Multi-Omics Analysis Reveals the Role of Changes in Platelet Activation Pathways in the Survival Outcome of Patients with Esophageal Squamous Cell Carcinoma.

Objective: The objective of this study was to integrate metabolomics and transcriptomics data to identify key diagnostic and prognostic markers for esophageal squamous cell carcinoma (ESCC). Plasma samples were collected from 85 ESCC patients at different stages and 50 healthy volunteers for non-targeted metabolomic analysis. Methods: Liquid chromatography-tandem mass spectrometry (LC-MS/MS) was employed for non-targeted metabolomic analysis. Subsequently, we integrated the metabolomic data with transcriptomic data from the Gene Expression Omnibus (GEO) and prognosis data from The Cancer Genome Atlas Program (TCGA) to perform pathway analysis. Our focus was on pathways that involve both metabolites and upstream genes, as they often exhibit higher accuracy. Results: Through the integration of metabolomics and transcriptomics, we identified significant alterations in the platelet activation pathway in ESCC. This pathway involves the participation of both metabolites and genes, making it a more accurate reflection of pathological changes associated with the disease. Notably, metabolite arachidonic acid (AA) and chemokine receptor type 2(CXCR2) were significantly downregulated in ESCC, while genes collagen type I alpha 1(COL1A1), collagen type I alpha 2(COL1A2), collagen type III alpha 1(COL3A1), type 3 inositol 1,4,5-trisphosphate receptor (ITPR3), and insulin-like growth factor II mRNA binding protein 3(IGF2BP3) were significantly upregulated, indicating the presence of tumor-induced platelet activation in ESCC. Further analysis of prognosis data revealed that high expression of COL1A1, IGF2BP3, and ITPR3 was associated with a favorable prognosis for ESCC, while high CXCR2 expression was linked to an adverse prognosis. In addition, we combined COL1A1, ITPR3, IGF2BP3, CXCR2, and AA to form a diagnostic biomarker panel. The receiver operating characteristic curve (ROC) demonstrated excellent diagnostic capability (AUC=0.987). Conclusion: Our study underscores the significant role of platelet activation pathways and related genes in the diagnosis and prognosis of ESCC patients. These findings offer promising insights for improving the clinical management of ESCC.

Effects of Cognitive Training in Flanker Task on Mobility of Older Adults: A Randomized Controlled Trail.

INTRODUCTION: Cognitive function is considered to be correlated with the older adults' mobility. Flanker task, reflecting the conflict resolution, is barely explored as a simple approach to train the older adults' cognitive function. Hence, the first aim of this study was to explore the effect of cognitive intervention adopting flanker task on mobility. The second aim of this study was to assess the effect of cognitive training by comparing it with physical training to disclose how much dosage of cognitive training can have the equal improvement of mobility with physical training. METHODS: 232 older adults (age, mean ± SD: 66.16 ± 7.08, female: 74.3%) were retrained and assigned into three groups (cognitive intervention group, physical exercise intervention group, and control group). The intervention lasted for 22 weeks (cognitive intervention: flanker task, 30 min per session, 3 sessions a week; physical exercise intervention: 30 min muscle and balance training session, twice a week, and 30 min daily walking and housework, 2-4 times a week). Grip strength, 30-s chair-stand test, single leg balance with eyes closed, and the timed "Up & Go" (TUG) were used as indicators of mobility. A mixed model analysis of variance (ANOVA), interaction effect, and simple effect were performed in statistical analysis. RESULTS: Both intervention groups improved mobility, and the results were similar behaviorally. However, the exercise intervention group performed better in 30-s chair-stand test (25.14 ± 0.67 vs. 23.71 ± 0.76 with p = 0.01) and single leg balance with eyes closed (8.15 ± 0.69 vs. 6.14 ± 0.43 with p < 0.001). CONCLUSION: 22-week cognitive intervention (for total 1,980 min) could improve the older adults' mobility to the similar extent of mild-to-moderate physical exercises (1,320 min of functional muscle and balance training and 1,980 daily physical activities), which ascertained the far transfer effects from cognition to untrained mobility domain and found a comparable dosage of cognitive and physical exercise training.

