Search

Exercise generates a site-specific increase in Reactive Oxygen Species (ROS) within muscle required for a beneficial adaptive response by activation of specific signalling pathways. Here, we demonstrate that Peroxiredoxin 2 (Prdx2), an abundant cytoplasmic 2-Cys peroxiredoxin, is required for the adaptive beneficial hormesis response to H2O2. A short bolus addition of H2O2increases mitochondrial capacity and improves myogenesis of cultured myoblasts, this beneficial adaptive response was suppressed in myoblasts with decreased expression of cytoplasmic Prdxs. A swimming exercise protocol inC. elegansincreased mitochondrial content, fitness, survival and longevity in wild type (N2) worms. In contrast,prdx-2mutant worms had decreased fitness, disrupted mitochondria, reduced survival and lifespan following exercise. Global proteomics following exercise identified distinct changes in the proteome of N2 andprdx-2mutants. Furthermore, a redox proteomic approach to quantify reversible oxidation of individual Cysteine residues revealed a relatively more oxidised redox state following exercise in theprdx-2mutants. Our results demonstrate that conserved cytoplasmic 2-Cys Peroxiredoxins are required for the beneficial adaptive response to a physiological stress.

Background The purpose of this study was to evaluate glycemic control in type 2 diabetes mellitus (T2DM) patients with coronary artery disease in China, as well as to look into therapeutic inertia among cardiologists. Methods From June 2021 to December 2021, a descriptive cross-sectional study was conducted in the Department of Cardiology at Shanghai Ruijin Hospital in China. The method of convenience sampling was used. Patients with coronary artery disease (including acute and chronic coronary syndrome) and T2DM were included in the study. Patients with renal insufficiency (eGFR 2), heart failure (left ventricular ejection fraction, LVEF

Convolutional neural networks (CNN) based object detection usually assumes that training and test data have the same distribution, which, however, does not always hold in real-world applications. In autonomous vehicles, the driving scene (target domain) consists of unconstrained road environments which cannot all possibly be observed in training data (source domain) and this will lead to a sharp drop in the accuracy of the detector. In this paper, we propose a domain adaptation framework based on pseudo-labels to solve the domain shift. First, the pseudo-labels of the target domain images are generated by the baseline detector (BD) and optimized by our data optimization module to correct the errors. Then, the hard samples in a single image are labeled based on the optimization results of pseudo-labels. The adaptive sampling module is approached to sample target domain data according to the number of hard samples per image to select more effective data. Finally, a modified knowledge distillation loss is applied in the retraining module, and we investigate two ways of assigning soft-labels to the training examples from the target domain to retrain the detector. We evaluate the average precision of our approach in various source/target domain pairs and demonstrate that the framework improves over 10% average precision of BD on multiple domain adaptation scenarios on the Cityscapes, KITTI, and Apollo datasets.

Background During cataract phacoemulsification surgery, an Intrepid® balanced (IB) tip can achieve a larger amplitude, which may lead to higher energy efficiency than a Kelman (K) tip when paired with a torsional phaco platform. In this retrospective cohort study, we compared their energy efficiency and damage to the cornea under a new energy setting. Methods The medical records of 104 eyes of 79 patients were reviewed, with 47 eyes belonging to the IB group and 57 eyes belonging to the K group. All surgeries were performed on an Alcon Centurion® platform with gravity infiltration. Surgical parameters, visual outcome, central corneal thickness (CCT) changes, and endothelial cell density (ECD) loss rate were recorded and calculated. Results No significant differences in postoperative best corrected visual acuity (BCVA), intraocular pressure (IOP), total ultrasound time, estimated fluid aspirated, CCT changes, or ECD loss rate were observed between the two groups. We divided the included eyes into soft nucleus and hard nucleus subgroups and found lower cumulative dissipated energy (CDE, 8.15 ± 8.02 vs 14.82 ± 14.16, P = 0.023), cumulative torsional energy (CTE, 8.06 ± 7.87 vs 14.13 ± 13.02, P = 0.027), and cumulative longitudinal energy (CLE, 0.09 ± 0.17 vs 0.69 ± 1.37, P = 0.017) in the IB group than in the K group, implying less energy used and higher energy efficiency of the IB tip. Conclusion Lower CLE in the IB group indicates fewer phaco tip obstructions and a significantly higher capability to conquer hard nuclei with IB tips with statistical significance. With an ultra-perfusion cannula, the balanced tip does not cause more corneal damage.

