of this study was to look at the association between modifiable lifestyle patterns and periodontitis. METHODS: Data were obtained from the National Health and Nutrition Examination Survey in 2009-2010 and 2011-2012. Smoke, drink, exercise, sleep duration, oral exams, and self-rated oral health were all lifestyle factors. The CDC/AAP classification/case definition was used to evaluate periodontitis. Drawing upon latent class analysis, distinct patterns of lifestyle were identified, with each participant exclusively affiliated with a single pattern. The association between lifestyle classes and periodontitis was then examined using ordinal logistic regression. RESULTS: 4686 (52%) of the total 9034 participants, with a mean age of 54.08, were women. Three lifestyle latent classes were found by fitting 2-10 models: "Class 1" (52%), " Class 2" (13%), and " Class 3" (35%). The "Class 1" displayed a prevalence of oral examination (75%), favorable self-rated oral health (92%), and engagement in physical activity (50%). The 'Class 2' exhibited the lowest alcohol consumption (64%) and smoking rates (73%) but the highest prevalence of physical inactivity (98%). The 'Class 3' showed a tendency for smoking (72%), alcohol consumption (78%), shorter sleep duration (50%), absence of oral examinations (75%), and suboptimal self-rated oral health (68%). The influencing variables for the latent classes of lifestyle were age, education, and poverty level. Periodontitis risk may rise by 24% for each additional unhealthy lifestyle practiced by participants (OR = 1.24, 95% CI: 1.18-1.31). The 'Class 3' (OR = 1.80, 95% CI: 1.52-2.13) had a greater risk of periodontitis compared to the 'Class 1'. CONCLUSIONS: Our analysis revealed that unhealthy lifestyle patterns are associated with periodontitis. These different lifestyle patterns need to be taken into account when developing public health interventions and clinical care.

Impact of bariatric surgery on carotid intima-media thickness and arterial stiffness in metabolically healthy obesity: a prospective study.

PURPOSE: Cardiovascular disease is one of the leading causes of mortality in patients with obesity. Metabolically healthy obesity (MHO), in which people do not have metabolic disorders, is a transient state of obesity. However, over the long term, a proportion of individuals with MHO develop metabolic syndrome (MetS). We aimed to investigate the effect of substantial weight loss following bariatric surgery in MHO on carotid intima-media thickness (CIMT) and pulse-wave velocity (PWV), which are independent predictors of subclinical atherosclerosis. METHODS: This prospective study included 38 patients (34 women, four men) undergoing bariatric surgery who had severe obesity but without comorbidities (hypertension, diabetes, and hyperlipidemia), and 28 control individuals who were matched for age and sex. CIMT and PWV of the left common carotid artery were measured. At 12-month follow-up after bariatric surgery, measurements were repeated in the 38 patients with obesity. RESULTS: Mean baseline body mass index (BMI) in the MHO group was 40.55 ± 3.59 kg/m2, which decreased by 33.1% after bariatric surgery. Compared with controls, CIMT and PWV were increased in MHO (543.53 ± 55.29 vs. 407.82 ± 53.09 µm, 6.70 ± 1.22 vs. 5.45 ± 0.74 m/s, respectively; all P < 0.001). At 12 months post-bariatric surgery, CIMT in MHO was lower than baseline (466.79 ± 53.74 vs. 543.53 ± 55.29 µm, P = 0.009), but PWV was not significantly different from baseline (6.27 ± 0.86 vs. 6.70 ± 1.22 m/s, P = 0.132). Multivariate regression showed that BMI was an independent predictor of CIMT (ß = 0.531, P < 0.001). CONCLUSION: Carotid artery structure and function were impaired in MHO, and improved carotid artery structure was associated with weight loss in MHO after bariatric surgery.

PD-1/CD80+ small extracellular vesicles from immunocytes induce cold tumours featured with enhanced adaptive immunosuppression.

Only a minority of cancer patients benefit from immune checkpoint blockade therapy. Sophisticated cross-talk among different immune checkpoint pathways as well as interaction pattern of immune checkpoint molecules carried on circulating small extracellular vesicles (sEV) might contribute to the low response rate. Here we demonstrate that PD-1 and CD80 carried on immunocyte-derived sEVs (I-sEV) induce an adaptive redistribution of PD-L1 in tumour cells. The resulting decreased cell membrane PD-L1 expression and increased sEV PD-L1 secretion into the circulation contribute to systemic immunosuppression. PD-1/CD80+ I-sEVs also induce downregulation of adhesion- and antigen presentation-related molecules on tumour cells and impaired immune cell infiltration, thereby converting tumours to an immunologically cold phenotype. Moreover, synchronous analysis of multiple checkpoint molecules, including PD-1, CD80 and PD-L1, on circulating sEVs distinguishes clinical responders from those patients who poorly respond to anti-PD-1 treatment. Altogether, our study shows that sEVs carry multiple inhibitory immune checkpoints proteins, which form a potentially targetable adaptive loop to suppress antitumour immunity.

