ATF4 Contributes to Abdominal Aortic Aneurysm Formation via Modulating M1 Macrophage Polarization and Inflammation.

Abdominal aortic aneurysm (AAA) is a potentially life-threatening vascular disease primarily in the male elderly population, but there is a lack of approved medical therapies to prevent the progression and rupture of AAA. Activating Transcription Factor 4 (ATF4) has been established to be involved in cardiovascular diseases, such as heart failure and calcific aortic valve disease. However, the role of ATF4 in the pathogenesis of AAA remains unclear. We found that ATF4 expression was significantly increased in patients with AAA and mouse models of AAA and was mainly confined to macrophages in arteries. ATF4 knockdown significantly attenuated aneurysm formation in experimental mouse model of AAA, while ATF4 overexpression promoted the development of AAA. RNA sequencing suggested that ATF4 was strongly related to the biological function of acute inflammatory response. Macrophages-specific ATF4 knockout significantly reduced the incidence and development of AAA, and decreased M1 polarization of macrophages in mice. Sphingomyelin phosphodiesterase 3 (SMPD3), a regulator of inflammatory responses in monocytes/macrophages, has been identified as a target gene of ATF4 through RNA sequencing, ChIP sequencing, and standard ChIP analyses. ATF4 induces M1 polarization of macrophages through the activation of SMPD3, thereby promoting inflammatory responses. Together, these results suggest that ATF4 mediated macrophage M1 polarization by regulating the expression of target genes SMPD3, leading to an increased inflammatory response, which further promotes the formation and development of AAA. These findings suggest ATF4 may be a new therapeutic target for AAA.

miR-181d-5p ameliorates hypercholesterolemia by targeting PCSK9.

Hypercholesterolemia is an independent risk factor for cardiovascular disease and lowering circulating levels of low-density lipoprotein cholesterol (LDL-C) can prevent and reduce cardiovascular events. microRNA-181d (miR-181d) can reduce the levels of triglycerides and cholesterol esters in cells. However, it is not known whether miR-181d-5p can lower levels of circulating LDL-C. Here, we generated two animal models of hypercholesterolemia to analyze the potential relationship between miR-181d-5p and LDL-C. In hypercholesterolemia model mice, adeno-associated virus (AAV)-mediated liver-directed overexpression of miR-181d-5p decreased the serum levels of cholesterol and LDL-C and the levels of cholesterol and triglyceride in the liver compared with control mice. Target Scan 8.0 indicated Proprotein convertase subtilisin/kexin type 9 (PCSK9) to be a possible target gene of miR-181d-5p, which was confirmed by in vitro experiments. miR-181d-5p could directly interact with both the PCSK9 3'-UTR and promoter to inhibit PCSK9 translation and transcription. Furthermore, Dil-LDL uptake assays in PCSK9 knockdown Huh7 cells demonstrated that miR-181d-5p promotion of LDL-C absorption was dependent on PCSK9. Collectively, our findings show that miR-181d-5p targets the PCSK9 3'-UTR to inhibit PCSK9 expression and to reduce serum LDL-C. miR-181d-5p is therefore a new therapeutic target for the development of anti-hypercholesterolemia drugs.

Effects of exogenous glycine betaine on growth and development of tomato seedlings under cold stress.

Low temperature is a type of abiotic stress affecting the tomato (Solanum lycopersicum) growth. Understanding the mechanisms and utilization of exogenous substances underlying plant tolerance to cold stress would lay the foundation for improving temperature resilience in this important crop. Our study is aiming to investigate the effect of exogenous glycine betaine (GB) on tomato seedlings to increase tolerance to low temperatures. By treating tomato seedlings with exogenous GB under low temperature stress, we found that 30 mmol/L exogenous GB can significantly improve the cold tolerance of tomato seedlings. Exogenous GB can influence the enzyme activity of antioxidant defense system and ROS levels in tomato leaves. The seedlings with GB treatment presented higher Fv/Fm value and photochemical activity under cold stress compared with the control. Moreover, analysis of high-throughput plant phenotyping of tomato seedlings also supported that exogenous GB can protect the photosynthetic system of tomato seedlings under cold stress. In addition, we proved that exogenous GB significantly increased the content of endogenous abscisic acid (ABA) and decreased endogenous gibberellin (GA) levels, which protected tomatoes from low temperatures. Meanwhile, transcriptional analysis showed that GB regulated the expression of genes involved in antioxidant capacity, calcium signaling, photosynthesis activity, energy metabolism-related and low temperature pathway-related genes in tomato plants. In conclusion, our findings indicated that exogenous GB, as a cryoprotectant, can enhance plant tolerance to low temperature by improving the antioxidant system, photosynthetic system, hormone signaling, and cold response pathway and so on.

