HIPK1 Inhibition Protects against Pathological Cardiac Hypertrophy by Inhibiting the CREB-C/EBPβ Axis

Inhibition of pathological cardiac hypertrophy is recognized as an important therapeutic strategy for heart failure, although effective targets are still lacking in clinical practice. Homeodomain interacting protein kinase 1 (HIPK1) is a conserved serine/threonine kinase that can respond to different stress signals, however, whether and how HIPK1 regulates myocardial function is not reported. Here, it is observed that HIPK1 is increased during pathological cardiac hypertrophy. Both genetic ablation and gene therapy targeting HIPK1 are protective against pathological hypertrophy and heart failure in vivo. Hypertrophic stress-induced HIPK1 is present in the nucleus of cardiomyocytes, while HIPK1 inhibition prevents phenylephrine-induced cardiomyocyte hypertrophy through inhibiting cAMP-response element binding protein (CREB) phosphorylation at Ser271 and inactivating CCAAT/enhancer-binding protein β (C/EBPβ)-mediated transcription of pathological response genes. Inhibition of HIPK1 and CREB forms a synergistic pathway in preventing pathological cardiac hypertrophy. In conclusion, HIPK1 inhibition may serve as a promising novel therapeutic strategy to attenuate pathological cardiac hypertrophy and heart failure

The gut microbiome in atherosclerotic cardiovascular disease

The gut microbiota may play a role in cardiovascular diseases. Here, the authors perform a metagenome-wide association study on stools from individuals with atherosclerotic cardiovascular disease and healthy controls, identifying microbial strains and functions associated with the disease

Clinical Characteristics of Inpatients With New-Onset Diabetes Mellitus in Eastern China: Based on Novel Clustering Analysis

IntroductionThis study aimed to explore the novel classification of inpatients with new-onset diabetes in Eastern China by the cluster-based classification method and compare the clinical characteristics among the different subgroups.MethodsA total of 1017 Inpatients with new-onset diabetes of five hospitals in Eastern China were included in the study. Clustering analysis was used to cluster the data into five subgroups according to six basic variables. The differences in clinical characteristics, treatments, and the prevalence of diabetes-related diseases among the five subgroups were analyzed by multiple groups comparisons and pairwise comparisons. The risk of diabetes-related diseases in the five subgroups was compared by calculating odd ratio (OR). P value < 0.05 was considered significant.ResultsFive subgroups were obtained by clustering analysis with the highest proportion of patients with severe insulin-deficient diabetes (SIDD) 451 (44.35%), followed by patients with mild age-related diabetes (MARD) 236 (23.21%), patients with mild obesity-related diabetes (MOD) 207 (20.35%), patients with severe insulin-resistant diabetes (SIRD) 81 (7.96%), and patients with severe autoimmune diabetes (SAID) 42 (4.13%). Five subtypes had their own unique characteristics and treatments. The prevalence and risk of diabetes-related complications and comorbidities were also significantly different among the five subtypes. Diabetic kidney disease (DKD) was the most common in SIRD group. Patients in SIDD, SIRD, and MARD groups were more likely to develop cardiovascular disease (CVD) and/or stroke, diabetic peripheral vascular disease (DPVD), and diabetic distal symmetric polyneuropathy (DSPN). The prevalence and risk of metabolic syndrome (MS) were the highest in MOD and SIRD groups. Patients in SAID group had the highest prevalence and risk of diabetic ketoacidosis (DKA). Patients with MOD were more likely to develop non-alcoholic fatty liver disease (NAFLD).ConclusionsThe inpatients with new-onset diabetes in Eastern China had the unique clustering distribution. The clinical characteristics, treatments, and diabetes-related complications and comorbidities of the five subgroups were different, which may provide the basis for precise treatments of diabetes

Sunflower Resistance to the Red Sunflower Seed Weevil (Coleoptera: Curculionidae)