Sepsis is a global disease burden, and approximately 40% of cases develop acute lung injury (ALI). Bone marrow mesenchymal stromal cells (BMSCs) and their exosomes are widely used in treating a variety of diseases including sepsis. As an acute phase protein, serum amyloid A1 (SAA1) regulates inflammation and immunity. However, the role of SAA1 in BMSCs-exosomes in septic lung injury remains to be elucidated. Exosomes derived from serum and BMSCs were isolated by ultracentrifugation. SAA1 was silenced or overexpressed in mouse BMSCs using lentiviral plasmids, containing either SAA1-targeting short interfering RNAs or SAA1 cDNA. Sepsis was induced by cecal ligation and puncture (CLP). LPS was used to induce ALI in mice. Mouse alveolar macrophages were isolated by flow cytometry. Levels of SAA1, endotoxin, TNF-α, and IL-6 were measured using commercial kits. LPS internalization was monitored by immunostaining. RT-qPCR or immunoblots were performed to test gene and protein expressions. Serum exosomes of patients with sepsis-induced lung injury had significantly higher levels of SAA1, endotoxin, TNF-α, and IL-6. Overexpression of SAA1 in BMSCs inhibited CLP- or LPS-induced lung injury and decreased CLP- or LPS-induced endotoxin, TNF-α, and IL-6 levels. Administration of the SAA1 blocking peptide was found to partially inhibit SAA1-induced LPS internalization by mouse alveolar macrophages and reverse the protective effect of SAA1. In conclusion, BMSCs inhibit sepsis-induced lung injury through exosomal SAA1. These results highlight the importance of BMSCs, exosomes, and SAA1, which may provide novel directions for the treatment of septic lung injury.

G-quadruplexes (G4s) are important in regulating DNA replication, repair and RNA transcription through interactions with specialized proteins. Dbp2 has been identified as a G4 DNA binding protein from Saccharomyces cerevisiae cell lysates. The majority of G4 motifs in Saccharomyces cerevisiae display 5-50 nt loops, only a few have 1-2 nt loops. Human DDX5 could unfold MycG4 DNA, whether Dbp2 also participates in remodeling G4 motifs with short loops in Saccharomyces cerevisiae remains elusive. Here we find that Dbp2 prefers G-rich substrates and binds MycG4 with a high affinity. Dbp2 possesses a dual function for different conformations of MycG4, destabilizing the folded MycG4 and inducing further folding of the unfolded MycG4. Similarly, DDX5 can unfold MycG4, but it exhibits a weaker MycG4 folding-promoting activity relative to Dbp2. Furthermore, Dbp2 facilitates DNA annealing activity in the absence of ATP, suggesting that Dbp2 can work on DNA substrates and possibly participate in DNA metabolism. Our results demonstrate that Dbp2 plays an important role in regulating the folding and unfolding activities of MycG4.

With the advancement of single-cell sequencing technology in recent years, an increasing number of researchers have turned their attention to the study of cell heterogeneity. In this study, we created a fish single-cell transcriptome database centered on zebrafish (Danio rerio). FishSCT currently contains single-cell transcriptomic data on zebrafish and 8 other fish species. We used a unified pipeline to analyze 129 datasets from 44 projects from SRA and GEO, resulting in 964/26,965 marker/potential marker information for 245 cell types, as well as expression profiles at single-cell resolution. There are 117 zebrafish datasets in total, covering 25 different types of tissues/organs at 36 different time points during the growth and development stages. This is currently the largest and most comprehensive online resource for zebrafish single-cell transcriptome data, as well as the only database dedicated to the collection of marker gene information of specific cell type and expression profiles at single-cell resolution for a variety of fish. A user-friendly web interface for information browsing, cell type identification, and expression profile visualization has been developed to meet the basic demand in related studies on fish transcriptome at the single-cell resolution.