Validation of the ANDON KD-595 automated upper-arm blood pressure monitor according to the universal standard.

OBJECTIVE: To validate the ANDON KD-595 automated upper-arm blood pressure monitor for clinical use and self-measurement blood pressure measurement according to the Association for the Advancement of Medical Instrumentation/European Society of Hypertension/International Organization for Standardization (AAMI/ESH/ISO) Universal Standard. METHODS: Same left-arm blood pressure was sequentially measured in 90 qualified adult participants and compared with a standard mercury sphygmomanometer. A total of 270 comparison pairs were obtained and analyzed according to the universal standard. RESULTS: For the validation Criterion 1 of the universal standard, the mean ± SD of the differences between the test device and reference blood pressure readings was 0.96 ±â€…5.35 and 0.82 ±â€…5.08 mmHg for SBP and DBP, respectively. For Criterion 2, the SDs of the averaged blood pressure differences between the test device and reference blood pressure per subject were 4.84 and 4.64 mmHg (with maximum allowed SDs of 6.87 and 6.89 mmHg) for SBP and DBP, respectively. CONCLUSION: The ANDON KD-595 automated upper-arm blood pressure monitor passed all the validation requirements according to the AAMI/ESH/ISO Universal Standard and can be recommended for clinical use and self-measurement blood pressure measurement in the general population.

Validation of the Wellvii VitalDetect blood pressure monitor in general population according to the International Standardization Organization 81060-2:2018.

OBJECTIVE: To evaluate the accuracy of the Wellvii VitalDetect automated oscillometric finger blood pressure monitor (single cuff size) for self/home blood pressure measurement according to the AAMI/ESH/ISO Universal Standard (ISO 81060-2:2018). METHODS: According to the universal standard, a total of 92 participants were recruited and finally blood pressure of 85 eligible participants was sequentially measured and compared with a standard mercury sphygmomanometer. RESULTS: A total of 255 comparison pairs were obtained and analyzed based on the universal standard. For the validation criterion 1 of the ISO 81060-2:2018 universal standard, the mean ± SD of the differences between the test device and reference blood pressure readings was 1.66 ±â€…7.67 and 1.04 ±â€…6.45 mmHg for systolic and diastolic blood pressure, respectively. For criterion 2, the SD of the averaged blood pressure differences between the test device and reference blood pressure per subject was ± 6.49 mmHg (pass ≤ 6.73 mmHg) and ± 5.67 mmHg (pass ≤ 6.86 mmHg) for systolic and diastolic blood pressure, respectively. CONCLUSION: The Wellvii VitalDetect automated finger blood pressure monitor passed all the requirements for validation by the ISO 81060-2:2018 universal standard and can be recommended for self/home blood pressure measurement in general population.

Machine Learning Models for Blood Glucose Level Prediction in Patients With Diabetes Mellitus: Systematic Review and Network Meta-Analysis.

