CCDC12 gene methylation in peripheral blood as a potential biomarker for breast cancer detection.

BACKGROUND: Aberrant DNA methylation has been identified as biomarkers for breast cancer detection. Coiled-coil domain containing 12 gene (CCDC12) implicated in tumorigenesis. This study aims to investigate the potential of blood-based CCDC12 methylation for breast cancer detection. METHODS: DNA methylation level of CpG sites (Cytosine-phosphate Guanine dinucleotides) in CCDC12 gene was measured by mass spectrometry in 255 breast cancer patients, 155 patients with benign breast nodules and 302 healthy controls. The association between CCDC12 methylation and breast cancer risk was evaluated by logistic regression and receiver operating characteristic curve analysis. RESULTS: A total of eleven CpG sites were analyzed. The CCDC12 methylation levels were higher in breast cancer patients. Compared to the lowest tertile of methylation level in CpG_6,7, CpG_10 and CpG_11, the highest quartile was associated with 82, 91 and 95% increased breast cancer risk, respectively. The CCDC12 methylation levels were associated with estrogen receptor (ER) and human epidermal growth factor 2 (HER2) status. In ER-negative and HER2-positive (ER-/HER2+) breast cancer subtype, the combination of four sites CpG_2, CpG_5, CpG_6,7 and CpG_11 methylation levels could distinguish ER-/HER2+ breast cancer from the controls (AUC = 0.727). CONCLUSION: The hypermethylation levels of CCDC12 in peripheral blood could be used for breast cancer detection.

Breast cancer detection could be facilitated by novel blood-based DNA methylation biomarkers.The methylation levels of CpG sites in CCDC12 were higher in breast cancer than those in controls.The combination of four sites CpG_2, CpG_5, CpG_6,7 and CpG_11 methylation levels could distinguish ER-/HER2+ breast cancer subtype from the controls.

Synthesis and photocatalytic property of Au-TiO2 nanocomposites with controlled morphologies in microfluidic chips.

We present an efficient approach for the consecutive synthesis of Au-TiO2 nanocomposites with controlled morphologies in a microfluidic chip. The seed-mediated growth method was employed to synthesize Au nanorods as the core, and TiO2 layers of varying thicknesses were deposited on the surface or tip of the Au nanorods. Au-TiO2 nanocomposites with core-shell, dumbbell, and dandelion-like structures can be precisely synthesized in a one-step manner within the microfluidic chip by finely tuning the flow rate of NaHCO3 and the amount of hexadecyl trimethyl ammonium bromide. Furthermore, we have investigated the photocatalytic activity of the synthesized nanocomposites, and it was found that Au NR-TiO2 core-shell nanostructure with a thin TiO2 shell exhibits superior catalytic performance. This work provides an effective and controlled method for the microscale preparation and photocatalytic application of various Au-TiO2 nanocomposite structures.

A Prediction Model for Clinical Outcomes of COVID-19 Hospitalized Patients: Construction and Accuracy Assessment.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic spread rapidly with considerable morbidity nationwide since China's liberalization in December 2022. Our work has focused on identifying different predictive factors from the laboratory examination of critically ill patients, and forecasting the unfavorable outcome of critically ill patients with COVID-19 through a combined diagnosis of biological markers. METHODS: We conducted a retrospective study at the Department of First Affiliated Hospital of Wenzhou Medical University, China, from December 24, 2022, to January 10, 2023, where 434 critically ill patients who met the inclusion criteria were involved. Machine analysis was employed to search for the parameters with the highest predictive value to calculate COVID-19 mortality by exploiting 66 typical laboratory results. RESULTS: Combined diagnosis of serum albumin (ALB), lactate dehydrogenase (LDH), direct bilirubin (Dbil), ferritin, pulse oxygen saturation (SpO2), and neutrophil count (NEUT#) was evaluated, and the result with the highest predictive value (NEUT#) was selected as the predictor for COVID-19 mortality with a sensitivity of 89.2% and a specificity of 77.4%. CONCLUSIONS: The increased levels of LDH, Dbil, ferritin, and NEUT#, along with lowered ALB and SpO2 levels are the most decisive variables for forecasting the mortality for COVID-19 according to our machine-learning-based model. The combined diagnosis could be used to improve further diagnostic performance.