Ionic Liquid Transdermal Patches of Two Active Ingredients Based on Semi-Ionic Hydrogen Bonding for Rheumatoid Arthritis Treatment.

Rheumatoid arthritis (RA) is a chronic autoimmune disease that leads to deformities and disabilities in patients. Conventional treatment focuses on delaying progression; therefore, new treatments are necessary. The present study reported a novel ionic liquid transdermal platform for efficient RA treatment, and the underlying mechanism was elucidated using FTIR, 1H-NMR, Raman, XPS, and molecular simulations. The results showed that the reversibility of the semi-ionic hydrogen bonding facilitated high drug loading and enhanced drug permeability. Actarit's drug loading had an approximately 11.34-times increase. The in vitro permeability of actarit and ketoprofen was improved by 5.46 and 2.39 times, respectively. And they had the same significant effect in vivo. Furthermore, through the integration of network pharmacology, Western blotting (WB), and radiology analyses, the significant osteoprotective effects of SIHDD-PSA (semi-ionic H-bond double-drug pressure-sensitive adhesive transdermal patch) were revealed through the modulation of the JAK-STAT pathway. The SIHDD-PSA significantly reduced paw swelling and inflammation in the rat model, and stimulatory properties evaluation confirmed the safety of SIHDD-PSA. In conclusion, these findings provide a novel approach for the effective treatment of RA, and the semi-ionic hydrogen bonding strategy contributes a new theoretical basis for developing TDDS.

Heterozygous mutations in factor H aggravate pathological damage in a stable IgA deposition model induced by Lactobacillus casei cell wall extract.

Introduction: Activation of complement through the alternative pathway (AP) has a key role in the pathogenesis of IgA nephropathy (IgAN). We previously showed, by intraperitoneal injection of Lactobacillus casei cell wall extract (LCWE), C57BL/6 mice develop mild kidney damage in association with glomerular IgA deposition. To further address complement activity in causing glomerular histological alterations as suggested in the pathogenesis of IgAN, here we used mice with factor H mutation (FHW/R) to render AP overactivation in conjunction with LCWE injection to stimulate intestinal production of IgA. Methods: Dose response to LCWE were examined between two groups of FHW/R mice. Wild type (FHW/W) mice stimulated with LCWE were used as model control. Results: The FHW/R mice primed with high dose LCWE showed elevated IgA and IgA-IgG complex levels in serum. In addition to 100% positive rate of IgA and C3, they display elevated biomarkers of kidney dysfunction, coincided with severe pathological lesions, resembling those of IgAN. As compared to wild type controls stimulated by the same high dose LCWE, these FHW/R mice exhibited stronger complement activation in the kidney and in circulation. Discussion: The new mouse model shares many disease features with IgAN. The severity of glomerular lesions and the decline of kidney functions are further aggravated through complement overactivation. The model may be a useful tool for preclinical evaluation of treatment response to complement-inhibitors.

Growth of millimeter-sized 2D metal iodide crystals induced by ion-specific preference at water-air interfaces.

Conventional liquid-phase methods lack precise control in synthesizing and processing materials with macroscopic sizes and atomic thicknesses. Water interfaces are ubiquitous and unique in catalyzing many chemical reactions. However, investigations on two-dimensional (2D) materials related to water interfaces remain limited. Here we report the growth of millimeter-sized 2D PbI2 single crystals at the water-air interface. The growth mechanism is based on an inherent ion-specific preference, i.e. iodine and lead ions tend to remain at the water-air interface and in bulk water, respectively. The spontaneous accumulation and in-plane arrangement within the 2D crystal of iodide ions at the water-air interface leads to the unique crystallization of PbI2 as well as other metal iodides. In particular, PbI2 crystals can be customized to specific thicknesses and further transformed into millimeter-sized mono- to few-layer perovskites. Additionally, we have developed water-based techniques, including water-soaking, spin-coating, water-etching, and water-flow-assisted transfer to recycle, thin, pattern, and position PbI2, and subsequently, perovskites. Our water-interface mediated synthesis and processing methods represents a significant advancement in achieving simple, cost-effective, and energy-efficient production of functional materials and their integrated devices.

LncRNA SNHG1 serves as a biomarker for systemic lupus erythematosus and participates in the disease progression.