BACKGROUND: Machine learning (ML) models provide more choices to patients with diabetes mellitus (DM) to more properly manage blood glucose (BG) levels. However, because of numerous types of ML algorithms, choosing an appropriate model is vitally important. OBJECTIVE: In a systematic review and network meta-analysis, this study aimed to comprehensively assess the performance of ML models in predicting BG levels. In addition, we assessed ML models used to detect and predict adverse BG (hypoglycemia) events by calculating pooled estimates of sensitivity and specificity. METHODS: PubMed, Embase, Web of Science, and Institute of Electrical and Electronics Engineers Explore databases were systematically searched for studies on predicting BG levels and predicting or detecting adverse BG events using ML models, from inception to November 2022. Studies that assessed the performance of different ML models in predicting or detecting BG levels or adverse BG events of patients with DM were included. Studies with no derivation or performance metrics of ML models were excluded. The Quality Assessment of Diagnostic Accuracy Studies tool was applied to assess the quality of included studies. Primary outcomes were the relative ranking of ML models for predicting BG levels in different prediction horizons (PHs) and pooled estimates of the sensitivity and specificity of ML models in detecting or predicting adverse BG events. RESULTS: In total, 46 eligible studies were included for meta-analysis. Regarding ML models for predicting BG levels, the means of the absolute root mean square error (RMSE) in a PH of 15, 30, 45, and 60 minutes were 18.88 (SD 19.71), 21.40 (SD 12.56), 21.27 (SD 5.17), and 30.01 (SD 7.23) mg/dL, respectively. The neural network model (NNM) showed the highest relative performance in different PHs. Furthermore, the pooled estimates of the positive likelihood ratio and the negative likelihood ratio of ML models were 8.3 (95% CI 5.7-12.0) and 0.31 (95% CI 0.22-0.44), respectively, for predicting hypoglycemia and 2.4 (95% CI 1.6-3.7) and 0.37 (95% CI 0.29-0.46), respectively, for detecting hypoglycemia. CONCLUSIONS: Statistically significant high heterogeneity was detected in all subgroups, with different sources of heterogeneity. For predicting precise BG levels, the RMSE increases with a rise in the PH, and the NNM shows the highest relative performance among all the ML models. Meanwhile, current ML models have sufficient ability to predict adverse BG events, while their ability to detect adverse BG events needs to be enhanced. TRIAL REGISTRATION: PROSPERO CRD42022375250; https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=375250.

Ahdc1 is a potent regulator of obesity and energy metabolism.

AT-hook DNA-binding motif-containing protein 1 (AHDC1) is a causal gene of intellectual disability/developmental delay in humans. The biological role of AHDC1 is unclear. Recently, some clues from AHDC1 mutation carriers hinted that AHDC1 may participate in body-weight regulation. In this first metabolic phenotype study of Ahdc1 deficiency, we generated a Ahdc1-deficienct mouse line and found that Ahdc1 deficiency in both male and female mice led to adiposity from weaning and obesity characterized by reduced energy expenditure and respiratory quotient, with progressive development of hyperleptinemia, insulin resistance, abnormal glycolipid metabolism, and fatty liver. Our findings show that Ahdc1 is a novel key regulator of obesity and energy metabolism, which provides new insight into the physiological mechanisms of obesity.NEW & NOTEWORTHY In this first metabolic phenotype study of Ahdc1 deficiency, we generated a survivable Ahdc1-deficient mouse line. We found that Ahdc1 deficiency in both male and female mice resulted in adiposity from weaning and obesity characterized by reduced energy expenditure and respiratory quotient. Additionally, there was a progressive development of hyperleptinemia, insulin resistance, abnormal glycolipid metabolism, and fatty liver. These findings demonstrate that Ahdc1 is a novel key regulator of obesity and energy metabolism.

Enhanced degradation of chloramphenicol via heterogeneous activation of peroxymonosulfate by Fe3O4 and gallic acid.