BK Channel Depletion Promotes Adipocyte Differentiation by Activating the MAPK/ERK Pathway.

The expression of large conductance calcium-activated potassium channels (BK channels) in adipose tissue has been identified for years. BK channel deletion can improve metabolism in vivo, but the relative mechanisms remain unclear. Here, we examined the effects of BK channels on the differentiation of adipose-derived stem cells (ADSCs) and the related mechanisms. BKα and ß1 subunits were expressed on adipocytes. We found that both deletion of the KCNMA1 gene, encoding the pore forming α subunit of BK channels, and the BK channel inhibitor paxilline increased the expression of key genes in the peroxisome proliferator activated receptor (PPAR) pathway and promoted adipogenetic differentiation of ADSCs. We also observed that the MAPK-ERK pathway participates in BK channel deficiency-promoted adipogenic differentiation of ADSCs and that ERK inhibitors blocked the differentiation-promoting effect of BK channel deficiency. Hyperplasia of adipocytes is considered beneficial for metabolic health. These results indicate that BK channels play an important role in adipose hyperplasia by regulating the differentiation of ADSCs and may become an important target for studying the pathogenesis and treatment strategies of metabolic disorder-related diseases.

RUNX1 methylation as a cancer biomarker in differentiating papillary thyroid cancer from benign thyroid nodules.

Aim: It remains a challenge to accurately identify malignancy of thyroid nodules when biopsy is indeterminate. The authors aimed to investigate the abnormal DNA methylation signatures in papillary thyroid cancer (PTC) compared with benign thyroid nodules (BTNs). Methods: The authors performed genome profiling by 850K array and RNA sequencing in early-stage PTC and BTN tissue samples. The identified gene was validated in two independent case-control studies using mass spectrometry. Results: Hypomethylation of RUNX1 in PTC was identified and verified (all odds ratios: ≥1.50). RUNX1 methylation achieved good accuracy in differentiating early-stage PTC from BTNs, especially for younger women. Conclusion: The authors disclosed a significant association between RUNX1 hypomethylation and PTC, suggesting RUNX1 methylation as a potential biomarker for companion diagnosis of malignant thyroid nodules.

Genome and proteomic analysis of risk factors for fatal outcome in children with severe community-acquired pneumonia caused by human adenovirus 7.

INTRODUCTION: Human adenovirus 7 (HAdV-7) is an important viral pathogen of severe pneumonia in children and a serious threat to health. METHODS: A cohort of 45 pediatric patients diagnosed with HAdV-7-associated severe pneumonia and admitted to the Pediatric Intensive Care Unit at the Children's Hospital of Chongqing Medical University from May 2018 to January 2020 were included. Risk factors of death were analyzed by the Cox proportional risk mode with Clinical data, serum, and nasopharyngeal aspirate adenovirus load, Genome analysis, Olink proteomics, and cytokine profile between dead and surviving patients were also analyzed. RESULTS: A total of 45 children with a median age of 12.0 months (interquartile range [IQR]: 6.5, 22.0) were included (female 14), including 14 (31.1%) who died. High serum viral load was an independent risk factor for mortality (hazard ratio [HR] = 2.16, 95% confidence interval [CI], 1.04-4.49, p = 0.039). BTB and CNC homology 1 (BACH1), interleukin-5 (IL-5), and IL-9 levels were significantly correlated with serum viral load (p = 0.0400, 0.0499, and 0.0290; r = 0.4663, 0.3339, and -0.3700, respectively), with significant differences between the dead and survival groups (p = 0.021, 0.001, and 0.021). CONCLUSIONS: Severe cytokine storm-associated high serum viral load after HAdV-7 infection may be the main mechanism responsible for poor prognosis in children.

Molecular Mechanism of Response and Adaptation of Antioxidant Enzyme System to Salt Stress in Leaves of Gymnocarpos przewalskii.

