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Left atrial ligation (LAL) of the chick embryonic heart is a model of the hypoplastic left heart syndrome (HLHS) where a purely mechanical intervention without genetic or pharmacological manipulation is employed to initiate cardiac malformation. It is thus a key model for understanding the biomechanical origins of HLHS. However, its myocardial mechanics and subsequent gene expressions are not well-understood. We performed finite element (FE) modeling and single-cell RNA sequencing to address this. 4D high-frequency ultrasound imaging of chick embryonic hearts at HH25 (ED 4.5) were obtained for both LAL and control. Motion tracking was performed to quantify strains. Image-based FE modeling was conducted, using the direction of the smallest strain eigenvector as the orientations of contractions, the Guccione active tension model and a Fung-type transversely isotropic passive stiffness model that was determined via micro-pipette aspiration. Single-cell RNA sequencing of left ventricle (LV) heart tissues was performed for normal and LAL embryos at HH30 (ED 6.5) and differentially expressed genes (DEG) were identified.After LAL, LV thickness increased by 33%, strains in the myofiber direction increased by 42%, while stresses in the myofiber direction decreased by 50%. These were likely related to the reduction in ventricular preload and underloading of the LV due to LAL. RNA-seq data revealed potentially related DEG in myocytes, including mechano-sensing genes (Cadherins, NOTCH1, etc.), myosin contractility genes (MLCK, MLCP, etc.), calcium signaling genes (PI3K, PMCA, etc.), and genes related to fibrosis and fibroelastosis (TGF-β, BMP, etc.). We elucidated the changes to the myocardial biomechanics brought by LAL and the corresponding changes to myocyte gene expressions. These data may be useful in identifying the mechanobiological pathways of HLHS.

Auxin affects all aspects of plant growth and development, including morphogenesis and adaptive responses. Auxin transmembrane transport is promoted by PIN formation (PIN) and a structurally similar PIN-like (PILS) gene family, which jointly controls the directional transport of the auxin between plant cells, and the accumulation of intracellular auxin. At present, there is no study investigating the roles of CslPIN and CslPILS gene family in root development in the tea plant (Camellia sinensis). In this study, 8 CslPIN and 10 CslPILS genes were identified in the tea plant, and their evolutionary relationships, physical and chemical properties, conserved motifs, cis-acting elements, chromosome location, collinearity, and expression characteristics were analyzed. The mechanism of CslPIN and CslPILS in the formation of tea adventitious roots (ARs) was studied by the AR induction system. Through functional verification, the regulation of CslPIN3 gene on root growth and development of tea plant was studied by over-expression of CslPIN3 in Arabidopsis thaliana and in situ hybridization in Camellia sinensis. The results confirmed CslPIN3 was involved in the regulation of root growth and development as well as auxin accumulation. This study provides a better insight into the regulatory mechanism of CslPIN and CslPILS gene family on the formation of AR in tea plant.

Disputes relating to cryptoassets have proliferated in recent years, along with the rise of the cryptoasset market. Some of these can be resolved using traditional principles of contract, tort or trust law, but proprietary issues raise particular conundrums. While cryptoassets have generally been accepted to be property, that is merely the starting point. To properly resolve proprietary disputes, it is necessary to provide a reasoned and robust explanation for why particular rules of title originally developed in the context of tangible property should apply. In turn, two foundational questions must be answered. First, what is the subject-matter of the property right in cryptoassets? And secondly, what is the proprietary effect of a blockchain transaction? These issues have received relatively little attention in the literature, which has focused on whether cryptoassets are property at all, and existing contributions (including the Law Commission's recent Consultation Paper on Digital Assets) which do engage these issues are far from reaching consensus. This paper critically examines those views and puts forward its own reasoned approach for the application of traditional rules of title to cryptoassets.

Drought and low temperature are two key environmental factors that induce adult citrus flowering. However, the underlying regulation mechanism is poorly understood. The bZIP transcription factor FD is a key component of the florigen activation complex (FAC) which is composed of FLOWERING LOCUS T (FT), FD, and 14-3-3 proteins. In this study, isolation and characterization of CiFD in citrus found that there was alternative splicing (AS) of CiFD, forming two different proteins (CiFDα and CiFDβ). Further investigation found that their expression patterns were similar in different tissues of citrus, but the subcellular localization and transcriptional activity were different. Overexpression of the CiFD DNA sequence (CiFD-DNA), CiFDα, or CiFDβ in tobacco and citrus showed early flowering, and CiFD-DNA transgenic plants were the earliest, followed by CiFDβ and CiFDα. Interestingly, CiFDα and CiFDβ were induced by low temperature and drought, respectively. Further analysis showed that CiFDα can form a FAC complex with CiFT, Ci14-3-3, and then bind to the citrus APETALA1 (CiAP1) promoter and promote its expression. However, CiFDβ can directly bind to the CiAP1 promoter independently of CiFT and Ci14-3-3. These results showed that CiFDβ can form a more direct and simplified pathway that is independent of the FAC complex to regulate drought-induced flowering through AS. In addition, a bHLH transcription factor (CibHLH96) binds to CiFD promoter and promotes the expression of CiFD under drought condition. Transgenic analysis found that CibHLH96 can promote flowering in transgenic tobacco. These results suggest that CiFD is involved in drought- and low-temperature-induced citrus flowering through different regulatory patterns.

