Short-chain fatty acids regulate erastin-induced cardiomyocyte ferroptosis and ferroptosis-related genes.

Background: Ferroptosis has been proven to contribute to the progression of myocardial ischemia/reperfusion (I/R) injury and can be inhibited or promoted by ATF3. Short-chain fatty acids (SCFAs) have shown benefits in various cardiovascular diseases with anti-inflammatory and antioxidant effects. However, the impact of SCFAs on ferroptosis in ischemic-stimulated cardiomyocytes remains unknown. This study aimed to investigate the effect of SCFAs on cardiomyocyte ferroptosis, the expression of ATF3, and its potential upstream regulators. Methods and results: The expression of ATF3, ferroptosis pathway geneset (FPG), and geneset of potential regulators for ATF3 (GPRA, predicted by the PROMO database) was explored in the public human myocardial infarction single-cell RNA-seq (sma) dataset. Cardiomyocyte data was extracted from the dataset and re-clustered to explore the FPG, ATF3, and GPRA expression patterns in cardiomyocyte subclusters. A dose-dependent toxic experiment was run to detect the suitable dose for SCFA treatment. The erastin-induced ferroptosis model and hypoxia-reoxygenation (H/R) model (10 h of hypoxia followed by 6 h of reoxygenation) were adopted to assess the effect of SCFAs via the CCK8 assay. Gene expression was examined via RT-PCR and western blot. Ferroptosis markers, including lipid peroxides and Fe2+, were detected using the liperfluo and ferroOrange probes, respectively. In the sma dataset, upregulated ferroptosis pathway genes were mainly found in the infarction-stimulated cardiac cells (border zone and fibrotic zone), particularly the cardiomyocytes and adipocytes. The ATF3 and some of its potential transcription factors (VDR, EGR3, PAX5, and SP1) can be regulated by SCFA. SCFA can attenuate erastin-induced lipid peroxidation in cardiomyocytes. SCFA treatment can also reverse erastin-induced Fe2+ increase but may strengthen the Fe2+ in the H/R model. We also precisely defined a ferroptosis subcluster of cardiomyocytes (CM09) that highly expressed FPG, ATF3, and GPRA. Conclusion: The ATF3 and the ferroptosis pathway are elevated in cardiomyocytes of injury-related cardiac regions (border zone, ischemic zone, and fibrotic zone). SCFA can attenuate cardiomyocyte ferroptosis and regulate the expression of ATF3. Our study offers novel insights into the potential targets of SCFAs in the cardiovascular system.

Association between tobacco smoke exposure and serum parathyroid hormone levels among US adults (NHANES 2003-2006).

Tobacco smoke exposure has been demonstrated to impede bone remodeling and diminish bone density, yet research regarding its correlation with parathyroid hormone (PTH) remains limited. This study aims to investigate the relationship between tobacco smoke exposure and serum PTH levels in adults aged 20 years and older. This study included 7,641 participants from two cycles of the National Health and Nutrition Examination Survey (NHANES, United States, 2003- 2006). Reflect tobacco smoke exposure through serum cotinine levels, and use an adjusted weighted multivariate linear regression model to test the independent linear relationship between serum cotinine and PTH. Stratified analysis was conducted to validate the sensitivity of the conclusions. Smooth curve fitting and threshold effect analysis were performed to assess the non-linear relationship. After comprehensive adjustment using weighted multivariate regression analysis, a negative correlation was found between serum cotinine and PTH levels. The interaction p-values in subgroup analyses were all greater than 0.05. Moreover, smooth curve fitting indicated a non-linear relationship between serum cotinine and PTH, with a turning point observed. Our research indicates that tobacco smoke exposure is negatively correlated and independent of serum parathyroid hormone levels, indicating that long-term tobacco smoke exposure may lead to parathyroid dysfunction in adults.

Design of a Zn-based nanozyme injectable multifunctional hydrogel with ROS scavenging activity for myocardial infarction therapy.

