Mitophagy in relation to chronic inflammation/ROS in aging.

Various assaults on mitochondria occur during the human aging process, contributing to mitochondrial dysfunction. This mitochondrial dysfunction is intricately connected with aging and diseases associated with it. In vivo, the accumulation of defective mitochondria can precipitate inflammatory and oxidative stress, thereby accelerating aging. Mitophagy, an essential selective autophagy process, plays a crucial role in managing mitochondrial quality control and homeostasis. It is a highly specialized mechanism that systematically removes damaged or impaired mitochondria from cells, ensuring their optimal functioning and survival. By engaging in mitophagy, cells are able to maintain a balanced and stable environment, free from the potentially harmful effects of dysfunctional mitochondria. An ever-growing body of research highlights the significance of mitophagy in both aging and age-related diseases. Nonetheless, the association between mitophagy and inflammation or oxidative stress induced by mitochondrial dysfunction remains ambiguous. We review the fundamental mechanisms of mitophagy in this paper, delve into its relationship with age-related stress, and propose suggestions for future research directions.

Is Takotsubo syndrome induced by patent ductus arteriosus occlusion?

Takotsubo syndrome (TTS), commonly referred to as "broken heart syndrome," is a distinctive form of acute and reversible heart failure that primarily affects young to middle-aged individuals, particularly women. While emotional or physical stressors often trigger TTS, rare cases have been linked to interventional procedures for congenital heart disease (CHD). Despite its recognition, the exact causes of TTS remain elusive. Research indicates that dysregulation in autonomic nerve function, involving sympathetic and parasympathetic activities, plays a pivotal role. Genetic factors, hormonal influences like estrogen, and inflammatory processes also contribute, unveiling potential gender-specific differences in its occurrence. Understanding these multifaceted aspects of TTS is crucial for refining clinical approaches and therapies. Continued research efforts will not only deepen our understanding of this syndrome but also pave the way for more targeted and effective diagnostic and treatment strategies. In this report, we conduct an in-depth analysis of a case involving a TTS patient, examining the illness progression and treatment procedures. The aim of this analysis is to enhance the understanding of TTS among primary care physicians. By delving into this case, we aspire to prevent misdiagnosis of typical TTS cases that patients may present, thereby ensuring a more accurate diagnosis and appropriate treatment.

Risks of Glaucoma among Individuals with Psoriasis: A Population-based Cohort Study.

BACKGROUND: Psoriasis is a chronic systemic disorder with ocular involvement. OBJECTIVES: The aim of the present study is to evaluate the risk of glaucoma among psoriatic patients. METHODS: Subjects of this cohort study were selected based on Chang Gung Research Database from January 1, 2003, to December 31, 2012. Follow-up ended on December 31, 2017. The participants of the control group were matched with the psoriatic group by gender, age, and index date at a 4:1 ratio. The hazard ratios of glaucoma were estimated using Cox regression analysis. We also evaluated the relationship between the risk of glaucoma and systemic therapies as well as phototherapy and topical corticosteroid in patients with psoriasis. RESULTS: A total of 6,682 patients with psoriasis and 26,728 matched controls were enrolled. The study population is composed of mainly Males accounting for 64.2% of the study population. The psoriatic group had higher incidence rates than the control group for glaucoma (adjusted hazard ratio 1.405 [95% confidence interval, 1.051-1.879]). Psoriatic patients receiving psoralen and ultraviolet-A (PUVA) therapy for more than 200 sessions had an increased risk of glaucoma. CONCLUSIONS: Psoriatic patients had an increased risk of glaucoma. Long-term PUVA therapy raised the risk of glaucoma in psoriatic populations.

Utilization of Multi-Parametric Quantitative Magnetic Resonance Imaging in the Early Diagnosis of Duchenne Muscular Dystrophy.

