Julolidinyl aza-BODIPYs as NIR-II fluorophores for the bioimaging of nanocarriers.

The aggregation-caused quenching (ACQ) rationale has been employed to improve the fluorescence imaging accuracy of nanocarriers by precluding free probe-derived interferences. However, its usefulness is undermined by limited penetration and low spatiotemporal resolution of NIR-I (700-900 nm) bioimaging owing to absorption and diffraction by biological tissues and tissue-derived autofluorescence. This study aimed to develop ACQ-based NIR-II (1000-1700 nm) probes to further improve the imaging resolution and accuracy. The strategy employed is to install highly planar and electron-rich julolidine into the 3,5-position of aza-BODIPY based on the larger substituent effects. The newly developed probes displayed remarkable photophysical properties, with intense absorption centered at approximately 850 nm and bright emission in the 950-1300 nm region. Compared with the NIR-I counterpart P2, the NIR-II probes demonstrated superior water sensitivity and quenching stability. ACQ1 and ACQ6 exhibited more promising ACQ effects with absolute fluorescence quenching at water fractions above 40% and higher quenching stability with less than 2.0% fluorescence reillumination in plasma after 24 h of incubation. Theoretical calculations verified that molecular planarity is more important than hydrophobicity for ACQ properties. Additionally, in vivo and ex vivo reillumination studies revealed less than 2.5% signal interference from prequenched ACQ1, in contrast to 15% for P2.

A telomere-to-telomere gap-free reference genome assembly of avocado provides useful resources for identifying genes related to fatty acid biosynthesis and disease resistance.

Avocado (Persea americana Mill.) is an economically valuable plant because of the high fatty acid content and unique flavor of its fruits. Its fatty acid content, especially the relatively high unsaturated fatty acid content, provides significant health benefits. We herein present a telomere-to-telomere gapless genome assembly (841.6 Mb) of West Indian avocado. The genome contains 40 629 predicted protein-coding genes. Repeat sequences account for 57.9% of the genome. Notably, all telomeres, centromeres, and a nucleolar organizing region are included in this genome. Fragments from these three regions were observed via fluorescence in situ hybridization. We identified 376 potential disease resistance-related nucleotide-binding leucine-rich repeat genes. These genes, which are typically clustered on chromosomes, may be derived from gene duplication events. Five NLR genes (Pa11g0262, Pa02g4855, Pa07g3139, Pa07g0383, and Pa02g3196) were highly expressed in leaves, stems, and fruits, indicating they may be involved in avocado disease responses in multiple tissues. We also identified 128 genes associated with fatty acid biosynthesis and analyzed their expression patterns in leaves, stems, and fruits. Pa02g0113, which encodes one of 11 stearoyl-acyl carrier protein desaturases mediating C18 unsaturated fatty acid synthesis, was more highly expressed in the leaves than in the stems and fruits. These findings provide valuable insights that enhance our understanding of fatty acid biosynthesis in avocado.

Quantitative analysis of sagittal curvatures of the tibial plafond by computed tomography.

Background: Although the talar morphology has been well understood, studies on the corresponding tibial plafond are still lacking. Based on computed tomography (CT) data, this quantitative study divided the tibial plafond into anterior and posterior regions on five sagittal sections. The objectives of this study were (I) to determine whether the sagittal curvatures of the tibial plafond can be quantitatively and accurately described using the double-diameter method; (II) to compare the difference between the anterior and posterior diameters on five sagittal sections. Methods: In this study, CT data were collected from 100 adult ankles, and the three-dimensional (3D) ankle joint model was reconstructed using CT images. An anatomical coordinate system of the 3D ankle joint model was created to establish the standard coronal and sagittal planes. The measurement outcomes of sagittal curvatures included: the anterior and posterior diameters, the distal tibial arc length (TiAL) and the distal tibial mortise depth (TMD) on five sagittal sections (the most medial, medial 1/4, middle, lateral 1/4 and the most lateral section). Subgroup analysis was performed to compare the differences between males and females. Results: Analysis of the sagittal curvatures showed that the anterior diameter of tibial plafond was significantly smaller than the posterior diameter on five sagittal sections with a mean difference ranging from 3.9 to 6.8 mm (P<0.001). For the anterior diameters, the anteromedial curve had the smallest diameter (35.3±5.3 mm), and the anterolateral curve had the largest diameter (38.0±5.8 mm). For the posterior diameter, the posteromedial curve had the smallest diameter (39.2±6.4 mm), and the posterolateral 1/4 curve had the largest diameter (43.5±6.9 mm). One-way analysis of variance (ANOVA) revealed significant differences in the anterior and posterior diameters among five groups (P<0.012). Subgroup analysis showed that gender partly affected the results of sagittal curvature measurements. Conclusions: The sagittal curvatures of the tibial plafond can be described quantitatively and accurately using anterior and posterior diameters. Our study showed that there were significant differences between the anterior and posterior diameters, and gender was an important factor influencing the sagittal curvatures of the tibial plafond.