The red sunflowerseed weevil, Smicronyx fulvus LeConte (Coleoptera: Curculionidae), is a major insect pest of sunflower in North Dakota, South Dakota, and Minnesota. Economic damage is caused by the larvae which are internal seed feeders. During the 1992-1995 growing seasons, sunflower accessions were artificially infested and evaluated for resistance to the red sunflower seed weevil. Accessions 170411, 253417, and 170424 were resistant to the red sunflower seed weevil. Morphological types within accessions170411 and 170424 varied for seed and pollen color and resistance to the red sunflower seed weevil. The resistant variant of accession170424 had 45% of the seed damage of the susceptible type. In accession 170411, damage in the resistant type was 55% of the susceptible. Antixenosis was the major resistance mechanism detected in accessions 170411 and 170424

Investigation on form and energy use of the rural residences in Beijing and surrounding cold areas under the self-sufficiency perspective

As a design theory on energy-saving housing, Self-sufficiency house is suited to the environment conditions of cold rural areas in China. Investigation on the rural residence form and energy use is the important foundation to carry out the research and design practice on self-sufficiency house. Taking Beijing and its surrounding rural areas as target, the paper combs current situation and technical requirements of rural residence based on self-sufficiency perspective. After surveying general residential condition and data, it analyzes the form, function, energy use and heating technology of rural residence, which will provide basic data and reference for post-study

DYNAMIC ANALYSIS OF THE GEAR-BOX CASE STRUCTURE BASED ON STIFFNESS COUPLING AND ITS LIFE ESTIMATION OF VIBRATION FATIGUE

This paper is mainly focused on the dynamical response and the structural fatigue situation of a manual gear-box case,which is based on the stiffness coupling with the effect of the gears. First of all,the FEM model was established and the accurate model was acquired by comparing the simulation results with the experiment results. Then,we established the coupling analysis model of structure dynamics considering on parts of gears,shafts as well as the structural flexible case,using the Romax software. The working processes under different gears were simulated accurately by the model and the bearing loads of the gearbox were obtained. Then we loaded the frequency bearing load on the FEM model and obtained the stress response of the danger area. Finally,the vibration fatigue life on the danger area of the gear-box case was calculated and analyzed by the sample assessment method

A Cost-Sensitive Sparse Representation Based Classification for Class-Imbalance Problem

Sparse representation has been successfully used in pattern recognition and machine learning. However, most existing sparse representation based classification (SRC) methods are to achieve the highest classification accuracy, assuming the same losses for different misclassifications. This assumption, however, may not hold in many practical applications as different types of misclassification could lead to different losses. In real-world application, much data sets are imbalanced of the class distribution. To address these problems, we propose a cost-sensitive sparse representation based classification (CSSRC) for class-imbalance problem method by using probabilistic modeling. Unlike traditional SRC methods, we predict the class label of test samples by minimizing the misclassification losses, which are obtained via computing the posterior probabilities. Experimental results on the UCI databases validate the efficacy of the proposed approach on average misclassification cost, positive class misclassification rate, and negative class misclassification rate. In addition, we sampled test samples and training samples with different imbalance ratio and use -measure, -mean, classification accuracy, and running time to evaluate the performance of the proposed method. The experiments show that our proposed method performs competitively compared to SRC, CSSVM, and CS4VM

The utility of urinary biomarker panel in predicting renal pathology and treatment response in Chinese lupus nephritis patients.