BACKGROUND: It is challenging to diagnose suspected Duchenne muscular dystrophy (DMD) patients in the very early stage of the disease. More evidence is needed to demonstrate the potential of quantitative MRI (qMRI) in precisely identifying patients before substantial physical decline occurs. PURPOSE: To assess the early diagnostic performance of multi-parametric qMRI for DMD patients, and the ability to identify DMD patients with mild functional decline. STUDY TYPE: Prospective. SUBJECTS: One hundred and forty DMD subjects (9.0 ± 2.2 years old), 24 male healthy controls (HCs) (9.2 ± 2.5 years old). FIELD STRENGTH/SEQUENCE: 3.0 T/3-point Dixon, T1-mapping, and T2-mapping. ASSESSMENT: qMRI measurements (fat fraction [FF], T1, and T2) of 11 thigh muscles (rectus femoris [RF], vastus lateralis [VL], vastus intermedius, vastus medialis, gracilis, sartorius, adductor longus, adductor magnus [AM], semitendinosus, semimembranosus, biceps femoris long head [BFLH]) on the right side were conducted. NorthStar ambulatory assessment (NSAA) score used to evaluate the function of DMD patients and divided them into three subgroups: mild (76-100 score), moderate (51-75 score), and severe (0-50 score) functional decline. STATISTICAL TESTS: Independent t-test, ANOVA analysis, and receiver operating characteristic (ROC) curves. A P-value <0.05 was considered statistically significant. RESULTS: Compared with HCs, FF and T2 were significantly higher in the group of all DMD patients, while T1 was significantly lower. The combination of T1 and T2 in RF, VL, AM, and BFLH achieved excellent area under curve (AUCs) (0.967-0.992) in differentiating five DMD patients without abnormal fat infiltration from HCs. Overall, T2 reached higher AUCs than FF and T1 in distinguishing DMD with mild functional decline from HCs, whereas FF achieved higher AUCs than T1 and T2 in distinguishing three DMD subgroups with functional decline. DATA CONCLUSION: Multi-parametric qMRI demonstrate effective diagnostic capabilities for DMD patients in the early stage of the disease, and can identify patients with mild physical decline. LEVEL OF EVIDENCE: 2 TECHNICAL EFFICACY: Stage 3.

Neuroprotective Effect of miR-483-5p Against Cardiac Arrest-Induced Mitochondrial Dysfunction Mediated Through the TNFSF8/AMPK/JNK Signaling Pathway.

Substantial morbidity and mortality are associated with postcardiac arrest brain injury (PCABI). MicroRNAs(miRNAs) are essential regulators of neuronal metabolism processes and have been shown to contribute to alleviated neurological injury after cardiac arrest. In this study, we identified miRNAs related to the prognosis of patients with neurological dysfunction after cardiopulmonary resuscitation based on data obtained from the Gene Expression Omnibus (GEO) database. Then, we explored the effects of miR-483-5p on mitochondrial biogenesis, mitochondrial-dependent apoptosis, and oxidative stress levels after ischemia‒reperfusion injury in vitro and in vivo. MiR-483-5p was downregulated in PC12 cells and hippocampal samples compared with that in normal group cells and hippocampi. Overexpression of miR-483-5p increased the viability of PC12 cells after ischemia‒reperfusion injury and reduced the proportion of dead cells. A western blot analysis showed that miR-483-5p increased the protein expression of PCG-1, NRF1, and TFAM and reduced the protein expression of Bax and cleaved caspase 3, inhibiting the release of cytochrome c from mitochondria and alleviating oxidative stress injury by inhibiting the production of ROS and reducing MDA activity. We confirmed that miR-483-5p targeted TNFSF8 to regulate the AMPK/JNK pathway, thereby playing a neuroprotective role after cardiopulmonary resuscitation. Hence, this study provides further insights into strategies for inhibiting neurological impairment after cardiopulmonary resuscitation and suggests a potential therapeutic target for PCABI.

Targeted Activation of HNF4α by AMPK Inhibits Apoptosis and Ameliorates Neurological Injury Caused by Cardiac Arrest in Rats.