In this study, we demonstrated the effective degradation of wide-spectrum antibiotic chloramphenicol (CAP) by Fe3O4/peroxymonosulfate (PMS) system modified by gallic acid (GA). GA/Fe3O4/PMS showed a substantially higher degradation rate (77.6%) than Fe3O4/PMS (8.3%). The active components were detected by electron spin-resonance spectroscopy (ESR) and the quenching experiments. The results showed that the hydroxyl radical (HO•) was the main reason for the degradation of CAP. In the GA/Fe3O4/PMS system, the trace amount of dissolved iron ion were not the main species that activated PMS. Surface characterization and theoretical simulations showed that Fe atoms on Fe3O4 were responsible for PMS activation rather than a homogenous reaction. Five probable CAP degradation pathways were identified by density functional theory (DFT) calculations and liquid-phase mass spectrometry. Finally, the reusability of Fe3O4 was measured, and the GA/Fe3O4/PMS system maintained high efficiency after 5 times applications. The total organic carbon (TOC) removal rate reached 46.5% after reacting for 12 h. The gallic acid effectively promotes the circulation of Fe(II)/Fe(III) on solid surfaces and enhanced the degradation capacity of the original system. The research proposed a new way of directly employing plant polyphenols to boost the degradation ability of contaminants in heterogeneous systems.

Metabolic systems approaches update molecular insights of clinical phenotypes and cardiovascular risk in patients with homozygous familial hypercholesterolemia.

BACKGROUND: Homozygous familial hypercholesterolemia (HoFH) is an orphan metabolic disease characterized by extremely elevated low-density lipoprotein cholesterol (LDL-C), xanthomas, aortic stenosis, and premature atherosclerotic cardiovascular disease (ASCVD). In addition to LDL-C, studies in experimental models and small clinical populations have suggested that other types of metabolic molecules might also be risk factors responsible for cardiovascular complications in HoFH, but definitive evidence from large-scale human studies is still lacking. Herein, we aimed to comprehensively characterize the metabolic features and risk factors of human HoFH by using metabolic systems strategies. METHODS: Two independent multi-center cohorts with a total of 868 individuals were included in the cross-sectional study. First, comprehensive serum metabolome/lipidome-wide analyses were employed to identify the metabolomic patterns for differentiating HoFH patients (n = 184) from heterozygous FH (HeFH, n = 376) and non-FH (n = 100) subjects in the discovery cohort. Then, the metabolomic patterns were verified in the validation cohort with 48 HoFH patients, 110 HeFH patients, and 50 non-FH individuals. Subsequently, correlation/regression analyses were performed to investigate the associations of clinical/metabolic alterations with typical phenotypes of HoFH. In the prospective study, a total of 84 HoFH patients with available follow-up were enrolled from the discovery cohort. Targeted metabolomics, deep proteomics, and random forest approaches were performed to investigate the ASCVD-associated biomarkers in HoFH patients. RESULTS: Beyond LDL-C, various bioactive metabolites in multiple pathways were discovered and validated for differentiating HoFH from HoFH and non-FH. Our results demonstrated that the inflammation and oxidative stress-related metabolites in the pathways of arachidonic acid and lipoprotein(a) metabolism were independently associated with the prevalence of corneal arcus, xanthomas, and supravalvular/valvular aortic stenosis in HoFH patients. Our results also identified a small marker panel consisting of high-density lipoprotein cholesterol, lipoprotein(a), apolipoprotein A1, and eight proinflammatory and proatherogenic metabolites in the pathways of arachidonic acid, phospholipid, carnitine, and sphingolipid metabolism that exhibited significant performances on predicting first ASCVD events in HoFH patients. CONCLUSIONS: Our findings demonstrate that human HoFH is associated with a variety of metabolic abnormalities and is more complex than previously known. Furthermore, this study provides additional metabolic alterations that hold promise as residual risk factors in HoFH population.

Detection of Various Microplastics in Patients Undergoing Cardiac Surgery.

