Unveiling the Twisted Aromatic Donor Effect on the Nonlinear Response of D-π-A Type Malononitrile-Derived Chromophores.

This study presents the design, synthesis, and comprehensive characterization of a novel series of D-π-A type malononitrile-derived chromophores, BTC-1 to BTC-4. Combining various spectroscopic techniques, nonlinear Z-scan measurements, and quantum chemical calculations, we revealed the intricate relationship between nonlinear optical properties and the interplay of molecular structure, intramolecular charge transfer (ICT), and dipole moments (µ). Our experimental and computational findings corroborate that the polarization degree in the ground state, the charge separation in the excited state and ICT collectively dictate the nonlinear optical properties of the compounds. Notably, BTC-1 exhibits an exceptional nonlinear absorption coefficient ß value (2 × 10-8 m W-1), attributed to its optimized charge transfer efficiency and pronounced degree of charge separation. Our findings provide actionable insights for the rational design of high-performance organic NLO materials with potential applications in advanced photonic devices.

Identification and characterization of Achromobacter spanius P-9 and elucidation of its deoxynivalenol-degrading potential.

Deoxynivalenol (DON) poses significant challenges due to its frequent contamination of grains and associated products. Microbial strategies for mitigating DON toxicity showed application potential. Eight bacterial isolates with DON degradation activity over 5% were obtained from various samples of organic fertilizer in this study. One of the isolates emerged as a standout, demonstrating a substantial degradation capability, achieving a 99.21% reduction in DON levels. This isolate, underwent thorough morphological, biochemical, and molecular characterization to confirm its identity, and was identified as a new strain of Achromobacter spanius P-9. Subsequent evaluations revealed that the strain P-9 retains its degradation activity after a 24-h incubation, reaching optimal performance at 35 °C with a pH of 8.0. Further studies indicated that Ca2+ ions enhance the degradation process, whereas Zn2+ ions exert an inhibitory effect. This is the pioneering report of DON degradation by Achromobacter spanius, illuminating its prospective utility in addressing DON contamination challenges.

Contemporary Incidence of Cognitive Impairment or Dementia in Patients undergoing Coronary Artery Bypass Grafting: A Systematic Review and Meta-analysis.

INTRODUCTION: Despite the high prevalence of cognitive impairment or dementia post coronary artery bypass grafting (CABG), the incidence of cognitive impairment or dementia post-CABG in contemporary practice is currently unclear. Therefore, this paper aims to investigate the incidence and associated risk factors of cognitive impairment or dementia in patients post-CABG. METHODS: A systematic search across three databases (PubMed, SCOPUS and Embase) was conducted for studies published in or after 2013 that reported cognitive impairment or dementia post-CABG. Subgroup analyses and meta-regression by risk factors were performed to determine their influence on the results. RESULTS: This analysis included 23 studies with a total of 2620 patients. The incidence of cognitive impairment or dementia less than one month, two to six months, and more than twelve months post-CABG was 35.96% (95%CI: 28.22-44.51, I2=87%), 21.33% (95%CI: 13.44-32.15, I2=88%) and 39.13% (95%CI: 21.72-58.84, I2=84%), respectively. Meta-regression revealed that studies with more than 80% of the cohort diagnosed with hypertension were significantly associated with incidence of cognitive impairment or dementia less than one-month post-CABG. CONCLUSION: This meta-analysis demonstrates a high incidence of cognitive impairment or dementia in patients post-CABG in contemporary practice, particularly less than one month post-CABG. We found that hypertension was a significant risk factor in the short term (less than one month) follow-up period for cognitive impairment or dementia post-CABG. Future research should be done to assess strategies to reduce cognitive impairment post-CABG. .

Enhancing simulation feasibility for multi-layer 2D MoS2 RRAM devices: reliability performance learnings from a passive network model.