Establishment of patient-derived organoids for guiding personalized therapies in breast cancer patients.

Breast cancer has become the most commonly diagnosed cancer. The intra- and interpatient heterogeneity induced a considerable variation in treatment efficacy. There is an urgent requirement for preclinical models to anticipate the effectiveness of individualized drug responses. Patient-derived organoids (PDOs) can accurately recapitulate the architecture and biological characteristics of the origin tumor, making them a promising model that can overtake many limitations of cell lines and PDXs. However, it is still unclear whether PDOs-based drug testing can benefit breast cancer patients, particularly those with tumor recurrence or treatment resistance. Fresh tumor samples were surgically resected for organoid culture. Primary tumor samples and PDOs were subsequently subjected to H&E staining, immunohistochemical (IHC) analysis, and whole-exome sequencing (WES) to make comparisons. Drug sensitivity tests were performed to evaluate the feasibility of this model for predicting patient drug response in clinical practice. We established 75 patient-derived breast cancer organoid models. The results of H&E staining, IHC, and WES revealed that PDOs inherited the histologic and genetic characteristics of their parental tumor tissues. The PDOs successfully predicted the patient's drug response, and most cases exhibited consistency between PDOs' drug susceptibility test results and the clinical response of the matched patient. We conclude that the breast cancer organoids platform can be a potential preclinical tool used for the selection of effective drugs and guided personalized therapies for patients with advanced breast cancer.

Multi-omics analysis elucidates the relationship between intratumor microbiome and host immune heterogeneity in breast cancer.

Research has indicated that intratumor microbiomes affect the occurrence, progression, and therapeutic response in many cancer types by influencing the immune system. We aim to evaluate the characteristics of immune-related intratumor microbiomes (IRIMs) in breast cancer (BC) and search for potential prognosis prediction factors and treatment targets. The clinical information, microbiome data, transcriptomics data of The Cancer Genome Atlas Breast Invasive Carcinoma (TCGA-BRCA) patients were obtained from Kraken-TCGA-Raw-Data and TCGA portal. The core tumor-infiltrating immune cell was identified using univariate Cox regression analysis. Based on consensus clustering analysis, BC patients were categorized into two immune subtypes, referred to as immune-enriched and immune-deficient subtypes. The immune-enriched subtype, characterized by higher levels of immune infiltration of CD8+ T and macrophage M1 cells, demonstrated a more favorable prognosis. Furthermore, significant differences in alpha-diversity and beta-diversity were observed between the two immune subtypes, and the least discriminant analysis effect size method identified 33 types of IRIMs. An intratumor microbiome-based prognostic signature consisting of four prognostic IRIMs (Acidibacillus, Succinimonas, Lachnoclostridium, and Pseudogulbenkiania) was constructed using the Cox proportional-hazard model, and it had great prognostic value. The prognostic IRIMs were correlated with immune gene expression and the sensitivity of chemotherapy drugs, specifically tamoxifen and docetaxel. In conclusion, our research has successfully identified two distinct immune subtypes in BC, which exhibit contrasting prognoses and possess unique epigenetic and intratumor microbiomes. The critical IRIMs were correlated with prognosis, tumor-infiltrating immune cell abundance, and immunotherapeutic efficacy in BC. Consequently, this study has identified potential IRIMs as biomarkers, providing a novel therapeutic approach for treating BC.IMPORTANCERecent research has substantiated the presence of the intratumor microbiome in tumor immune microenvironment, which could influence tumor occurrence and progression, as well as provide new opportunities for cancer diagnosis and treatment. This study identified the critical immune-related intratumor microbiome (Acidibacillus, Succinimonas, Lachnoclostridium, and Pseudogulbenkiania), which were correlated with prognosis, tumor-infiltrating immune cell abundance, and immunotherapeutic efficacy in breast cancer and might be the novel target to regulate immunotherapy in BC.