Previous studies have shown that AMPK plays an important role in cerebral ischemia-reperfusion injury by participating in apoptosis, but the exact mechanism and target of action remains unclear. This study aimed to investigate the protective mechanism of AMPK activation on brain injury secondary to cardiac arrest. HE, Nills and TUNEL assays were used to evaluate neuronal damage and apoptosis. The relationships between AMPK, HNF4α and apoptotic genes were verified by ChIP-seq, dual-luciferase and WB assays. The results showed that AMPK improved the 7-day memory function of rats, and reduced neuronal cell injury and apoptosis in the hippocampal CA1 region after ROSC, while the use of HNF4α inhibitor weakened the protective effect of AMPK. Further research found that AMPK positively regulated the expression of HNF4α, and AMPK could promote the expression of Bcl-2 and inhibit the expression of Bax and Cleaved-Caspase 3. In vitro experiments showed that AMPK ameliorated neuronal injury by inhibiting apoptosis through the activation of HNF4α. Combined with ChIP-seq, JASPAR analysis and Dual-luciferase assay, the binding site of HNF4α to the upstream promoter of Bcl-2 was found. Taken together, AMPK attenuates brain injury after CA by activating HNF4α to target Bcl-2 to inhibit apoptosis.

Genome-Wide Identification of Proline Transporter Gene Family in Non-Heading Chinese Cabbage and Functional Analysis of BchProT1 under Heat Stress.

Non-heading Chinese cabbage prefers cool temperatures, and heat stress has become a major factor for reduced yield. The proline transporter protein (ProT) is highly selective for proline transport, contributing to the heat tolerance of non-heading Chinese cabbage. However, there has been no systematic study on the identification and potential functions of the ProT gene family in response to heat stress in non-heading Chinese cabbage. We identified six BchProT genes containing 11-12 transmembrane helices characteristic of membrane proteins through whole-genome sequencing. These genes diverged into three evolutionary branches and exhibited similarity in motifs and intron/exon numbers. Segmental duplication is the primary driving force for the amplification of BchProT. Notably, many stress-related elements have been identified in the promoters of BchProT using cis-acting element analysis. The expression level of BchProT6 was the highest in petioles, and the expression level of BchProT1 was the highest under high-temperature stress. Subcellular localization indicated their function at cell membranes. Heterologous expression of BchProT1 in Arabidopsis plants increased proline transport synthesis under heat-stress conditions. This study provides valuable information for exploring the molecular mechanisms underlying heat tolerance mediated by members of the BchProT family.

Mitophagy-mediated inflammation and oxidative stress contribute to muscle wasting in cancer cachexia.

Cancer cachexia is commonly seen in patients with malignant tumors, which usually leads to poor life quality and negatively affects long-term prognosis and survival. Mitochondria dysfunction and enhanced autophagy are well-established to play an important role in skeletal muscle wasting. However, whether mitophagy is engaged in the pathogenesis of cancer cachexia requires further investigation. This study comprised a clinical study and animal experimentation. Clinical data such as CT images and laboratory results were obtained and analyzed. Then mice model of cancer cachexia and mitophagy inhibition were established. Data including skeletal muscle mass and function, mitochondria structure and function, inflammatory factors as well as ROS concentration. Mitophagy was enhanced in cancer cachexia patients with increased inflammatory factors. Greater disruption of skeletal muscle fiber and mitochondria structure were seen in cancer cachexia, with a higher level of inflammatory factors and ROS expression in skeletal muscle. Meanwhile, ATP production was undermined, indicating a close relationship with mitophagy, inflammation, and oxidative stress in the skeletal muscle of cancer cachexia mice models. In conclusion, mitophagy is activated in cancer cachexia and may play a role in skeletal muscle atrophy, and inflammation and oxidative stress might participate in mitophagy-related skeletal muscle injury.

Plasma-derived extracellular vesicles transfer microRNA-130a-3p to alleviate myocardial ischemia/reperfusion injury by targeting ATG16L1.