The existing strategies for myocardial infarction therapy mainly focus on reinstating myocardial blood supply, often disregarding the intrinsic and intricate microenvironment created by elevated levels of reactive oxygen species (ROS) that accompanies myocardial infarction. This microenvironment entails cardiomyocytes apoptosis, substantial vascular cell death, excessive inflammatory infiltration and fibrosis. In such situation, the present study introduces a zinc-based nanozyme injectable multifunctional hydrogel, crafted from ZIF-8, to counteract ROS effects after myocardial infarction. The hydrogel exhibits both superoxide dismutase (SOD)-like and catalase (CAT)-like enzymatic activities, proficiently eliminating surplus ROS in the infarcted region and interrupting ROS-driven inflammatory cascades. Furthermore, the hydrogel's exceptional immunomodulatory ability spurs a notable transformation of macrophages into the M2 phenotype, effectively neutralizing inflammatory factors and indirectly fostering vascularization in the infarcted region. For high ROS and demanding for zinc of the infarcted microenvironment, the gradual release of zinc ions as the hydrogel degrades further enhances the bioactive and catalytic performance of the nanozymes, synergistically promoting cardiac function post myocardial infarction. In conclusion, this system of deploying catalytic nanomaterials within bioactive matrices for ROS-related ailment therapy not only establishes a robust foundation for biomedical material development, but also promises a holistic approach towards addressing myocardial infarction complexities. STATEMENT OF SIGNIFICANCE: Myocardial infarction remains the leading cause of death worldwide. However, the existing strategies for myocardial infarction therapy mainly focus on reinstating myocardial blood supply. These therapies often ignore the intrinsic and intricate microenvironment created by elevated levels of reactive oxygen species (ROS). Hence, we designed an injectable Zn-Based nanozyme hydrogel with ROS scavenging activity for myocardial infarction therapy. ALG-(ZIF-8) can significantly reduce ROS in the infarcted area and alleviate the ensuing pathological process. ALG-(ZIF-8) gradually releases zinc ions to participate in the repair process and improves cardiac function. Overall, this multifunctional hydrogel equipped with ZIF-8 makes full use of the characteristics of clearing ROS and slowly releasing zinc ions, and we are the first to test the therapeutic efficacy of Zinc-MOFs crosslinked-alginate hydrogel for myocardial infarction.

An Intrinsically Magnetic Epicardial Patch for Rapid Vascular Reconstruction and Drug Delivery.

Myocardial infarction (MI) is a major cause of mortality worldwide. The major limitation of regenerative therapy for MI is poor cardiac retention of therapeutics, which results from an inefficient vascular network and poor targeting ability. In this study, a two-layer intrinsically magnetic epicardial patch (MagPatch) prepared by 3D printing with biocompatible materials like poly (glycerol sebacate) (PGS) is designed, poly (ε-caprolactone) (PCL), and NdFeB. The two-layer structure ensured that the MagPatch multifariously utilized the magnetic force for rapid vascular reconstruction and targeted drug delivery. MagPatch accumulates superparamagnetic iron oxide (SPION)-labelled endothelial cells, instantly forming a ready-implanted organization, and rapidly reconstructs a vascular network anastomosed with the host. In addition, the prefabricated vascular network within the MagPatch allowed for the efficient accumulation of SPION-labelled therapeutics, amplifying the therapeutic effects of cardiac repair. This study defined an extendable therapeutic platform for vascularization-based targeted drug delivery that is expected to assist in the progress of regenerative therapies in clinical applications.

Prognostic analysis of cutaneous Kaposi sarcoma based on a competing risk model.

The data regarding the prognosis of cutaneous Kaposi sarcoma (KS) was limited. The current study aimed to explore the risk factors and develop a predictive model for the prognosis of cutaneous KS patients. Data were extracted from Surveillance, Epidemiology, and End Results database from 2000 to 2018 and randomly divided into training and validation cohort. The Kaplan-Meier analysis, cumulative incidence function based on the competing risk model and Fine-Gray multivariable regression model was used to identify the prognostic factors and then construct a 5-, 10-, and 15-year KS-specific death (KSSD) nomogram for patients. The concordance index (C-index), area under the curve (AUC) of operating characteristics and calibration plots were used to evaluate the performance of the model. The clinical utility of the model was measured by decision curve analysis (DCA). In 2257 cutaneous KS patients identified from database, the overall median survival time was about 13 years. Radiotherapy (p = 0.013) and surgery (p < 0.001) could lower the KSSD, while chemotherapy (p = 0.042) and surgery (p < 0.001) could increase the overall survival (OS) of patients with metastatic and localized lesions, respectively. Race, number of lesions, surgery, extent of disease, year of diagnosis and age were identified as risk factors associated with cutaneous KS-specific survival. Performance of the nomogram was validated by calibration and discrimination, with C-index values of 0.709 and AUC for 5-, 10-, and 15-year-KSSD of 0.739, 0.728 and 0.725 respectively. DCA indicated that the nomogram had good net benefits in clinical scenarios. Using a competing-risk model, this study firstly identified the prognostic factors, and constructed a validated nomogram to provide individualized assessment and reliable prognostic prediction for cutaneous KS patients.