Expansion microscopy allows super resolution imaging of cellular structures by fluorescence microscopy. However, current protocols achieving large expansion factors (near 8 and beyond), are only applicable to cultured cells and thin tissue slices, but not to bulk tissue in general. Here, we present a method that allows unlimited cycles of expansion of bulk tissue with high isotropy, which we term as Cyc-ExM. The protocol uses identical gel recipe and denaturation reagents in each expansion cycle, which provides ease to the procedure. Cyc-ExM expands biological tissues ~9 fold in each dimension from 7 cycles of expansion and 17-27 fold from 10 cycles. The covalent staining procedure was also optimized to reveal ultrastructural features. Besides, Cyc-ExM is compatible with antibody labeling and multi-scale 3D imaging. Despite volume dilution of signal during expansion, we developed a signal amplification method achieving 8-fold increase in signal, which greatly facilitates the resolution of sub-organelle structures within various tissues.

Two-dimensional (2D) metal-organic framework nanosheets (MONs) or membranes are classes of periodic, crystalline polymeric materials that may show unprecedented physicochemical properties due to their modular structures, high surface areas, and high aspect ratios. Yet preparing 2D MONs from multiple components and two different types of polymerization reaction remains challenging and less explored. Here, we report the synthesis of MOF films via interfacial polymerization, which involves three active monomers for simultaneous polycondensation and polycoordination taking place in a confined interface. The well-defined lamellar structure of the MOF films allowed feasible and scalable exfoliation to produce free-standing 2D MONs with high aspect ratio up to 2000:1 and ultrathin thickness (∼1.7 nm). The pore structure was revealed by high-resolution TEM images with near-atomic precision. The imide-linkage of MONs provided superior thermal (up to 530 °C) and good chemical stability in the pH range from 3 to 12. More importantly, the MONs exhibited exceptional catalytic activity and superior reusability for the hydroboration reactions of alkynes, in which the turnover frequency (TOF) reached 41734 h

A high-quality baseline transcriptome is a valuable resource for developmental research as well as a useful reference for other studies. We gathered 41 samples representing 11 tissues/organs from 22 important developmental time points within 197 days of fertilization of grass carp eggs in order to systematically examine the role of lncRNAs and alternative splicing in fish development. We created a high-quality grass carp baseline transcriptome with a completeness of up to 93.98 percent by combining strand-specific RNA sequencing and single-molecule real-time RNA sequencing technologies, and we obtained temporal expression profiles of 33,055 genes and 77,582 transcripts during development and tissue differentiation. A family of short interspersed elements was preferentially expressed at the early stage of zygotic activation in grass carp, and its possible regulatory components were discovered through analysis. Additionally, after thoroughly analyzing alternative splicing events, we discovered that retained intron (RI) alternative splicing events change significantly in both zygotic activation and tissue differentiation. During zygotic activation, we also revealed the precise regulatory characteristics of the underlying functional RI events.

The strategic position of the core area of the Huaihai Economic Zone is very important. The evaluation and analysis of the listed companies’ innovation ability in this core area effectively reflect the level of innovation ability of regional enterprises and uncover the differences and influencing factors of the enterprise innovation ability level across different cities and industries; this would provide a reference for further improving the enterprise innovation ability level in the Huaihai Economic Zone. Given this context, data are collected from the CSMAR database on 37 listed companies in eight cities in the Huaihai Economic Zone core area from 2017 to 2021, and an innovation ability evaluation index is constructed from the innovation input and innovation output dimensions of listed companies. The results show that the innovation ability of listed companies in the region is weak; the main reason for the lack of innovation ability of listed companies is the lack of capital investment and talent investment; the innovation primacy of Xuzhou listed enterprises is not high. Finally, in view of the improvement of the innovation ability of listed enterprises in the core field, corresponding suggestions are put forward from the aspects of increasing innovation investment, optimizing the innovation environment and improving the innovation leading force in Xuzhou.