The work described in this thesis focuses on the development of inhibitors for the Influenza A virus (IAV) by developing multivalent carbohydrate-based ligands (Figure 1). The neuraminidase enzyme (NA) plays an important role in the virus life cycle and the spread of the virus. This makes blocking NA a very promising direction for inhibition of the flu. We designed new compounds that rely on multivalency. By linking our designed monovalent units to di- and tetravalent scaffolds, inhibitors were obtained with a potent inhibitory effect in several assays. Chapter 2, efforts to obtain a suitable ligand to be used in the synthesis of multivalent NA inhibitors are described, based on the goals mentioned above. We modified the oseltamivir carboxylate (OC) mimic 3-pentyl analogue, by extending one branch of the pentyl part. This way the molecule could be conjugated to a spacer in order to explore multivalency effects. In addition to the difficulties associated with the glycosylation step, the preparation of the target ligand involved a number of other synthetic challenges.Chapter 3 benefited from previous work in our group where a new rigid spacer was designed and synthesized. The rigid spacer was designed by replacing two carbohydrate groups with two phenyl groups. However, the introduction of the phenyl groups posed a solubility problem. To solve this problem, we screened building blocks for a better solubility.Chapter 4, we show the successful synthesis and characterization of dimer with 5 different lengths and rigid spacers. We attempted to synthesize the tetramers, which were designed to bind to the four binding sites of the tetrameric NA. Unfortunately, none of the tetramers could be dissolved in normal solvents (organic & water). We therefore focused on divalent ligands. Their syntheses were possible by a combination of chemical scaffold synthesis, glycosylation and CuAAC ‘click’ conjugation. Besides the development of optimal molecular designs to inhibit NA, effective methods to evaluate the inhibition activities are also crucial for the research. Here in Chapter 5, we focused on the evaluation of the mono- and divalent inhibitors that have been described in chapters 2 and 4. Two kinds of the Influenza virus proteins were used: Spain N9 and Wisconsin N1 which derived from the NA gene of H7N9 and H1N1, respectively. The compounds were first tested for their ability to inhibit NA activity using recombinant soluble tetrameric N1 and N9 proteins and the MUNANA substrate. Next, we analyzed the inhibitory activity of the different compounds on virus particles rather than recombinant NA proteins as the source of NA activity. A 4-day CPE assay was set up to assess the ability of the compounds to inhibit virus infection. MDCK cells in a 96- well format was infected with H1N1 virus in the presence of a dilution range of the different compounds, and the lowest concentration of the compounds that could prevent cytopathogenic effects and killing of the cells resulting from virus replication was determined. In this process we also attempted to analyze whether these compounds showed additional HA inhibition using a BLI assay.

At present, high-precision GNSS positioning technology is an important means to monitor the health of bridges and other structures. However, the GNSS signal of reference stations and monitoring stations used for bridge monitoring can easily be blocked by bridge towers, vehicles, or other objects, resulting in low positioning accuracy and insufficient availability of GNSS, which affects the effectiveness of bridge structural health monitoring. Therefore, according to the characteristics of bridge structure, this paper proposes to take the bridge tower monitoring station as a moving-base station to build the baselines with other monitoring stations and use the moving-base RTK-GNSS method to realize the relative positioning, so as to improve the availability of GNSS in the application of bridge structure health monitoring. In this paper, the moving-base RTK-GNSS model is derived and verified via GNSS monitoring data of the Ganzhou dedicated high-speed railway bridge. The results show that the ambiguity in the fixing rate can be improved using the moving-base RTK-GNSS method with the tower monitoring station as the reference station. The deformation and vibration characteristics of each monitoring point can be reflected, and the displacement and vibration amplitude estimation accuracy can achieve results better than 4 mm. Therefore, the moving-base RTK-GNSS method can be used as an alternative scheme when the observation environment of the base station is poor or the banded engineering monitoring is applied, so as to improve the monitoring capability of GNSS.

Macrophage migration inhibitory factor (MIF) is involved in various immune-mediated pathologies and regulates both innate and adaptive immune reactions, thus being related to several acute and chronic inflammatory diseases such as rheumatoid arthritis, septic shock, and atherosclerosis. Its role in acute and chronic brain pathologies, such as stroke and neurodegenerative diseases, has attracted increasing attention in recent years. In response to stimuli like hypoxia, inflammation or infection, different cell types can rapidly release MIF, including immune cells, endothelial cells, and neuron cells. Notably, clinical data from past decades also suggested a possible link between serum MIF levels and the severity of stroke and the evolving of neurodegenerative diseases. In this review, we summarize the major and recent findings focusing on the mechanisms of MIF modulating functions in brain injury and neurodegenerative diseases, which may provide important therapeutic targets meriting further investigation.

The COVID-19 pandemic brought rapid and radical changes to higher education, and academic libraries adapted and devised solutions. This article will review the initiatives that the University of Manitoba Libraries (UML) implemented prior to the pandemic, as well as the library’s response, focusing on the performance of these initiatives in the past two years. These initiatives are new service models including a fully virtual library, new technologies, such as self-service lockers, and structural reorganization, for example, the creation of functional teams. The review will demonstrate how the above initiatives ensured the continuity of library services during the pandemic. The pandemic is viewed as a touchstone that tested the trends of the academic library community in an extreme situation. The success of the library services provided by the UML inspires positive thinking about the forward direction for public research university libraries.

