MicroRNA-181 in cardiovascular disease: Emerging biomarkers and therapeutic targets.

Cardiovascular disease (CVD) is the leading cause of death worldwide. MicroRNAs (MiRNAs) have attracted considerable attention for their roles in several cardiovascular disease states, including both the physiological and pathological processes. In this review, we will briefly describe microRNA-181 (miR-181) transcription and regulation and summarize recent findings on the roles of miR-181 family members as biomarkers or therapeutic targets in different cardiovascular-related conditions, including atherosclerosis, myocardial infarction, hypertension, and heart failure. Lessons learned from these studies may provide new theoretical foundations for CVD.

Nanoplastics causes heart aging/myocardial cell senescence through the Ca2+/mtDNA/cGAS-STING signaling cascade.

BACKGROUND: Nanoplastics (NPs) are now a new class of pollutants widely present in the soil, atmosphere, freshwater and marine environments. Nanoplastics can rapidly penetrate cell membranes and accumulate in human tissues and organs, thus posing a potential threat to human health. The heart is the main power source of the body. But up to now, the toxicological effects of long-term exposure to nanoplastics on the heart has not been revealed yet. RESULTS: We evaluated the effects of long term exposure of nanoplastics on cardiac cell/tissue in vitro and in vivo model. Furthermore, we explored the molecular mechanism by which nanoplastics exposure causes myocardial cell senescence. Immunohistochemistry, indirect immunofluorescence and ELISA were performed to detect the effects of nanoplastics on heart aging. We found that nanoplastics were able to induce significant cardiac aging through a series of biochemical assays in vivo. In vitro, the effects of nanoplastics on cardiac cell were investigated, and found that nanoplastics were able to internalize into cardiomyocytes in time and dose-dependant manner. Further biochemical analysis showed that nanoplastics induces cardiomyocytes senescence by detecting a series of senescence marker molecules. Molecular mechanism research shows that nanoplastics may cause mitochondrial destabilization by inducing oxidative stress, which leads to the leakage of mtDNA from mitochondria into the cytoplasm, and then cytoplasm-localized mt-DNA activates the cGAS-STING signaling pathway and promotes inflammation response, ultimately inducing cardiomyocytes senescence. CONCLUSIONS: In this work, we found that nanoplastics exposure induces premature aging of heart. Current research also reveals the molecular mechanism by which nanoplastics induces cardiomyocyte senescence. This study laid the foundation for further studying the potential harm of nanoplastics exposure on heart.

Development and validation of a predictive model for the diagnosis of bladder tumors using narrow band imaging.

PURPOSE: At present, the prediction of bladder tumor nature during cystoscopy is partially dependent on the clinician's own experience. Subjective factors may lead to excessive biopsy or delayed treatment. The purpose of our study is to establish a reliable model for predicting the nature of bladder tumors using narrow band imaging. METHODS: From November 2021 to November 2022, the clinical data of 231 patients who required a cystoscopy were prospectively collected at our center. Cystoscopy was performed in 219 eligible patients, in which both tumor and vascular morphology characteristics were recorded. Pathological results were used as the diagnostic standard. A logistic regression analysis was used to screen out factors related to tumor pathology. Bootstrap resampling was used for internal validation. A total of 71 patients from four other centers served as an external validation cohort. RESULTS: The following diagnostic factors were identified: tumor morphology (cauliflower-like or algae-like lesions), vascular morphology (dotted or circumferential vessels), tumor boundary (clear or unclear), and patients' symptoms (gross hematuria) and were included in the prediction model. The internal validation results showed that the area under the curve was 0.94 (95% CI 0.92-0.97), and the P value from the goodness-of-fit test was 0.97. After external validation, the results showed the area under the curve was 0.89 (95% CI 0.82-0.97) and the P value of the goodness-of-fit test was 0.24. CONCLUSION: A diagnostic prediction nomogram was established for bladder cancer. The verification results showed that the prediction model has good prediction performance.