Microplastics have been detected in human stool, lungs, and placentas, which have direct exposure to the external environment through various body cavities, including the oral/anal cavity and uterine/vaginal cavity. Crucial data on microplastic exposure in completely enclosed human organs are still lacking. Herein, we used a laser direct infrared chemical imaging system and scanning electron microscopy to investigate whether microplastics exist in the human heart and its surrounding tissues. Microplastic specimens were collected from 15 cardiac surgery patients, including 6 pericardia, 6 epicardial adipose tissues, 11 pericardial adipose tissues, 3 myocardia, 5 left atrial appendages, and 7 pairs of pre- and postoperative venous blood samples. Microplastics were not universally present in all tissue samples, but nine types were found across five types of tissue with the largest measuring 469 µm in diameter. Nine types of microplastics were also detected in pre- and postoperative blood samples with a maximum diameter of 184 µm, and the type and diameter distribution of microplastics in the blood showed alterations following the surgical procedure. Moreover, the presence of poly(methyl methacrylate) in the left atrial appendage, epicardial adipose tissue, and pericardial adipose tissue cannot be attributed to accidental exposure during surgery, providing direct evidence of microplastics in patients undergoing cardiac surgery. Further research is needed to examine the impact of surgery on microplastic introduction and the potential effects of microplastics in internal organs on human health.

Curvature geometry in 2D materials.

The two-dimensional (2D) material family can be regarded as the extreme externalization form of the matter in the planar 2D space. These atomically thin materials have abundant curvature structures, which will significantly affect their atomic configurations and physicochemical properties. Curvature engineering offers a new tuning freedom beyond the thoroughly studied layer number, grain boundaries, stacking order, etc. The precise control of the curvature geometry in 2D materials can redefine this material family. Special attention will be given to this emerging field and highlight possible future directions. With the step-by-step achievement in understanding the curvature engineering effect in 2D materials and establishing reliable delicate curvature controlling strategies, a brand-new era of 2D materials research could be developed.

Vascular smooth muscle cells specific deletion of angiopoietin-like protein 8 prevents angiotensin II-promoted hypertension and cardiovascular hypertrophy.

AIMS: Angiopoietin-like protein 8 (ANGPTL8) plays important roles in lipid metabolism, glucose metabolism, inflammation, and cell proliferation and migration. Clinical studies have indicated that circulating ANGPTL8 concentrations are increased in patients with hypertension and positively associated with blood pressure. ANGPTL8 deficiency ameliorates blood pressure in mice treated with chronic intermittent hypoxia. Currently, little is known regarding the pathophysiological role of the vascular smooth muscle cell (VSMC)-derived ANGPTL8 in hypertension and hypertensive cardiovascular remodelling. METHODS AND RESULTS: Circulating ANGPTL8 concentrations, as determined by enzyme-linked immunosorbent assay, were significantly higher in hypertensive patients than in controls (524.51 ± 26.97 vs. 962.92 ± 15.91 pg/mL; P < 0.001). In hypertensive mice [angiotensin II (AngII) treatment for 14 days] and spontaneously hypertensive rats, ANGPTL8 expression was increased and predominantly located in VSMCs. In AngII-treated mice, systolic and diastolic blood pressure in Tagln-Cre-ANGPTL8fl/fl mice were approximately 15-25 mmHg lower than that in ANGPTL8fl/fl mice. AngII-induced vascular remodelling, vascular constriction, and increased expression of cell markers of proliferation (PCNA and Ki67) and migration (MMP-2 and MMP-9) were strikingly attenuated in Tagln-Cre-ANGPTL8fl/fl mice compared with ANGPTL8fl/fl mice. Furthermore, the AngII-induced increase in the heart size, heart weight, heart/body weight ratio, cardiomyocyte cross-sectional area, and collagen deposition was ameliorated in Tagln-Cre-ANGPTL8fl/fl mice compared with ANGPTL8fl/fl mice. In rat artery smooth muscle cells, ANGPTL8-short hairpin RNA decreased intracellular calcium levels and prevented AngII-induced proliferation and migration through the PI3K-Akt pathway, as shown using LY294002 (inhibitor of PI3K) and Akt inhibitor VIII. CONCLUSION: This study suggests that ANGPTL8 in VSMCs plays an important role in AngII-induced hypertension and associated cardiovascular remodelling. ANGPTL8 may be a novel therapeutic target against pathological hypertension and hypertensive cardiovascular hypertrophy.

ANGPTL8 deletion attenuates abdominal aortic aneurysm formation in ApoE-/- mice.