Localized delivery of anti-inflammatory agents using extracellular matrix-nanostructured lipid carriers hydrogel promotes cardiac repair post-myocardial infarction.

A challenge in treating cardiac injury is the low heart-specificity of the drugs. Nanostructured lipid carriers (NLCs) are a relatively new format of lipid nanoparticles which have been used to deliver RNA and drugs. However, lipid nanoparticles exhibit higher affinity to the liver than the heart. To improve the delivery efficiency of NLCs into the heart, NLCs can be embedded into a scaffold and be locally released. In this study, a cardiac extracellular matrix (ECM) hydrogel-NLC composite was developed as a platform for cardiac repair. ECM-NLC composite gels at physiological conditions and releases payloads into the heart over weeks. ECM-NLC hydrogel carrying colchicine, an anti-inflammation agent, improved cardiac repair after myocardial infarction in mice. Transcriptome analysis indicated that Egfr downstream effectors participated in ECM-NLC-colchicine induced heart repair. In conclusion, ECM-NLC hydrogel is a potential platform for sustained and localized delivery of biomolecules into the heart, and loading appropriate medicines further increases the therapeutic efficacy of ECM-NLC hydrogel for cardiovascular diseases.

Clinical characteristics of primary parathyroid adenoma and its relationship with coexisting papillary thyroid carcinoma: a clinical retrospective study.

Background: Parathyroid adenoma (PA) is a common but relatively poorly understood endocrine tumor. A significant number of PA patients also have papillary thyroid carcinoma (PTC). The clinicopathological characteristics of PA and its relationship with PTC need further study. Methods: The clinical data of 99 PA patients were reviewed and the clinicopathologic features of PA were analyzed. PTC occurred in 22 PA patients. The clinicopathologic features of 22 patients with PA + PTC and 77 patients with PA alone were compared. According to age, gender and thyroid surgery methods, 22 PA + PTC patients were matched with 1,123 patients with PTC alone during the same period. The pathological characteristics of the two groups of patients were compared. All data analysis was performed using SPSS23.0, variables were compared by t-test, chi square test or Mann Whitney U-test as appropriate. Results: Ninety-nine PA patients (21 males, 78 females) with a median age of 51 [10-80] years were included. The preoperative parathyroid hormone (PTH) (P=0.007) and preoperative blood calcium (P=0.036) of male patients were higher than those of female patients, and the proportion of asymptomatic patients (P=0.008) and postoperative PTH level (P=0.013) were lower. The preoperative PTH level (P=0.002), preoperative blood calcium level (P=0.004), preoperative alkaline phosphatase (ALP) level (P=0.018) and postoperative PTH levels (P=0.023) in PA + PTC group were lower than those in PA group. The asymptomatic rate was higher in PTC + PA group than that in PA group (P<0.001). There was no statistical difference between PA + PTC group and PTC group in multifocal tumor, capsule invasion, lymph node metastasis (P>0.05). The lymph node metastasis rate in PA + PTC group (9/215) was significantly lower than that in PTC group (37/337) (P=0.005). Conclusions: PA exhibited the following characteristics: occurred in all age groups; more common in women but more severe in men; more located in the lower pole. The coexistence of PTC and PA did not promote the progression of PA, nor did it increase the aggressiveness of PTC. Conversely, their co-existence may lead to early diagnosis of the disease. PA patients (22.2%) also have PTC, so surgeons should pay attention to thyroid disease to prevent the need for reoperation.

Construction of cuproptosis-related gene signature to predict the prognosis and immunotherapy efficacy of patients with bladder cancer through bioinformatics analysis and experimental validation.