Hepatitis C virus (HCV) is a leading cause of liver cirrhosis and hepatocellular carcinoma globally. Sofosbuvir/velpatasvir (SOF/VEL) is an effective pan-genotypic direct-acting antiviral combination for treatment of chronic HCV infection. While the addition of ribavirin (RBV) to SOF/VEL improved sustained virological response (SVR12) in genotype 3 (GT3) decompensated cirrhosis patients, the benefits of RBV in GT3 compensated cirrhosis patients receiving SOF/VEL remains unclear.To evaluate the efficacy and safety of SOF/VEL, with or without RBV in GT3 compensated cirrhosis patients.We searched four electronic databases (PubMed/Medline, Embase, Cochrane Library and Web of Science) from inception up to June 2021 using both free text and MeSH terms. There was no restriction on language, geography, publication dates and publication status (full text or abstracts). All GT3 compensated cirrhosis patients treated with 12 wk of SOF/VEL, with or without RBV, were included, regardless of age, gender or prior treatment experience. The primary outcome was sustained virological response 12-wk post-treatment (SVR12). The secondary outcome was treatment-related adverse events, as defined by symptomatic anemia requiring transfusion or a drop in hemoglobin beyond 2 g/dL. The pooled relative risk (RR), 95%CI and heterogeneity (From 1752 citations, a total of seven studies (2 randomized controlled trials, 5 cohort studies) with 1088 subjects were identified. The SVR12 was similar in GT3 compensated cirrhosis patients, regardless of the use of RBV, for both the intention-to-treat RR 1.03, 95%CI: 0.99-1.07;Ribavirin was not associated with higher SVR12 in GT3 compensated cirrhosis patients receiving SOF/VEL. Our findings suggest a limited role for RBV as routine add-on therapy to SOF/VEL in GT3 compensated cirrhosis patients.

Distal radius fractures are common and are managed with or without surgery. Current evidence indicates surgical treatment is not superior to nonsurgical treatment at 12 months.Does surgical treatment for displaced distal radius fractures in patients 60 years or older provide better patient-reported wrist pain and function outcomes than nonsurgical treatment at 24 months?In this secondary analysis of a combined multicenter randomized clinical trial (RCT) and a parallel observational study, 300 patients were screened from 19 centers in Australia and New Zealand. Of these, 166 participants were randomized to surgical or nonsurgical treatment. Participants who declined randomization (n = 134) were included in the parallel observational group with the same treatment options and follow-up. Participants were followed up at 3, 12, and 24 months by a blinded assessor. The 24-month outcomes are reported herein. Data were collected from December 1, 2016, to December 31, 2020, and analyzed from February 4 to October 21, 2021.Surgical treatment consisting of open reduction and internal fixation using a volar-locking plate (VLP group) and nonsurgical treatment consisting of closed reduction and cast immobilization (CR group).The primary outcome was patient-reported function using the Patient-Rated Wrist Evaluation (PRWE) questionnaire. Secondary outcomes included health-related quality of life, wrist pain, patient-reported treatment success, patient-rated bother with appearance, and posttreatment complications.Among the 166 randomized and 134 observational participants (300 participants; mean [SD] age, 71.2 [7.5] years; 269 women [89.7%]), 151 (91.0%) randomized and 118 (88.1%) observational participants were followed up at 24 months. In the RCT, no clinically important difference occurred in mean PRWE scores at 24 months (13.6 [95% CI, 9.1-18.1] points for VLP fixation vs 15.8 [95% CI, 11.3-20.2] points for CR; mean difference, 2.1 [95% CI, -4.2 to 8.5]; P = .50). There were no between-group differences in all other outcomes except for patient-reported treatment success, which favored VLP fixation (33 of 74 [44.6%] in the CR group vs 54 of 72 [75.0%] in the VLP fixation group reported very successful treatment; P = .002). Rates of posttreatment complications were generally low and similar between treatment groups, including deep infection (1 of 76 [1.3%] in the CR group vs 0 of 75 in the VLP fixation group) and complex regional pain syndrome (2 of 76 [2.6%] in the CR group vs 1 of 75 [1.3%] in the VLP fixation group). The 24-month trial outcomes were consistent with 12-month outcomes and with outcomes from the observational group.Consistent with previous reports, these findings suggest that VLP fixation may not be superior to CR for displaced distal radius fractures for patient-rated wrist function in persons 60 years or older during a 2-year period. Significantly higher patient-reported treatment success at 2 years in the VLP group may be attributable to other treatment outcomes not captured in this study.ANZCTR.org Identifier: ACTRN12616000969460.

Excessive nitrogen fertilizer application is harmful to the environment and reduces the quality of cereal crops. Maintaining crop yields under low nitrogen (LN) conditions and improving quality are important goals for cereal crop breeding. Although the effects of nitrogen assimilation on crop nitrogen-use efficiency (NUE) have been intensively studied, natural variations of the key assimilation genes underlying grain development and quality are largely unclear. Here, we identified an NUE-associated gene, OsGS1;1, encoding glutamine synthase, through genome-wide association analysis, followed by validation experiments and functional analysis. Fifteen single-nucleotide polymorphisms in the OsGS1;1 region led to alternative splicing that generated two functional transcripts: OsGS1;1a and OsGS1;1b. The elite haplotype of OsGS1;1 showed high OsGS1;1b activity, which improved NUE, affected grain development, and reduced amylose content. The results show that OsGS1;1, which is induced under LN conditions, affects grain formation by regulating sugar metabolism and may provide a new avenue for the breeding of high-yield and high-quality rice (Oryza sativa).

Core–shell nanostructures are widely used, and their photoacoustic (PA) properties are important for applications. However, the relations between their structural parameters and the properties of the PA spectrum are indirect because most theoretical models have been reported for them in the time domain. In this study, we develop a complete model in the frequency domain to analyze the PA response of core–shell particles. As in the case of solid spheres, the core-shell particles have pronounced resonant modes. The PA mode varies with the thickness of the shell and the radius of the core. Under single-pulse irradiation, PA signals of gold–silica nanospheres obtained by our theory agreed with those of the theory in the time domain and experiments. Under multi-pulse irradiation, the magnitude of the PA signals peaked whether the repeated excitation itself or its harmonic was equal to the PA mode. The structure could thus be monitored by the PA signals. These findings enrich PA theory and may inspire new techniques for the noninvasive characterization of nanoparticles.