Effects of walking speeds and durations on the plantar pressure gradient and pressure gradient angle.

BACKGROUND: Walking exercise has been demonstrated to improve health in people with diabetes. However, it is largely unknown the influences of various walking intensities such as walking speeds and durations on dynamic plantar pressure distributions in non-diabetics and diabetics. Traditional methods ignoring time-series changes of plantar pressure patterns may not fully capture the effect of walking intensities on plantar tissues. The purpose of this study was to investigate the effect of various walking intensities on the dynamic plantar pressure distributions. In this study, we introduced the peak pressure gradient (PPG) and its dynamic patterns defined as the pressure gradient angle (PGA) to quantify dynamic changes of plantar pressure distributions during walking at various intensities. METHODS: Twelve healthy participants (5 males and 7 females) were recruited in this study. The demographic data were: age, 27.1 ± 5.8 years; height, 1.7 ± 0.1 m; and weight, 63.5 ± 13.5 kg (mean ± standard deviation). An insole plantar pressure measurement system was used to measure plantar pressures during walking at three walking speeds (slow walking 1.8 mph, brisk walking 3.6 mph, and slow running 5.4 mph) for two durations (10 and 20 min). The gradient at a location is defined as the unique vector field in the two-dimensional Cartesian coordinate system with a Euclidean metric. PGA was calculated by quantifying the directional variation of the instantaneous peak gradient vector during stance phase of walking. PPG and PGA were calculated in the plantar regions of the first toe, first metatarsal head, second metatarsal head, and heel at higher risk for foot ulcers. Two-way ANOVA with Fisher's post-hoc analysis was used to examine the speed and duration factors on PPG and PGA. RESULTS: The results showed that the walking speeds significantly affect PPG (P < 0.05) and PGA (P < 0.05), and the walking durations does not. No interaction between the walking duration and speed was observed. PPG in the first toe region after 5.4 mph for either 10 or 20 min was significantly higher than 1.8 mph. Meanwhile, after 3.6 mph for 20 min, PPG in the heel region was significantly higher than 1.8 mph. Results also indicate that PGA in the forefoot region after 3.6 mph for 20 min was significantly narrower than 1.8 mph. CONCLUSIONS: Our findings indicate that people may walk at a slow speed at 1.8 mph for reducing PPG and preventing PGA concentrated over a small area compared to brisk walking at 3.6 mph and slow running at 5.4 mph.

Effects of different intensities of continuous training on vascular inflammation and oxidative stress in spontaneously hypertensive rats.

We aimed to study the effects and underlying mechanism of different intensities of continuous training (CT) on vascular inflammation and oxidative stress in spontaneously hypertensive rats (SHR). Rats were divided into five groups (n = 12): Wistar-Kyoto rats sedentary group (WKY-S), sedentary group (SHR-S), low-intensity CT group (SHR-L), medium-intensity CT group (SHR-M) and high-intensity CT group (SHR-H). Changes in body mass, heart rate and blood pressure were recorded. The rats were euthanized after 14 weeks, and blood and vascular tissue samples were collected. Haematoxylin and Eosin staining was used to observe the aortic morphology, and Western blot was used to detect the expression of mesenteric artery proteins. After CT, the mean arterial pressures improved in SHR-L and SHR-M and increased in SHR-H compared with those in SHR-S. Vascular inflammation and oxidative stress levels significantly subsided in SHR-L and SHR-M (p < 0.05), whereas in SHR-H, only vascular inflammation significantly subsided (p < 0.05), and oxidative stress remained unchanged (p > 0.05). AMPK and SIRT1/3 expressions in SHR-L and SHR-M were significantly up-regulated than those in SHR-S (p < 0.05). These results indicated that low- and medium-intensity CT can effectively reduce the inflammatory response and oxidative stress of SHR vascular tissue, and high-intensity CT can improve vascular tissue inflammation but not oxidative stress.