Extracellular vesicles (EVs) are implicated in myocardial ischemia/reperfusion (I/R) injury as modulators by shuttling diverse cargoes, including microRNAs (miRNAs). The current study was initiated to unravel the potential involvement of plasma-derived EVs carrying miR-130a-3p on myocardial I/R injury. Rats were induced with moderate endoplasmic reticulum stress, followed by isolation of plasma-derived EVs. Then, an I/R rat model and hypoxia/reoxygenation (H/R) cardiomyoblast model were established to simulate a myocardial I/R injury environment where miR-130a-3p was found to be abundantly expressed. miR-130a-3p was confirmed to target and negatively regulate autophagy-related 16-like 1 (ATG16L1) in cardiomyoblasts. Based on a co-culture system, miR-130a-3p delivered by EVs derived from plasma protected H/R-exposed cardiomyoblasts against H/R-induced excessive cardiomyoblast autophagy, inflammation, and damage, improving cardiac dysfunction as well as myocardial I/R-induced cardiac dysfunction and tissue injury. The mechanism underlying the functional role of EVs-loaded miR-130a-3p was found to be dependent on its targeting relation with ATG16L1. The protective action of EV-carried miR-130a-3p was further re-produced in a rat model serving as in vivo validation as evidenced by improved cardiac function, tissue injury, myocardial fibrosis, and myocardial infarction. Collectively, miR-130a-3p shuttled by plasma-derived EVs was demonstrated to alleviate excessive cardiomyoblast autophagy and improve myocardial I/R injury.

Utilization of T1-Mapping for the pelvic and thigh muscles in Duchenne Muscular Dystrophy: a quantitative biomarker for disease involvement and correlation with clinical assessments.

BACKGROUND: Little is known about the disease distribution and severity detected by T1-mapping in Duchenne muscular dystrophy (DMD). Furthermore, the correlation between skeletal muscle T1-values and clinical assessments is less studied. Hence, the purposes of our study are to investigate quantitative T1-mapping in detecting the degree of disease involvement by detailed analyzing the hip and thigh muscle, future exploring the predicting value of T1-mapping for the clinical status of DMD. METHODS: Ninety-two DMD patients were included. Grading fat infiltration and measuring the T1-values of 19 pelvic and thigh muscles (right side) in axial T1-weighted images (T1WI) and T1-maps, respectively, the disease distribution and severity were evaluated and compared. Clinical assessments included age, height, weight, BMI, wheelchair use, timed functional tests, NorthStar ambulatory assessment (NSAA) score, serum creatine kinase (CK) level. Correlation analysis were performed between the muscle T1-value and clinical assessments. Multiple linear regression analysis was conducted for the independent association of T1-value and motor function. RESULTS: The gluteus maximus had the lowest T1-value, and the gracilis had the highest T1-value. T1-value decreased as the grade of fat infiltration increased scored by T1WI (P < 0.001). The decreasing of T1-values was correlated with the increase of age, height, weight, wheelchair use, and timed functional tests (P < 0.05). T1-value correlated with NSAA (r = 0.232-0.721, P < 0.05) and CK (r = 0.208-0.491, P < 0.05) positively. T1-value of gluteus maximus, tensor fascia, vastus lateralis, vastus intermedius, vastus medialis, and adductor magnus was independently associated with the clinical motor function tests (P < 0.05). Interclass correlation coefficient (ICC) analysis and Bland-Altman plots showed excellent inter-rater reliability of T1-value region of interest (ROI) measurements. CONCLUSION: T1-mapping can be used as a quantitative biomarker for disease involvement, further assessing the disease severity and predicting motor function in DMD.

The AP2 Transcription Factor BrSHINE3 Regulates Wax Accumulation in Nonheading Chinese Cabbage.