Fabrication of carboxymethyl cellulose/hyaluronic acid/polyvinylpyrrolidone composite pastes incorporation of minoxidil-loaded ferulic acid-derived lignin nanoparticles and valproic acid for treatment of androgenetic alopecia.

Androgenetic alopecia (AGA) is a transracial and cross-gender disease worldwide with a higher prevalence among young individuals. Traditional oral or subcutaneous injections are often used to treat AGA, however, they may cause severe side-effects and therefore effective treatments for AGA are currently lacking. In this work, to treat AGA, we developed a composite paste system based on minoxidil (MXD)-loaded nanoparticles and valproic acid (VPA) with the assistance of roller-microneedles (roller-MNs). The matrix of composite paste systems is carboxymethyl cellulose (CMC), hyaluronic acid (HA) and polyvinylpyrrolidone (PVP). The roller-MNs can create microchannels in the skin to enhance drug transdermal efficiency. With the combined effects of the stimulation hair follicle (HF) regrowth by upregulating Wnt/beta-catenin of VPA and the mechanical microchannels induced by roller-MNs, the as-prepared composite paste systems successfully boost perifollicular vascularization, and activate hair follicle stem cells, thereby inducing notably faster hair regeneration at a lower administration frequency on AGA mouse model compared with minoxidil. This approach offers several benefits, including the avoidance of efficacy loss due to the liver's first-pass effect associated with oral drug, reduction in the risk of infection from subcutaneous injection, and significant decrease in the side effects of lower-dose MXD.

Zearalenone induces the senescence of cardiovascular cells in vitro and in vivo.

Zearalenone is a contaminant in food and feed products. It has been reported that zearalenone could lead to serious damage to health. So far, it is unclear whether zearalenone could lead to cardiovascular aging-related injury. For this, we assessed the effect of zearalenone on cardiovascular aging. Cardiomyocyte cell lines and primary coronary endothelial cells were used as two cell models in vitro experiments, and Western-blot, indirect immunofluorescence, and flow cytometry were performed to study the effect of zearalenone on cardiovascular aging. Experimental results indicated zearalenone treatment increased Sa-ß-gal positive cell ratio, and the expression of senescence markers (p16 and p21) was significantly upregulated. Additionally zearalenone upregulated the inflammation and oxidative stress in cardiovascular cells. Furthermore, the effect of zearalenone on cardiovascular aging was also evaluated in vivo, and the results indicated that zearalenone treatment also led to the aging of myocardial tissue. These findings suggest that zearalenone could lead to cardiovascular aging-related injury. Furthermore, we also preliminarily explored the potential effect of zeaxanthin (which is a powerful antioxidant) on zearalenone-caused aging-related damage in vitro cell model, and found that zeaxanthin could alleviate zearalenone-induced aging-related damage. Collectively, the most important finding of the current work is that zearalenone could lead to cardiovascular aging. Next in importance, we also found that zeaxanthin could partially alleviate zearalenone-induced cardiovascular aging in vitro, indicating that zeaxanthin can be used as a drug or functional food to treat cardiovascular damage caused by zearalenone.

Association of job stress, FK506 binding protein 51 (FKBP5) gene polymorphisms and their interaction with sleep disturbance.