Cardiac Ischemic Preconditioning Promotes MG53 Secretion Through H2O2-Activated Protein Kinase C-δ Signaling.

BACKGROUND: Ischemic heart disease is the leading cause of morbidity and mortality worldwide. Ischemic preconditioning (IPC) is the most powerful intrinsic protection against cardiac ischemia/reperfusion injury. Previous studies have shown that a multifunctional TRIM family protein, MG53 (mitsugumin 53; also called TRIM72), not only plays an essential role in IPC-mediated cardioprotection against ischemia/reperfusion injury but also ameliorates mechanical damage. In addition to its intracellular actions, as a myokine/cardiokine, MG53 can be secreted from the heart and skeletal muscle in response to metabolic stress. However, it is unknown whether IPC-mediated cardioprotection is causally related to MG53 secretion and, if so, what the underlying mechanism is. METHODS: Using proteomic analysis in conjunction with genetic and pharmacological approaches, we examined MG53 secretion in response to IPC and explored the underlying mechanism using rodents in in vivo, isolated perfused hearts, and cultured neonatal rat ventricular cardiomyocytes. Moreover, using recombinant MG53 proteins, we investigated the potential biological function of secreted MG53 in the context of IPC and ischemia/reperfusion injury. RESULTS: We found that IPC triggered robust MG53 secretion in rodents in vivo, perfused hearts, and cultured cardiac myocytes without causing cell membrane leakage. Mechanistically, IPC promoted MG53 secretion through H2O2-evoked activation of protein kinase-C-δ. Specifically, IPC-induced myocardial MG53 secretion was mediated by H2O2-triggered phosphorylation of protein kinase-C-δ at Y311, which is necessary and sufficient to facilitate MG53 secretion. Functionally, systemic delivery of recombinant MG53 proteins to mimic elevated circulating MG53 not only restored IPC function in MG53-deficient mice but also protected rodent hearts from ischemia/reperfusion injury even in the absence of IPC. Moreover, oxidative stress by H2O2 augmented MG53 secretion, and MG53 knockdown exacerbated H2O2-induced cell injury in human embryonic stem cell-derived cardiomyocytes, despite relatively low basal expression of MG53 in human heart. CONCLUSIONS: We conclude that IPC and oxidative stress can trigger MG53 secretion from the heart via an H2O2-protein kinase-C-δ-dependent mechanism and that extracellular MG53 can participate in IPC protection against cardiac ischemia/reperfusion injury.

Effects of Muscle Fatigue and Recovery on Complexity of Surface Electromyography of Biceps Brachii.

This study aimed to investigate the degree of regularity of surface electromyography (sEMG) signals during muscle fatigue during dynamic contractions and muscle recovery after cupping therapy. To the best of our knowledge, this is the first study assessing both muscle fatigue and muscle recovery using a nonlinear method. Twelve healthy participants were recruited to perform biceps curls at 75% of the 10 repetitions maximum under four conditions: immediately and 24 h after cupping therapy (-300 mmHg pressure), as well as after sham control (no negative pressure). Cupping therapy or sham control was assigned to each participant according to a pre-determined counter-balanced order and applied to the participant's biceps brachii for 5 min. The degree of regularity of the sEMG signal during the first, second, and last 10 repetitions (Reps) of biceps curls was quantified using a modified sample entropy (Ems) algorithm. When exercise was performed immediately or 24 h after sham control, Ems of the sEMG signal showed a significant decrease from the first to second 10 Reps; when exercise was performed immediately after cupping therapy, Ems also showed a significant decrease from the first to second 10 Reps but its relative change was significantly smaller compared to the condition of exercise immediately after sham control. When exercise was performed 24 h after cupping therapy, Ems did not show a significant decrease, while its relative change was significantly smaller compared to the condition of exercise 24 h after sham control. These results indicated that the degree of regularity of sEMG signals quantified by Ems is capable of assessing muscle fatigue and the effect of cupping therapy. Moreover, this measure seems to be more sensitive to muscle fatigue and could yield more consistent results compared to the traditional linear measures.