Association Between Diverse Cell Death Patterns Related Gene Signature and Prognosis, Drug Sensitivity, and Immune Microenvironment in Glioblastoma.

Glioblastoma (GBM) is the most invasive type of glioma and is difficult to treat. Diverse programmed cell death (PCD) patterns have a significant association with tumor initiation and progression. A novel prognostic model based on PCD genes may serve as an effective tool to predict the prognosis of GBM. The study incorporated 11 PCD patterns, namely apoptosis, necroptosis, pyroptosis, ferroptosis, cuproptosis, entotic cell death, netotic cell death, parthanatos, lysosome-dependent cell death, autophagy-dependent cell death, alkaliptosis, and oxeiptosis, to develop the model. To construct and validate the model, both bulk and single-cell transcriptome data, along with corresponding clinical data from GBM cases, were obtained from the TCGA-GBM, REMBRANDT, CGGA, and GSE162631 datasets. A cell death-related signature containing 14 genes was constructed with the TCGA-GBM cohort and validated in the REMBRANDT and CGGA datasets. GBM patients with a higher cell death index (CDI) were significantly associated with poorer survival outcomes. Two separate clusters associated with clinical outcomes emerged from unsupervised analysis. A multivariate Cox regression analysis was conducted to examine the association of CDI with clinical characteristics, and a prognostic nomogram was developed. Drug sensitivity analysis revealed high-CDI GBM patients might be resistant to carmustine while sensitive to 5-fluorouracil. Less abundance of natural killer cells was found in GBM cases with high CDI and bulk transcriptome data. A cell death-related prognostic model that could predict the prognosis of GBM patients with good performance was established, which could discriminate between the prognosis and drug sensitivity of GBM.

Rotational gland dissection for refractory granulomatous mastitis: A single-center retrospective study.

BACKGROUND: Refractory granulomatous mastitis (RGM) is a chronic benign breast disease that commonly occurred in women of childbearing age and is usually treated with surgery, with numerous cases suffering from unsatisfied postoperative recovery of breast shape, high rates of surgical complications, and even high recurrence. This study tries to evaluate the efficacy of an innovative surgical procedure, the rotational gland dissection for the treatment of RGM. METHODS: 129 patients with RGM who underwent surgical treatment at the Second Affiliated Hospital of Xi'an Jiaotong University between Apr. 2017 and May. 2021 were retrospectively included in this study. The article analyzed the age, local symptoms, lesion location, and size, days in hospital, recurrence rate, and satisfaction rate of the patients. RESULTS: Patients ranged in age from 19 to 58 years, with a median age of onset of 32 years. In 63 patients (48.84%), their lesions coverage exceeded two quadrants, and 52.71% of patients had lesions larger than 10 cm2. The average days in hospital of patients was 7.5 days, and 85.27% of them were satisfied with their post-surgery breast appearance. Within the median follow-up of 56 months, only 3.10% of patients experienced a recurrence of mastitis on the operation side. CONCLUSION: This novel surgical procedure we created is an effective treatment for RGM with a high success rate, high patient satisfaction, and low recurrence rate, and is significantly superior to other studies for it has the largest sample size and longest follow-up in this field.

Ultra-Low Loading of Ultra-Small Fe3 O4 Nanoparticles on Nonmodified CNTs to Improve Green EMI Shielding Capability of Rubber Composites.