Background: Sleep disturbance is an outcome of multiple factors including environmental and genetic influences. Job stress, a complex environmental factor, likely affects sleep quality, significantly reducing the quality of life of workers. Additionally, FK506 binding protein 51 (FKBP5) may be a pathogenic factor for sleep disturbance as it regulates hypothalamic-pituitary-adrenal (HPA) axis activity, where HPA axis has been found to be involved in the regulation mechanism of sleep and stress response. Objectives: The main aim of this study was to investigate the association between job stress and FKBP5 gene polymorphism as well as their interaction with sleep disturbance in Chinese workers; to date, these relationships have not been explored. Methods: This is a cross-sectional study. A total of 675 railway workers (53.8% male) completed a short Effort-Reward Imbalance questionnaire and the Pittsburgh Sleep Quality Index. The SNaPshot single nucleotide polymorphism (SNP) assay was carried out by screening for FKBP5 SNPs in every participant. Generalized multifactor dimensionality reduction (GMDR) was used to identify the strongest G×E interaction combination. Results: The findings showed that job stress was significantly associated with sleep disturbance; specifically, scores on the PSQI subscales (sleep disturbance, sleep medication, and daytime dysfunction) exhibited significant differences between the two job stress groups (X2 = 18.10, p = 0.01). Additionally, the FKBP5 SNP rs1360780-TT (adjusted odds ratio [AOR] = 4.98, 95% confidence interval [CI] = 2.80-8.84) and rs3800373-CC genotype (AOR = 2.06, CI = 1.10-3.86) were associated with an increased risk of sleep disturbance. Job stress and rs1360780 and rs3800373 variants showed a high-dimensional interaction with sleep disturbance as determined by the GMDR model. Conclusion: The FKBP5 gene may increase susceptibility to job stress and result in sleep disturbance, especially in the presence of negative work-related events. These findings contribute to the field of sleep disturbance prevention and treatment.

HDAC Inhibitors Alleviate Uric Acid-Induced Vascular Endothelial Cell Injury by Way of the HDAC6/FGF21/PI3K/AKT Pathway.

ABSTRACT: Uric acid (UA) accumulation triggers endothelial dysfunction, oxidative stress, and inflammation. Histone deacetylase (HDAC) plays a vital role in regulating the pathological processes of various diseases. However, the influence of HDAC inhibitor on UA-induced vascular endothelial cell injury (VECI) remains undefined. Hence, this study aimed to investigate the effect of HDACs inhibition on UA-induced vascular endothelial cell dysfunction and its detailed mechanism. UA was used to induce human umbilical vein endothelial cell (HUVEC) injury. Meanwhile, potassium oxonate-induced and hypoxanthine-induced hyperuricemia mouse models were also constructed. A broad-spectrum HDAC inhibitor trichostatin A (TSA) or selective HDAC6 inhibitor TubastatinA (TubA) was given to HUVECs or mice to determine whether HDACs can affect UA-induced VECI. The results showed pretreatment of HUVECs with TSA or HDAC6 knockdown-attenuated UA-induced VECI and increased FGF21 expression and phosphorylation of AKT, eNOS, and FoxO3a. These effects could be reversed by FGF21 knockdown. In vivo, both TSA and TubA reduced inflammation and tissue injury while increased FGF21 expression and phosphorylation of AKT, eNOS, and FoxO3a in the aortic and renal tissues of hyperuricemia mice. Therefore, HDACs, especially HDAC6 inhibitor, alleviated UA-induced VECI through upregulating FGF21 expression and then activating the PI3K/AKT pathway. This suggests that HDAC6 may serve as a novel therapeutic target for treating UA-induced endothelial dysfunction.

Abnormally elevated EZH2-mediated H3K27me3 enhances osteogenesis in aortic valve interstitial cells by inhibiting SOCS3 expression.