Background: A new form of cell death, copper-dependent cell death (termed cuproptosis), was illustrated in a recent scientific study. However, the biological function or prognostic value of cuproptosis regulators in bladder cancer (BLCA) remains unknown. Materials and Methods: Sequencing data obtained from BLCA samples in TCGA and GEO databases were preprocessed for analysis. Biological function and immune cell infiltration levels evaluated by gene set variation analysis (GSVA) were employed to calculate enrichment scores. Iteration least absolute shrinkage and selection operator (LASSO) and COX regression model were employed to select feature genes and construct a novel cuproptosis-related (CR) score signature. The genomics of drug sensitivity in cancer (GDSC) and tumor immune dysfunction and exclusion (TIDE) analysis were used to predict the chemotherapy and immunotherapy efficacy for BLCA patients. The relative expression of the genes involved in the signature was also verified by real-time quantitative PCR (qRT-PCR) in cell lines and tissues. Results: Expression abundance and the prognostic value of cuproptosis regulators proved that cuproptosis might play a vital part in the carcinogenesis of BLCA. GSVA revealed that cuproptosis regulators might be associated with metabolism and metastasis-related pathways such as TGF-ß, protein secretion, oxidative Phosphorylation, MYC targets, MTORC1, and adipogenesis pathways. CR scores could predict the prognosis and evaluate the chemotherapy and immunotherapy efficacies of BLCA. CR scores were positively correlated with EMT, MYC, MTORC1, HEDGEHOG, and E2F signaling pathways; meanwhile, they were negatively correlated with several immune cell infiltration levels such as CD8+ T cells, γδT cells, and activated dendritic cells. Several GEO datasets were used to validate the power of prognostic prediction, and a nomogram was also established for clinical use. The expressions of DDX10, RBM34, and RPL17 were significantly higher in BLCA cell lines and tissues in comparison with those in the corresponding normal controls. Conclusion: Cuproptosis might play an essential role in the progression of BLCA. CR scores could be helpful in the investigation of prognostic prediction and therapeutic efficacy and could make contributions to further studies in BLCA.

Case report and literature review: Malignant adenomyoepithelioma after breast augmentation.

Background: Breast malignant adenomyoepithelioma (MAME) after breast augmentation has never been reported. Case summary: We reported a case of a 55-year-old woman who was diagnosed with breast MAME 16 years after breast augmentation. Breast augmentation was performed on the patient with two 200 ml round textured prostheses in the subpectoral plane through axillary incisions in 2004. However, a breast ultrasound in 2020 revealed a suspicious malignant lump in the right breast, which was finally confirmed as MAME by pathology. Skin-sparing modified radical mastectomy and immediate breast reconstruction with expander implantation were performed. Subsequently, the patient received three cycles of chemotherapy with the regimen of anthracycline and cyclophosphamide. In the following nearly 2 years of follow-up, no tumor recurrence and metastasis were found, and the overall treatment was satisfactory for the patient. Conclusion: Here, we present a unique case in which a patient was diagnosed with breast MAME after breast augmentation. Skin-sparing modified radical mastectomy and immediate breast reconstruction with expander implantation are feasible approaches that yield at least short-term oncological safety and acceptable aesthetic results. However, whether there is a potential relationship between MAME and breast implants remains to be further explored. Meanwhile, due to the rarity of breast MAME, more authoritative strategies considering both oncological safety and aesthetics to seek better long-term therapeutic effects are needed.

Individualized model for predicting pathological complete response to neoadjuvant chemotherapy in patients with breast cancer: A multicenter study.