From a material design perspective, the incorporation of Fe3 O4 @carbon nanotube (Fe3 O4 @CNT) hybrids is an effective approach for reconciling the contradictions of high shielding and low reflection coefficients, enabling the fabrication of green shielding materials and reducing the secondary electromagnetic wave pollution. However, the installation of Fe3 O4 nanoparticles on nonmodified and nondestructive CNT walls remains a formidable challenge. Herein, a novel strategy for fabricating the above-mentioned Fe3 O4 @CNTs and subsequently assembling segregated Fe3 O4 @CNT networks in natural rubber (NR) matrices is proposed. The advanced and unique structure, magnetism, and lossless conductivity endow the as-obtained Fe3 O4 @CNT/NR with a shielding effectiveness (SE) of 63.8 dB and a low reflection coefficient of 0.24, which indicates a prominent green-shielding capability that surpasses those of previously reported green-shielding materials. Moreover, the specific SE reaches 531 dB cm-1 , exceeding that of those of previously reported carbon/polymer composites. Meanwhile, the outstanding conductivity enables the composite to reach a saturation temperature of ≈95 °C at a driving voltage of 1.5 V with long-term stability. Therefore, the as-fabricated Fe3 O4 @CNT/rubber composites represent an important development in green-shielding materials that are applied in cold environment.

Development and validation of a nomogram model for prediction of stroke-associated pneumonia associated with intracerebral hemorrhage.

BACKGROUND: We aimed to establish risk factors for stroke-associated pneumonia (SAP) following intracerebral hemorrhage (ICH) and develop an efficient and convenient model to predict SAP in patients with ICH. METHODS: Our study involved 1333 patients consecutively diagnosed with ICH and admitted to the Neurology Department of the First Affiliated Hospital of Wenzhou Medical University. The 1333 patients were randomly divided (3:1) into the derivation cohort (n = 1000) and validation Cohort (n = 333). Variables were screened from demographics, lifestyle-related factors, comorbidities, clinical symptoms, neuroimaging features, and laboratory tests. In the derivation cohort, we developed a prediction model with multivariable logistic regression analysis. In the validation cohort, we assessed the model performance and compared it to previously reported models. The area under the receiver operating characteristic curve (AUROC), GiViTI calibration belt, net reclassification index (NRI), integrated discrimination index (IDI) and decision curve analysis (DCA) were used to assess the prediction ability and the clinical decision-making ability. RESULTS: The incidence of SAP was 19.9% and 19.8% in the derivation (n = 1000) and validation (n = 333) cohorts, respectively. We developed a nomogram prediction model including age (Odds Ratio [OR] 1.037, 95% confidence interval [CI] 1.020-1.054), male sex (OR 1.824, 95% CI 1.206-2.757), multilobar involvement (OR 1.851, 95% CI 1.160-2.954), extension into ventricles (OR 2.164, 95% CI 1.456-3.215), dysphagia (OR 3.626, 95% CI 2.297-5.725), disturbance of consciousness (OR 2.113, 95% CI 1.327-3.362) and total muscle strength of the worse side (OR 0.93, 95% CI 0.876-0.987). Compared with previous models, our model was well calibrated and showed significantly higher AUROC, better reclassification ability (improved NRI and IDI) and a positive net benefit for predicted probability thresholds between 10% and 73% in DCA. CONCLUSIONS: We developed a simple, valid, and clinically useful model to predict SAP following ICH, with better predictive performance than previous models. It might be a promising tool to assess the individual risk of developing SAP for patients with ICH and optimize decision-making.

Latency-associated peptide (LAP)+CD4+ regulatory T cells prevent atherosclerosis by modulating macrophage polarization.