Using Bidimensional Multiscale Entropy Analysis of Ultrasound Images to Assess the Effect of Various Walking Intensities on Plantar Soft Tissues.

Walking performance is usually assessed by linear analysis of walking outcome measures. However, human movements consist of both linear and nonlinear complexity components. The purpose of this study was to use bidimensional multiscale entropy analysis of ultrasound images to evaluate the effects of various walking intensities on plantar soft tissues. Twelve participants were recruited to perform six walking protocols, consisting of three speeds (slow at 1.8 mph, moderate at 3.6 mph, and fast at 5.4 mph) for two durations (10 and 20 min). A B-mode ultrasound was used to assess plantar soft tissues before and after six walking protocols. Bidimensional multiscale entropy (MSE2D) and the Complexity Index (CI) were used to quantify the changes in irregularity of the ultrasound images of the plantar soft tissues. The results showed that the CI of ultrasound images after 20 min walking increased when compared to before walking (CI4: 0.39 vs. 0.35; CI5: 0.48 vs. 0.43, p < 0.05). When comparing 20 and 10 min walking protocols at 3.6 mph, the CI was higher after 20 min walking than after 10 min walking (CI4: 0.39 vs. 0.36, p < 0.05; and CI5: 0.48 vs. 0.44, p < 0.05). This is the first study to use bidimensional multiscale entropy analysis of ultrasound images to assess plantar soft tissues after various walking intensities.

Glucose-Sensitive Myokine/Cardiokine MG53 Regulates Systemic Insulin Response and Metabolic Homeostasis.

BACKGROUND: Mitsugumin 53 (MG53 or TRIM72), a striated muscle-specific E3 ligase, promotes ubiquitin-dependent degradation of the insulin receptor and insulin receptor substrate-1 and subsequently induces insulin resistance, resulting in metabolic syndrome and type 2 diabetes mellitus (T2DM). However, it is unknown how MG53 from muscle regulates systemic insulin response and energy metabolism. Increasing evidence demonstrates that muscle secretes proteins as myokines or cardiokines that regulate systemic metabolic processes. We hypothesize that MG53 may act as a myokine/cardiokine, contributing to interorgan regulation of insulin sensitivity and metabolic homeostasis. METHODS: Using perfused rodent hearts or skeletal muscle, we investigated whether high glucose, high insulin, or their combination (conditions mimicking metabolic syndrome or T2DM) alters MG53 protein concentration in the perfusate. We also measured serum MG53 levels in rodents and humans in the presence or absence of metabolic diseases, particularly T2DM. The effects of circulating MG53 on multiorgan insulin response were evaluated by systemic delivery of recombinant MG53 protein to mice. Furthermore, the potential involvement of circulating MG53 in the pathogenesis of T2DM was assessed by neutralizing blood MG53 with monoclonal antibodies in diabetic db/db mice. Finally, to delineate the mechanism underlying the action of extracellular MG53 on insulin signaling, we analyzed the potential interaction of MG53 with extracellular domain of insulin receptor using coimmunoprecipitation and surface plasmon resonance assays. RESULTS: Here, we demonstrate that MG53 is a glucose-sensitive myokine/cardiokine that governs the interorgan regulation of insulin sensitivity. First, high glucose or high insulin induces MG53 secretion from isolated rodent hearts and skeletal muscle. Second, hyperglycemia is accompanied by increased circulating MG53 in humans and rodents with diabetes mellitus. Third, systemic delivery of recombinant MG53 or cardiac-specific overexpression of MG53 causes systemic insulin resistance and metabolic syndrome in mice, whereas neutralizing circulating MG53 with monoclonal antibodies has therapeutic effects in T2DM db/db mice. Mechanistically, MG53 binds to the extracellular domain of the insulin receptor and acts as an allosteric blocker. CONCLUSIONS: Thus, MG53 has dual actions as a myokine/cardiokine and an E3 ligase, synergistically inhibiting the insulin signaling pathway. Targeting circulating MG53 opens a new therapeutic avenue for T2DM and its complications.

