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Abstract Background HDAC4 is a key regulator of chondrocyte hypertrophy and skeletal development, but it is not clear whether the increase in vascular invasion at growth plates is related to HDAC4 expression. To determine it, we investigated the relationship between HDAC4 and angiogenesis in both in vivo and in vitro models. Methods HDAC4 was deleted in Col2α1-Cre; HDAC4fl/fl mice. Growth of the Col2α1-Cre; HDAC4d/d mice was compared with HDAC4fl/fl mice at postnatal days 2, 4, 6, and 8. X-rays were taken to examine skeletal development. At postnatal days 14 and 21, mice were euthanized for specimen collection. Murine chondrocytes were isolated from the ventral parts of rib cages of 6-day-old mice (C57Bl/6) and transfected with a vector expressing HDAC4 as a fusion protein with green fluorescent protein (GFP). Relative expression levels of HDAC4, VEGF, and Hif1α were measured in these cells by Western blot, RT-qPCR, enzyme-linked immunosorbent, histology, and immunohistochemistry assays. Results The Col2α1-Cre; HDAC4d/d mice were markedly smaller compared with the control mice. At postnatal days 14 and 21, the Col2α1-Cre; HDAC4d/d mice exhibited a shortened growth plate, a larger secondary ossification center, and stronger staining of CD31 and CD34 compared to control mice. The isolated chondrocyte cells exhibited a high transfection efficiency of HDAC4 which resulted in the detection of a significant decrease in VEGF and Hif1α levels compared with the control chondrocytes. Conclusions HDAC4 expression in chondrocytes contributes to angiogenesis in the growth plate, and its absence in vivo negatively affects growth plates.

Abstract Background Depression and sleep disturbances are associated with increased risks of various diseases and mortality, but their impacts on mortality in cancer survivors remain unclear. The objective of this study was to characterize the independent and joint associations of depressive symptoms and sleep disturbances with mortality outcomes in cancer survivors. Methods This population-based prospective cohort study included cancer survivors aged ≥ 20 years (n = 2947; weighted population, 21,003,811) from the National Health and Nutrition Examination Survey (NHANES) 2007–2018 cycles. Depressive symptoms and sleep disturbances were self-reported. Depressive symptoms were assessed using the Patient Health Questionnaire 9 (PHQ-9). Death outcomes were determined by correlation with National Death Index records through December 31, 2019. Primary outcomes included all-cause, cancer-specific, and noncancer mortality. Results During the median follow-up of 69 months (interquartile range, 37–109 months), 686 deaths occurred: 240 participants died from cancer, 146 from heart disease, and 300 from other causes. Separate analyses revealed that compared with a PHQ-9 score (0–4), a PHQ-9 score (5–9) was associated with a greater risk of all-cause mortality (hazard ratio [HR], 1.28; 95% CI, 1.03–1.59), and a PHQ-9 score (≥ 10) was associated with greater risk of all-cause mortality (HR, 1.37; 95% CI, 1.04–1.80) and noncancer mortality (HR, 1.45; 95% CI, 1.01–2.10). Single sleep disturbances were not associated with mortality risk. In joint analyses, the combination of a PHQ-9 score ≥ 5 and no sleep disturbances, but not sleep disturbances, was associated with increased risks of all-cause mortality, cancer-specific mortality, and noncancer mortality. Specifically, compared with individuals with a PHQ-9 score of 0–4 and no sleep disturbances, HRs for all-cause mortality and noncancer mortality in individuals with a PHQ-9 score of 5–9 and no sleep disturbances were 1.72 (1.21–2.44) and 1.69 (1.10–2.61), respectively, and 2.61 (1.43–4.78) and 2.77 (1.27–6.07), respectively, in individuals with a PHQ-9 score ≥ 10 and no sleep disturbances; HRs for cancer-specific mortality in individuals with a PHQ-9 score ≥ 5 and no sleep disturbances were 1.95 (1.16–3.27). Conclusions Depressive symptoms were linked to a high risk of mortality in cancer survivors. The combination of a PHQ-9 score (≥ 5) and an absence of self-perceived sleep disturbances was associated with greater all-cause mortality, cancer-specific mortality, and noncancer mortality risks, particularly in individuals with a PHQ-9 score (≥ 10).

Abstract Background Breast cancer (BC) is the most common malignant tumor around the world. Timely detection of the tumor progression after treatment could improve the survival outcome of patients. This study aimed to develop machine learning models to predict events (defined as either (1) the first tumor relapse locally, regionally, or distantly; (2) a diagnosis of secondary malignant tumor; or (3) death because of any reason.) in BC patients post-treatment. Methods The patients with the response of stable disease (SD) and progressive disease (PD) after neoadjuvant chemotherapy (NAC) were selected. The clinicopathological features and the survival data were recorded in 1 year and 5 years, respectively. Patients were randomly divided into the training set and test set in the ratio of 8:2. A random forest (RF) and a logistic regression were established in both of 1-year cohort and the 5-year cohort. The performance was compared between the two models. The models were validated using data from the Surveillance, Epidemiology, and End Results (SEER) database. Results A total of 315 patients were included. In the 1-year cohort, 197 patients were divided into a training set while 87 were into a test set. The specificity, sensitivity, and AUC were 0.800, 0.833, and 0.810 in the RF model. And 0.520, 0.833, and 0.653 of the logistic regression. In the 5-year cohort, 132 patients were divided into the training set while 33 were into the test set. The specificity, sensitivity, and AUC were 0.882, 0.750, and 0.829 in the RF model. And 0.882, 0.688, and 0.752 of the logistic regression. In the external validation set, of the RF model, the specificity, sensitivity, and AUC were 0.765, 0.812, and 0.779. Of the logistics regression model, the specificity, sensitivity, and AUC were 0.833, 0.376, and 0.619. Conclusion The RF model has a good performance in predicting events among BC patients with SD and PD post-NAC. It may be beneficial to BC patients, assisting in detecting tumor recurrence.