LncRNAs play an important role in autoimmune diseases. The purpose of this study was to explore the role of lncRNA SNHG1 in systemic lupus erythematosus (SLE), and laid a theoretical foundation for the study of SLE. The basic clinical information of all subjects was first collected for statistical analysis, and SNHG1 expression in the serum of all subjects was detected by RT-qPCR. The value of SNHG1 in the diagnosis of SLE was assessed by ROC. The correlation between SNHG1 and each blood sample index was analyzed by Pearson correlation analysis. The role of SNHG1 in primary peripheral blood mononuclear cells (PBMCs) apoptosis was explored. SNHG1 expression is relatively upregulated in patients with SLE compared to healthy people. SNHG1 expression was positively correlated with SLEDAI score, IgG, CRP, and ESR, and negatively correlated with C3 and C4. ROC indicated that SNHG1 has the potential to assist in the diagnosis of SLE. PBMCs apoptosis in SLE was higher than that in control group, the knockdown and overexpression of SNHG1 could correspondingly inhibit and promote PBMCs apoptosis. SNHG1 has the potential to be a diagnosis marker for SLE and may be involved in regulating PBMCs apoptosis.

Serum long non-coding Ribonucleic Acid H19 serves as a biomarker for systemic lupus erythematosus and participates in the disease progression.

AIM: This study aimed to investigate the expression of H19 and its possible molecular mechanism in systemic lupus erythematosus (SLE). METHODS: The expression of H19 and miR-19b in serum and peripheral blood mononuclear cells (PBMCs) were detected by reverse transcription quantitative polymerase chain reaction (RT-qPCR). Receiver operator characteristic (ROC) curve was constructed to evaluate the diagnostic value of serum H19 in SLE. Pearson correlation coefficient was used to analyze the correlation between serum levels of H19 and miR-19b. Flow cytometry and Cell counting kit-8 (CCK-8) assay were performed to detect cell apoptosis and viability. The levels of pro-inflammatory and anti-inflammatory factors were measured by enzyme-linked immunosorbent assay (ELISA). Luciferase reporter gene assay was conducted to verify the interaction between H19 and miR-19b. RESULTS: The expression of H19 and miR-19b in SLE group were up-regulated and down-regulated, respectively. Serum H19 has certain clinical diagnostic value in SLE. In in vitro studies, overexpression of H19 can significantly inhibit the viability of PBMCs and promote apoptosis and inflammatory response of PBMCs by interacting with miR-19b. CONCLUSIONS: The expression of H19 is upregulated in patients with SLE and plays a role in cell function and inflammation by targeting miR-19b in PBMCs, which may be one of the pathological mechanisms of SLE.

Metastatic Lung Adenocarcinoma Received Combined 177 Lu-FAP-2286 Radiation Therapy and Targeted Therapy.

ABSTRACT: A 56-year-old man with metastatic lung adenocarcinoma received combined 177 Lu-FAP-2286 radiation therapy and targeted therapy. After 1 treatment cycle, improvement of symptoms and radiological remission was observed. Moreover, the patient did not report any adverse effects.

Nomogram for preoperative differentiation of benign and malignant breast tumors using contrast-enhanced cone-beam breast CT (CE CB-BCT) quantitative imaging and assessment features.

PURPOSE: Breast cancer's impact necessitates refined diagnostic approaches. This study develops a nomogram using radiology quantitative features from contrast-enhanced cone-beam breast CT for accurate preoperative classification of benign and malignant breast tumors. MATERIAL AND METHODS: A retrospective study enrolled 234 females with breast tumors, split into training and test sets. Contrast-enhanced cone-beam breast CT-images were acquired using Koning Breast CT-1000. Quantitative assessment features were extracted via 3D-slicer software, identifying independent predictors. The nomogram was constructed to preoperative differentiation benign and malignant breast tumors. Calibration curve was used to assess whether the model showed favorable correspondence with pathological confirmation. Decision curve analysis confirmed the model's superiority. RESULTS: The study enrolled 234 female patients with a mean age of 50.2 years (SD ± 9.2). The training set had 164 patients (89 benign, 75 malignant), and the test set had 70 patients (29 benign, 41 malignant). The nomogram achieved excellent predictive performance in distinguishing benign and malignant breast lesions with an AUC of 0.940 (95% CI 0.900-0.940) in the training set and 0.970 (95% CI 0.940-0.970) in the test set. CONCLUSION: This study illustrates the effectiveness of quantitative radiology features derived from contrast-enhanced cone-beam breast CT in distinguishing between benign and malignant breast tumors. Incorporating these features into a nomogram-based diagnostic model allows for breast tumor diagnoses that are objective and possess good accuracy. The application of these insights could substantially increase reliability and efficacy in the management of breast tumors, offering enhanced diagnostic capability.