Wax is an acellular structural substance attached to the surface of plant tissues. It forms a protective barrier on the epidermis of plants and plays an important role in resisting abiotic and biotic stresses. In this paper, nonheading Chinese cabbage varieties with and without wax powder were observed using scanning electron microscopy, and the surface of waxy plants was covered with a layer of densely arranged waxy crystals, thus differentiating them from the surface of waxless plants. A genetic analysis showed that wax powder formation in nonheading Chinese cabbage was controlled by a pair of dominant genes. A preliminary bulked segregant analysis sequencing (BSA-seq) assay showed that one gene was located at the end of chromosome A09. Within this interval, we identified BraA09000626, encoding an AP2 transcription factor homologous to Arabidopsis AtSHINE3, and we named it BrSHINE3. By comparing the CDS of the gene in the two parental plants, a 35 bp deletion in the BrSHINE3 gene of waxless plants resulted in a frameshift mutation. Tissue analysis showed that BrSHINE3 was expressed at significantly higher levels in waxy plant rosette stage petioles and bolting stage stems than in the tissues of waxless plants. We speculate that this deletion in BrSHINE3 bases in the waxless material may inhibit wax synthesis. The overexpression of BrSHINE3 in Arabidopsis induced the accumulation of wax on the stem surface, indicating that BrSHINE3 is a key gene that regulates the formation of wax powder in nonheading Chinese cabbage. The analysis of the subcellular localization showed that BrSHINE3 is mainly located in the nucleus and chloroplast of tobacco leaves, suggesting that the gene may function as a transcription factor. Subsequent transcriptome analysis of the homology of BrSHINE3 downstream genes in nonheading Chinese cabbage showed that these genes were downregulated in waxless materials. These findings provide a basis for a better understanding of the nonheading Chinese cabbage epidermal wax synthesis pathway and provide important information for the molecular-assisted breeding of nonheading Chinese cabbage.

Effect of Nickel Ions on the Physiological and Transcriptional Responses to Carbon and Nitrogen Metabolism in Tomato Roots under Low Nitrogen Levels.

Nickel (Ni) is an essential trace element for plant growth and a component of the plant body that has many different functions in plants. Although it has been confirmed that nickel ions (Ni2+) havea certain regulatory effect on nitrogen (N) metabolism, there are not enough data to prove whether exogenous Ni2+ can increase the carbon (C) and N metabolism in the roots of tomato seedlingsunder low-nitrogen (LN) conditions. Therefore, through the present experiment, we revealed the key mechanism of Ni2+-mediated tomato root tolerance to LN levels. Tomato plants were cultured at two different N levels (7.66 and 0.383 mmol L-1) and two different Ni2+ levels (0 and 0.1 mg L-1 NiSO4 6H2O) under hydroponic conditions. After nine days, we collected roots for physiological, biochemical, and transcriptome sequencing analyses and found that the activities of N assimilation-related enzymes decreased at LN levels. In contrast, Ni2+ significantly increased the activities of N assimilation-related enzymes and increased the contents of nitrate (NO3-), ammonium (NH4+), and total amino acids. Through root transcriptomic analysis, 3738 differentially expressed genes (DEGs) were identified. DEGs related to C and N metabolism were downregulated after LN application. However, after Ni2+ treatment, PK, PDHB, GAPDH, NR, NiR, GS, GOGAT, and other DEGs related to C and N metabolism were significantly upregulated. In conclusion, our results suggest that Ni2+ can regulate the C and N metabolism pathways in tomato roots to alleviate the impact of LN levels.

Second-generation antipsychotics induce cardiotoxicity by disrupting spliceosome signaling: Implications from proteomic and transcriptomic analyses.

Second-generation antipsychotics (SGAs) are first-line drugs that are prescribed for mental disorders in clinic. Severe cardiotoxicity has been widely reported and thus limits their clinical application. This study aimed to identify the common mechanism underlying SGAs-induced cardiotoxicity using dual-omics analyses. Balb/C mice were intraperitoneally injected with two representative SGAs, olanzapine (2.5 mg/kg) and clozapine (25 mg/kg), at clinically comparable doses for 0, 7, 14 and 21 days. Our results showed that both SGAs induced cardiomyocyte degeneration, inflammation infiltration, and cardiac fibrosis, all of which worsened with time. Proteomic analysis revelaed that 22 differentially expressed (DE) proteins overlapped in olanzapine and clozapine-treated hearts. These proteins were significantly enriched in muscle contraction, amino acid metabolism and spliceosomal assembly by GO term analysis and spliceosome signaling was among the top enriched pathways by KEGG analysis. Among the 22 DE proteins, three spliceosome signal proteins were validated in a dynamic detection, and their expression significantly correlated with the extent of SGAs-induced cardiac fibrosis. Following the spliceosome signaling dysregulation, RNA sequencing revealed that alternative splicing events in the mouse hearts were markedly enhanced by SGAs treatments, and the production of vast transcript variants resulted in dysregulation of multiple pathways that are critical for cardiomyocytes adaptation and cardiac remodeling. Pladienolide B, a specific inhibitor of mRNA splicing, successfully corrected SGAs-induced alternative splicing and significantly attenuated the secretion of pro-inflammatory factors and cell deaths induced by SGAs exposure. Our study concluded that the spliceosome signaling was a common pathway driving SGAs cardiotoxicity. Pharmacological inhibition of the spliceosome signaling represents a novel therapeutic strategy against SGAs cardiotoxicity.

