Miracle-dz/UniFAR-FTUs huggingface dataset:
Sirt6 regulates lifespan in Drosophila melanogaster

Significance Sirt6 is well known for its role in regulating the aging process, particularly for its ability to extend lifespan in mice when overexpressed. However, the underlying molecular mechanisms responsible for lifespan regulation by Sirt6 are not well understood. Here, we characterized dSirt6 in fruit flies (Drosophila melanogaster). We found that dSirt6 functions very similarly to mammalian Sirt6 at the molecular and biochemical levels. Furthermore, overexpressing dSirt6 increased lifespan in flies. dSirt6 overexpression extends lifespan, in part, by opposing the activity of Myc, a master regulator of protein synthesis, which is associated with decreased protein synthesis. These findings have relevance for the treatment of age-related disease by modulating Sirt6 activity. Sirt6 is a multifunctional enzyme that regulates diverse cellular processes such as metabolism, DNA repair, and aging. Overexpressing Sirt6 extends lifespan in mice, but the underlying cellular mechanisms are unclear. Drosophila melanogaster are an excellent model to study genetic regulation of lifespan; however, despite extensive study in mammals, very little is known about Sirt6 function in flies. Here, we characterized the Drosophila ortholog of Sirt6, dSirt6, and examined its role in regulating longevity; dSirt6 is a nuclear and chromatin-associated protein with NAD+-dependent histone deacetylase activity. dSirt6 overexpression (OE) in flies produces robust lifespan extension in both sexes, while reducing dSirt6 levels shortens lifespan. dSirt6 OE flies have normal food consumption and fertility but increased resistance to oxidative stress and reduced protein synthesis rates. Transcriptomic analyses reveal that dSirt6 OE reduces expression of genes involved in ribosome biogenesis, including many dMyc target genes. dSirt6 OE partially rescues many effects of dMyc OE, including increased nuclear size, up-regulation of ribosome biogenesis genes, and lifespan shortening. Last, dMyc haploinsufficiency does not convey additional lifespan extension to dSirt6 OE flies, suggesting dSirt6 OE is upstream of dMyc in regulating lifespan. Our results provide insight into the mechanisms by which Sirt6 OE leads to longer lifespan.
Genetic Algorithm Optimization of Interior Ballistic Design Using High Load Density Propellant

The combustion characteristics of desensitized packed propellant were researched.By the modern optimization method,the multi-objective optimization model of interior ballistics of gun was built based on the genetic algorithm,and some key problems such as disposing method of constraints and genetic strategy,were investigated.The potential to improve the velocity by using this charge technology was analyzed.Aiming at the difficulty in ignition of desensitized packed propellant,the feasibility to use electro-thermal chemical technology to ignite the packed charge was discussed.The study results show that genetic algorithm is an effective method for multi-objective optimization problems of interior ballistic,and this method can be used in the design of interior ballistics of gun.
Inhibition of sphingolipid de novo synthesis counteracts muscular dystrophy

Duchenne muscular dystrophy (DMD), the most common muscular dystrophy, is a severe muscle disorder, causing muscle weakness, loss of independence, and premature death. Here, we establish the link between sphingolipids and muscular dystrophy. Transcripts of sphingolipid de novo biosynthesis pathway are up-regulated in skeletal muscle of patients with DMD and other muscular dystrophies, which is accompanied by accumulation of metabolites of the sphingolipid pathway in muscle and plasma. Pharmacological inhibition of sphingolipid synthesis by myriocin in the mdx mouse model of DMD ameliorated the loss in muscle function while reducing inflammation, improving Ca2+ homeostasis, preventing fibrosis of the skeletal muscle, heart, and diaphragm, and restoring the balance between M1 and M2 macrophages. Myriocin alleviated the DMD phenotype more than glucocorticoids. Our study identifies inhibition of sphingolipid synthesis, targeting multiple pathogenetic pathways simultaneously, as a strong candidate for treatment of muscular dystrophies.
Osteocalcin and Risks of Incident Diabetes and Diabetic Kidney Disease: A 4.6-Year Prospective Cohort Study