The antioxidant enzyme system is the main defense system responsible for maintaining cellular reactive oxygen species (ROS) homeostasis and normal plant growth and development after saline stress. In this study, we identified and characterized the members of the SOD, APX and CAT gene families of the antioxidant enzyme system in Gymnocarpos przewalskii, using plant physiology and molecular biology methods, and analyzed the pattern of enzyme activity in response to NaCl stress. It was found that seven, six and two genes of SOD, APX and CAT gene families, respectively, were expressed in the leaf tissue of G. przewalskii, in which most of the genes were significantly upregulated under NaCl stress, and the enzymatic activities were in accordance with the gene expression. Three positive selection sites in the GpCAT1 gene can increase the hydrophilicity of the GpCAT1 protein, increase the volume of the active site and increase the affinity for H2O2, thus improving the catalytic efficiency of GpCAT1. The results of the present study provide new insights for further investigations of the evolution and function of the SOD, APX and CAT gene families in G. przewalskii and their essential roles under salt stress, and the findings will be useful for revealing the molecular mechanism of salt tolerance and breeding of salt-tolerant plants.

Efficacy of atosiban for repeated embryo implantation failure: A systematic review and meta-analysis.

Background: Repeated embryo implantation failure (RIF) posed a significant challenge in assisted reproduction. Evidence of its therapeutic effectiveness including atosiban used around embryo transfer to improve pregnancy outcomes in RIF patients undergoing in vitro fertilization-embryo transfer (IVF-ET) remained inconsistent. This study aimed to explore the efficacy of atosiban on pregnancy outcomes of patients with RIF who received IVF-ET. Methods: The research was designed using the PICOS format. A systematic search of four English databases, PubMed, EMBASE, Web of Science, Cochrane Library, and one Chinse database, China National Knowledge Infrastructure (CNKI) was conducted. The time range was from inception to December 10, 2022. Then trials comparing the efficacy of atosiban and control group on pregnancy outcomes in RIF patients who receive IVF-ET were included. Subgroup analysis and sensitivity analysis were performed to reduce the influence of heterogeneity between included studies. Risk ratio (RR) and 95% confidence interval (CI) were calculated. The main outcome measure was clinical pregnancy rate (CPR). For the analyses, StataMP 17.0 (Stata Corporation, USA) was used. Results: Two prospective randomized controlled trials (RCTs), one prospective cohort study and four retrospective cohort studies were included. Our results showed that atosiban was associated with higher clinical pregnancy rate (RR=1.54, 95% CI: 1.365-1.735, P < 0.001, I2 = 0.0%). The results of subgroup analysis based on study types (prospective randomized controlled clinical trial, retrospective cohort study and prospective cohort study) showed that in all types of studies, CPR of atosiban group was significantly higher than controlled group. The results of subgroup analysis based upon the diagnostic criteria of number of previous embryo transfer failures showed that the intervention of atosiban improved the CPR whether in participants with 2 previous ET failures or in participants with 3 previous ET failures. Nevertheless, the incidence of ectopic pregnancy, multiple pregnancy, and miscarriages were not significantly different between the case and control groups. Conclusion: For women who are undergoing IVF-ET and have experienced repeated embryo implantation failure, atosiban may be an important factor in enhancing pregnancy outcomes. To confirm this conclusion, more thorough, prospective randomized controlled studies of sizable sample sizes with well design are required.

Subchorionic Hematoma Association with Pregnancy Complications and Outcomes in the Third Trimester.

INTRODUCTION: Our objective was to explore the clinical features, pregnancy complications, and outcomes of subchorionic hematomas (SCHs) in the third trimester. MATERIAL AND METHODS: This was a retrospective analysis and evaluation of 1112 cases diagnosed with SCHs from January 2014 to December 2020. Comparisons were performed according to the clinical features (e.g., number of pregnancies, parity, gestational weeks, and age), pregnancy complications, and outcomes associated with SCHs. RESULTS: In total, 71.85% (799/1112) of the patients were diagnosed with different pregnancy complications. The overall rates of gestational diabetes mellitus (GDM), hypertensive disorder complicating pregnancy (HDCP), premature rupture of membranes (PROM), and IVF were 12.14%, 7.55%, 17.27%, and 10.34%, respectively. The positive rates for newborn outcomes such as premature birth and low birth weight (LBW) were 9.35% and 6.47%, respectively. There was a significant relationship between repeated pregnancies and the incidence of GDM (p < 0.05), but not HDCP, PROM, or IVF. The proportion of SCH patients who conceived through IVF was significantly higher among primiparas than among multiparas (p < 0.05), but was not significantly different in terms of GDM, HDCP, or PROM. Premature birth was not a high-risk factor for most SCH patients with HDCP, IVF, or PROM (p < 0.05), most of whom delivered at term. The rate of cesarean sections for SCH patients with GDM, HDCP, or IVF was significantly higher than that for vaginal deliveries (p < 0.05), but this was not affected by age. CONCLUSIONS: The coexistence of SCHs with HDCP, IVF, or PROM lacked an effective predictive value for premature birth, but increased the rate of a cesarean section.