Angiopoietin-like protein 8 (ANGPTL8) plays important roles in lipid metabolism, glucose metabolism, inflammation, and cell proliferation and migration. Clinical studies have indicated that circulating ANGPTL8 levels are increased in patients with thoracic aortic dissection (TAD). TAD shares several risk factors with abdominal aortic aneurysm (AAA). However, the role of ANGPTL8 in AAA pathogenesis has never been investigated. Here, we investigated the effect of ANGPTL8 knockout on AAA in ApoE-/- mice. ApoE-/-ANGPTL8-/- mice were generated by crossing ANGPTL8-/- and ApoE-/- mice. AAA was induced in ApoE-/- using perfusion of angiotensin II (AngII). ANGPTL8 was significantly up-regulated in AAA tissues of human and experimental mice. Knockout of ANGPTL8 significantly reduced AngII-induced AAA formation, elastin breaks, aortic inflammatory cytokines, matrix metalloproteinase expression, and smooth muscle cell apoptosis in ApoE-/- mice. Similarly, ANGPTL8 sh-RNA significantly reduced AngII-induced AAA formation in ApoE-/- mice. ANGPTL8 deficiency inhibited AAA formation, and ANGPTL8 may therefore be a potential therapeutic target for AAA.

Role of microglial metabolic reprogramming in Parkinson's disease.

Parkinson's disease (PD) is a common age-related neurodegenerative disorder characterized by damage to nigrostriatal dopaminergic neurons. Key pathogenic mechanisms underlying PD include alpha-synuclein misfolding and aggregation, impaired protein clearance, mitochondrial dysfunction, oxidative stress, and neuroinflammation. However, to date, no study has confirmed the specific pathogenesis of PD. Similarly, current PD treatment methods still have shortcomings. Although some emerging therapies have proved effective for PD, the specific mechanism still needs further clarification. Metabolic reprogramming, a term first proposed by Warburg, is applied to the metabolic energy characteristics of tumor cells. Microglia have similar metabolic characteristics. Pro-inflammatory M1 type and anti-inflammatory M2 type are the two types of activated microglia, which exhibit different metabolic patterns in glucose, lipid, amino acid, and iron metabolism. Additionally, mitochondrial dysfunction may be involved in microglial metabolic reprogramming by activating various signaling mechanisms. Functional changes in microglia resulting from metabolic reprogramming can cause changes in the brain microenvironment, thus playing an important role in neuroinflammation or tissue repair. The involvement of microglial metabolic reprogramming in PD pathogenesis has been confirmed. Neuroinflammation and dopaminergic neuronal death can effectively be reduced by inhibiting certain metabolic pathways in M1 microglia or reverting M1 cells to the M2 phenotype. This review summarizes the relationship between microglial metabolic reprogramming and PD and provides strategies for PD treatment.

Diagnostic accuracy of an oscillometric blood pressure monitor for atrial fibrillation screening.

OBJECTIVE: Atrial fibrillation is the most common arrhythmia of clinical significance and hypertension is one of its major risk factors. This study aimed to evaluate the diagnostic accuracy of an automated oscillometric blood pressure (BP) monitor with the function of atrial fibrillation detection for atrial fibrillation screening. MATERIALS AND METHODS: Patients attending outpatient cardiology clinics were recruited for atrial fibrillation screening by the BP monitor with triplicate BP measurements for atrial fibrillation detection. Furthermore, a single-lead ECG was recorded simultaneously for comparison as the reference standard. The diagnostic test's evaluation index were analyzed, including sensitivity, specificity, and receiver operator characteristic (ROC) analysis. RESULTS: A total of 295 participants were analyzed including 166 males and 129 females, with an average age of 72.5 ±â€…5.9 years. The sensitivity and specificity for atrial fibrillation detection by the device were 1.000 and 0.904, respectively, with the area under the ROC curve of 0.952 (95% confidence interval: 0.929-0.975, P  < 0.001). Furthermore, the device had a Kappa-value of 0.781 ( P  < 0.001) with the single-lead ECG in detecting atrial fibrillation. CONCLUSION: The automated oscillometric BP monitor (G.LAB MD41A0) with atrial fibrillation detection function has high sensitivity and specificity with good accuracy for atrial fibrillation screening, which could be used as a reliable screening tool for the early detection of atrial fibrillation with potential benefits.