Highlights 1. Avidin-stabilized gold nanoclusters (Av–Au NCs) were synthesized for the first time by a water-bath method. 2. The synthesized Av–Au NCs not only exhibited intense blue and red emissions under 374 nm excitation, but also retained the native functionality of avidin to bind to biotin. 3. The fluorescent signal amplification system constructed by the interaction of Av–Au NCs with biotin was successfully applied to detect target DNA in vitro.

Abstract Background Chemotherapy is widely used to treat hepatocellular carcinoma (HCC). Although sorafenib (SO) is the only chemotherapy drug approved by FDA for treatment of HCC, it is associated with several disadvantages including low water solubility, low bioavailability, lack of targeting and easily causes systemic toxicity. In recent years, nanocarriers have shown promise in drug delivery to effectively solve these problems. Herein, we used SO-loaded nanocarriers to overcome the defects of chemotherapy during treatment of HCC. Specifically, we encapsulated pH-sensitive hollow mesoporous Prussian blue nanoparticles (HMPB) with SO (an inhibitor of multi-kinase and accelerant of ferroptosis) to act as carriers and facilitate drug release. We also coated its surface with a layer of pH-responsive chitosan (CS) to block the drug and increase biocompatibility. Finally, we successfully constructed HP/SO/CS nanocomposites for targeted delivery of chemotherapeutic drugs, with the aim of initiating chemotherapy and ferroptosis for dual treatment of tumors. In vitro and in vivo experiments were performed for evaluation of the nanocomposites’ anti-tumor efficacy by using liver cancer cells and mice, respectively. Results The nanocomposites specifically targeted tumor cells through enhancing permeability and retention (EPR) effect. Results from in vitro experiments showed that the nanocarriers not only promoted cell apoptosis and reduced the number of cells for chemotherapy, but also promoted accumulation of reactive oxygen species (ROSs). In vivo experiments showed that mice in the nanocomposite-treated group exhibited the smallest tumor sizes and body weights, with no obvious damage to normal tissues and organs. Conclusion Taken together, these findings indicated that nanocarriers had an effective inhibitory effect on HCC cells. This safe and multifunctional treatment model was a valuable option for the treatment of HCC, as well as other cancers. Graphical Abstract

Abstract Background The aim of this study was to evaluate the relationship between pre-treatment plasma fibrinogen (Fib) level and pathological complete response (pCR) to neoadjuvant chemotherapy (NAC) in breast cancer patients and to assess the role of plasma Fib as a predictive factor. Methods Data from 1004 consecutive patients with invasive breast cancer who received NAC and subsequent surgery were retrospectively analysed. Both univariate and multivariate analyses based on logistic regression model were performed to identify clinicopathological factors associated with pCR to NAC. Cox regression model was used to determine the correlation between clinical or pathological parameters and recurrence-free survival (RFS). The Kaplan-Meier method and the log-rank test were applied in the survival analysis. Results The median value of Fib, rather than other plasma coagulation parameters, was significantly increased in non-pCR patients compared with pCR patients (P = 0.002). Based on the cut-off value estimated by the receiver operating characteristic (ROC) curve analysis, patients were divided into low or high Fib groups (Fib 5 cm group (77.5% vs 58.4%, log-rank, P = 0.0168). Conclusions This study demonstrates that low pre-treatment plasma Fib (Fib

Abstract Background Age-related macular degeneration (AMD) can cause vision loss or blindness in elderly. The associations between single nucleotide polymorphism (SNP) and AMD in Chinese Tujia ethnic minority group are still unclear. Methods A total of 2122 Tujia volunteers were recruited and 197 of them were diagnosed with AMD (either dry or wet type).Then the blood specimens of these 197 AMD patients and 404 controls from the remaining 1925 normal Tujia volunteers were collected to detect the frequencies of 39 chosen SNPs. The Bonferroni method was used to correct the P values from the Fisher’s exact test. Results The mean age of the 197 AMD patients(113 males and 84 females) was 68.4197 years old. No significant differences in allelic and genotypic frequencies were found for all the 39 SNPs between the patients and controls. However, weak correlations between 10 SNPs (CFH rs1329428 TT genotype, CFH rs3753394 CC genotype and T allele, CFH rs1410996 AA genotype, CFH rs800292 AA genotype, CFH rs800292 A allele, VEGF rs833061 TT genotype and C allele, VEGF rs2010963 CG genotype, VEGFR2 rs1531289 TT genotype, ARMS2 rs10490924 TT genotype, KCTD10 rs238104 GC genotype, rs1531289 T allele and ARMS2 rs10490924 T allele) and AMD were shown. Conclusions The effects of 39 SNPs have found no associations with the morbidity of AMD in Chinese Tujia ethnic minority group.

Abstract Background Long noncoding RNAs (lncRNAs) have been reported to have potential diagnostic and prognostic values for numerous cancers. However, the plasma expression of lncRNA BLACAT1 and its clinical value in patients with papillary thyroid cancer (PTC) remain unknown. Methods The expression profile of BLACAT1 in 87 PTC patients (case group) and 36 patients with nodular goiter (control group) were investigated by qRT-PCR. The Kaplan–Meier method was used for RFS curves, and the univariate survival differences were analyzed by the log-rank test. Results BLACAT1 expression was downregulated in the plasma of case group compared with control group (P = 0.003). We also found that low plasma BLACAT1 expression was correlated with lymph node metastasis (LNM) (P