While two-dimensional (2D) MoS2 has recently shown promise as a material for resistive random-access memory (RRAM) devices due to its demonstrated resistive switching (RS) characteristics, its practical application faces a significant challenge in industry regarding its limited yield and endurance. Our earlier work introduced an effective switching layer model to understand RS behavior in both mono- and multi-layered MoS2. However, functioning as a phenomenological percolation modeling tool, it lacks the capability to accurately simulate the intricate current-voltage (I-V) characteristics of the device, thereby hindering its practical applicability in 2D RRAM research. In contrast to the established conductive filament model for oxide-based RRAM, the RS mechanism in 2D RRAM remains elusive. This paper presents a novel simulator aimed at providing an intuitive, visual representation of the stochastic behaviors involved in the RS process of multi-layer 2D MoS2 RRAM devices. Building upon the previously proposed phenomenological simulator for 2D RRAM, users can now simulate both the I-V characteristics and the resistive switching behaviors of the RRAM devices. Through comparison with experimental data, it was observed that yield and endurance characteristics are linked to defect distributions in MoS2.

Arrhythmogenic right ventricular cardiomyopathy with sustained ventricular tachycardia: a case report.

INTRODUCTION: Arrhythmogenic right ventricular cardiomyopathy (ARVC) is an infrequent hereditary disorder distinguished by fibrofatty replacement of the myocardium in the right ventricular, which predisposes individuals to life-threatening arrhythmias. This case delineates an ARVC patient who suffered recurrent bouts of sustained ventricular tachycardia (VT). In this case, we mainly discuss the application of myocardial contrast echocardiography (MCE) in displaying myocardial fibrosis in patients with ARVC. CASE PRESENTATION: A 43-year-old male experienced three episodes of unexplained VT over an eight-year period, accompanied by symptoms of chest discomfort, palpitations and dizziness. Coronary angiography revealed no significant coronary stenosis. The electrocardiogram (ECG) results indicated characteristic epsilon waves in right precordial leads, and subsequent echocardiography identified right ventricular enlargement and right ventricular systolic dysfunction. MCE further disclosed regional myocardial ischemia at the epicardium of the left ventricular apex. Ultimately, cardiovascular magnetic resonance imaging (CMR) corroborated the ARVC diagnosis, highlighting linear intensification in the right ventricle during the delayed enhancement. CONCLUSION: Prompt identification of ARVC is crucial for timely intervention and management. MCE may offer an effective and valuable technique for the detection of myocardial involvement in ARVC patient.

Elucidating the Diagnostic Complexity of Round Cell Sarcoma with EWSR1-CREM Fusion: A Comprehensive Case Study.

Sarcomas, particularly undifferentiated small round cell sarcomas of bone and soft tissue, pose significant diagnostic challenges due to their nonspecific morphology and the necessity for comprehensive molecular analyses. This paper discusses a rare case of round cell sarcoma exhibiting the EWSR1-CREM fusion, offering insights into the complexities of its diagnosis and management. The patient, a 15-year-old female with a history of Type 1 diabetes, presented with persistent right thigh tenderness and swelling. MRI revealed a large necrotic mass in the retroperitoneal region. Histological analysis showed a well-demarcated tumor with diverse cellular morphologies and distinct necrotic areas. Immunohistochemical (IHC) tests identified dot-like staining for Desmin and Vimentin but negative results for several markers, including Cytokeratin and CD45. Strong ALK positivity was noted. Next-generation sequencing with the Illumina TruSight™ Oncology 500 assay revealed the fusion gene EWSR1-CREM, along with benign and uncertain mutations in other genes. The tumor's morphology and immunoprofile, along with molecular findings, led to a diagnosis of round cell sarcoma with EWSR1-CREM fusion. This case adds to the spectrum of tumors associated with this fusion, often presenting diverse morphologies. The rarity of EWSR1-CREM fusion sarcomas poses a challenge in treatment, highlighted by the development of pulmonary metastases and disease progression after surgical excision in this patient despite the lack of an effective targeted therapy. In conclusion, this case emphasizes the need for a multidisciplinary diagnostic approach in complex sarcomas and highlights the importance of continued research on rare sarcomas, their genetic underpinnings, and potential therapeutic targets.