Background Given the complexity of living donor hepatectomy, it is expected that high hospital volume will better outcomes. This study aims to evaluate post-operative outcomes for living donor hepatectomy in a medium volume liver transplant centre and compare to outcomes in high volume centres. Also, it serves as a validation tool for framework of structure-process-outcome model for safe living donor hepatectomy program. Methods 204 donors who underwent donor hepatectomy between June 1996 to September 2019 were reviewed retrospectively and compared to outcomes in high volume centres. Results At 6 months, overall donor morbidity rate was 20/204 (9.8%). Wound complications were most common at 5/204 (2.5%). Majority of complications were either Clavien grade 1 or 2 and only 3 donors had Clavien grade 3 complications. There was zero donor mortality. Discussion Our centre's donor morbidity rate of 9.8% is the one of the lowest reported in the published literature. With increased experience, stringent donor selection and enhanced perioperative care by a multi-disciplinary team, outcomes in a medium volume centre can match the outcomes reported in high volume centres. The framework for quality in terms of structure, process and outcomes is presented which can be adopted for developing programs.

Aims Antibiotic prophylaxis involving timely administration of appropriately dosed antibiotic is considered effective to reduce the risk of surgical site infection (SSI) after total hip and total knee arthroplasty (THA/TKA). Cephalosporins provide effective prophylaxis, although evidence regarding the optimal timing and dosage of prophylactic antibiotics is inconclusive. The aim of this study is to examine the association between cephalosporin prophylaxis dose, timing, and duration, and the risk of SSI after THA/TKA. Methods A prospective multicentre cohort study was undertaken in consenting adults with osteoarthritis undergoing elective primary TKA/THA at one of 19 high-volume Australian public/private hospitals. Data were collected prior to and for one-year post surgery. Logistic regression was undertaken to explore associations between dose, timing, and duration of cephalosporin prophylaxis and SSI. Data were analyzed for 1,838 participants. There were 264 SSI comprising 63 deep SSI (defined as requiring intravenous antibiotics, readmission, or reoperation) and 161 superficial SSI (defined as requiring oral antibiotics) experienced by 249 (13.6%) participants within 365 days of surgery. Results In adjusted modelling, factors associated with a significant reduction in any SSI and deep SSI included: correct weight-adjusted dose (any SSI; adjusted odds ratio (aOR) 0.68 (95% confidence interval (CI) 0.47 to 0.99); p = 0.045); commencing preoperative cephalosporin within 60 minutes (any SSI, aOR 0.56 (95% CI 0.36 to 0.89); p = 0.012; deep SSI, aOR 0.29 (95% CI 0.15 to 0.59); p < 0.001) or 60 minutes or longer prior to skin incision (aOR 0.35 (95% CI 0.17 to 0.70); p = 0.004; deep SSI, AOR 0.27 (95% CI 0.09 to 0.83); p = 0.022), compared to at or after skin incision. Other factors significantly associated with an increased risk of any SSI, but not deep SSI alone, were receiving a non-cephalosporin antibiotic preoperatively (aOR 1.35 (95% CI 1.01 to 1.81); p = 0.044) and changing cephalosporin dose (aOR 1.76 (95% CI 1.22 to 2.57); p = 0.002). There was no difference in risk of any or deep SSI between the duration of prophylaxis less than or in excess of 24 hours. Conclusion Ensuring adequate, weight-adjusted dosing and early, preoperative delivery of prophylactic antibiotics may reduce the risk of SSI in THA/TKA, whereas the duration of prophylaxis beyond 24 hours is unnecessary. Cite this article: Bone Jt Open 2022;3(3):252–260.

Tea (Camellia sinensis) is one of the significant cash crops in China. As a leaf crop, nitrogen supply can not only increase the number of new shoots and leaves but also improve the tenderness of the former. However, a conundrum remains in science, which is the molecular mechanism of nitrogen use efficiency, especially long non-coding RNA (lncRNA). In this study, a total of 16,452 lncRNAs were identified through high-throughput sequencing analysis of lateral roots under nitrogen stress and control conditions, of which 9,451 were differentially expressed lncRNAs (DE-lncRNAs). To figure out the potential function of nitrogen-responsive lncRNAs, co-expression clustering was employed between lncRNAs and coding genes. KEGG enrichment analysis revealed nitrogen-responsive lncRNAs may involve in many biological processes such as plant hormone signal transduction, nitrogen metabolism and protein processing in endoplasmic reticulum. The expression abundance of 12 DE-lncRNAs were further verified by RT-PCR, and their expression trends were consistent with the results of RNA-seq. This study expands the research on lncRNAs in tea plants, provides a novel perspective for the potential regulation of lncRNAs on nitrogen stress, and valuable resources for further improving the nitrogen use efficiency of tea plants.