Highly immunosuppressive HLADRhi regulatory T cells are associated with unfavorable outcomes in cervical squamous cell carcinoma.

Regulatory T cells (Tregs) are crucial for the maintenance of peripheral tolerance, but they also limit beneficial responses through cancer-induced immunoediting. The roles of Treg subsets in cervical squamous cell carcinoma (CSCC) are currently unknown. Here, we aimed to perform an extensive study with an increased resolution of the Treg compartment in the peripheral blood and tumor tissues of CSCC patients. We first identified that an HLADRhi Treg population in the peripheral blood was significantly increased in CSCC patients compared to precancer patients and healthy donors. We found that HLADRhi Tregs express high levels of a panel of inhibition and activation markers and the TCR-responsive transcription factors BATF and IRF4. However, this Treg subset showed reduced calcium influx after TCR crosslinking. In addition, HLADRhi Tregs are highly proliferative and vulnerable to apoptosis. Further studies demonstrated that the HLADRhi Tregs display high levels of suppressive activity. Quantitative multiplexed immunohistochemistry revealed that an increase in the number of tumor-infiltrating HLADRhi Tregs is associated with unfavorable classical risk parameters of advanced disease stage and stromal invasion. Context-based quantification revealed that a high frequency of stromal HLADRhi Tregs in patients is significantly associated with worse progression-free survival. In the current study, we characterized a population of highly activated and immunosuppressive HLADRhi Tregs in CSCC patients. An increased HLADRhi Treg frequency may be a potential biomarker to stratify CSCC patients and evaluate therapeutic efficacies in personalized immuno-oncology studies.

Tumoral PD-1hiCD8+ T cells are partially exhausted and predict favorable outcome in triple-negative breast cancer.

Tumor-infiltrating PD-1hi dysfunctional CD8+ T cells have been identified in several tumors but largely unexplored in breast cancer (BC). Here we aimed to extensively explore PD-1hiCD8+ T cells in BC, focusing on the triple-negative BC (TNBC) subtype. Flow cytometry was used to study the phenotypes and functions of CD8+ T-cell subsets in peripheral blood and surgical specimens from treatment-naive BC patients. RNA-seq expression data generated to dissect the molecular features of tumoral PD-1neg, PD-1lo and PD-1hi CD8+ T cells. Further, the associations between tumoral PD-1hi CD8+ T cells and the clinicopathological features of 503 BC patients were explored. Finally, multiplexed immunohistochemistry (mIHC) was performed to evaluate in situ PD-1hiCD8+ T cells on the tissue microarrays (TMAs, n=328) for prognostic assessment and stratification of TNBC patients. PD-1hiCD8+ T cells found readily detectable in tumor tissues but rarely in peripheral blood. These cells shared the phenotypic and molecular features with exhausted and tissue-resident memory T cells (TRM) with a skewed TCR repertoire involvement. Interestingly, PD-1hiCD8+ T cells are in the state of exhaustion characterized by higher T-BET and reduced EOMES expression. PD-1hiCD8+ T cells found preferentially enriched within solid tumors, but predominant stromal infiltration of PD-1hiCD8+ T subset was associated with improved survival in TNBC patients. Taken together, tumoral PD-1hiCD8+ T-cell subpopulation in BC is partially exhausted, and their abundance signifies 'hot' immune status with favorable outcomes. Reinvigorating this population may provide further therapeutic opportunities in TNBC patients.

Phytopathogenic fungus hosts a plant virus: A naturally occurring cross-kingdom viral infection.