USP30 promotes the progression of breast cancer by stabilising Snail.

Breast cancer (BC) is the most prevalent tumour in women worldwide. USP30 is a deubiquitinase that has been previously reported to promote tumour progression and lipid synthesis in hepatocellular carcinoma. However, the role of USP30 in breast cancer remains unclear. Therefore, we investigated its biological action and corresponding mechanisms in vitro and in vivo. In our study, we found that USP30 was highly expressed in breast cancer samples and correlated with a poor patient prognosis. Knockdown of USP30 significantly suppressed the proliferation, invasion and migration abilities of BC cells in vitro and tumour growth in vivo, whereas overexpression of USP30 exhibited the opposite effect. Mechanistically, we verified that USP30 interacts with and stabilises Snail to promote its protein expression through deubiquitination by K48-linked polyubiquitin chains and then accelerates the EMT program. More importantly, USP30 reduced the chemosensitivity of BC cells to paclitaxel (PTX). Collectively, these data demonstrate that USP30 promotes the BC cell EMT program by stabilising Snail and attenuating chemosensitivity to PTX and may be a potential therapeutic target in BC.

Cancer-associated fibroblast-derived gene signature discriminates distinct prognoses by integrated single-cell and bulk RNA-seq analyses in breast cancer.

BACKGROUND: Cancer-associated fibroblasts (CAFs) are one of the most predominant cellular subpopulations in the tumor stroma and play an integral role in cancer occurrence and progression. However, the prognostic role of CAFs in breast cancer remains poorly understood. METHODS: We identified a number of CAF-related biomarkers in breast cancer by combining single-cell and bulk RNA-seq analyses. Based on univariate Cox regression as well as Least Absolute Shrinkage and Selection Operator (LASSO) regression analysis, a novel CAF-associated prognostic model was developed. Breast cancer patients were grouped according to the median risk score and further analyzed for outcome, clinical characteristic, pathway activity, genomic feature, immune landscape, and drug sensitivity. RESULTS: A total of 341 CAF-related biomarkers were identified from single-cell and bulk RNA-seq analyses. We eventually screened eight candidate prognostic genes, including CERCAM, EMP1, SDC1, PRKG1, XG, TNN, WLS, and PDLIM4, and constructed the novel CAF-related prognostic model. Grouped by the median risk score, high-risk patients showed a significantly worse prognosis and exhibited distinct pathway activities such as uncontrolled cell cycle progression, angiogenesis, and activation of glycolysis. In addition, the combined risk score and tumor mutation burden significantly improved the ability to predict patient prognosis. Importantly, patients in the high-risk group had a higher infiltration of M2 macrophages and a lower infiltration of CD8+ T cells and activated NK cells. Finally, we calculated the IC50 for a range of anticancer drugs and personalized the treatment regimen for each patient. CONCLUSION: Integrating single-cell and bulk RNA-seq analyses, we identified a list of compositive CAF-associated biomarkers and developed a novel CAF-related prognostic model for breast cancer. This robust CAF-derived gene signature acts as an excellent predictor of patient outcomes and treatment responses in breast cancer.

[Short-term effectiveness of unilateral biportal endoscopy technique in treatment of lumbar lateral saphenous fossa combined with intervertebral foramina stenosis via contralateral sublaminar approach].