Background: The chemotherapeutic doxorubicin (DOX) promotes severe skeletal muscle atrophy, which induces skeletal muscle weakness and fatigue. Soluble guanylate cyclase (sGC) contributes to a variety of pathophysiological processes, but whether it is involved in DOX-induced skeletal muscle atrophy is unclear. The present study aimed to stimulate sGC by vericiguat, a new oral sGC stimulator, to test its role in this process.Methods: Mice were randomly divided into four groups: control group, vericiguat group, DOX group, and DOX + vericiguat group. Exercise capacity was evaluated before the mice were sacrificed. Skeletal muscle atrophy was assessed by histopathological and molecular biological methods. Protein synthesis and degradation were monitored in mice and C2C12 cells.Results: In this study, a significant decrease in exercise capacity and cross-sectional area (CSA) of skeletal muscle fibers was found in mice following DOX treatment. Furthermore, DOX decreased sGC activity in mice and C2C12 cells, and a positive correlation was found between sGC activity and CSA of skeletal muscle fibers in skeletal muscle. DOX treatment also impaired protein synthesis, shown by puromycin detection, and activated ubiquitin-proteasome pathway. Following sGC stimulation, the CSA of muscle fibers was elevated, and exercise capacity was enhanced. Stimulation of sGC also increased protein synthesis and decreased ubiquitin-proteasome pathway. In terms of the underlying mechanisms, AKT/mTOR and FoxO1 pathways were impaired following DOX treatment, and stimulation of sGC restored the blunted pathways.Conclusion: These results unravel sGC stimulation can improve skeletal muscle atrophy and increase the exercise capacity of mice in response to DOX treatment by enhancing protein synthesis and inhibiting protein degradation. Stimulation of sGC may be a potential treatment of DOX-induced skeletal muscle dysfunction.

Using a deep learning algorithm in the development of a computer-aided system for colon polyp detection is effective in reducing the miss rate. This study aimed to develop a system for colon polyp detection and classification. We used a data augmentation technique and conditional GAN to generate polyp images for YOLO training to improve the polyp detection ability. After testing the model five times, a model with 300 GANs (GAN 300) achieved the highest average precision (AP) of 54.60% for SSA and 75.41% for TA. These results were better than those of the data augmentation method, which showed AP of 53.56% for SSA and 72.55% for TA. The AP, mAP, and IoU for the 300 GAN model for the HP were 80.97%, 70.07%, and 57.24%, and the data increased in comparison with the data augmentation technique by 76.98%, 67.70%, and 55.26%, respectively. We also used Gaussian blurring to simulate the blurred images during colonoscopy and then applied DeblurGAN-v2 to deblur the images. Further, we trained the dataset using YOLO to classify polyps. After using DeblurGAN-v2, the mAP increased from 25.64% to 30.74%. This method effectively improved the accuracy of polyp detection and classification.

Purpose Methods and materials Results Conclusion Personal information and conflict of interest References, Purpose: This study aimed to explore alterations in brain surface-based morphometry sulcal depth in patients with idiopathic tinnitus before and after 24 weeks of sound therapy. As one of the quantitative measures of the cerebral cortex, sulcal depth has...

Purpose Methods and materials Results Conclusion Personal information and conflict of interest References, Purpose: The iron accumulation in the brains of people with Parkinson's disease (PD) is presumed to be correlated with freezing of gait (FOG).To explore the changes of iron deposition in the brain of Parkinson's patients and its correlation with freezing...

This study aims to investigate how exercise-induced myocardial hypertrophy preconditioning affects cardiac fibroblasts in the context of myocardial fibrosis, a chronic disease that can cause cardiac arrhythmia and heart failure. Heart failure was induced in male C57BL/6 mice via Transverse aortic constriction, and some mice were given swimming exercise before surgery to test the effects of exercise-induced myocardial hypertrophy preconditioning on myocardial fibrosis. Myocardial tissue was evaluated for fibrosis, senescent cells, and apoptotic cells. Myocardial fibroblasts from rats were cultured and treated with norepinephrine to induce fibrosis which were then treated with si-Nrf2 and analyzed for markers of fibrosis, senescence, apoptosis, and cell proliferation. Exercise-induced myocardial hypertrophy preconditioning reduced myocardial fibrosis in mice, as shown by decreased mRNA expression levels of fibrosis-related indicators and increased cell senescence. In vitro data indicated that norepinephrine (NE) treatment increased fibrosis-related markers and reduced apoptotic and senescent cells, and this effect was reversed by pre-conditioning in PRE+NE group. Preconditioning activated Nrf2 and downstream signaling genes, promoting premature senescence in cardiac fibroblasts and tissues isolated from preconditioned mice. Moreover, Nrf2 knockdown reversed proapoptotic effects, restored cell proliferation, reduced senescence-related protein expression, and increased oxidative stress markers and fibrosis-related genes, indicating Nrf2‘s crucial role in regulating oxidative stress response of cardiac fibroblasts. Exercise-induced myocardial hypertrophy preconditioning improves myocardial fibrosis which is Nrf2-dependent, indicating the protective effect of hypertrophy preconditioning. These findings may contribute to the development of therapeutic interventions to prevent or treat myocardial fibrosis.

We examine how AI deployment influences people's bias-correcting behavior in hiring context.

Purpose Methods and materials Results Conclusion Personal information and conflict of interest References, Purpose: This study aimed to evaluate the microstructural alterations of white matter fiber tracts by using high angular resolution diffusion imaging (HARDI) in patients with Parkinson’s Disease (PD), and to explore the correlations between mean fractional...