Background: Pathological complete response (pCR) is considered a surrogate for favorable survival in breast cancer (BC) patients treated with neoadjuvant chemotherapy (NACT), which is the goal of NACT. This study aimed to develop and validate a nomogram for predicting the pCR probability of BC patients after NACT based on the clinicopathological features. Methods: A retrospective analysis of 527 BC patients treated with NACT between January 2018 and December 2021 from two institutions was conducted. Univariate and multivariate logistic regression analyses were performed to select the most useful predictors from the training cohort (n = 225), and then a nomogram model was developed. The performance of the nomogram was evaluated with respect to its discrimination, calibration, and clinical usefulness. Internal validation and external validation were performed in an independent validation cohort of 96 and 205 consecutive BC patients, respectively. Results: Among the 18 clinicopathological features, five variables were selected to develop the prediction model, including age, American Joint Committee on Cancer (AJCC) T stage, Ki67 index before NACT, human epidermal growth factor receptor 2 (HER2), and hormone receptor (HR) status. The model showed good discrimination with an area under the receiver operating characteristic curve (AUC) of 0.825 (95% CI, 0.772 to 0.878) in the training cohort, and 0.755 (95% CI, 0.658 to 0.851) and 0.79 (95% CI, 0.724 to 0.856) in the internal and external validation cohorts, respectively. The calibration curve presented good agreement between prediction by nomogram and actual observation, and decision curve analysis (DCA) indicated that the nomogram had good net benefits in clinical scenarios. Conclusion: This study constructed a validated nomogram based on age, AJCC T stage, Ki67 index before NACT, HER2, and HR status, which could be non-invasively applied to personalize the prediction of pCR in BC patients treated with NACT.

Comparison of clinicopathological features and prognosis of papillary thyroid carcinoma and microcarcinoma: A population-based propensity score matching analysis.

Background: Overtreatment of papillary thyroid microcarcinoma (PTMC) has become a common concern. This study aimed to compare clinicopathological features between PTMC and papillary thyroid carcinoma (PTC) and to explore whether surgery can confer significant survival benefits in all patients with PTC or PTMC. Methods: Data of 145,951 patients with PTC registered in Surveillance, Epidemiology, and End Results (SEER) database and 8,751 patients with PTC in our institution were retrospectively collected. Patients with tumors less than 10 mm in diameter were classified as PTMC cohort and the rest as PTC cohort. Clinicopathological features between PTMC and PTC were compared on the basis of SEER cohort and validated with institutional data. Survival analysis was conducted to explore the effect of surgery on the prognosis of patients. To minimize potential confounders and selection bias, we performed propensity score matching (PSM) analysis to match more comparable cohorts. Results: Compared with PTC, PTMC exhibited the following characteristics: more common in women and whites, older age at diagnosis, lower proportion of follicular variants, intraglandular dissemination, extraglandular and capsular invasion, higher proportion of multifocality, fewer lymph node and distant metastases, and higher cancer-specific survival (CSS) and overall survival (OS) (all p-value < 0.05). Regarding treatment, patients with PTMC received a lower proportion of radiotherapy, chemotherapy, and total thyroidectomy but a higher proportion of lobectomy and/or isthmectomy. There was no significant difference in CSS for patients with PTMC at stage T1N0M0 with or without surgery (P = 0.36). Conclusion: Generally, PTMC showed higher biological indolence than PTC, which meant a higher survival rate for patients in both OS and CSS. For patients with PTMC at staged T1N0M0, active surveillance (AS) may be a potentially feasible management strategy. However, the maintenance of good medical compliance and the management of psychological burden cannot be ignored for patients included in AS.

Nontoxic Tb3+-induced hyaluronic nano-poached egg aggregates for colorimetric and luminescent detection of Fe3+ ions.

This study demonstrates that a luminescent Tb3+ complex with green emission can be complexed with hyaluronic (hya) to form nanoparticles. The structure of complexation is composed of a Tb(acac)2phen core with a hya surface, similar to those of the nano-poached eggs. What makes the structure unique is that Tb(acac)2phen and hya are connected by chemical bonds. To confirm their utility, we illustrate that the luminescence is rapidly and selectively quenched in the presence of Fe3+. Initial cytotoxicity experiments with human liver carcinoma cells show that the luminescent lanthanide complexes are cytotoxic, however, complexing lanthanides to hya renders them cytocompatible. The new complex integrates the advantages of superior lanthanide luminescence, the unique shape of nano-poached eggs, compatibility with aqueous systems, and cytocompatibility. Tb3+-induced hyaluronic nano-poached eggs (THNE) can, therefore, be used for Fe3+ detection in aqueous systems.

SCN8A epileptic encephalopathy mutations display a gain-of-function phenotype and divergent sensitivity to antiepileptic drugs.