OBJECTIVE We aimed to examine the relationship between osteocalcin (OC) and the risk of incident diabetes and the risk of incident diabetic kidney disease (DKD). RESEARCH DESIGN AND METHODS We followed 5,396 participants without diabetes (nondiabetes subcohort) and 1,174 participants with diabetes and normal kidney function (diabetes subcohort) at baseline. Logistic regression and modified Poisson regression models were used to estimate the relative risk (RR) of baseline OC levels with incident diabetes and DKD. RESULTS During a mean 4.6-year follow-up period, 296 cases of incident diabetes and 184 cases of incident DKD were identified. In the nondiabetes subcohort, higher OC levels were linearly associated with a decreased risk of diabetes (RR for 1-unit increase of loge-transformed OC 0.51 [95% CI 0.35–0.76]; RR for highest vs. lowest quartile 0.65 [95% CI 0.44–0.95]; P for trend < 0.05). In the diabetes subcohort, OC levels were linearly inversely associated with incident DKD (RR for 1-unit increase of loge-transformed OC 0.49 [95% CI 0.33–0.74]; RR for highest vs. lowest quartile 0.56 [95% CI 0.38–0.83]; P for trend < 0.05), even independent of baseline estimated glomerular filtration rate and urinary albumin-to-creatinine ratio. No significant interactions between OC and various subgroups on incident diabetes or DKD were observed. CONCLUSIONS Lower OC levels were associated with an increased risk of incident diabetes and DKD.
Power equipment identification in infrared image based on Hu invariant moments

Aiming at the problems of low efficiency and poor real-time by manual of power equipment recognition in power system infrared detection,digital image processing was proposed to realize the efficient and accurate recognition based on the images obtained from the Infrared image.Firstly,the high temperature point was found as seed in power equipment from the message of infrared temperature.The background was removed effectively by region growing method to obtain the binary image of entire equipment.Secondly,Hu invariant moments and its improved algorithm were selected as the methods of feature extraction.Hu invariant moments of binary images were calculated,and feature vectors of power equipment were obtained.Finally,classifier based on BP neural network was designed to achieve different power equipment recognition,which will be used in fault diagnosis with temperature message.The research results indicate that,this method can receive a high recognition rate for different equipment and has less time-consuming,so that it will get a good prospect.
Technical Note: Toward implementation of MR-guided radiation therapy for Laryngeal cancer with healthy volunteer imaging and a custom MR-CT larynx phantom.

PURPOSE Internal motion of the larynx can cause normal tissue toxicity and/or tumor underdosage during radiotherapy. MR-guided radiation therapy (MRgRT) provides improved soft-tissue contrast for patient setup, and real-time gating of radiation based on cine imaging of tumor motion, potentially making it an advantageous modality for laryngeal treatments. However, there are potential concerns regarding the small target size, proximity to heterogeneous tissue interfaces in the airway that may cause dosimetric errors in the presence of the magnetic field, and uncertainty about the ability of MR-linear accelerator (MR-Linac) systems to visualize and track laryngeal motion. To date, there have been no reports of the use of MRgRT for laryngeal treatments. METHODS A healthy volunteer was imaged on a ViewRay MRIdian MR-Linac. Organs-at-risk and a laryngeal pseudo target were contoured and used to generate a stereotactic body radiotherapy plan. A custom phantom was created using 3D-printing based on structures delineated on the volunteer images to construct an enclosure containing the target and airway anatomy, with a gap for radiochromic film, and filled with gelatin . The treatment plan was mapped onto the phantom and delivered dose assessed on radiochromic film with global normalization and a 10% dose threshold. A cine MR of the volunteer was acquired to assess the magnitude of larynx motion with speaking and swallowing, and system's ability to gate radiation. RESULTS A clinically acceptable laryngeal treatment plan and larynx phantom that was MR and CT-visible were successfully created. The delivered dose had good agreement with the treatment plan with a gamma passing rate of 96.5% (3%/2mm). The MR-Linac was able to visualize, track, and gate larynx motion. CONCLUSIONS The MRgRT workflow for laryngeal treatments was assessed and performed in preparation for clinical implementation on the MR-Linac, demonstrating that it is feasible to treat laryngeal cancer patients on the MR-Linac. This article is protected by copyright. All rights reserved.
Intravascular Versus Surface Cooling in Patients Resuscitated From Cardiac Arrest: A Systematic Review and Network Meta-Analysis With Focus on Temperature Feedback