Objective: To investigate the short-term effectiveness of unilateral biportal endoscopy (UBE) in treatment of lumbar lateral saphenous fossa combined with intervertebral foramina stenosis via contralateral sublaminar approach. Methods: A clinical data of 15 patients with lumbar lateral saphenous fossa combined with intervertebral foramina stenosis, who were admitted between September 2021 and December 2023 and met selective criteria, was retrospectively analyzed. There were 5 males and 10 females with an average age of 70.3 years (range, 46-83 years). Surgical segment was L 4, 5 in 12 cases and L 5, S 1 in 3 cases. The disease duration was 12-30 months (mean, 18.7 months). All patients were treated by UBE via contralateral sublaminar approach. The operation time, intraoperative blood loss, postoperative hospital stay, and the occurrence of complications were recorded. The visual analogue scale (VAS) score was used to evaluate the degree of lower back and leg pain before and after operation; the Japanese Orthopaedic Association (JOA) score and the Oswestry disability index (ODI) were used to evaluate the lumbar function; and the clinical outcome was evaluated using the MacNab criteria at 6 months after operation. Postoperative MRI and CT were taken to observe whether the lateral saphenous fossa and intervertebral foramen stenosis were removed or not, and the cross-sectional area of the spinal canal (CSA-SC), cross-sectional area of the intervertebral foramen (CSA-IVF), and cross-sectional area of the facet joint (CSA-FJ) were measured. Results: The operation time was 55-200 minutes (mean, 127.5 minutes); the intraoperative blood loss was 10-50 mL (mean, 27.3 mL); the length of postoperative hospital stay was 3-12 days (mean, 6.8 days). All patients were followed up 6-12 months (mean, 8.9 months). At 1 day, 1 month, 3 months, and 6 months after operation, the VAS scores of low back and leg pain and ODI scores after operation were significantly lower than preoperative scores and showed a gradual decrease with time; the JOA scores showed a gradual increase with time; the differences in the above indexes between different time points were significant ( P<0.05). The clinical outcome was rated as excellent in 10 cases, good in 4 cases, and poor in 1 case according to the MacNab criteria at 6 months after operation, with an excellent and good rate of 93.33%. Imaging review showed that the compression on the lateral saphenous fossa and intervertebral foramina had been significantly relieved, and the affected articular process joint was preserved to the maximum extent; the CSA-SC and CSA-IVF at 3 days after operation significantly increased compared to the preoperative values ( P<0.05), and the CSA-FJ significantly reduced ( P<0.05). Conclusion: The UBE via contralateral sublaminar approach can effectively reduce pressure in the lateral saphenous fossa and the intervertebral foramina of the same segment while preserving the bilateral articular process joints. The short-term effectiveness is good and it is expected to avoid fusion surgery caused by iatrogenic instability of the lumbar spine. However, further follow-up is needed to clarify the mid- and long-term effectiveness.

Acute toxicity of deoxynivalenol and bioremediation of a highly effective deoxynivalenol degrading Achromobacter spanius P-9 on zebrafish embryos and adults.

Deoxynivalenol (DON) is one of the mostly concerned mycotoxins and several microbes showed bioremediation effects on DON toxic effects. In this study, the acute toxicity of a new DON degrading strain Achromobacter spanius P-9 with DON on zebrafish embryos and adults were firstly performed. For zebrafish embryos, bacterial concentrations of 2.5 × 107 CFU/mL and 5.0 × 107 CFU/mL had no significant effects on growth and development. However, at 7.5 × 107 CFU/mL, some effects were observed, and at 10.0 × 107 CFU/mL, the embryo survival rate decreased to 70%, with 3.3% teratogenicity. Higher bacterial concentrations correlated with faster heart rates. DON (100 µg/mL) significantly reduced embryo survival to 36.7% in 96 h. Bacterial solutions at 7.5 × 107 CFU/mL and 10.0 × 107 CFU/mL expanded the zebrafish intestinal tissue wall, while DON at 100 µg/mL negatively impacted intestinal morphology. Liver tissue in zebrafish exposed to Achromobacter spanius P-9 showed no significant differences from the control group. However, exposure to DON solution increased liver fluorescence intensity and caused liver cell changes, including edema, vacuolization, and blurred boundaries. For adult zebrafish, the ROS and 8-OHdG contents in the exposure group increased with the increase of bacterial solution concentration, the SOD enzyme activity, CAT enzyme activity, GST enzyme activity and MDA was not significantly different with the control group. Compared with the control group, the content of ROS, GST enzyme activity, MDA and 8-OHdG after DON treatment showed an upward trend, SOD and CAT enzyme activities showed a decreasing trend. Achromobacter spanius P-9 has no obvious inhibitory effect on the growth and development of zebrafish embryos and has no obvious death and toxicity during the growth of adult fish, providing data support for the future application of this strain in the biodegradation of DON.