CB1R Promotes Chronic Alcohol-Induced Neuronal Necroptosis in Mice Prefrontal Cortex.

AIMS: Alcohol abuse induces multiple neuropathology and causes global burden to human health. Prefrontal cortex (PFC) is one of the most susceptible regions to alcohol-induced neuropathology. However, precise mechanisms underlying these effects on PFC remain to be elucidated. Herein, we investigated whether RIP1/RIP3/MLKL-mediated necroptosis was involved in the alcohol-induced PFC injury, and explored the effect that cannabinoid receptors (CBRs) exerted on the neurotoxicity of alcohol. METHODS: In this study, dynamic development of neuronal necroptosis in the PFC region was monitored after 95% (v/v) alcohol vapor administration for 15 and 30 days, respectively. Selective CBRs agonists or inverse agonists were pretreated according to the experimental design. All the PFC tissues were isolated and further examined by biochemical and histopathological analyses. RESULTS: It was found that chronic alcohol exposure increased the protein level of MLKL and also the phosphorylated levels of RIP1, RIP3 and MLKL in a time-dependent manner, all of which indicated the activation of necroptosis signaling. Particularly, compared to astrocytes, neurons from the PFC showed more prototypical necrotic morphology in response to alcohol insults. In parallel, an increased protein level of CB1R was also found after 15 and 30 days alcohol exposure. Administration of specific inverse agonists of CB1R (AM251 and AM281), but not its agonists or CB2R modulators, significantly alleviated the RIP1/RIP3/MLKL-mediated neuronal necroptosis. CONCLUSION: We reported the involvement of RIP1/RIP3/MLKL-mediated necroptosis in alcohol-induced PFC neurotoxicity, and identified CB1R as a critical regulator of neuronal necroptosis that enhanced our understanding of alcohol-induced neuropathology in the PFC.

Exposure characteristics and risk assessment of VOCs from Chinese residential cooking.

In comparison with various restaurant cuisines, common cooking methods are more represented in residential cooking. Rather than the exhaust pipe or the ambient environment in the cooking room, the respiration zone better reflects the health risks for operators. In this study, the concentrations of total volatile organic compound (TVOC) released from six typical cooking methods were monitored online in the respiratory zone, and the VOCs were analysed by GC-MS. The results demonstrated that the intensities of exposure to TVOC for the different cooking methods decreased as follows: stir-frying (3.809 mg/m3) > quick-frying (2.724 mg/m3) > deep-frying (2.465 mg/m3) > boiling (1.161 mg/m3)≈stewing (1.149 mg/m3) > limit in China (0.600 mg/m3) > steaming (0.440 mg/m3). The intense ventilation mode of the ventilator reduced exposure to TVOC by 45-63% relative to the medium mode. Eleven types of VOCs (approximately 200 compounds) were found in Chinese residential cooking fumes, and the predominant contaminants were aldehydes, followed by alkanes, unsaturated aldehydes, alcohols and alkenes. The mass percentage of aromatic hydrocarbons in all VOCs emitted from Chinese residential cooking was only 1%, while the value was 17-48% for commercial restaurants. The results of a health risk assessment revealed that the total potential carcinogenic risk level for VOCs released by six residential cooking methods decreased as follows: deep-frying (5.75) > stir-frying (3.95) > quick-frying (2.94) > stewing (1.99) > boiling (1.73) > steaming (1.48). Chinese residential cooking, and especially deep frying, has potential health impacts for the operator.

Proteomic Analysis of Brain Regions Reveals Brain Regional Differences and the Involvement of Multiple Keratins in Chronic Alcohol Neurotoxicity.