OBJECTIVE: The aim of the study was to compare the effect of intravascular cooling (IC), surface cooling with temperature feedback (SCF), and surface cooling without temperature feedback (SCnoF) on neurologic outcome and survival in patients successfully resuscitated from cardiac arrest (CA) and treated with targeted temperature management (TTM) at 32–34°C. DATA SOURCES: We performed a systematic review on Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, MEDLINE, SCOPUS, CINAHL, Web of Science, and Clinical Trials up to June 30, 2021. STUDY SELECTION: We included randomized and nonrandomized studies on IC, SCF, and SCnoF in adult humans resuscitated from CA undergoing TTM, reporting neurologic outcome or survival. DATA EXTRACTION: We performed a network meta-analysis to assess the comparative effects of IC, SCF, and SCnoF. The overall effect between two cooling methods included the effect of direct and indirect comparisons. Results are given as odds ratios (OR) and 95% CIs. Rankograms estimated the probability of TTM methods being ranked first, second, and third best interventions. DATA SYNTHESIS: A total of 14 studies involving 4,062 patients met the inclusion criteria. Four studies were randomized controlled studies, and 10 studies were nonrandomized observational studies. IC compared with SCnoF was significantly associated with better neurologic outcome (OR, 0.6; 95% CI, 0.49–0.74) and survival (OR, 0.8; 95% CI, 0.66–0.96). IC compared with SCF, and SCF compared with SCnoF did not show significant differences in neurologic outcome and survival. The rankogram showed that IC had the highest probability to be the most beneficial cooling method, followed by SCF and SCnoF. CONCLUSIONS: Our results suggest that in patients resuscitated from CA and treated with TTM at 32–34°C, IC has the highest probability of being the most beneficial cooling method for survival and neurologic outcome.
An improved representation of the relationship between photosynthesis and stomatal conductance leads to more stable estimation of conductance parameters and improves the goodness‐of‐fit across diverse data sets

Stomata play a central role in surface–atmosphere exchange by controlling the flux of water and CO2 between the leaf and the atmosphere. Representation of stomatal conductance (gsw) is therefore an essential component of models that seek to simulate water and CO2 exchange in plants and ecosystems. For given environmental conditions at the leaf surface (CO2 concentration and vapor pressure deficit or relative humidity), models typically assume a linear relationship between gsw and photosynthetic CO2 assimilation (A). However, measurement of leaf‐level gsw response curves to changes in A are rare, particularly in the tropics, resulting in only limited data to evaluate this key assumption. Here, we measured the response of gsw and A to irradiance in six tropical species at different leaf phenological stages. We showed that the relationship between gsw and A was not linear, challenging the key assumption upon which optimality theory is based—that the marginal cost of water gain is constant. Our data showed that increasing A resulted in a small increase in gsw at low irradiance, but a much larger increase at high irradiance. We reformulated the popular Unified Stomatal Optimization (USO) model to account for this phenomenon and to enable consistent estimation of the key conductance parameters g0 and g1. Our modification of the USO model improved the goodness‐of‐fit and reduced bias, enabling robust estimation of conductance parameters at any irradiance. In addition, our modification revealed previously undetectable relationships between the stomatal slope parameter g1 and other leaf traits. We also observed nonlinear behavior between A and gsw in independent data sets that included data collected from attached and detached leaves, and from plants grown at elevated CO2 concentration. We propose that this empirical modification of the USO model can improve the measurement of gsw parameters and the estimation of plant and ecosystem‐scale water and CO2 fluxes.
Vanillin attenuates thioacetamide‐induced renal assault by direct and indirect mediation of the TGFβ, ERK and Smad signalling pathways in rats