Construction of molecular subtype model of osteosarcoma based on endoplasmic reticulum stress and tumor metastasis-related genes.

Introduction: Osteosarcoma, the prevailing primary bone malignancy among children and adolescents, is frequently associated with treatment failure primarily due to its pronounced metastatic nature. Methods: This study aimed to establish potential associations between hub genes and subtypes for the treatment of metastatic osteosarcoma. Differentially expressed genes were extracted from patients diagnosed with metastatic osteosarcoma and a control group of non-metastatic patients, using the publicly available gene expression profile (GSE21257). The intersection of these gene sets was determined by focusing on endoplasmic reticulum (ER) stress-related genes sourced from the GeneCards database. We conducted various analytical techniques, including functional and pathway enrichment analysis, WGCNA analysis, protein-protein interaction (PPI) network construction, and assessment of immune cell infiltration, using the intersecting genes. Through this analysis, we identified potential hub genes. Results: Osteosarcoma subtype models were developed using molecular consensus clustering analysis, followed by an examination of the associations between each subtype and hub genes. A total of 138 potential differentially expressed genes related to endoplasmic reticulum (ER) stress were identified. These genes were further investigated using Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and Gene Set Enrichment Analysis (GSEA) pathways. Additionally, the PPI interaction network revealed 38 interaction relationships among the top ten hub genes. The findings of the analysis revealed a strong correlation between the extent of immune cell infiltration and both osteosarcoma metastasis and the expression of hub genes. Notably, the differential expression of the top ten hub genes was observed in osteosarcoma clusters 1 and 4, signifying their significant association with the disease. Conclusion: The identification of ten key genes linked to osteosarcoma metastasis and endoplasmic reticulum stress bears potential clinical significance. Additionally, exploring the molecular subtype of osteosarcoma has the capacity to guide clinical treatment decisions, necessitating further investigations and subsequent clinical validations.

A novel ß-cyclodextrin-assisted enhancement strategy for portable and sensitive detection of miR-21 in human serum.

Benefiting from our discovery that ß-cyclodextrin (ß-CD) could enhance the catalytic activity of invertase through hydrogen bonding to improve detection sensitivity, a highly sensitive and convenient biosensor for the detection of miR-21 was proposed, which is based on the simplicity of reading signals from a personal glucose meter (PGM), combined with self-assembled signal amplification probes and the performance of ß-CD as an enhancer. In the presence of miR-21, magnetic nanoparticle coupled capture DNA (MNPs-cDNA) could capture it and then connect assist DNA/H1-invertase (aDNA/H1) and self-assembled signal amplification probes (H1/H2) in turn. As a result, a "super sandwich" structure was formed. The invertase on MNPs-cDNA could catalyze the hydrolysis of sucrose to glucose and this catalytic process could be enhanced by ß-CD. The PGM signal exhibited a linear correlation with miR-21 concentration within the range of 25 pmol L-1 to 3 nmol L-1, and the detection limit was as low as 5 pmol L-1 with high specificity. Moreover, the recoveries were 103.82-124.65% and RSD was 2.59-6.43%. Furthermore, the biosensor was validated for the detection of miR-21 in serum, and the results showed that miR-21 levels in serum samples from patients with Diffuse Large B-Cell Lymphoma (DLBCL) (n = 12) were significantly higher than those from healthy controls (n = 12) (P < 0.001). Therefore, the ingenious combination of PGM-based signal reading, self-assembled signal amplification probes and ß-CD as an enhancer successfully constructed a convenient, sensitive and specific biosensing method, which is expected to be applied to clinical diagnosis.

Correlation between essential and toxic elements in maternal blood during early pregnancy and atrial septal defects/ventricular septal defects/patent ductus arteriosus in offspring.