Regional citrate anticoagulation for continuous renal replacement therapy in newborns.

Background: Regional citrate anticoagulant (RCA) is recommended as the preferred anticoagulant regimen for continuous renal replacement therapy (CRRT) in adults; however, it is rarely reported in neonates due to concerns associated with their immature liver. Few studies have reported on the use of RCA to evaluate the safety and efficacy of RCA-CRRT in neonates. Method: In this retrospective observational study, we reviewed the clinical records of neonates who underwent RCA-CRRT at our pediatric intensive care unit between September 2015 to January 2021. Results: A total of 23 neonates underwent 57 sessions of RCA-CRRT. Their mean age was 10.1 ± 6.9 days and mean weight was 3.0 ± 0.7 kg (range, 0.95-4 kg). The mean filter life was 31.54 ± 19.58 h (range, 3.3-72.5 h). Compared to pretreatment values, the total-to-ionized calcium ratio (T/iCa) on RCA-CRRT increased (2.00 ± 34 0.36 vs. 2.19 ± 0.40, P = 0.056) as did the incidence of T/iCa levels >2.5 (11.4 vs. 14.3, P = 0.477), albeit not significantly. Using a post-treatment T/iCa threshold of 2.5, we divided all the cases into citrate accumulation (CA) and non-CA (NCA) groups. Compared with the NCA group, the CA group had significantly higher body weight (3.64 ± 0.32 kg vs. 2.95 ± 0.41 kg, P = 0.033) and significantly lower blood flow rate per body weight ml/kg/min (3.08 ± 0.08 vs. 4.07 ± 0.71, P = 0.027); however, there was no significant difference between the two groups in terms of age, corrected gestational age, the PRISM-III score, and biochemical tests. Conclusion: RCA-CRRT is safe and effective for neonates. After appropriate adjustments of the RCA-CRRT parameters, the incidence of CA was not higher in neonates than in children or adults, and CA was not found to be significantly correlated with age or corrected gestational age.

Thermal Annealing Effect on Surface-Enhanced Raman Scattering of Gold Films Deposited on Liquid Substrates.

We prepare metal films with various thicknesses on liquid substrates by thermal evaporation and investigate the annealing effect on these films. Gold films deposited on a silicone oil surface consist of a large number of branched aggregates, which contains plenty of gold nanoparticles. This characteristic morphology is mainly attributed to the isotropic and free-sustained liquid substrate. Thermal annealing results in the reintegration of nanoparticles; thus, the surface morphology and microstructure of gold films change significantly. The dependence of annealing conditions on the surface-enhanced Raman scattering performance of gold films is studied, in which gold films show favorable Raman activity when annealed at certain annealing temperature and the experimental results are verified by simulation analysis. The study on the optimal annealing temperature of surface-enhanced Raman scattering substrate will pave the way for the potential application of films deposited on liquid surfaces in microfluidics and enhanced Raman detection.

Integrin ligands block mechanical signal transduction in baroreceptors.

Baroreceptors are nerve endings located in the adventitia of the carotid sinus and aortic arch. They act as a mechanoelectrical transducer that can sense the tension stimulation exerted on the blood vessel wall by the rise in blood pressure and transduce the mechanical force into discharge of the nerve endings. However, the molecular identity of mechanical signal transduction from the vessel wall to the baroreceptor is not clear. We discovered that exogenous integrin ligands, such as RGD, IKVAV, YIGSR, PHSRN, and KNEED, could restrain pressure-dependent discharge of the aortic nerve in a dose-dependent and reversible manner. Perfusion of RGD at the baroreceptor site in vivo can block the baroreceptor reflex. An immunohistochemistry study showed the binding of exogenous RGD to the nerve endings under the adventitia of the rat aortic arch, which may competitively block the binding of integrins to ligand motifs in extracellular matrix. These findings suggest that connection of integrins with extracellular matrix plays an important role in the mechanical coupling process between vessel walls and arterial baroreceptors.