BACKGROUND AND AIMS: The osteogenic transition of aortic valve interstitial cells (AVICs) plays a critical role for the progression of calcific aortic valve disease (CAVD). Enhancer of zeste homolog 2 (EZH2) is an important methyltransferase for histone H3 Lys27 (H3K27) that has been found to be involved in osteogenesis. Here, we investigated the effect and mechanism of EZH2 in CAVD progression. METHODS: High throughout mRNA sequencing, qRT-PCR and immunoblot were performed to screen differentially expressed genes in non-CAVD and CAVD aortic valves. To investigate the role of EZH2 and SOCS3 in osteogenesis, AVICs were treated with siRNA, adenovirus and specific inhibitors, then osteogenic markers and mineralized deposits were examined. In vivo, the morphology and function of aortic valves were investigated by HE stain and echocardiography in ApoE-/- mice fed a long-term western diet (WD). RESULTS: We discovered that EZH2 was upregulated and SOCS3 was downregulated in calcified aortic valves. In AVICs, inhibition or silencing of EZH2 attenuated the osteogenic responses. On the other hand, demethylases inhibitor (GSK-J4) enhanced osteogenic transition of AVICs. Moreover, SOCS3 knockdown enhanced the expression of osteogenic markers, while SOCS3 overexpression suppressed osteogenesis and calcification. The chromatin immunoprecipitation and restored experiments indicated that EZH2 directly targeted SOCS3 to promote osteogenic responses of AVICs. In vivo, treatment with EZH2 inhibitor through intraperitoneal injection attenuated aortic valve thickening, calcification and dysfunction induced by WD. CONCLUSIONS: Collectively, we found that EZH2-mediated H3K27me3 enhanced osteogenesis and microcalcification of AVICs via inhibiting SOCS3 expression, which provides potential targets for future therapeutic interventions of CAVD.

IRX2 activated by jumonji domain-containing protein 2A is crucial for cardiac hypertrophy and dysfunction in response to the hypertrophic stimuli.

BACKGROUND: Iroquois homeobox 2 (IRX2) is a member of the Iroquois family whose upregulation has been potentially correlated to cardiac hypertrophy. This work studied the function of IRX2 and its related molecules in hypertrophic cardiomyopathy (HCM). METHODS: A GEO dataset GSE32453 was analyzed to identify aberrantly expressed genes in HCM. Altered expression of IRX2 was induced in mice by lentivirus injection, followed by angiotensin II (Ang II) treatment to induce HCM. The function of IRX2 knockdown in ventricular dysfunction, heart volume and pathological changes in mice, and in surface area, oxidative stress and apoptosis of isolated cardiomyocytes were examined. Binding relationship between jumonji domain-containing protein 2A (JMJD2A) and IRX2 was predicted by online tools and validated. The interaction between JMJD2A and IRX2 in HCM development was examined by joint interventions. RESULTS: IRX2 was highly expressed in heart tissues with HCM. IRX2 knockdown prevented mice from Ang II-induced ventricular dysfunction, cardiac hypertrophy, inflammation and fibrosis in mouse heart, and it decreased the levels of cardiac hypertrophy-related markers, oxidative stress response, and apoptosis of Ang II-treated cardiomyocytes. JMJD2A catalyzed demethylation of H3K9me3 near the IRX2 promoter to activate its transcription. JMJD2A knockdown similarly exerted protective functions against cardiac hypertrophy in vivo and in vitro, but the protection was blocked upon further IRX2 upregulation. IRX2 was found to increase the Wnt/ß-catenin signaling activation. CONCLUSION: This work reports that JMJD2A activates IRX2 transcription and the Wnt/ß-catenin signaling to induce cardiac hypertrophy and dysfunction in HCM.

Machine learning models in heart failure with mildly reduced ejection fraction patients.

Objective: Heart failure with mildly reduced ejection fraction (HFmrEF) has been recently recognized as a unique phenotype of heart failure (HF) in current practical guideline. However, risk stratification models for mortality and HF re-hospitalization are still lacking. This study aimed to develop and validate a novel machine learning (ML)-derived model to predict the risk of mortality and re-hospitalization for HFmrEF patients. Methods: We assessed the risks of mortality and HF re-hospitalization in HFmrEF (45-49%) patients enrolled in the TOPCAT trial. Eight ML-based models were constructed, including 72 candidate variables. The Harrell concordance index (C-index) and DeLong test were used to assess discrimination and the improvement in discrimination between models, respectively. Calibration of the HF risk prediction model was plotted to obtain bias-corrected estimates of predicted versus observed values. Results: Least absolute shrinkage and selection operator (LASSO) Cox regression was the best-performing model for 1- and 6-year mortality, with a highest C-indices at 0.83 (95% CI: 0.68-0.94) over a maximum of 6 years of follow-up and 0.77 (95% CI: 0.64-0.89) for the 1-year follow-up. The random forest (RF) showed the best discrimination for HF re-hospitalization, scoring 0.80 (95% CI: 0.66-0.94) and 0.85 (95% CI: 0.71-0.99) at the 6- and 1-year follow-ups, respectively. For risk assessment analysis, Kansas City Cardiomyopathy Questionnaire (KCCQ) subscale scores were the most important predictor of readmission outcome in the HFmrEF patients. Conclusion: ML-based models outperformed traditional models at predicting mortality and re-hospitalization in patients with HFmrEF. The results of the risk assessment showed that KCCQ score should be paid increasing attention to in the management of HFmrEF patients.