BACKGROUND: Congenital heart defects (CHDs) are the most common congenital malformation in the world. Recent studies have found that essential and toxic trace element levels may play a crucial role in the risk of neonatal malformation. However, the relationships between element levels in early pregnancy and CHD risk among humans remain unclear. This study investigates the association between maternal essential element (copper [Cu], zinc [Zn], calcium [Ca], manganese [Mg] and iron [Fe]) and toxic element (lead [Pb] and cadmium [Cd]) levels during early pregnancy and CHDs. METHODS: A hospital-based case-control study was conducted, including 181 cases and 218 controls. Eligible participants underwent antenatal examination during gestational weeks 11-14 and trace element levels were detected by the atomic absorption method. Multi-variable logistic regression was used to examine the associations between the level of maternal trace elements and CHD risks. RESULTS: Higher levels of Ca in early pregnancy were associated with lower risk of ASD/VSD risks. Moreover, higher Fe, Pb, and Cd levels in the first trimester were associated with higher risks of all CHD and the subtypes risks, and the tests for trend were significant (all p < .05). The restricted cubic spline analysis showed that there was a nonlinear inverted u-shaped dose-response relationship between levels of Zn, Pb, and Cd in the first trimester and risk of CHDs (non-linearity test p < .05). CONCLUSIONS: A moderate increase in Zn and Ca levels and a decrease in Pb and Cd levels during early pregnancy are needed to reduce the incidence of CHDs in the Chinese population.

Monitoring response to neoadjuvant therapy for breast cancer in all treatment phases using an ultrasound deep learning model.

Purpose: The aim of this study was to investigate the value of a deep learning model (DLM) based on breast tumor ultrasound image segmentation in predicting pathological response to neoadjuvant chemotherapy (NAC) in breast cancer. Methods: The dataset contains a total of 1393 ultrasound images of 913 patients from Renmin Hospital of Wuhan University, of which 956 ultrasound images of 856 patients were used as the training set, and 437 ultrasound images of 57 patients underwent NAC were used as the test set. A U-Net-based end-to-end DLM was developed for automatically tumor segmentation and area calculation. The predictive abilities of the DLM, manual segmentation model (MSM), and two traditional ultrasound measurement methods (longest axis model [LAM] and dual-axis model [DAM]) for pathological complete response (pCR) were compared using changes in tumor size ratios to develop receiver operating characteristic curves. Results: The average intersection over union value of the DLM was 0.856. The early-stage ultrasound-predicted area under curve (AUC) values of pCR were not significantly different from those of the intermediate and late stages (p< 0.05). The AUCs for MSM, DLM, LAM and DAM were 0.840, 0.756, 0.778 and 0.796, respectively. There was no significant difference in AUC values of the predictive ability of the four models. Conclusion: Ultrasonography was predictive of pCR in the early stages of NAC. DLM have a similar predictive value to conventional ultrasound for pCR, with an add benefit in effectively improving workflow.

Photoactive Poly-L-Lysine gel with resveratrol-magnesium metal polyphenol network: A promising strategy for preventing tracheal anastomotic complications following surgery.

Postoperative complications at the anastomosis site following tracheal resection are a prevalent and substantial concern. However, most existing solutions primarily focus on managing symptoms, with limited attention given to proactively preventing the underlying pathological processes. To address this challenge, we conducted a drug screening focusing on clinically-relevant polyphenolic compounds, given the growing interest in polyphenolic compounds for their potential role in tissue repair during wound healing. This screening led to the identification of resveratrol as the most promising candidate for mitigating tracheal complications, as it exhibited the most significant efficacy in enhancing the expression of vascular endothelial growth factor (VEGF) while concurrently suppressing the pivotal fibrosis factor: transforming growth factor-beta 1 (TGF-ß1), showcasing its robust potential in addressing these issues. Building upon this discovery, we further developed an innovative photosensitive poly-L-lysine gel integrated with a resveratrol-magnesium metal polyphenol network (MPN), named Res-Mg/PL-MA. This design allows for the enables sustained release of resveratrol and synergistically enhances the expression of VEGF and also promotes resistance to tensile forces, aided by magnesium ions, in an anastomotic tracheal fistula animal models. Moreover, the combination of resveratrol and poly-L-lysine hydrogel effectively inhibits bacteria, reduces local expression of key inflammatory factors, and induces polarization of macrophages toward an anti-inflammatory phenotype, as well as inhibits TGF-ß1, consequently decreasing collagen production levels in an animal model of post-tracheal resection. In summary, our novel Res-Mg/PL-MA hydrogel, through antibacterial, anti-inflammatory, and pro-vascularization mechanisms, effectively prevents complications at tracheal anastomosis, offering significant promise for translational applications in patients undergoing tracheal surgeries.