AIMS: Alcohol abuse has attracted public attention and chronic alcohol exposure can result in irreversible structural changes in the brain. The molecular mechanisms underlying alcohol neurotoxicity are complex, mandating comprehensive mining of spatial protein expression profile. METHODS: In this study, mice models of chronic alcohol intoxication were established after 95% alcohol vapor administration for 30 consecutive days. On Day 30, striatum (the dorsal and ventral striatum) and hippocampus, the two major brain regions responsible for learning and memorizing while being sensitive to alcohol toxicity, were collected. After that, isobaric tags for relative and absolute quantitation -based quantitative proteomic analysis were carried out for further exploration of the novel mechanisms underlying alcohol neurotoxicity. RESULTS: Proteomic results showed that in the striatum, 29 proteins were significantly up-regulated and 17 proteins were significantly down-regulated. In the hippocampus, 72 proteins were significantly up-regulated, while 2 proteins were significantly down-regulated. Analysis of the overlay proteins revealed that a total of 102 proteins were consistently altered (P < 0.05) in both hippocampus and striatum regions, including multiple keratins such as Krt6a, Krt17 and Krt5. Ingenuity pathway analysis revealed that previously reported diseases/biofunctions such as dermatological diseases and developmental disorders were enriched in those proteins. Interestingly, the glucocorticoid receptor (GR) signaling was among the top enriched pathways in both brain regions, while multiple keratins from the GR signaling such as Krt1 and Krt17 exhibited significantly opposite expression patterns in the two brain nuclei. Moreover, there are several other involved pathways significantly differed between the hippocampus and striatum. CONCLUSIONS: Our data revealed brain regional differences upon alcohol consumption and indicated the critical involvement of keratins from GR signaling in alcohol neurotoxicity. The differences in proteomic results between the striatum and hippocampus suggested a necessity of taking into consideration brain regional differences and intertwined signaling pathways rather than merely focusing on single nuclei or molecule during the study of drug-induced neurotoxicity in the future.

Quantitative Evaluation of Myocardial Strain After Myocardial Infarction with Cardiovascular Magnetic Resonance Tissue-Tracking Imaging.

To investigate the value of cardiovascular magnetic resonance tissue-tracking (CMR-TT) imaging in the differentiation of subendocardial and transmural myocardial infarction (MI) and determine whether strain parameters are enable to detect adverse left ventricular (LV) remodeling.Global peak circumferential, longitudinal, and radial strains (GPCS, GPLS, GPRS) and segmental peak circumferential, longitudinal, and radial strains (PCS, PLS, PRS) in accordance with the 16-segment model were all derived. All positive segments were divided into two groups according to transmural degree. All patients were dichotomized in accordance with the existence of LV remodeling, which was defined as infarct size (IS) > 24%.Patients with MI showed significant lower GPRS, GPCS, and GPLS than the control group (16.41% ± 8.92%, -8.77%± 3.51%, -7.54% ± 2.43% versus 32.41% ± 12.99%, -14.92% ± 3.32%, -11.50% ± 2.51%). Lower PRS [3.25% (-5.57, 7.835) versus 19.94% (12.50, 30.75), P < 0.001] and PCS (-3.81 ± 4.60% versus -8.97± 4.43%, P < 0.001) can be found in transmural infarcted segments compared to subendocardial infarcted segments. PLS between transmural and subendocardial infarcted segments (-4.03% ± 4.88% versus -4.34% ± 4.98%), without however statistical significance (P = 0.523). The optimal cutoff value for PRS in the discriminate diagnosis of MI was 8.97% with a sensitivity of 81.8% and specificity of 98.0%. The optimal cutoff value for PCS was -7.56% with a sensitivity of 83.6% and specificity of 72.1%. Receiver operating characteristic (ROC) analysis revealed an optimal cutoff GPRS of 15.45%, and GPCS of -6.72% yielded high diagnostic accuracy in the identification of remodeling, which was higher than left ventricular ejection fraction (LVEF).CMR-TT can differentiate between subendocardial and transmural infarction and detect LV remodeling, and the diagnostic value was superior to conventional functional parameters.