RATIONALE: A persistent autoimmune and inflammatory response plays a critical role in the progression of atherosclerosis. The transcription factor forkhead box P3 (Foxp3)+CD4+ regulatory T cells (Foxp3+ Tregs) attenuate atherosclerosis. Latency-associated peptide (LAP)+CD4+ T cells are a new class of Tregs whose role in atherosclerosis is unknown. OBJECTIVE: To investigate the function of CD4+LAP+ Tregs in inhibiting inflammation and preventing atherosclerosis. METHODS AND RESULTS: Depletion of CD4+LAP+ Tregs results in aggravated inflammation and atherosclerotic lesions. Mechanistically, CD4+LAP+ Treg depletion was associated with decreased M2-like macrophages and increased Th1 and Th17 cells, characterized by increased unstable plaque promotion and decreased expression of inflammation-resolving factors in both arteries and immune organs. In contrast, adoptive transfer of CD4+LAP+ Tregs to ApoE-/- mice or CD4-/-ApoE-/- mice led to decreased atherosclerotic lesions. Compared with control animals, adoptive transfer of CD4+LAP+ Tregs induced M2-like macrophage differentiation within the atherosclerotic lesion and spleen, associated with increased collagen and α-SMA in plaques and decreased expression of MMP-2 and MMP-9. Mechanistic studies reveal that isolated CD4+LAP+ Tregs exhibit a tolerance phenotype, with increased expression of inhibitory cytokines and coinhibitory molecules. After coculture with CD4+LAP+ Tregs, monocytes/macrophages display typical features of M2 macrophages, including upregulated expression of CD206 and Arg-1 and decreased production of MCP-1, IL-6, IL-1ß and TNF-α, which was almost abrogated by transwell and partially TGF-ß1 neutralization. RNA-seq analysis showed different gene expression profiles between CD4+LAP+ Tregs and LAP-CD4+ T cells and between CD4+LAP+ Tregs of ApoE-/- mice and CD4+LAP+ Tregs of C57BL/6 mice, of which Fancd2 and IL4i1 may contribute to the powerful inhibitory properties of CD4+LAP+ Tregs. Furthermore, the number and the suppressive properties of CD4+LAP+ Tregs were impaired by oxLDL. CONCLUSIONS: Our data indicate that the remaining CD4+LAP+ Tregs play a protective role in atherosclerosis by modulating monocyte/macrophage differentiation and regulatory factors, which may partly explain the protective effect of T cells tolerance in atherosclerosis. Moreover, adoptive transfer of CD4+LAP+ Tregs constitutes a novel approach to treat atherosclerosis.

Causal associations of Sjögren's syndrome with cancers: a two-sample Mendelian randomization study.

BACKGROUND: Several observational studies have explored the associations between Sjögren's syndrome (SS) and certain cancers. Nevertheless, the causal relationships remain unclear. Mendelian randomization (MR) method was used to investigate the causality between SS and different types of cancers. METHODS: We conducted the two-sample Mendelian randomization with the public genome-wide association studies (GWASs) summary statistics in European population to evaluate the causality between SS and nine types of cancers. The sample size varies from 1080 to 372,373. The inverse variance weighted (IVW) method was used to estimate the causal effects. A Bonferroni-corrected threshold of P < 0.0031 was considered significant, and P value between 0.0031 and 0.05 was considered to be suggestive of an association. Sensitivity analysis was performed to validate the causality. Moreover, additional analysis was used to assess the associations between SS and well-accepted risk factors of cancers. RESULTS: After correcting the heterogeneity and horizontal pleiotropy, the results indicated that patients with SS were significantly associated with an increased risk of lymphomas (odds ratio [OR] = 1.0010, 95% confidence interval [CI]: 1.0005-1.0015, P = 0.0002) and reduced risks of prostate cancer (OR = 0.9972, 95% CI: 0.9960-0.9985, P = 2.45 × 10-5) and endometrial cancer (OR = 0.9414, 95% CI: 0.9158-0.9676, P = 1.65 × 10-5). Suggestive associations were found in liver and bile duct cancer (OR = 0.9999, 95% CI: 0.9997-1.0000, P = 0.0291) and cancer of urinary tract (OR = 0.9996, 95% CI: 0.9992-1.0000, P = 0.0281). No causal effect of SS on other cancer types was detected. Additional MR analysis indicated that causal effects between SS and cancers were not mediated by the well-accepted risk factors of cancers. No evidence of the causal relationship was observed for cancers on SS. CONCLUSIONS: SS had significant causal relationships with lymphomas, prostate cancer, and endometrial cancer, and suggestive evidence of association was found in liver and bile duct cancer and cancer of urinary tract, indicating that SS may play a vital role in the incidence of these malignancies.

The Low-Cycle Fatigue Behavior, Microstructure Evolution, and Life Prediction of SS304: Influence of Temperature.