International audience; Human DDX5 and its yeast ortholog Dbp2 are ATP-dependent RNA helicases that play a keyrole in normal cell processes, cancer development and viral infection. The crystal structure ofthe RecA1-like domain of DDX5 is available, but the global structure of DDX5/Dbp2subfamily proteins remains to be elucidated. Here, we report the first X-ray crystal structuresof the Dbp2 helicase core alone and in complex with adenosine diphosphate nucleotide (ADP)at 3.22 Å and 3.05 Å resolutions, respectively. The structures of the ADP-bound post-hydrolysisstate and apo-state demonstrate the conformational changes that occur when the nucleotides arereleased. Our results showed that the helicase core of Dbp2 shifted between open and closedconformation in solution, but the unwinding activity was hindered when the helicase core wasrestricted to a single conformation. A small-angle X-ray scattering (SAXS) experiment showedthat the disordered amino- (N-) and carboxy- (C-) tails are flexible in solution. Truncationmutations confirmed that the N- and C-tails were critical for the nucleic acid binding, ATPase,and unwinding activities, with the C-tail being exclusively responsible for the annealing activity.Furthermore, we labeled the terminal tails to observe the conformational changes between thedisordered tails and the helicase core upon binding nucleic acid substrates. Specifically, wefound that the nonstructural N- and C-tails bind to RNA substrates and tether them to thehelicase core domain, thereby conferring full helicase activities to the Dbp2 protein. Thisdistinct structural characteristic provides new insight into the mechanism of DEAD-box RNAhelicases.

Evasion of growth suppression is among the prominent hallmarks of cancer. Phosphatase and tensin homolog (PTEN) and p53 tumor-suppressive pathways are compromised in most human cancers, including glioblastoma (GB). Hence, these signaling pathways are an ideal point of focus for novel cancer therapeutics. Recombinant viruses can selectivity kill cancer cells and carry therapeutic genes to tumors. Specifically, oncolytic viruses (OV) have been successfully employed for gene delivery in GB animal models and showed potential to neutralize immunosuppression at the tumor site. However, the associated systemic immunogenicity, inefficient transduction of GB cells, and inadequate distribution to metastatic tumors have been the major bottlenecks in clinical studies. Mesenchymal stem cells (MSCs), with tumor-tropic properties and immune privilege, can improve OVs targeting. Remarkably, combining the two approaches can address their individual issues. Herein, we summarize findings to advocate the reactivation of tumor suppressors p53 and PTEN in GB treatment and use MSCs as a "Trojan horse" to carry oncolytic viral cargo to disseminated tumor beds. The integration of MSCs and OVs can emerge as the new paradigm in cancer treatment.

Glioblastoma (GB) is the most lethal form of primary brain neoplasm. TMZ is the first-line standard treatment, but the strong resistance constrains the efficacy in clinical use. GB contains glioma stem cells (GSCs), which contribute to TMZ resistance, promote cell survival evolvement, and repopulate the tumor mass. This review summarizes the TMZ-resistance mechanisms and discusses several potential therapies from the conservative opinion of GSC-targeted therapy orientation to the current view of TMZ resistance-aimed efficacy, which will provide an understanding of the role of heterogeneity in drug resistance and improve therapeutic efficacy in general.