Migrasome, a migration-dependent organelle.

Migrasomes are organelles produced by migrating cells that form on retraction fibers and are released during cell migration. Migrasomes are involved in physiological and pathological processes such as intercellular communication, cell homeostasis maintenance, signal transduction, disease occurrence and development, and cancer metastasis. In addition, methods and techniques for studying migrasomes are constantly evolving. Here, we review the discovery, formation process, regulation, and known functions of migrasomes, summarize the commonly used specific markers of migrasomes, and the methods for observing migrasomes. Meanwhile, this review also discusses the potential applications of migrasomes in physiological processes, disease diagnosis, treatment, and prognosis, and looks forward to their wider application in biomedicine. In addition, the study of migrasomes will also reveal a new perspective on the mechanism of intercellular communication and promote the further development of life science.

Age­integrated breast imaging reporting and data system assessment model to improve the accuracy of breast cancer diagnosis.

Early diagnosis is an effective strategy for decreasing breast cancer mortality. Ultrasonography is one of the most predominant imaging modalities for breast cancer owing to its convenience and non-invasiveness. The present study aimed to develop a model that integrates age with Breast Imaging Reporting and Data System (BI-RADS) lexicon to improve diagnostic accuracy of ultrasonography in breast cancer. This retrospective study comprised two cohorts: A training cohort with 975 female patients from Renmin Hospital of Wuhan University (Wuhan, China) and a validation cohort with 500 female patients from Maternal and Child Health Hospital of Hubei Province (Wuhan, China). Logistic regression was used to construct a model combining BI-RADS score with age and to determine the age-based prevalence of breast cancer to predict a cut-off age. The model that integrated age with BI-RADS scores demonstrated the best performance compared with models based solely on age or BI-RADS scores, with an area under the curve (AUC) of 0.872 (95% CI: 0.850-0.894, P<0.001). Furthermore, among participants aged <30 years, the prevalence of breast cancer was lower than the lower limit of the reference range (2%) for BI-RADS subcategory 4A lesions but within the reference range for BI-RADS category 3 lesions, as indicated by linear regression analysis. Therefore, it is recommended that management for this subset of participants are categorized as BI-RADS category 3, meaning that biopsies typically indicated could be replaced with short-term follow-up. In conclusion, the integrated assessment model based on age and BI-RADS may enhance accuracy of ultrasonography in diagnosing breast lesions and young patients with BI-RADS subcategory 4A lesions may be exempted from biopsy.

TRPM7 facilitates fibroblast-like synoviocyte proliferation, metastasis and inflammation through increasing IL-6 stability via the PKCα-HuR axis in rheumatoid arthritis.