To study the fatigue failure and microstructure evolution behavior of SS304, low-cycle fatigue tests are conducted at room temperature (RT), 300 °C, and 650 °C. The results indicate that, because of the influence of the dislocation walls, carbon-containing precipitates, and deformation twins, the cyclic hardening behavior is presented at RT. However, different from the cyclic hardening behavior at RT, the cyclic softening behavior of SS304 can be observed due to the dynamic recovery and recrystallization containing dislocation rearrangement and annihilation at 300 °C and 650 °C. In addition, two fatigue crack initiation modes are observed. At RT, the single fatigue crack initiation mode is observed. At high temperatures, multiple crack initiation modes are presented, resulting from the degradation of material properties. Furthermore, a new fatigue life prediction model considering the temperature is conducted as a reference for industrial applications.

Detoxification of aflatoxin B1 by Bacillus aryabhattai through conversion of double bond in terminal furan.

AIMS: This study aimed to screen a bacterial strain with high detoxifying capability for aflatoxin B1 (AFB1), verify its biotransformation efficiency, and detoxification process. METHODS AND RESULTS: A total of 350 samples collected from different environmental niche were screened using coumarin as the sole carbon source. High Performance Liquid Chromatography (HPLC) was used to detect residues of AFB1, and 16S rRNA sequencing was performed on the isolated strain with the highest AFB1 removal ratio for identification. The detoxified products of this strain were tested for toxicity in Escherichia coli as well as LO2, Caco-2, and HaCaT human cell lines. HPLC-MS was applied to further confirm the AFB1 removal and detoxification process. CONCLUSIONS: We identified a strain from plant leaf designated as DT with high AFB1-detoxifying ability that is highly homologous to Bacillus aryabhattai. The optimum detoxification conditions of this strain were 37°C and pH 8.0, resulting in 82.92% removal ratio of 2 µg mL-1 AFB1 in 72 h. The detoxified products were nontoxic for E. coli and significantly less toxic for the LO2, Caco-2, and HaCaT human cell lines. HPLC-MS analysis also confirmed the significant drop of the AFB1 characteristic peak. Two possible metabolic products, C19H15O8 (m/z 371) and C19H19O8 (m/z 375), were observed by mass spectrometry. Potential biotransformation pathway was based on the cleavage of double bond in the terminal furan of AFB1. These generated components had different chemical structures with AFB1, manifesting that the attenuation of AFB1 toxicity would be attributed to the destruction of lactone structure of AFB1 during the conversion process.

Deficiency of protein inhibitor of activated STAT3 exacerbates atherosclerosis by modulating VSMC phenotypic switching.

BACKGROUND AND AIMS: Phenotypic switching of vascular smooth muscle cells (VSMCs) plays an essential role in the development of atherosclerosis. Protein inhibitor of activated STAT (Pias) regulates VSMCs phenotype via acting as sumo E3 ligase to promote protein sumoylation. Our previous study indicated that Pias3 expression decreased in atherosclerotic lesions. Therefore, this study aimed to explore the role of Pias3 on VSMCs phenotype switching during atherosclerosis. METHODS: ApoE-/- and ApoE-/-Pias3-/- double-deficient mice were fed with high-fat/high-cholesterol diet to induce atherosclerosis. Aorta tissues and primary VSMCs were collected to assess plaque formation and VSMCs phenotype. In vitro, Pias3 was overexpressed in A7r5, a VSMCs cell line, by transfection with Pias3 plasmid. Real-time quantitative PCR, immunoblotting, immunoprecipitation, were used to analyze the effect of Pias3 on VSMCs phenotypic switching. RESULTS: Pias3 deficiency significantly exacerbated atherosclerotic plaque formation and promoted VSMCs phenotypic switching to a synthetic state within lesion. In vitro, overexpressing Pias3 in VSMCs increased the expression of contractile markers (myosin heavy chain 11, calponin 1), while it decreased the level of synthetic marker (vimentin). Additionally, Pias3 overexpression blocked PDGF-BB-induced VSMCs proliferation and migration. Immunoprecipitation and mass spectrometry results showed that Pias3 enhanced sumoylation and ubiquitination of vimentin, and shortened its half-life. Moreover, the ubiquitination level of vimentin was impaired by 2-D08, a sumoylation inhibitor. This suggests that Pias3 might accelerate the ubiquitination-degradation of vimentin by promoting its sumoylation. CONCLUSIONS: These results indicate that Pias3 might ameliorate atherosclerosis progression by suppressing VSMCs phenotypic switching and reducing vimentin protein stability.