Given the urgent need for non-invasive biomarkers of LN, we aim to identify novel urinary biomarkers that facilitate diagnosis, assessment of disease activity and prediction of treatment response in a retrospective SLE cohort. A total of 154 SLE patients and 55 healthy controls were enrolled, among whom 73 were active LN patients. We measured renal activity by renal SLEDAI. The treatment response of the active LN patients who finished 6-month induction therapy was assessed based on the American College of Rheumatology response criteria. The expression levels of 10 urinary biomarkers (UBMs): β2-MG, calbindin D, cystatin C, IL-18, KIM-1, MCP-1, nephrin, NGAL, VCAM-1, and VDBP were tested using Luminex high-throughput proteomics technology. All but urinary nephrin levels were significantly increased in active LN compared to healthy controls. uCystatinC, uMCP-1, uKIM-1 levels were significantly higher in active LN group compared to inactive LN group. Correlation analysis revealed positive correlation between uCystatinC, uKIM-1, uMCP-1, uNGAL, uVDBP and RSLEDAI score. In renal pathology, uCystatinC, uKIM-1, uVCAM-1, and uVDBP positively correlated with activity index (AI) while uVCAM-1 positively correlated with chronicity index (CI). Moreover, the combination of uVCAM-1, uCystatinC, uKIM-1 discriminated proliferative LN from membranous LN with an AUC of 0.80 (95%CI: 0.69-0.90). Most importantly, baseline uNGAL demonstrated good prediction ability to discriminate responders from non-responders in active LN patients after 6-month induction therapy. Using a multiplex bead technique, we have identified the combination of uVCAM-1, uCystatinC, uKIM-1 as a biomarker panel to reflect renal pathology and NGAL as a promising urinary biomarker to both reflect disease activity and predict treatment response

Effect of tap dance on plantar pressure, postural stability and lower body function in older patients at risk of diabetic foot: a randomized controlled trial

Introduction To examine the effects of tap dance (TD) on dynamic plantar pressure, static postural stability, ankle range of motion (ROM), and lower extremity functional strength in patients at risk of diabetic foot (DF).Research design and methods A randomised, single-blinded, two-arm prospective study of 40 patients at risk of DF was conducted. The intervention group (n=20) received 16 weeks of TD training (60 min/session×3 sessions/week). The control group attended four educational workshops (1 hour/session×1 session/month). Plantar pressure, represented by the primary outcomes of peak pressure (PP) and pressure-time integral (PTI) over 10 areas on each foot, was measured using the Footscan platform system. Secondary outcomes comprised static postural stability, ankle ROM and lower extremity functional strength.Results Reductions in intervention group PP (right foot: mean differences=4.50~27.1, decrease%=25.6~72.0; left foot: mean differences=−5.90~6.33, decrease%=−22.6~53.2) and PTI at 10 areas of each foot (right foot: mean differences=1.00~12.5, decrease%=10.4~63.6; left foot: mean differences=0.590~25.3, decrease%=21.9~72.6) were observed. Substantial PP and PTI differences were noted at the second through fourth metatarsals, medial heel and lateral heel in the right foot. Substantial PP and PTI differences were detected at metatarsals 1 and 2 and metatarsal 2 in the left foot, respectively. Moderate training effects were found in plantar flexion ROM of both feet, lower extremity functional strength, and length of center-of-pressure trajectory with eyes closed and open (r=0.321–0.376, p<0.05).Conclusions A 16-week TD training program can significantly improve ankle ROM, lower extremity functional strength, and static postural stability. To attain greater improvements in plantar pressure, a longer training period is necessary.Trial registration number ChiCTR1800014714

Screening E3 Substrates Using a Live Phage Display Library

<div><p>Ubiquitin ligases (E3s) determine specificity of ubiquitination by recognizing target substrates. However, most of their substrates are unknown. Most known substrates have been identified using distinct approaches in different laboratories. We developed a high-throughput strategy using a live phage display library as E3 substrates in <i>in vitro</i> screening. His-ubiquitinated phage, enriched with Ni-beads, could effectively infect <i>E. coli</i> for amplification. Sixteen natural potential substrates and many unnatural potential substrates of E3 MDM2 were identified through 4 independent screenings. Some substrates were identified in different independent experiments. Additionally, 10 of 12 selected candidates were ubiquitinated by MDM2 <i>in vitro</i>, and 3 novel substrates, DDX42, TP53RK and RPL36a were confirmed <i>ex vivo</i>. The whole strategy is rather simple and efficient. Non-degradation substrates can be discovered. This strategy can be extended to any E3s as long as the E3 does not ubiquitinate the empty phage.</p> </div