Impact of preoperative biliary drainage on postoperative complications and prognosis after pancreaticoduodenectomy: A single-center retrospective cohort study.

Background and objectives: Obstructive jaundice is common in patients with pancreaticobiliary malignancies. Preoperative biliary drainage (PBD) can alleviate cholestasis; however, no consensus has been reached on the impact of PBD on the incidence of surgery-related complications and patient survival. This study aimed to evaluate the effect among patients treated with PBD. Methods: This retrospective study examined the clinical and follow-up prognostic data of 160 patients with pancreaticobiliary malignancies who underwent pancreaticoduodenectomy (PD) at Beijing Friendship Hospital, Capital Medical University, from January 2016 to July 2020. Outcomes were compared between patients who underwent PBD (PBD group) and those who did not (control group). Changes in biochemical indicators were evaluated before and after drainage in the PBD group. Between-group differences in inflammatory indicators after PD were assessed using the Wilcoxon signed-rank test. Postoperative complications were classified according to the Clavien-Dindo classification system. The effects of PBD and biliary drainage efficiency on postoperative complications were evaluated using the chi-square test and binary logistics regression. The Kaplan-Meier analysis was used for between-group comparison of survival analysis. Univariate and multivariate regression analyses were performed to identify prognostic factors of survival. Results: Total 160 patients were enrolled,the mean age of the study sample was 62.75 ± 6.75 years. The distribution of pancreaticobiliary malignancies was as follows: 34 cases of pancreatic head cancer, 61 cases of distal bile duct cancer, 20 cases of duodenal papilla cancer, 39 cases of duodenal ampullary cancer, and 6 cases of malignant intraductal papillary mucinous neoplasm (IPMN). PBD was performed in 90 of the 160 patients, with PBD performed using an endoscopic retrograde cholangiopancreatography (ERCP) approach in 55 patients and with percutaneous transhepatic cholangiography (PTC) used in the remaining 35 cases. The mean duration of drainage in the PBD group was 12.8 ± 8.8 days. The overall rate of complications was 48.05% (37/77) in the control group and 65.55% (59/90) in the PBD group with non-significant difference (χ2 = 3.527, p=0.473). In logsitics regression analysis, PBD was also not a risk factor for postoperative complications OR=1.77, p=0.709). The overall rate of postoperative complications was significantly higher among patients who underwent PBD for >2 weeks (χ2 = 6.102, p=0.013), with the rate of severe complications also being higher for this subgroup of PBD patients (χ2 = 4.673, p=0.03). The overall survival time was 47.9 ± 2.45 months, with survival being slightly lower in the PBD group (43.61 ± 3.26 months) than in the control group (52.24 ± 3.54 months), although this difference was not significant (hazard ratio (HR)=0.65, p=0.104). Conclusion: In patients with malignant biliary obstruction, PBD does not affect the incidence of postoperative complications after pancreaticoduodenectomy nor does it affect patient survival. Prolonged biliary drainage (>2 weeks) may increase the incidence of overall postoperative complications and severe complications.

Impact of changing treatment strategy based on circulating tumor cells on postoperative survival of breast cancer.