Visualized machine learning models combined with propensity score matching analysis in single PR-positive breast cancer prognosis: a multicenter population-based study.

The characteristics of single PR-positive (ER-PR+, sPR+) breast cancer (BC) and its prognosis are not well elucidated due to its rarity and conflicting evidence. There is a lack of an accurate and efficient model for predicting survival, thereby rendering treatment challenging for clinicians. Whether endocrine therapy should be intensified in sPR+ BC patients was another controversial clinical topic. We constructed and cross-validated XGBoost models that showed high precision and accuracy in predicting the survival of patients with sPR+ BC cases (1-year: AUC=0.904; 3-year: AUC=0.847; 5-year: AUC=0.824). The F1 score for the 1-, 3-, and 5-year models were 0.91, 0.88, and 0.85, respectively. The models exhibited superior performance in an external, independent dataset (1-year: AUC=0.889; 3-year: AUC=0.846; 5-year: AUC=0.821). Further, intensified endocrine therapy did not provide a significant overall survival benefit compared to initial or no endocrine therapy (P=0.600, HR: 1.46; 95% CI: 0.35-6.17). Propensity-score matching (PSM)-adjusted data showed that there was no statistically significant difference in the prognosis between ER-PR+HER2+ and ER-PR-HER2+ BC. Patients having the ER-PR+HER2- subtype had a slightly worse prognosis than those with the ER-PR-HER2- subtype. In conclusion, XGBoost models can be highly reproducible and effective in predicting survival in patients with sPR+ BC. Our findings revealed that patients with sPR-positive BC may not benefit from endocrine therapy. Patients with sPR+ BC may benefit from intensive adjuvant chemotherapy compared to endocrine therapy.

Gelatin Improves the Performance of Oregano Essential Oil Nanoparticle Composite Films-Application to the Preservation of Mullet.

In this study, the addition of oregano oil chitosan nanoparticles (OEO-CSNPs) was conducted to enhance the comprehensive properties of gelatin films (GA), and the optimal addition ratio of nanoparticles was determined for its application in the preservation of mullet. Oregano oil chitosan nanoparticles were organically combined with gelatin at different concentrations (0%, 2%, 4%, 6% and 8%) to obtain oregano oil-chitosan nanoparticle-GA-based composite films (G/OEO-CSNPs), and thereafter G/OEO-CSNPs were characterized and investigated for their preservative effects on mullet. Subsequent analysis revealed that OEO-CSNPs were uniformly dispersed in the GA matrix, and that G/OEO-CSNPs had significantly improved mechanical ability, UV-visible light blocking performance and thermal stability. Furthermore, the nanoparticles exhibited excellent antioxidant and antibacterial properties, and they improved the films' suitability as edible packaging. The attributes of the G/OEO-CSNPs were optimized, the films had the strongest radical scavenging and lowest water solubility, and electron microscopy also showed nanoparticle penetration into the polymer when the concentration of OEO-CSNPs was 6% (thickness = 0.092 ± 0.001, TS = 47.62 ± 0.37, E = 4.06 ± 0.17, water solubility = 48.00 ± 1.11). Furthermore, the GA-based composite film containing 6% OEO-CSNPs was able to inhibit microbial growth, slow fat decomposition and protein oxidation, reduce endogenous enzyme activity, and delay the spoilage of mullet during the refrigeration process, all of which indicate its excellent potential for meat preservation application.

Baicalein enhances immune response in TNBC by inhibiting leptin expression of adipocytes.

Triple-negative breast cancer (TNBC) is a special pathological type of breast cancer (BC) with poor prognosis. Obesity is shown to be involved in TNBC tumor progression. The interaction between obesity and BC has generated great attention in recent years, however, the mechanism is still unclear. Here, we showed that leptin secreted by adipocytes upregulated PD-L1 expression in TNBC through the p-STAT3 signaling pathway and that baicalein inhibited PD-L1 expression in tumor microenvironment by suppressing leptin transcription of adipocytes. Collectively, our findings suggest that leptin may be the key factor participating in obesity-related tumor progression and that baicalein can break through the dilemma to boost the anti-tumor immune response.