De novo missense mutations in SCN8A gene encoding voltage-gated sodium channel NaV1.6 are linked to a severe form of early infantile epileptic encephalopathy named early infantile epileptic encephalopathy type13 (EIEE13). The majority of the patients with EIEE13 does not respond favorably to the antiepileptic drugs (AEDs) in clinic and has a significantly increased risk of death. Although more than 60 EIEE13-associated mutations have been discovered, only few mutations have been functionally analyzed. In this study we investigated the functional influences of mutations N1466T and N1466K, two EIEE13-associated mutations located in the inactivation gate, on sodium channel properties. Sodium currents were recorded from CHO cells expressing the mutant and wide-type (WT) channels using the whole-cell patch-clamp technique. We found that, in comparison with WT channels, both the mutant channels exhibited increased window currents, persistent currents (INaP) and ramp currents, suggesting that N1466T and N1466K were gain-of-function (GoF) mutations. Sodium channel inhibition is one common mechanism of currently available AEDs, in which topiramate (TPM) was effective in controlling seizures of patients carrying either of the two mutations. We found that TPM (100 µM) preferentially inhibited INaP and ramp currents but did not affect transient currents (INaT) mediated by N1466T or N1466K. Among the other 6 sodium channel-inhibiting AEDs tested, phenytoin and carbamazepine displayed greater efficacy than TPM in suppressing both INaP and ramp currents. Functional characterization of mutants N1466T and N1466K is beneficial for understanding the pathogenesis of EIEE13. The divergent effects of sodium channel-inhibiting AEDs on INaP and ramp currents provide insight into the development of therapeutic strategies for the N1466T and N1466K-associated EIEE13.

Corrosion self-warning and repair tracking of polymeric coatings based on stimulus responsive nanosensors.

Smart polymeric coatings with early corrosion self-warning and damage self-repairing characteristics have garnered tremendous interest due to their ability to sense corrosion reactions and repair coating defects. However, tracking the repair process and its underlying protection mechanism is highly challenging. Herein, we report the construction of a novel composite coating by incorporating multifunctional nanosensors (graphene oxide-zeolitic imidazole frameworks loaded with 1,10-phenanthroline) into a thermo-responsive polyurethane. Under damaging events, the localized acidity derived from metal corrosion stimulates the decomposition of the nanosensors to produce 1,10-phenanthroline and benzimidazole. The generated ferrous ions are rapidly sensed by the released 1,10-phenanthroline to produce a conspicuous red color, which warns of the corrosion occurrence. In profiting from the photothermal effect of graphene oxide, the composite coating exhibits efficient crack closure behavior under near-infrared light irradiation. Morphology observation indicates that a coating scratch (about 30 µm wide) almost closed with 20 s of irradiation. The photothermally activated crack closure combined with benzimidazole inhibition endows the prepared coating with superior self-repairing performance. Interestingly, the change in color intensity around the coating defect can assist in tracking the repair process. Therefore, this work provides a novel strategy to visualize microscopic behaviors during damage and repair processes.

Real-time intraoperative near-infrared autofluorescence imaging to locate the parathyroid glands: A preliminary report.

Identification and localization of parathyroid glands (PGs) remains a challenge for surgeons. The aim of this study was to evaluate the efficiency of intraoperative near-infrared autofluorescence (NIRAF) imaging to detect PGs in thyroid and parathyroid diseases. Seventy-six patients undergoing surgery for thyroid or parathyroid diseases between July 9, 2020 and August 20, 2021 were retrospectively analyzed. Intraoperative carbon nanoparticle (CN) negative imaging and handheld NIRAF imaging were successively performed for each patient. Of 206 PGs that needed to be identified for surgery, 162 were identified by NIRAF imaging, with a theoretical rate of identification of 78.64%. This was higher than the rate of identification with CN negative imaging, which was 75.73%. The number of PGs identified by NIRAF imaging and CN negative imaging did not differ significantly in either total thyroidectomy or thyroid lobectomy. In addition, the autofluorescence (AF) intensity of secondary parathyroid adenoma was weaker than that of normal PGs. NIRAF imaging is potentially a more efficient tool for identification of PGs than CN negative imaging, with a shorter learning curve and lower risk. It may not be well-suited to secondary hyperthyroidism or adenoma, but it was more efficient at identifying excised specimens than visual identification by a surgeon.

Autologous Skin Fibroblast-Based PLGA Nanoparticles for Treating Multiorgan Fibrosis.