Inflammation and fibrosis are two pathological features of chronic kidney disease (CKD). Renal fibrosis is considered to be one of the most important conditions, as it may be the result of excessive extracellular matrix protein production and deposition, or prolonged exposure to nephrotoxic substances or drugs. Unfortunately, no suitable therapies or medications are currently available to prevent renal fibrosis. We conducted this study for the evaluation of the protective potential of vanillin by reversing TAA (250 mg/kg TAA for 6 weeks) induced renal injury in rats. The concentrations of the proteins tumour necrosis factor alpha (TNFα), interleukin‐6 (IL‐6), extracellular signal regulated kinase 1/2 (Erk1/2), and transforming growth factor beta‐1 (TGF‐β1) in kidney tissues were assessed using ELISA. Kidney Injury Molecule‐1 (KIM‐1) and mothers against decapentaplegic homologue 2, 3 (SMAD 2, 3) expressions were evaluated using real time PCR. We also estimated the expression of α‐smooth muscle actin (α‐SMA) using immunohistochemistry. Treatment with vanillin (100 mg/kg) significantly ameliorated kidney Injury and improved the kidney function. Vanillin treatment also significantly decreased the malondialdehyde (MDA) content, and elevated glutathione peroxidase (GPx) and catalase (CAT) activities in kidney tissues. Vanillin also reduced α‐SMA renal expression and TNFα, IL‐6, TGF‐β1, and Erk1/2 renal levels. Vanillin significantly decreased the expression of the genes encoding KIM‐1 and SMAD 2, 3 and ameliorated histological abnormalities in kidney architecture. Our molecular docking findings showed that vanillin has a good binding mode inside TGF‐β type I receptors (ALK5) biding site.
Biological nanopores for sensing applications

Biological nanopores are proteins with transmembrane pore that can be embedded in lipid bilayer. With the development of single‐channel current measurement technologies, biological nanopores have been reconstituted into planar lipid bilayer and used for single‐molecule sensing of various analytes and events such as single‐molecule DNA sensing and sequencing. To improve the sensitivity for specific analytes, various engineered nanopore proteins and strategies are deployed. Here, we introduce the origin and principle of nanopore sensing technology as well as the structure and associated properties of frequently used protein nanopores. Furthermore, sensing strategies for different applications are reviewed, with focus on the alteration of buffer condition, protein engineering, and deployment of accessory proteins and adapter‐assisted sensing. Finally, outlooks for de novo design of nanopore and nanopore beyond sensing are discussed.
The ‘other’ big complication: how chronic kidney disease impacts on cancer risks and outcomes

ABSTRACT Cancer is the second leading cause of death in people with chronic kidney disease (CKD) after cardiovascular disease. The incidence of CKD in patients with cancer is higher than in the non-cancer population. Across various populations, CKD is associated with an elevated risk of cancer incidence and cancer death compared with people without CKD, although the risks are cancer site-specific. Higher risk of cancer is detectable in mild CKD [estimated glomerular filtration rate (eGFR) 60–89 mL/min/1.73 m2], although this risk is more obvious if sensitive markers of kidney disease are used, such as cystatin C. Independent of eGFR, albuminuria is associated with increased risk of site-specific cancer incidence and death. Here, we explore the potential mechanisms for the increased risk of cancer observed in CKD, including patient factors (shared risks such as cardiometabolic disease, obesity, smoking, diet, lifestyle and environment), disease (genetic, inflammatory and infective) and treatment factors. In particular, we discuss the ways in which renal adverse events associated with conventional chemotherapies and newer systemic anti-cancer therapies (including targeted and immunotherapies) may contribute to worse cancer outcomes in people with CKD. Finally, we review the potential benefits of acknowledging increased risk of cancer in risk prediction tools used for the management of CKD.
Non-invasive tests of non-alcoholic fatty liver disease