Background: We sought to explore the impact of changing treatment strategy based on circulating tumor cells (CTC) on postoperative survival of breast cancer. Methods: We retrospectively analyzed records of patients who underwent surgery for early-stage breast cancer at Beijing Friendship Hospital from January 2016 to January 2018 and regularly underwent CTC examination after surgery. During the regular examination and CTC monitoring, the patients with positive CTC results and without distant metastasis had their treatment regimen changed. Results: Of 109 patients who received CTC examination regularly after surgery, 61 (56.0%) were CTC-positive during postoperative follow-up, including 33 ER or PR-positive, and 28 ER and PR-negative patients. Of the 33 ER or PR-positive patients, 20 changed endocrine therapy drugs. Compared with those without replacement, those with changed endocrine therapy strategy had higher CTC clearance rates (90.0% vs. 53.8%, p=0.04) and significantly lower CTC-positive values (1.70 ± 1.72 vs. 0.62 ± 0.65, p = 0.04). Among the 28 patients who were CTC positive and ER and PR-negative, 11 used capecitabine. Compared with non-users, the capecitabine users had higher CTC clearance rates (100.0% vs. 52.9%, p=0.01) and more significant decrease in CTC-positive values (2.09 ± 1.14 vs. 0.82 ± 1.67, p=0.04). Disease-free survival (DFS) at 1, 3, and 5 years was significantly longer in those who changed treatment than in those who did not (respectively, 96.6% vs. 89.6%, 92.8% vs. 56.9%, 69.0% vs. 47.8%, p<0.01). By changing the treatment strategy, CTC-positive patients achieved DFS that was not significantly different from CTC-negative patients (95.0% vs. 97.7%, 77.5% vs. 82.9%, 57.6% vs. 59.9%, p=0.20). Conclusion: Timely change of treatment strategy for breast cancer patients with positive CTC results after surgery may improve CTC clearance rate and DFS.

lncRNA polymorphism affects the prognosis of gastric cancer.

BACKGROUND: Previous studies have found that lncRNA polymorphisms are associated with the prognosis of gastric cancer (GC), but the specific roles of many lncRNA polymorphism sites in gastric cancer are still unclear. Our study aims to deeply explore the relationship between genetic polymorphism of lncRNA and the prognosis of GC. METHODS: The genotypes of candidate SNP locus were detected by Sequenom Mass ARRAY SNP. We deeply analyzed the association of lncRNA polymorphisms with GC prognosis by univariate and multivariate Cox regression, stratified analysis, conjoint analysis, and log-rank test. RESULTS: We found that mutations at rs2579878 and rs10036719 loci reduced the risk of poor prognosis of GC. Stratified analysis showed that rs2795025, rs10036719, and rs12516079 polymorphisms were all associated with tumor prognosis. In addition, conjoint analyses showed that the interaction between these two polymorphic sites (rs2795025 and rs12516079) could increase the risk of poor prognosis. Multivariate analysis also found that the AG/AA genotype of rs10036719 and AG genotype of rs12516079 were independent prognostic factors. Moreover, the high expression of both CCDC26 and LINC02122 were shown to be associated with the poor survival status of GC patients. CONCLUSIONS: We find that the genetic polymorphism of lncRNA plays a role in the development of GC and is closely related to the survival time of patients. It could serve as a predictor of the prognosis of GC.

Gene-environment interaction between circadian clock gene polymorphisms and job stress on the risk of sleep disturbances.