Transient receptor potential melastatin 7 (TRPM7) is a cation channel that plays a role in the progression of rheumatoid arthritis (RA), yet its involvement in synovial hyperplasia and inflammation has not been determined. We previously reported that TRPM7 affects the destruction of articular cartilage in RA. Herein, we further confirmed the involvement of TRPM7 in fibroblast-like synoviocyte (FLS) proliferation, metastasis and inflammation. We observed increased TRPM7 expression in FLSs derived from human RA patients. Pharmacological inhibition of TRPM7 protected primary RA-FLSs from proliferation, metastasis and inflammation. Furthermore, we found that TRPM7 contributes to RA-FLS proliferation, metastasis and inflammation by increasing the intracellular Ca2+ concentration. Mechanistically, the PKCα-HuR axis was demonstrated to respond to Ca2+ influx, leading to TRPM7-mediated RA-FLS proliferation, metastasis and inflammation. Moreover, HuR was shown to bind to IL-6 mRNA after nuclear translocation, which could be weakened by TRPM7 channel inhibition. Additionally, adeno-associated virus 9-mediated TRPM7 silencing is highly effective at alleviating synovial hyperplasia and inflammation in adjuvant-induced arthritis rats. In conclusion, our findings unveil a novel regulatory mechanism involved in the pathogenesis of RA and suggest that targeting TRPM7 might be a potential strategy for the prevention and treatment of RA.

Extracellular CIRP induces abnormal activation of fibroblast-like synoviocytes from patients with RA via the TLR4-mediated HDAC3 pathways.

The development of rheumatoid arthritis (RA) is closely related to the excessive activation of fibroblast-like synoviocytes (FLSs), which are regulated by a variety of endogenous proinflammatory molecules. Extracellular cold-inducible RNA-binding protein (CIRP), as a novel endogenous proinflammatory molecule, plays an important role in inflammatory diseases. More importantly, the synovial concentration of CIRP in patients with RA was significantly higher than that in patients with osteoarthritis (OA). Thus, this study aimed to investigate the role of extracellular CIRP in the abnormal activation of RA-FLSs and its related mechanisms. Our study showed that extracellular CIRP induced proliferation, migration and invasion of RA-FLSs, increased the expression of N-cadherin and MMP-3, and promoted the release of IL-1ß and IL-33. However, blocking of extracellular CIRP with C23 inhibited CIRP-induced abnormal activation of RA-FLSs and alleviated the arthritis severity in AA rats. Accumulating evidence suggests that the activity and proinflammatory effects of CIRP are mediated through Toll-like receptor 4 (TLR4). Further studies demonstrated that the TLR4 knockdown inhibited CIRP-induced abnormal activation, and histone deacetylase 3 (HDAC3) expression in RA-FLSs. In addition, we found that HDAC3 knockdown and the specific inhibitor RGFP966 significantly suppressed CIRP-induced abnormal activation of RA-FLSs. We further found that treatment with HDAC3 specific inhibitor effectively alleviated the severity of arthritis in AA rats. Taken together, these findings indicate that extracellular CIRP induces abnormal activation of RA-FLSs via the TLR4-mediated HDAC3 pathways.

Efferocytosis: Unveiling its potential in autoimmune disease and treatment strategies.

Efferocytosis is a crucial process whereby phagocytes engulf and eliminate apoptotic cells (ACs). This intricate process can be categorized into four steps: (1) ACs release "find me" signals to attract phagocytes, (2) phagocytosis is directed by "eat me" signals emitted by ACs, (3) phagocytes engulf and internalize ACs, and (4) degradation of ACs occurs. Maintaining immune homeostasis heavily relies on the efficient clearance of ACs, which eliminates self-antigens and facilitates the generation of anti-inflammatory and immunosuppressive signals that maintain immune tolerance. However, any disruptions occurring at any of the efferocytosis steps during apoptosis can lead to a diminished efficacy in removing apoptotic cells. Factors contributing to this inefficiency encompass dysregulation in the release and recognition of "find me" or "eat me" signals, defects in phagocyte surface receptors, bridging molecules, and other signaling pathways. The inadequate clearance of ACs can result in their rupture and subsequent release of self-antigens, thereby promoting immune responses and precipitating the onset of autoimmune diseases such as systemic lupus erythematosus, rheumatoid arthritis, type 1 diabetes, and multiple sclerosis. A comprehensive understanding of the efferocytosis process and its implications can provide valuable insights for developing novel therapeutic strategies that target this process to prevent or treat autoimmune diseases.