Causal effects of COVID-19 on cancer risk: A Mendelian randomization study.

In contemporary literature, little attention has been paid to the association between coronavirus disease-2019 (COVID-19) and cancer risk. We performed the Mendelian randomization (MR) to investigate the causal associations between the three types of COVID-19 exposures (critically ill COVID-19, hospitalized COVID-19, and respiratory syndrome coronavirus 2 (SARS-CoV-2) infection) and 33 different types of cancers of the European population. The results of the inverse-variance-weighted model indicated that genetic liabilities to critically ill COVID-19 had suggestive causal associations with the increased risk for HER2-positive breast cancer (odds ratio [OR] = 1.0924; p-value = 0.0116), esophageal cancer (OR = 1.0004; p-value = 0.0226), colorectal cancer (OR = 1.0010; p-value = 0.0242), stomach cancer (OR = 1.2394; p-value = 0.0331), and colon cancer (OR = 1.0006; p-value = 0.0453). The genetic liabilities to hospitalized COVID-19 had suggestive causal associations with the increased risk for HER2-positive breast cancer (OR = 1.1096; p-value = 0.0458), esophageal cancer (OR = 1.0005; p-value = 0.0440) as well as stomach cancer (OR = 1.3043; p-value = 0.0476). The genetic liabilities to SARS-CoV-2 infection had suggestive causal associations with the increased risk for stomach cancer (OR = 2.8563; p-value = 0.0019) but with the decreasing risk for head and neck cancer (OR = 0.9986, p-value = 0.0426). The causal associations of the above combinations were robust through the test of heterogeneity and pleiotropy. Together, our study indicated that COVID-19 had causal effects on cancer risk.

Selection of an aggregation-caused quenching-based fluorescent tracer for imaging studies in nano drug delivery systems.

In order to develop and optimize nano drug delivery systems (NDDSs), it is crucial to understand their in vivo fate. We previously found that P2 (Aza-BODIPY) and P4 (BODIPY) as aggregation-caused quenching (ACQ) probes could be used to unravel the biofate of various nanoparticles owing to their water-sensitive emission. However, previous studies also found that quenched ACQ probe aggregates showed repartition into hydrophobic physiologically relevant constituents, resulting in fluorescence re-illumination. In this paper, we screened various types of fluorophores for ACQ and their re-illumination performance and focused on Aza-BODIPY dyes. BODIPY and Aza-BODIPY dyes were identified to be advantageous over other fluorophores. Some BODIPY and Aza-BODIPY dyes were selected as potential probes with improved performance against re-illumination. The best performing probes were Aza-C7 and Aza-C8. Aza-C7-loaded PMs were found to have decreased fluorescence re-illumination properties over P2 and DiR.

Temperature and Strain Rate Dependence on the Tensile Mechanical Properties, Constitutive Equations, and Fracture Mechanisms of MarBN Steel.

The effect of strain rate and temperature on the thermomechanical behavior and microstructure of MarBN steel is studied with the strain rates of 5 × 10-3 and 5 × 10-5 s-1 from room temperature (RT) to 630 °C. At high strain rates of 5 × 10-3 s-1, the Holloman and Ludwigson equations can better predict tensile plastic properties. In contrast, under low strain rates of 5 × 10-5 s-1, coupling of the Voce and Ludwigson equations appears to predict the flow relationship at RT, 430, and 630 °C. However, the deformation microstructures have the same evolution behavior under strain rates and temperatures. Geometrically necessary dislocations appear along the grain boundaries and increase the dislocation density, which results in the formation of the low-angle grain boundaries and a decrease in the number of twinning. The strengthening sources of MarBN steel include grain boundary strengthening, dislocation interactions, and multiplication. The fitted R2 values of these models (JC, KHL, PB, VA, ZA) to plastic flow stress at 5 × 10-5 s-1 are greater than 5 × 10-3 s-1 for MarBN steel. Due to the flexibility and minimum fitting parameters, the phenomenological models of JC (RT and 430 °C) and KHL (630 °C) give the best prediction accuracy under both strain rates.