RATIONALE: Sleep disturbances was associated with numerous adverse health outcomes. Many studies have reported that long-term exposure to job stress can lead to sleep disturbances, which may be influenced by genetic and environmental factors. OBJECTIVES: This cross-sectional study investigated whether circadian clock gene polymorphisms modulated the influence of job stress on sleep disturbances in a Chinese Han population, which to our best knowledge has not been explored. METHODS: The Effort-Reward Imbalance (ERI) scale and the Pittsburgh Sleep Quality Index (PSQI) were both used to access job stress and sleep disturbances. The SNaPshot SNP assay was carried out by screening for circadian clock gene polymorphisms in every participant. Interactions associated with sleep disturbances were assessed by linear hierarchical regression analysis and SPSS macros (PROCESS). RESULTS: Linear hierarchical regression analysis showed that job stress was significantly related to sleep disturbances. Likewise, our study found a significant effect of PER2 rs2304672 polymorphisms on sleep disturbances (p < 0.01), after controlling for confounding factors. In addition, the PER2 rs2304672 genotype modulated the relationship between job stress and sleep disturbances (ß = 0.414, p = 0.007). Interestingly, further analysis of the results of the PER2 gene rs2304672 × job stress interaction showed that rs2304672 G-allele carriers had a high-risk effect on sleep disturbances under high job stress. CONCLUSIONS: Our results suggest that the PER2 rs2304672 polymorphism may modulate the influence of job stress on sleep disturbances. These findings contribute to the field of sleep disturbances prevention and treatment.

Night shift work and depression among Chinese workers: the mediating role of sleep disturbances.

BACKGROUND: Depression is considered as a global problem. Recently, the prevalence of depression among night shift workers has been attracting people's attention. This study aims to explore the associations among night shift work, shift frequency and depression among Chinese workers and to explore whether sleep disturbances are a critical factor. METHODS: The cross-sectional survey consists of 787 autoworkers from a manufacturing plant in Fuzhou, China. Information about night shift work, shift frequency, depression, and sleep disturbances were collected from work records and responses to the Patient Health Questionnaire (PHQ-9) and the Pittsburgh Sleep Quality Index (PSQI). A mediation model was generated to examine relationship between night shift work, sleep disturbances, and depression. RESULTS: Our results found that night shift work, shift frequency, sleep disturbances, and depression had positive and significant relationships in a sample of Chinese workers. Night shift work, shift frequency and sleep disturbances were associated with an increased risk of depression among workers (OR: 4.23, 95% CI 2.55-7.00; 3.91, 2.31-6.63; 6.91, 4.40-10.86, respectively). Subsequent mediation analysis found that the association between night shift work and depression appeared to be partially mediated by sleep disturbances. CONCLUSION: These findings suggest that appropriate intervention and management strategies should be considered to alleviate the mental health burden of night shift workers.

A photochromic and scintillation Eu-MOF with visual X-ray detection in bright and dark environments.

The detection of X-rays has always been a frontier of scientific research. An Eu-MOF with both X-ray-induced photochromic and scintillation properties has been synthesized through the combination of a photochromism-active viologen ligand and rare earth Eu element with high-efficiency absorption of X-rays. In a bright environment, Eu-MOF exhibits different color changes under high-energy X-rays and low-energy X-rays, which can effectively distinguish X-rays. Eu-MOF can also be used for X-ray detection by scintillation properties in dark environments. This work provides a new perspective on the design of multifunctional materials that can perform simple X-ray detection in different environments.

Deep Volumetric Descriptor Learning for Dense Correspondence of Cone-Beam Computed Tomography via Spectral Maps.

The deep neural network has achieved great success in 3D volumetric correspondence. These methods infer the dense displacement or velocity fields directly from the extracted volumetric features without addressing the intrinsic structure correspondence, being prone to shape and pose variations. On the other hand, the spectral maps address the intrinsic structure matching in the low dimensional embedding space, remain less involved in volumetric image correspondence. This paper presents an unsupervised deep volumetric descriptor learning neural network via the low dimensional spectral maps to address the dense volumetric correspondence. The neural network is optimized by a novel criterion on descriptor alignments in the spectral domain regarding the supervoxel graph. Aside from the deep convolved multi-scale features, we explicitly address the supervoxel-wise spatial and cross-channel dependencies to enrich deep descriptors. The dense volumetric correspondence is formulated as the low-dimensional spectral mapping. The proposed approach has been applied to both synthetic and clinically obtained cone-beam computed tomography images to establish dense supervoxel-wise and up-scaled voxel-wise correspondences. Extensive series of experimental results demonstrate the contribution of the proposed approach in volumetric descriptor extraction and consistent correspondence, facilitating attribute transfer for segmentation and landmark location. The proposed approach performs favorably against the state-of-the-art volumetric descriptors and the deep registration models, being resilient to pose or shape variations and independent of the prior transformations.