A telehealth program benefits discharged patients with heart failure.

BACKGROUND: Heart failure (HF) remains a major cause of mortality, hospitalisations, and poor quality of life. The mortality and readmission rate of HF patients after discharge are still high due to poor self-care and adherence, or inability to detect signs of deterioration. Telehealth programs may benefit a broad range of patients and reduce the suffering from HF. We aimed to investigate the impact of a 12-week telehealth program on outcomes among discharged patients with HF. METHODS: Study population was consisted of 425 patients discharged between Jan 2020 to Aug 2020. All enrolled participants were diagnosed as HF and underwent standard treatments. At discharge, they were randomised into the telehealth or control group. The intervention was based on telephone support biweekly. After 12-week follow-up, patients' outcomes including mortality, readmission, disease condition, adherence, self-care behaviours, and mental health were compared between the groups. RESULTS: The telehealth program significantly improved the HF symptoms in patients (p < 0.001). Patients in telehealth group showed better adherence compared to control (p = 0.002). Moreover, the intervention enhanced patients' self-care skills, indicated by the increased ratio of individuals knowing how to evaluate the cardiac function (p = 0.009) and purchasing medicines (p = 0.03). In addition, the telehealth program significantly improved the mental health status of patients (p = 0.03). CONCLUSION: The telehealth program is beneficial for improving HF symptoms, adherence, self-care skills and mental health status of discharged patients and support the future use of this program to manage patients and reduce the burden attributed to the condition.

Large-conductance Ca2 +-activated K+ channel ß1-subunit maintains the contractile phenotype of vascular smooth muscle cells.

Background: Vascular smooth muscle cells (VSMCs) phenotype switching is very important during the pathogenesis and progression of vascular diseases. However, it is not well understood how normal VSMCs maintain the differentiated state. The large-conductance Ca2+-activated K+ (BKCa) channels are widely expressed in VSMCs and regulate vascular tone. Nevertheless, there is limited understanding of the role of the BKCa channel in modulation of the VSMC phenotype. Methods and results: We assessed BKCa channel expression levels in normal and injured carotid arteries from rats of the balloon-injury model. A strong decrease of BKCa-ß1 was seen in the injured carotid arteries, accompanied by a parallel decrease of the VSMC contractile markers. BKCa-ß1 in primary rat aortic VSMCs was decreased with the increase of passage numbers and the stimulation of platelet-derived growth factor (PDGF)-BB. Conversely, transforming growth factor ß upregulated BKCa-ß1. Meanwhile, the BKCa-ß1 level was positively associated with the levels of VSMC contractile proteins. Intravenous injection of PDGF-BB induced downregulation of BKCa-ß1 expression in the carotid arteries. Knockdown of BKCa-ß1 favored VSMC dedifferentiation, characterized by altered morphology, abnormal actin fiber organization, decreased contractile proteins expression and reduced contractile ability. Furthermore, the resultant VSMC dedifferentiated phenotype rendered increased proliferation, migration, enhanced inflammatory factors levels, and matrix metalloproteinases activity. Studies using primary cultured aortic VSMCs from human recapitulated key findings. Finally, protein level of BKCa-ß1 was reduced in human atherosclerotic arteries. Conclusion: BKCa-ß1 is important in the maintenance of the contractile phenotype of VSMCs. As a novel endogenous defender that prevents pathological VSMC phenotype switching, BKCa-ß1 may serve as a potential therapeutic target for treating vascular diseases including post-injury restenosis and atherosclerosis.

PVT1/miR-145-5p/HK2 modulates vascular smooth muscle cells phenotype switch via glycolysis: The new perspective on the spiral artery remodeling.