Here we develop a new scheme of projective quantum Monte-Carlo (QMC) simulation combining unbiased zero-temperature (projective) determinant QMC and variational Monte-Carlo based on Gutzwiller projection wave function, dubbed as ``Gutzwiller projection QMC''. The numerical results demonstrate that employment of Gutzwiller projection trial wave function with minimum energy strongly speed up the convergence of computational results, thus tremendously reducing computational time in the simulation. More remarkably, we present an example that sign problem is enormously alleviated in the Gutzwiller projection QMC, especially in the regime where sign problem is severe. Hence, we believe that Gutzwiller projection QMC paves a new route to improving the efficiency, and alleviating sign problem in QMC simulation on interacting fermionic systems., Comment: 5 pages, 4 figures

The complicated interactions between genetic background, environment and lifestyle factors make it difficult to study the genetic basis of complex phenotypes, such as cognition and anxiety levels, in humans. However, environmental and other factors can be tightly controlled in mouse studies. The Collaborative Cross (CC) is a mouse genetic reference population whose common genetic and phenotypic diversity is on par with that of humans. Therefore, we leveraged the power of the CC to assess 52 behavioral measures associated with locomotor activity, anxiety level, learning and memory. This is the first application of the CC in novel object recognition tests, Morris water maze tasks, and fear conditioning tests. We found substantial continuous behavioral variations across the CC strains tested, and mapped six quantitative trait loci (QTLs) which influenced these traits, defining candidate genetic variants underlying these QTLs. Overall, our findings highlight the potential of the CC population in behavioral genetic research, while the identified genomic loci and genes driving the variation of relevant behavioral traits provide a foundation for further studies.

Root development and plasticity are assessed via diverse endogenous and environmental cues, including phytohormones, nutrition, and stress. In this study, we observed that roots in model plant Arabidopsis thaliana exhibited waving and oscillating phenotypes under normal conditions but lost this pattern when subjected to alkaline stress. We later showed that alkaline treatment disturbed the auxin gradient in roots and increased auxin signal in columella cells. We further demonstrated that the auxin efflux transporter PIN-FORMED 7 (PIN7) but not PIN3 was translocated to vacuole lumen under alkaline stress. This process is essential for root response to alkaline stress because the pin7 knockout mutants retained the root waving phenotype. Moreover, we provided evidence that the PIN7 vacuolar transport might not depend on the ARF-GEFs but required the proper function of an ESCRT subunit known as FYVE domain protein required for endosomal sorting 1 (FREE1). Induced silencing of FREE1 disrupted the vacuolar transport of PIN7 and reduced sensitivity to alkaline stress, further highlighting the importance of this cellular process. In conclusion, our work reveals a new role of PIN7 in regulating root morphology under alkaline stress.

Membrane properties are emerging as important cues for the spatiotemporal regulation of hormone signaling. Lysophosphatidic acid (LPA) evokes multiple biological responses by activating G protein–coupled receptors in mammals. In this study, we demonstrated that LPA derived from the mitochondrial glycerol-3-phosphate acyltransferases GPAT1 and GPAT2 is a critical lipid-based cue for auxin-controlled embryogenesis and plant growth in Arabidopsis thaliana . LPA levels decreased, and the polarity of the auxin efflux carrier PIN-FORMED1 (PIN1) at the plasma membrane (PM) was defective in the gpat1 gpat2 mutant. As a consequence of distribution defects, instructive auxin gradients and embryonic and postembryonic development are severely compromised. Further cellular and genetic analyses revealed that LPA binds directly to PIN1, facilitating the vesicular trafficking of PIN1 and polar auxin transport. Our data support a model in which LPA provides a lipid landmark that specifies membrane identity and cell polarity, revealing an unrecognized aspect of phospholipid patterns connecting hormone signaling with development.

Chronic inflammation of bone tissue often results in bone defects and hazards to tissue repair and regeneration. Cannabidiol (CBD) is a natural cannabinoid with multiple biological activities, including anti-inflammatory and osteogenic potential. This study aimed to investigate the efficacy and mechanisms of CBD in the promotion of bone marrow mesenchymal stem cells (BMSCs) osteogenic differentiation in the inflammatory microenvironment.BMSCs isolated from C57BL/6 mice, expressed stem cell characteristic surface markers and presented multidirectional differentiation potential. The CCK-8 assay was applied to evaluate the effects of CBD on BMSCs' vitality, and demonstrating the safety of CBD on BMSCs. Then, BMSCs were stimulated with lipopolysaccharide (LPS) to induce inflammatory microenvironment. We found that CBD intervention down-regulated mRNA expression levels of inflammatory cytokines and promoted cells proliferation in LPS-treated BMSCs, also reversed the protein and mRNA levels downregulation of osteogenic markers caused by LPS treatment. Moreover, CBD intervention activated the cannabinoid receptor 2 (CB2) and the p38 mitogen-activated protein kinase (MAPK) signaling pathway. While AM630, a selective CB2 inhibitor, reduced phosphorylated (p)-p38 levels. In addition, AM630 and SB530689, a selective p38 MAPK inhibitor, attenuated the enhancement of osteogenic markers expression levels by CBD in inflammatory microenvironment, respectively.CBD promoted osteogenic differentiation of BMSCs via the CB2/p38 MAPK signaling pathway in the inflammatory microenvironment.