Unsupervised random forest for affinity estimation.

This paper presents an unsupervised clustering random-forest-based metric for affinity estimation in large and high-dimensional data. The criterion used for node splitting during forest construction can handle rank-deficiency when measuring cluster compactness. The binary forest-based metric is extended to continuous metrics by exploiting both the common traversal path and the smallest shared parent node. The proposed forest-based metric efficiently estimates affinity by passing down data pairs in the forest using a limited number of decision trees. A pseudo-leaf-splitting (PLS) algorithm is introduced to account for spatial relationships, which regularizes affinity measures and overcomes inconsistent leaf assign-ments. The random-forest-based metric with PLS facilitates the establishment of consistent and point-wise correspondences. The proposed method has been applied to automatic phrase recognition using color and depth videos and point-wise correspondence. Extensive experiments demonstrate the effectiveness of the proposed method in affinity estimation in a comparison with the state-of-the-art.

Similarities and Differences Between HFmrEF and HFpEF.

The new guidelines classify heart failure (HF) into three subgroups based on the ejection fraction (EF): HF with reduced EF (HFrEF), HF with mid-range EF (HFmrEF), and HF with preserved EF (HFpEF). The new guidelines regarding the declaration of HFmrEF as a unique phenotype have achieved the goal of stimulating research on the basic characteristics, pathophysiology, and treatment of HF patients with a left ventricular EF of 40-49%. Patients with HFmrEF have more often been described as an intermediate population between HFrEF and HFpEF patients; however, with regard to etiology and clinical indicators, they are more similar to the HFrEF population. Concerning clinical prognosis, they are closer to HFpEF because both populations have a good prognosis and quality of life. Meanwhile, growing evidence indicates that HFmrEF and HFpEF show heterogeneity in presentation and pathophysiology, and the emergence of this heterogeneity often plays a crucial role in the prognosis and treatment of the disease. To date, the exact mechanisms and effective treatment strategies of HFmrEF and HFpEF are still poorly understood, but some of the current evidence, from observational studies and post-hoc analyses of randomized controlled trials, have shown that patients with HFmrEF may benefit more from HFrEF treatment strategies, such as beta-blockers, angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, mineralocorticoid receptor antagonists, and sacubitril/valsartan. This review summarizes available data from current clinical practice and mechanistic studies in terms of epidemiology, etiology, clinical indicators, mechanisms, and treatments to discuss the potential association between HFmrEF and HFpEF patients.

mGWAS identification of six novel single nucleotide polymorphism loci with strong correlation to gastric cancer.

BACKGROUND: Metabolite genome-wide association studies (mGWAS) are key for understanding the genetic regulation of metabolites in complex diseases including cancers. Although mGWAS has revealed hundreds of metabolomics quantitative trait loci (mQTLs) in the general population, data relating to gastric cancer (GC) are still incomplete. METHODS: We identified mQTLs associated with GC by analyzing genome-wide and metabolome-wide datasets generated from 233 GC patients and 233 healthy controls. RESULTS: Twenty-two metabolites were statistically different between GC cases and healthy controls, and all of them were associated with the risk of gastric cancer. mGWAS analyses further revealed that 9 single nucleotide polymorphisms (SNPs) were significantly associated with 3 metabolites. Of these 9 SNPs, 6 loci were never reported in the previous mGWAS studies. Surprisingly, 4 of 9 SNPs were significantly enriched in genes involved in the T cell receptor signaling pathway. CONCLUSIONS: Our study unveiled several novel GC metabolite and genetic biomarkers, which may be implicated in the prevention and diagnosis of gastric cancer.