Value of Cardiac Magnetic Resonance Fractal Analysis Combined With Myocardial Strain in Discriminating Isolated Left Ventricular Noncompaction and Dilated Cardiomyopathy.

BACKGROUND: Excessive trabeculation is present in isolated left ventricular noncompaction (LVNC) and dilated cardiomyopathy (DCM), which sometimes makes the differentiation between these two difficult. Fractal dimension (FD) is a unitless measure value of how completely the object fills space, which can assess the extent of myocardial trabeculae quantitatively. PURPOSE: To compare the trabeculae features and myocardial strain derived from cardiac MR between LVNC and DCM. STUDY TYPE: Respective case-control series. POPULATION: In all, 35 LVNC patients and 30 DCM patients were enrolled, and 20 healthy volunteers were selected as a control group. FIELD STRENGTH/SEQUENCE: 5 T with 8-channel phased-array cardiac receiver coil including steady-state free precession cine imaging. ASSESSMENT: The degree of left ventricular trabeculation was evaluated by a semiautomatic tool based on fractal analysis. Myocardial deformation was assessed by feature tracking. STATISTICAL TESTS: Independent samples Student's t-test, Mann-Whitney U-test, receiver operating characteristics (ROC) curves, and Spearman's rank coefficient were conducted. RESULTS: Max apical FD and mean global FD were higher in the LVNC group than in the DCM group (1.433 ± 0.074 vs. 1.341 ± 0.062, P < 0.001; 1.323 ± 0.036 vs. 1.267 ± 0.041, P < 0.001, respectively). For diagnosing LVNC, max apical FD was 1.392 (area under the curve [AUC] = 0.881, 95% confidence interval [CI]: 0.804-0.957), and the cutoff value of mean global FD was 1.283 (AUC = 0.895, 95% CI: 0.828-0.961). The global peak longitudinal strain value of the left ventricle (GPLS) showed significant differences between the LVNC group and DCM group [-6.49 (-11.41, -4.90) vs. -4.61 (-5.87, -3.61), P = 0.006]. The diagnostic accuracy for LVNC is highest when using FDs in coordination with GPLS (AUC = 0.93, 95% CI: 0.86-0.98, P < 0.001). DATA CONCLUSION: Fractal analysis provides a quantitative measurement of myocardial trabeculation. The combination of fractal analysis with myocardial strain provides a novel biomarker in distinguishing LVNC from DCM. LEVEL OF EVIDENCE: 3 Technical Efficacy Stage: 2 J. Magn. Reson. Imaging 2019;50:153-163.

Metabolomics analysis reveals that elevated atmospheric CO2 alleviates drought stress in cucumber seedling leaves.

Elevated atmospheric CO2 alleviates moderate to severe drought stresses at physiological level in cucumber. To investigate the underlying metabolic mechanisms, cucumber seedlings were treated with two [CO2] and three water treatments combinations, and their leaves were analyzed using a non-targeted metabolomics approach. The results showed that elevated [CO2] changed 79 differential metabolites which were mainly associated with alanine, aspartate and glutamate metabolism; arginine and proline metabolism; TCA cycle; and glycerophospholipid metabolism under moderate drought stress. Moreover, elevated [CO2] promoted the accumulation of secondary metabolites; including isoferulic acid, m-coumaric acid and salicyluric acid. Under severe drought stress, elevated [CO2] changed 26 differential metabolites which mainly involved in alanine, aspartate and glutamate metabolism; pyruvate metabolism; arginine and proline metabolism; glyoxylate and dicarboxylate metabolism; cysteine and methionine metabolism; starch and sucrose metabolism; glycolysis or gluconeogenesis; and pyrimidine metabolism. In addition, elevated [CO2] accumulated carbohydrates, 1,2,3-trihydroxybenzene, pyrocatechol, glutamate, and l-gulonolactone, to allow adaption to severe drought. In conclusion, the metabolites and metabolic pathways associated with the alleviation of drought stresses by elevated [CO2] were different according to the level of drought stress. Our results may provide a theoretical basis for CO2 fertilization and application of exogenous metabolites to enhance drought tolerance of cucumber.