The transmission of viral infections between plant and fungal hosts has been suspected to occur, based on phylogenetic and other findings, but has not been directly observed in nature. Here, we report the discovery of a natural infection of the phytopathogenic fungus Rhizoctonia solani by a plant virus, cucumber mosaic virus (CMV). The CMV-infected R. solani strain was obtained from a potato plant growing in Inner Mongolia Province of China, and CMV infection was stable when this fungal strain was cultured in the laboratory. CMV was horizontally transmitted through hyphal anastomosis but not vertically through basidiospores. By inoculation via protoplast transfection with virions, a reference isolate of CMV replicated in R. solani and another phytopathogenic fungus, suggesting that some fungi can serve as alternative hosts to CMV. Importantly, in fungal inoculation experiments under laboratory conditions, R. solani could acquire CMV from an infected plant, as well as transmit the virus to an uninfected plant. This study presents evidence of the transfer of a virus between plant and fungus, and it further expands our understanding of plant-fungus interactions and the spread of plant viruses.

Central role of E3 ubiquitin ligase MG53 in insulin resistance and metabolic disorders.

Insulin resistance is a fundamental pathogenic factor present in various metabolic disorders including obesity and type 2 diabetes. Although skeletal muscle accounts for 70-90% of insulin-stimulated glucose disposal, the mechanism underlying muscle insulin resistance is poorly understood. Here we show in mice that muscle-specific mitsugumin 53 (MG53; also called TRIM72) mediates the degradation of the insulin receptor and insulin receptor substrate 1 (IRS1), and when upregulated, causes metabolic syndrome featuring insulin resistance, obesity, hypertension and dyslipidaemia. MG53 expression is markedly elevated in models of insulin resistance, and MG53 overexpression suffices to trigger muscle insulin resistance and metabolic syndrome sequentially. Conversely, ablation of MG53 prevents diet-induced metabolic syndrome by preserving the insulin receptor, IRS1 and insulin signalling integrity. Mechanistically, MG53 acts as an E3 ligase targeting the insulin receptor and IRS1 for ubiquitin-dependent degradation, comprising a central mechanism controlling insulin signal strength in skeletal muscle. These findings define MG53 as a novel therapeutic target for treating metabolic disorders and associated cardiovascular complications.

Using Multiscale Entropy to Assess the Efficacy of Local Cooling on Reactive Hyperemia in People with a Spinal Cord Injury.

Pressure ulcers are one of the most common complications of a spinal cord injury (SCI). Prolonged unrelieved pressure is thought to be the primary causative factor resulting in tissue ischemia and eventually pressure ulcers. Previous studies suggested that local cooling reduces skin ischemia of the compressed soft tissues based on smaller hyperemic responses. However, the effect of local cooling on nonlinear properties of skin blood flow (SBF) during hyperemia is unknown. In this study, 10 wheelchair users with SCI and 10 able-bodied (AB) controls underwent three experimental protocols, each of which included a 10-min period as baseline, a 20-min intervention period, and a 20-min period for recovering SBF. SBF was measured using a laser Doppler flowmetry. During the intervention period, a pressure of 60 mmHg was applied to the sacral skin, while three skin temperature settings were tested, including no temperature change, a decrease by 10 °C, and an increase by 10 °C, respectively. A multiscale entropy (MSE) method was employed to quantify the degree of regularity of blood flow oscillations (BFO) associated with the SBF control mechanisms during baseline and reactive hyperemia. The results showed that under pressure with cooling, skin BFO both in people with SCI and AB controls were more regular at multiple time scales during hyperemia compared to baseline, whereas under pressure with no temperature change and particularly pressure with heating, BFO were more irregular during hyperemia compared to baseline. Moreover, the results of surrogate tests indicated that changes in the degree of regularity of BFO from baseline to hyperemia were only partially attributed to changes in relative amplitudes of endothelial, neurogenic, and myogenic components of BFO. These findings support the use of MSE to assess the efficacy of local cooling on reactive hyperemia and assess the degree of skin ischemia in people with SCI.

Green Quantification Strategy Combined with Chemometric Analysis for Triglycerides in Seeds Used in Traditional Chinese Medicine.