Introduction Pharmacy students should be eHealth literate by being skilful in searching, evaluating and applying online health information. Mobile health applications should be utilised when making clinical decisions to achieve optimal patient care with the ever-changing pharmacy practice. This study aims to explore the eHealth literacy and mobile health application utilisation amongst pharmacy undergraduates. Methods A cross-sectional study was conducted from March to April 2021. An online survey, consisting of socio-demographic characteristics, Internet use, eHealth Literacy Scale and mobile health application utilisation, was distributed amongst pharmacy undergraduates in public and private universities in Malaysia. Data analysis included descriptive statistics, one-way analysis of variance test, Mann–Whitney U test and Kruskal–Wallis test Results A total of 415 participants completed the survey (response rate = 82.5%). The median eHealth Literacy Scale score (out of 40) was 31.0 ± 3.0 (interquartile range). More than one-third of participants (34.7%) were found to have low eHealth literacy. Many lacked confidence in making health decisions from online information (42.4%) and skills in distinguishing between high-quality and low-quality health resources (35.2%). Only 70.4% of the participants had mobile health applications installed on their smartphones and/or tablets. Some students felt that they were neither knowledgeable nor skilful enough to utilise mobile health applications (24.8%), whereas 23.9% were unaware of the mobile health applications available. Conclusion In summary, the eHealth literacy of Malaysian pharmacy students can be further enhanced by incorporating eHealth literacy-focused programmes into the curriculum. Moreover, pharmacy students’ mobile health application utilisation can be improved through increased awareness and support from universities.

Crown roots (CRs) are major components of the rice root system. They form at the basal node of the shoot, and their development is greatly influenced by environmental factors. Ammonium nitrogen is known to impact plant root development through ammonium transporters (AMTs), but it remains unclear whether ammonium and AMTs play roles in rice CR formation. In this study, we revealed a significant role of ammonium, rather than nitrate, in regulating rice CR development. High ammonium supply increases CR formation but inhibits CR elongation. Genetic evidence showed that ammonium regulation of CR development relies on ammonium uptake mediated jointly by ammonium transporters OsAMT1;1, OsAMT1;2; OsAMT1;3, and OsAMT2;1, but not on root acidification which was the result of ammonium uptake. OsAMTs are also needed for glutamine-induced CR formation. Furthermore, we showed that polar auxin transport dependent on the PIN auxin efflux carriers acts downstream of ammonium uptake and assimilation to activate local auxin signaling at CR primordia, in turn promoting CR formation. Taken together, our results highlight a critical role for OsAMTs in cooperatively regulating CR formation through regulating auxin transport under nitrogen-rich conditions.

This study was conducted to synthesize bi-component ZrO2/Ag nanotubes through anodization and photoreduction methods. The synthesized nanotubes were characterized and adsorption tests were carried out to evaluate its performance in removing heavy metal, lead (II). ZrO2 nanotubes were synthesized by anodizing zirconium foil in an electrolyte composed of glycerol, ammonium fluoride, formamide, and distilled water. The effect of anodizing time and the annealing process on the morphology of synthesized nanotubes were studied. Bi-component ZrO2/Ag nanotubes were prepared through photochemical reduction which silver precursor solution undergoes Ultraviolet (UV) irradiation in the presence of the active reducing agent. Larger pore diameter and longer length of synthesized nanotubes were formed at the longer anodizing time and the walls of nanotubes were smoother without annealing. The effect of the initial heavy metal concentration and contact time on the adsorption efficiency of synthesized nanotubes was evaluated using lead (II) as the heavy metal ions. Overall, the percentage removal of lead (II) increased with longer adsorption time and higher initial concentration of the lead (II) ions.

International audience; Although workplace incivility has received increasing attention in organizational research over the past two decades, there have been recurring questions about its construct validity, especially vis-à-vis other forms of workplace mistreatment. Also, the antecedents of experienced incivility remain understudied, leaving an incomplete understanding of its nomological network. In this meta-analysis using Schmidt and Hunter's [Methods of meta-analysis: Correcting error and bias in research findings (3rd ed.), Sage] random-effect meta-analytic methods, we validate the construct of incivility by testing its reliability, convergent and discriminant validity, as well as its incremental predictive validity over other forms of mistreatment. We also extend its nomological network by drawing on the perpetrator predation framework to systematically study the antecedents of experienced incivility. Based on 105 independent samples and 51,008 participants, we find extensive support for incivility's construct validity. Besides, we demonstrate that demographic characteristics (gender, race, rank, and tenure), personality traits (agreeableness, conscientiousness, neuroticism, negative affectivity, and self-esteem), and contextual factors (perceived uncivil climate and socially supportive climate) are important antecedents of experienced incivility, with contextual factors displaying a stronger association with incivility. In a supplementary primary study with 457 participants, we find further support for the construct validity of incivility. We discuss the theoretical and practical implications of this study. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

As an emerging weakly supervised learning framework, partial label learning considers inaccurate supervision where each training example is associated with multiple candidate labels among which only one is valid. In this article, a first attempt toward employing dimensionality reduction to help improve the generalization performance of partial label learning system is investigated. Specifically, the popular linear discriminant analysis (LDA) techniques are endowed with the ability of dealing with partial label training examples. To tackle the challenge of unknown ground-truth labeling information, a novel learning approach named Delin is proposed which alternates between LDA dimensionality reduction and candidate label disambiguation based on estimated labeling confidences over candidate labels. On one hand, the (kernelized) projection matrix of LDA is optimized by utilizing disambiguation-guided labeling confidences. On the other hand, the labeling confidences are disambiguated by resorting to k NN aggregation in the LDA-induced feature space. Extensive experiments over a broad range of partial label datasets clearly validate the effectiveness of Delin in improving the generalization performance of well-established partial label learning algorithms.

– Although the International Court of Justice is the principal judicial organ of the United Nations and is often tasked to resolve inter-state disputes concerning a wide array of subject matter, neither its rules nor jurisprudence readily disclose any consistent or even clear approach on the issue of standard of proof. We make the case that a tiered approach to standard of proof can and should be adopted, and in doing so, identify the various factors that may be relevant in understanding the court’s different positions in different situations.