Abstract For the detection of steatosis, quantitative ultrasound imaging techniques have achieved great progress in past years. Magnetic resonance imaging proton density fat fraction is currently the most accurate test to detect hepatic steatosis. Some blood biomarkers correlate with non-alcoholic steatohepatitis, but the accuracy is modest. Regarding liver fibrosis, liver stiffness measurement by transient elastography (TE) has high accuracy and is widely used across the world. Magnetic resonance elastography is marginally better than TE but is limited by its cost and availability. Several blood biomarkers of fibrosis have been used in clinical trials and hold promise for selecting patients for treatment and monitoring treatment response. This article reviews new developments in the non-invasive assessment of non-alcoholic fatty liver disease (NAFLD). Accumulating evidence suggests that various non-invasive tests can be used to diagnose NAFLD, assess its severity, and predict the prognosis. Further studies are needed to determine the role of the tests as monitoring tools. We cannot overemphasize the importance of context in selecting appropriate tests.
Diagnostic value of reticulocyte indices for the assessment of the iron status of cats with chronic kidney disease

Abstract Background Reticulocyte indices have been suggested as alternatives to transferrin saturation (TSAT) for iron status assessment in humans and dogs but they have not been evaluated thoroughly in cats. Objectives To assess the value of the reticulocyte indices for the diagnosis of iron deficiency in cats with chronic kidney disease (CKD) and chronic hematuria associated with subcutaneous ureteral bypasses (SUBs). Animals Sixty‐four cats: 16 healthy, 14 CKD without SUB, and 34 CKD with SUB. Methods Prospective observational cross‐sectional study of cats presented for routine nephrology visits. Primary outcomes included assessment of the diagnostic values of erythrocyte indices (mean corpuscular volume, hemoglobin, and hemoglobin concentration: MCV, MCH, and MCHC) and reticulocyte indices (mean corpuscular volume, MCVr; corpuscular hemoglobin, CHr), using TSAT as reference. Results Iron deficiency was diagnosed in 9/64 cats (14%). A receiver‐operating characteristic curve analysis yielded a moderate discriminatory value for CHr in this diagnosis: area under the curve [AUC] = . 75 (95% confidence interval, 0.48‐0.89); P = . 006; sensitivity 67%, specificity 82% for a cutoff of 15.9 pg. This compared favorably to MCVr (AUC = .63; P = .29), MCV (AUC = .58; P = .45), MCH (AUC = .64; P = .19), and MCHC (AUC = .7; P = .03). Conclusion and Clinical Importance CHr added moderate value to the diagnosis of iron deficiency in cats with CKD.
Effects of a Self-Monitoring Quality of Life Intervention in Outpatients with Breast Cancer: A Preliminary Report of A Randomized Controlled Trial

Objective: This preliminary report used data from a randomized controlled clinical trial to investigate the beneficial effects of a self-monitoring quality of life (SMQOL) intervention on communication, medical care and patient outcomes in Japanese women with breast cancer. Methods: This study compared a SMQOL intervention group with a control group that received usual care after 4 months on self-efficacy aspects of patient–physician communication among outpatients with breast cancer in Japan using the Perceived Efficacy in Patient–Physician Interactions (PEPPI) questionnaire. Patients were randomly assigned to the intervention and control groups using permuted-block randomization. The intervention groups were asked to complete a paper-based quality-of-life (QOL) questionnaire in addition to the usual care provided in the control group. Analysis of covariance was used to assess the difference in PEPPI scores between the intervention and control groups. Additionally, subgroup analyses were performed for outpatients with breast cancer accompanied by depression or anxiety. Results: In total, 232 patients were eligible for this study and randomized. Seven patients did not answer the PEPPI questionnaire at baseline after group allocation, leaving 225 patients for inclusion in the analyses. The modified intention-to-treat ITT analysis showed the SMQOL intervention had no significant effect on PEPPI total score (P = 0.226). We found a significant between-group difference in PEPPI total score in the anxiety group (P = 0.045), namely, the self-efficacy aspects of patient–physician communication of those with anxiety in the intervention group were better than for those in the control group after 4 months. Conclusion: Use of the SMQOL had beneficial effects on communication self-efficacy between patients and physicians for outpatients with breast cancer, those with anxiety.