INTRODUCTION: Vascular smooth muscle cells (VSMC) switched from a contractile phenotype to a synthetic phenotype during the decidual spiral artery (SPAs) remodeling process. The lncRNA plasmacytoma variant translocation 1 (PVT1) and glucose metabolism have been found to regulate the VSMC phenotype switch. This study aimed to analyze the dynamic expression of PVT1 and glycolytic key enzymes hexokinase2 (HK2) at different remodeling stages in early human pregnancy and elucidate the underlying mechanism of the PVT1/miR-145-5p/HK2 axis involved in the spiral artery remodeling. METHODS: qRT-PCR, Western blot (WB) analysis, Immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH) were used to detect the expression and localization of PVT1 and HK2 in decidual tissue. HA-VSMCs were transfected with specific siRNA, shRNA and plasmids to regulate corresponding genes. Extracellular lactate, cellular ATP, ROS, and intracellular NADPH levels were measured using the corresponding assay kits. Migration was measured by wound-healing and Transwell assays. Contractile phenotypic markers α-SMA, MYH11 with calponin and synthetic phenotypic markers OPN and vimentin were detected by WB. The PDC model was used to detect the degree of spiral arterial remodeling. RESULTS: PVT1 and HK2 were upregulated with gestational age (GA) increasing in decidual tissue during the early pregnancy. HK2 regulated the glycolytic activity and VSMC phenotype switch in vitro. PVT1 regulated the glycolytic activity and VSMC phenotype switch through HK2. PVT1 played a ceRNA role in regulating HK2 expression by sponging miR-145-5p. PVT1 and HK2 influenced spiral artery remodeling in the PDC model. DISCUSSION: PVT1 and HK2 were upregulated, and miR-145-5p was downregulated in decidua with the GA increasing. Meanwhile, the PVT1/miR-145-5p/HK2 axis may be involved in regulating the phenotypic switch and migratory capacity of VSMCs by affecting glycolysis in decidual SPAs remodeling.

Unravelling the roles of Autophagy in OSCC: A renewed perspective from mechanisms to potential applications.

Oral squamous cell carcinoma (OSCC) is associated with a low survival rate and a high disability rate, making it a serious health burden, particularly in Southeast Asian countries. Therefore, improvements in the diagnosis, treatment, and prognosis prediction of OSCC are highly warranted. Autophagy has a significant impact on cancer development. Studies on autophagy in various human cancers have made outstanding contributions; however, the relationship between autophagy and OSCC remains to be explored. This review highlights the roles of autophagy in OSCC and discusses the relationship between autophagy and Epithelial-mesenchymal transition. Considering the lack of OSCC biomarkers, we focus on the studies involving OSCC-related bioinformatics analysis and molecular targets. Based on some classical targets, we summarize several key autophagy-related biomarkers with a considerable potential for clinical application, which may become the hotspot of OSCC research. In conclusion, we elaborate on the interrelationship between autophagy and OSCC and highlight the shortcomings of current studies to provide insights into the potential clinical strategies.

Plasma Exosomal miR-199a-5p Derived from Preeclampsia with Severe Features Impairs Endothelial Cell Function via Targeting SIRT1.

Preeclampsia (PE) is a pregnancy complication with high maternal and fetal morbidity and mortality rates. During pregnancy, the concentration of exosomes in the maternal blood circulation would increase, establishing that plasma exosomes play a role in the development of pregnancy. Our previous study implied the important role of exosomal miR-199a-5p in preeclampsia with severe features (sPE). This study aims to reveal the role of exosomal miR-199a-5p in contribution to the development of sPE. The results showed that the expression of miR-199a-5p was significantly higher in plasma exosomes and placenta tissue from patients with sPE than that in normal pregnant women. Additionally, hydrogen peroxide (H2O2) could upregulate the expression of miR-199a-5p in BeWo cells and cell-derived exosomes. In terms of the regulatory effect, exosomal miR-199a-5p was observed to inhibit the expression of SIRT1 in human umbilical venous endothelial cells (HUVECs). Moreover, the treatment of both miR-199a-5p-overexpressed exosomes and SIRT1 inhibitor EX527 could decrease the nitric oxide production, elevate the intracellular reactive oxygen species level, and enhance the expressions of ICAM-1 and VCAM-1 of HUVECs. Thus, our findings suggest that the upregulated plasma exosomal miR-199a-5p in sPE might result from the trophoblast of the impaired placenta under oxidative stress. Furthermore, exosomal miR-199a-5p could impair the endothelial cell function via targeting SIRT1, contributing to the development of preeclampsia.