Providing group study rooms is an important service offered by a university library to support learning and collaboration. A good room booking system should be convenient for students to use and would require a minimum involvement of library staff regarding managing bookings and keys. This article studied the implementation of the Juno Secure Room Booking system at the library to replace LibCal, which is a popular room booking system used by a large number of university libraries in North America. This article discussed the advantages that the Juno system has compared to LibCal, the design of an online booking website using the Juno Application Programming Interface (API), and the enhancement the library designed and developed based on student feedback. This article also discussed how the library successfully engaged a college to use this system to manage study rooms for classes and exams.

Brain-derived neurotrophic factor (BDNF) regulates neuronal plasticity by targeting the tyrosine kinase B receptor (TrkB) receptor, but limited researches concentrate on the role of BDNF/TrkB signaling in vestibular compensation. In this study, rats with unilateral vestibular dysfunction were established by unilateral labyrinthectomy (UL) and infusion with siBDNF or 7, 8-Dihydroxyflavone (7,8-DHF, a TrkB receptor agonist). The behavioral scores of rats with vestibular deficits were determined and the rotarod test was performed after UL. BDNF and TrkB levels after UL were determined by western blot and quantitative reverse transcription PCR (qRT-PCR). 5-bromo-2ʹ-deoxyuridine (BrdU)-positive cells (newly generated cells) and GAD67-positive cells (GABAergic neurons) were identified by immunohistochemistry. Glial fibrillary acidic protein (GFAP) (astrocyte marker)-positive cells were identified and GABA type A receptor (GABAAR) expression was detected by immunofluorescence. We found that after UL, BDNF and TrkB levels were up-regulated with a maximum value at 4 h, and then progressively down-regulated during 4 h ~ 7 d. Blocking BDNF/TrkB signaling inhibited the recovery from vestibular deficits, decreased the numbers of newly generated cells and astrocytes in medial vestibular nucleus (MVN), inferior vestibular nerve (IVN), superior vestibular nerve (SVN) and lateral vestibular nucleus (LVN), and disrupted the balances of GABAergic neurons and GABAAR expressions in the left (lesioned) side and right (intact) side of MVN, whereas activation of BDNF/TrkB signaling caused opposite results. The current study indicated that BDNF/TrkB signaling avails vestibular compensation, depending on the number of newly generated cells and astrocytes, the rebalance of GABAergic neurons, and GABAAR expression in bilateral MVN.

Rhizosphere microorganisms interact with plant roots by producing chemical signals that regulate root development. However, the distinct bioactive compounds and signal transduction pathways remain to be identified. Here, we showed that sesquiterpenes are the main volatile compounds produced by plant-beneficial Trichoderma guizhouense NJAU4742. Inhibition of sesquiterpene biosynthesis eliminated the promoting effect of this strain on root growth, indicating its involvement in plant-fungus cross-kingdom signalling. Sesquiterpene component analysis identified cedrene, a highly abundant sesquiterpene in strain NJAU4742, to stimulate plant growth and root development. Genetic analysis and auxin transport inhibition showed that the TIR1 and AFB2 auxin receptors, IAA14 auxin-responsive protein, and ARF7 and ARF19 transcription factors affected the response of lateral roots to cedrene. Moreover, the AUX1 auxin influx carrier and PIN2 efflux carrier were also found to be indispensable for cedrene-induced lateral root formation. Confocal imaging showed that cedrene affected the expression of pPIN2:PIN2:GFP and pPIN3:PIN3:GFP, which might be related to the effect of cedrene on root morphology. These results suggested that a novel sesquiterpene molecule from plant-beneficial T. guizhouense regulates plant root development through the transport and signalling of auxin.

Aims To evaluate whether biomarkers derived from fluorodeoxyglucose positron emission tomography-computed tomography (FDG PET-CT) performed prior to (prePET) and during the third week (interim PET; iPET) of radiotherapy can predict treatment outcomes in human papillomavirus (HPV)-positive oropharyngeal squamous cell carcinoma (OPC). Materials and methods This retrospective analysis included 46 patients with newly diagnosed OPC treated with definitive (chemo)radiation and all patients had confirmed positive HPV status (HPV+OPC) based on p16 immunohistochemistry. The maximum standardised uptake value (SUVmax), metabolic tumour volume (MTV) and total lesional glycolysis (TLG) of primary, index node (node with the highest TLG) and total lymph nodes and their median percentage (≥50%) reductions in iPET were analysed, and correlated with 5-year Kaplan–Meier and multivariable analyses (smoking, T4, N2b-3 and AJCC stage IV), including local failure-free survival, regional failure-free survival, locoregional failure-free survival (LRFFS), distant metastatic failure-free survival (DMFFS), disease-free survival (DFS) and overall survival. Results There was no association of outcomes with prePET parameters observed on multivariate analysis. A complete metabolic response of primary tumour was seen in 13 patients; the negative predictive value for local failure was 100%. More than a 50% reduction in total nodal MTV provided the best predictor of outcomes, including LRFFS (88% versus 47.1%, P = 0.006, hazard ratio = 0.153) and DFS (78.2% versus 41.2%, P = 0.01, hazard ratio = 0.234). More than a 50% reduction in index node TLG was inversely related to DMFFS: a better nodal response was associated with a higher incidence of distant metastatic failure (66.7% versus 100%, P = 0.009, hazard ratio = 3.0). Conclusion The reduction (≥50%) of volumetric nodal metabolic burden can potentially identify a subgroup of HPV+OPC patients at low risk of locoregional failure but inversely at higher risk of distant metastatic failure and may have a role in individualised adaptive radiotherapy and systemic therapy.