Fibrotic diseases remain a substantial health burden with few therapeutic approaches. A hallmark of fibrosis is the aberrant activation and accumulation of myofibroblasts, which is caused by excessive profibrotic cytokines. Conventional anticytokine therapies fail to undergo clinical trials, as simply blocking a single or several antifibrotic cytokines cannot abrogate the profibrotic microenvironment. Here, biomimetic nanoparticles based on autologous skin fibroblasts are customized as decoys to neutralize multiple fibroblast-targeted cytokines. By fusing the skin fibroblast membrane onto poly(lactic-co-glycolic) acid cores, these nanoparticles, termed fibroblast membrane-camouflaged nanoparticles (FNPs), are shown to effectively scavenge various profibrotic cytokines, including transforming growth factor-ß, interleukin (IL)-11, IL-13, and IL-17, thereby modulating the profibrotic microenvironment. FNPs are sequentially prepared into multiple formulations for different administration routines. As a proof-of-concept, in three independent animal models with various organ fibrosis (lung fibrosis, liver fibrosis, and heart fibrosis), FNPs effectively reduce the accumulation of myofibroblasts, and the formation of fibrotic tissue, concomitantly restoring organ function and indicating that FNPs are a potential broad-spectrum therapy for fibrosis management.

A novel l-histidine based ionic liquid (LHIL) as an efficient corrosion inhibitor for mild steel.

A novel l-histidine based ionic liquid (LHIL) was developed and successfully synthesized. Its structure was confirmed by Fourier-transform infrared spectroscopy, UV-vis spectroscopy, X-ray photoelectron spectroscopy, 1H-NMR and high-resolution mass spectrometry. The outstanding corrosion inhibition effect of the LHIL on mild steel in 1 M hydrochloric acid was thoroughly evaluated by Tafel plots, electrochemical impedance spectroscopy, and localized electrochemical strategies. The results revealed that the corrosion of mild steel was effectively suppressed by the adsorption of LHIL on its surface, and the best inhibition efficiency reached 98.8%. The adsorption behavior of LHIL on steel obeyed the Langmuir adsorption isotherm, which involved both chemisorption and physisorption. Theoretical calculations indicated the strong chemisorption of LHIL on steel, as proved by the low energy gap (ΔE = 0.0522 eV) and high binding energy (E binding = 303.47 kcal mol-1), which clearly confirmed the effectiveness of LHIL for steel protection.

Prognostic Analysis for Patients With Parathyroid Carcinoma: A Population-Based Study.

BACKGROUND: Parathyroid carcinoma (PC) is a rare but often lethal malignancy for which staging system, prognostic indicators, and treatment guidelines are still not established. We aimed to explore the prognostic parameters and construct a nomogram for cancer-specific survival (CSS) of PC. METHODS: A retrospective analysis of 604 PC patients in the SEER database from 2001 through 2018 was performed. All the cases were randomly assigned to the training cohort (n = 424) or the validation cohort (n = 180) at a ratio of 7:3. The Kaplan-Meier method and Cox regression model were applied to estimate the CSS and risk factors, and a nomogram was constructed. The predictive accuracy and discriminative ability of the nomogram in CSS were assessed by concordance index (C-index), the area under the curve (AUC) of receiver operating characteristics (ROC), and the calibration curve. RESULTS: Age at diagnosis > 70 years [hazard ratio (HR): 3.55, 95% CI: 1.07-11.78, p = 0.039] and tumor size > 35 mm (HR 4.22, 95% CI: 1.67-10.68, p = 0.002) were associated with worse CSS. Compared with distant metastasis, localized (HR 0.17, 95% CI: 0.06-0.47, p = 0.001) and regional lesions (HR 0.22, 95% CI: 0.07-0.66, p = 0.007) showed an improved CSS rate. Parathyroidectomy was the recommended treatment (p = 0.02). The C-index of the nomogram was 0.826, and the AUC for 5-, 10-, and 15-year CSS was 83.7%, 79.7%, and 80.7%, respectively. The calibration curve presented good agreement between prediction by nomogram and actual observation. CONCLUSION: Age at diagnosis > 70 years, tumor size > 35 mm, and distant metastasis were independent risk factors for PC-specific mortality. Parathyroidectomy was currently the most recommended treatment for PC. This nomogram provided individualized assessment and reliable prognostic prediction for patients with PC.