Metabolomic Approach to Screening Homozygotes in Chinese Patients with Severe Familial Hypercholesterolemia.

Homozygous familial hypercholesterolemia (HoFH) is a rare inborn-errors-of-metabolism disorder characterized by devastatingly elevated low-density lipoprotein cholesterol (LDL-C) and premature cardiovascular disease. The gold standard for screening and diagnosing HoFH is genetic testing. In China, it is expensive and is always recommended for the most likely HoFH subjects with aggressive LDL-C phenotype. However, the LDL-C levels of HoFH patients and a substantial proportion of heterozygous FH (HeFH) patients overlapped considerably. Here, we performed a cost-effective metabolomic profiling on genetically diagnosed HoFH (n = 69) and HeFH patients (n = 101) with overlapping LDL-C levels, aiming to discovery a unique metabolic pattern for screening homozygotes in patients with severe FH. We demonstrated a differential serum metabolome profile in HoFH patients compared to HeFH patients. Twenty-one metabolomic alterations showed independent capability in differentiating HoFH from severe HeFH. The combined model based on seven identified metabolites yielded a corrected diagnosis in 91.3% of HoFH cases with an area under the curve value of 0.939. Collectively, this study demonstrated that metabolomic profiling serves as a useful and economical approach to preselecting homozygotes in FH patients with severe hypercholesterolemia and may help clinicians to conduct selective genetic confirmation testing and familial cascade screening.

Accumulation of Intracellular Ferrous Iron in Inflammatory-Activated Macrophages.

Macrophages are important innate immune cells which can be polarized into heterogeneous populations. The inflammatory-activated M1 cells are known to be involved in all kinds of inflammatory diseases, which were also found to be associated with dysregulation of iron metabolism. While iron overload is known to induce M1 polarization, the valence states of iron and its intracellular dynamics during macrophage inflammatory activation have not been identified. In this study, THP-1-derived macrophages were polarized into M1, M2a, M2b, M2c, and M2d cells, and intracellular ferrous iron (Fe(II)) was measured by our previously developed ultrasensitive Fe(II) fluorescent probe. Significant accumulation of Fe(II) was only observed in M1 cells, which was different from the alterations of total iron. Time-dependent change of intracellular Fe(II) during the inflammatory activation was also consistent with the expression shifts of transferrin receptor CD71, ferrireductase Steap3, and Fe(II) exporter Slc40a1. In addition, accumulation of Fe(II) was also found in the colon macrophages of mice with ulcerative colitis, which was positively correlated to inflammatory phenotypes, including the productions of NO, IL-1ß, TNF-α, and IL-6. Collectively, these results demonstrated the specific accumulation of Fe(II) in inflammatory-activated macrophages, which not only enriched our understanding of iron homeostasis in macrophages, but also indicated that Fe(II) could be further developed as a potential biomarker for inflammatory-activated macrophages.

Recent research progress on metabolic syndrome and risk of Parkinson's disease.

Parkinson's disease (PD) is one of the most widespread neurodegenerative diseases. PD is associated with progressive loss of substantia nigra dopaminergic neurons, including various motor symptoms (e.g., bradykinesia, rigidity, and resting tremor), as well as non-motor symptoms (e.g., cognitive impairment, constipation, fatigue, sleep disturbance, and depression). PD involves multiple biological processes, including mitochondrial or lysosomal dysfunction, oxidative stress, insulin resistance, and neuroinflammation. Metabolic syndrome (MetS), a collection of numerous connected cerebral cardiovascular conditions, is a common and growing public health problem associated with many chronic diseases worldwide. MetS components include central/abdominal obesity, systemic hypertension, diabetes, and atherogenic dyslipidemia. MetS and PD share multiple pathophysiological processes, including insulin resistance, oxidative stress, and chronic inflammation. In recent years, MetS has been linked to an increased risk of PD, according to studies; however, the specific mechanism remains unclear. Researchers also found that some related metabolic therapies are potential therapeutic strategies to prevent and improve PD. This article reviews the epidemiological relationship between components of MetS and the risk of PD and discusses the potentially relevant mechanisms and recent progress of MetS as a risk factor for PD. Furthermore, we conclude that MetS-related therapies are beneficial for the prevention and treatment of PD.