Triglycerides are the primary constituents of some seed kernels used in traditional Chinese medicine. Quality control of seed kernels containing multiple components with an environmentally friendly method is indispensable for establishing their quality standards (called monographs) in pharmacopeia. Using coix seeds (Semen Coicis) as an example, a green quantification strategy was proposed by combining C8 core-shell particles with single standard to determine multicomponent technologies to quantify seven triglycerides simultaneously. A core-shell column, namely, Halo C8 (3.0 × 100 mm, 2.7 µm), was used. Methanol was used as the mobile phase at a flow rate of 0.3 mL/min, enabling UV detection of the elutes. Seven triglycerides were well separated in 20 min, and simultaneously quantified using triolein as a single standard. The conversion factor for each standard was set as 1.0 on ELSD, while for the conversion factors at 203 nm, the values increased with the reduction of linoleate. The recovery values were all in the range of 97 - 107% (RSD < 3.0%). The RSD values of precision, including intraday and intermediate precision, were < 3.0% when the total content of triglycerides was calculated. The linearity reached r ≥ 0.9990, and the limit of quantitation reached 40 - 70 ng. Forty-nine batches of coix seeds from four different places of origins and eight batches of adulterants were evaluated and differentiated using principal component analysis. In addition, the validated method was used successfully to quantity seven triglycerides in Semen Persicae, Semen Armeniacae Amarum, and Semen Pruni.

Comparative Analysis of Fruit Ripening-Related miRNAs and Their Targets in Blueberry Using Small RNA and Degradome Sequencing.

MicroRNAs (miRNAs) play vital roles in the regulation of fruit development and ripening. Blueberry is an important small berry fruit crop with economical and nutritional value. However, nothing is known about the miRNAs and their targets involved in blueberry fruit ripening. In this study, using high-throughput sequencing of small RNAs, 84 known miRNAs belonging to 28 families and 16 novel miRNAs were identified in white fruit (WF) and blue fruit (BF) libraries, which represent fruit ripening onset and in progress, respectively. Among them, 41 miRNAs were shown to be differentially expressed during fruit maturation, and 16 miRNAs representing 16 families were further chosen to validate the sRNA sequencing data by stem-loop qRT-PCR. Meanwhile, 178 targets were identified for 41 known and 7 novel miRNAs in WF and BF libraries using degradome sequencing, and targets of miR160 were validated using RLM-RACE (RNA Ligase-Mediated (RLM)-Rapid Amplification of cDNA Ends) approach. Moreover, the expression patterns of 6 miRNAs and their targets were examined during fruit development and ripening. Finally, integrative analysis of miRNAs and their targets revealed a complex miRNA-mRNA regulatory network involving a wide variety of biological processes. The findings will facilitate future investigations of the miRNA-mediated mechanisms that regulate fruit development and ripening in blueberry.

Upregulation of MG53 induces diabetic cardiomyopathy through transcriptional activation of peroxisome proliferation-activated receptor α.

BACKGROUND: Diabetic cardiomyopathy, which contributes to >50% diabetic death, is featured by myocardial lipid accumulation, hypertrophy, fibrosis, and cardiac dysfunction. The mechanism underlying diabetic cardiomyopathy is poorly understood. Recent studies have shown that a striated muscle-specific E3 ligase Mitsugumin 53 (MG53, or TRIM72) constitutes a primary causal factor of systemic insulin resistance and metabolic disorders. Although it is most abundantly expressed in myocardium, the biological and pathological roles of MG53 in triggering cardiac metabolic disorders remain elusive. METHODS AND RESULTS: Here we show that cardiac-specific transgenic expression of MG53 induces diabetic cardiomyopathy in mice. Specifically, MG53 transgenic mouse develops severe diabetic cardiomyopathy at 20 weeks of age, as manifested by insulin resistance, compromised glucose uptake, increased lipid accumulation, myocardial hypertrophy, fibrosis, and cardiac dysfunction. Overexpression of MG53 leads to insulin resistant via destabilizing insulin receptor and insulin receptor substrate 1. More importantly, we identified a novel role of MG53 in transcriptional upregulation of peroxisome proliferation-activated receptor alpha and its target genes, resulting in lipid accumulation and lipid toxicity, thereby contributing to diabetic cardiomyopathy. CONCLUSIONS: Our results suggest that overexpression of myocardial MG53 is sufficient to induce diabetic cardiomyopathy via dual mechanisms involving upregulation of peroxisome proliferation-activated receptor alpha and impairment of insulin signaling. These findings not only reveal a novel function of MG53 in regulating cardiac peroxisome proliferation-activated receptor alpha gene expression and lipid metabolism, but also underscore MG53 as an important therapeutic target for diabetes mellitus and associated cardiomyopathy.