Angiopoietin-like protein 8 deficiency attenuates thoracic aortic aneurysm/dissection development in ß-aminopropionitrile monofumarate-induced model mice.

Thoracic aortic aneurysm/dissection (TAAD) is a life-threatening cardiovascular disorder. Endoplasmic reticulum stress (ERS) and vascular smooth muscle cell (VSMC) apoptosis are involved in TAAD progression. The Protein kinase R (PKR)-like endoplasmic reticulum kinase (PERK) pathway is associated with VSMC apoptosis. Serum Angiopoietin-Like Protein 8 (ANGPTL8) levels are associated with aortic diameter and rupture rate of TAAD. However, a direct role of ANGPTL8 in TAAD has not been determined. ß-Aminopropionitrile monofumarate (BAPN) was used to induce TAAD in C57BL/6 mice. ANGPTL8 knockout mice were used to detect the effects of ANGPTL8 on TAAD development. ANGPTL8knockdown in vitro was used to analyze the role of ANGPTL8 in VSMCs and ERS. In addition, over-expression of ANGPTL8 in VSMCs and a PERK inhibitor were used to assess the effect of ANGPTL8 on the PERK pathway. ANGPTL8 levels were increased in the aortic wall and VSMCs of BAPN-induced TAAD mice. Compared with BAPN-treated wild-type mice, ANGPTL8 knockout significantly reduced the rupture rate of TAAD to 0 %. In addition, the protein levels of proinflammatory cytokines and matrix metalloproteinase 9 (MMP9) and ERS proteins were decreased in the aorta wall. Angptl8 shRNA decreased MMP9 and ERS protein levels in VSMCs in vitro. Overexpression of ANGPTL8 significantly increased the levels of ERS proteins and MMPs, while a PERK inhibitor significantly decreased the effects of ANGPTL8 in VSMCs. ANGPTL8 contributed to TAAD development by inducing ERS activation and degradation of extracellular matrix in the aorta wall. Inhibition of ANGPTL8 may therefore represent a new strategy for TAAD therapy.

Estimating the frost damage index in lettuce using UAV-based RGB and multispectral images.

Introduction: The cold stress is one of the most important factors for affecting production throughout year, so effectively evaluating frost damage is great significant to the determination of the frost tolerance in lettuce. Methods: We proposed a high-throughput method to estimate lettuce FDI based on remote sensing. Red-Green-Blue (RGB) and multispectral images of open-field lettuce suffered from frost damage were captured by Unmanned Aerial Vehicle platform. Pearson correlation analysis was employed to select FDI-sensitive features from RGB and multispectral images. Then the models were established for different FDI-sensitive features based on sensor types and different groups according to lettuce colors using multiple linear regression, support vector machine and neural network algorithms, respectively. Results and discussion: Digital number of blue and red channels, spectral reflectance at blue, red and near-infrared bands as well as six vegetation indexes (VIs) were found to be significantly related to the FDI of all lettuce groups. The high sensitivity of four modified VIs to frost damage of all lettuce groups was confirmed. The average accuracy of models were improved by 3% to 14% through a combination of multisource features. Color of lettuce had a certain impact on the monitoring of frost damage by FDI prediction models, because the accuracy of models based on green lettuce group were generally higher. The MULTISURCE-GREEN-NN model with R2 of 0.715 and RMSE of 0.014 had the best performance, providing a high-throughput and efficient technical tool for frost damage investigation which will assist the identification of cold-resistant green lettuce germplasm and related breeding.