Gravity-Driven Multiple Collision-Enhanced Catalytic Soot Combustion over a Space-Open Array Catalyst Consisting of Ultrathin Ceria Nanobelts.

More than 122 times higher contact efficiency between soot and catalysts is achieved over the as-prepared CeO(2) nanobelt array catalysts as compared with the powder nanoparticle catalyst. A novel gravity-driven multiple collision-enhanced soot combustion mechanism is proposed for the first time.

Abatement of SO2-NOx binary gas mixtures using a ferruginous active absorbent: Part I. Synergistic effects and mechanism.

A novel ferruginous active absorbent, prepared by fly ash, industrial lime and the additive Fe(VI), was introduced for synchronous abatement of binary mixtures of SO2-NOx from simulated coal-fired flue gas. The synergistic action of various factors on the absorption of SO2 and NOx was investigated. The results show that a strong synergistic effect exists between Fe(VI) dose and reaction temperature for the desulfurization. It was observed that in the denitration process, the synergy of Fe(VI) dose and Ca/(S+N) had the most significant impact on the removal of NO, followed by the synergy of Fe(VI) and reaction temperature, and then the synergy of reaction temperature and flue gas humidity. A scanning electron microscope (SEM) and an accessory X-ray energy spectrometer (EDS) were used to observe the surface characteristics of the raw and spent absorbent as well as fly ash. A reaction mechanism was proposed based on chemical analysis of sulfur and nitrogen species concentrations in the spent absorbent. The Gibbs free energy, equilibrium constants and partial pressures of the SO2-NOx binary system were determined by thermodynamics.

The relationship between family history of cancer, coping style and psychological distress.

OBJECTIVE: To investigate the relationship between family history of cancer, coping style and psychological distress. METHODS: Total 80 patients with family history of cancer and 72 normal controls were analyzed using self-reporting inventory (SCL-90), coping style scale and impact of event scale-revised (IES-R). RESULTS: 1. Between the two groups of patients, there were significant differences in anxiety, depression, cancer-specific distress and coping style. 2. Psychological distress (anxiety, depression and cancer-specific distress) had positive correlation with negative coping style and family history. 3. Negative coping style played an intermediary role in the family history and psychological distress. CONCLUSION: The negative coping style will predispose to a more stronger psychological distress among the individuals with family history of cancer.

Expert Performance in Action Anticipation: Visual Search Behavior in Volleyball Spiking Defense from Different Viewing Perspectives.

Volleyball spiking requires defenders to possess exceptional anticipatory skills. However, most volleyball defense video eye-tracking studies have used fixed or off-court perspectives, failing to replicate real-world environments. This study explored different visual search behaviors between elite and novice volleyball players from various viewing perspectives using video eye tracking. We examined spiking anticipation in 14 competitive elite, 13 semi-elite, and 11 novice players. We captured spiking videos from three on-court perspectives using GoPro cameras mounted on the defenders' heads, closely replicating real game scenarios. For comparison, we recorded baseline videos using a fixed camera. The present study revealed that competitive and semi-elite players demonstrated higher accuracy than novices. Competitive elite players used fewer fixations, indicating that their superior performance was related to stable visual search patterns. All participant groups, regardless of skill level, showed similar visual allocation among areas of interest (AOIs). However, notable differences in visual search patterns and AOI allocation were observed between baseline and on-court perspective videos. From the baseline perspective, the participants primarily utilized global perception and peripheral vision, focusing more on the setter zone or the spiker's trunk. Conversely, from the on-court perspective, they employed more fixations, focusing more intensely on the spiker's detailed movements.