Summary With the continuous development of high-throughput sequencing technology, bioinformatic analysis of omics data plays an increasingly important role in life science research. Many R packages are widely used for omics analysis, such as DESeq2, clusterProfiler and STRINGdb. And some online tools based on them have been developed to free bench scientists from programming with these R packages. However, the charts generated by these tools are usually in a fixed, non-editable format and often fail to clearly demonstrate the details the researchers intend to express. To address these issues, we have created Visual Omics, an online tool for omics data analysis and scientific chart editing. Visual Omics integrates multiple omics analyses which include differential expression analysis, enrichment analysis, protein domain prediction and protein–protein interaction analysis with extensive graph presentations. It can also independently plot and customize basic charts that are involved in omics analysis, such as various PCA/PCoA plots, bar plots, box plots, heat maps, set intersection diagrams, bubble charts and volcano plots. A distinguishing feature of Visual Omics is that it allows users to perform one-stop omics data analyses without programming, iteratively explore the form and layout of graphs online and fine-tune parameters to generate charts that meet publication requirements. Availability and implementation Visual Omics can be used at http://bioinfo.ihb.ac.cn/visomics. Source code can be downloaded at http://bioinfo.ihb.ac.cn/software/visomics/visomics-1.1.tar.gz. Supplementary information Supplementary data are available at Bioinformatics online.

On‐body propagation channels show significant polarization selectivity that has dominant impacts on the on‐body link quality in wireless body area networks. For on‐body relay channels over long distances across the body, the antenna polarization configurations of the relaying nodes are crucial to determine the relay performance, thereby requiring polarization optimization schemes. In this article, narrow band flat‐fading on‐body channels at 2.484 GHz are measured to analyse their polarization distribution above the skin under static postures. The measured on‐body channels show full‐space polarization convergence and dispersion, which are modelled by an extended 3 by 3 channel polarization matrix, and a statistical channel model is also proposed. Multi‐hop polarized on‐body relay channels are analysed on the relay link capacity, which shows polarization dependency between adjacent hop channels when relaying nodes are mounted by linearly polarized antennas. Both regular and iterative polarization selection algorithms are then designed to optimise the antenna polarization configuration of the nodes. Simulations based on the proposed polarization distribution model show significant link capacity increases for two‐hop and tfhree‐hop on‐body relay channels by the optimization algorithms. The results confirm the necessity of proper polarization selection schemes for on‐body relay channels.

The aims of the study were to assess the contribution of resilience, coping style, and COVID-19 stress on the quality of life (QOL) in frontline health care workers (HCWs). The study was a cross-sectional surveyperformed among 309 HCWs in a tertiaryhospital during the outbreak of COVID-19 in China. Data were collected through an anonymous, self-rated questionnaire, including demographic data, a 10-item COVID-19 stress questionnaire, Generic QOL Inventory-74, Connor-Davidson Resilience Scale, and the Simplified Coping Style Questionnaire. Hierarchical regression was used to analyse the relationship between the study variables and the QOL. Among the 309 participants, resilience and active coping were positively correlated with the QOL (P

Heat stress (HS) results in health problems in animals. This study was conducted to investigate the effect and the underlying mechanism of HS on the proliferation and differentiation process of 3T3-L1 preadipocytes. 3T3-L1 preadipocytes were treated at 37 °C or 41.5 °C. HS up-regulated the mRNA and protein expression level of heat shock protein 70 (HSP70). Furthermore, the proliferation of 3T3-L1 preadipocytes were significantly inhibited after HS treatment for 2 days. A large number of accumulated lipid droplets were observed under the microscope after HS treatment for 8 days. Notably, the result of oil red O staining showed that the number of lipid droplets increased significantly and the differentiation ability of the cells was enhanced after HS. Moreover, after 2 and 8 d of differentiation, HS increased the transcription levels of fat synthesis genes including peroxisome proliferators activated receptor γ (PPARγ), fatty acid binding protein 2 (AP2), fatty acid synthase (FAS) and CCAAT enhancer binding protein α (CEBPα) genes, while decreasing the transcription levels of lipid decomposition genes including ATGL and HSL genes. In addition, HS reduced the expression of AMPK and PGC-1α, as well as the dephosphorylation of AMPK. 5-Aminoimidazole-4-carboxamide ribonucleotide (AICAR) can eliminate HS induced lipogenesis by activating AMPK. These results indicated that HS inhibited the proliferation of 3T3-L1 preadipocytes and promoted lipid accumulation by inhibiting the AMPK-PGC-1α signaling pathway in 3T3-L1 preadipocytes. This work lays a theoretical foundation for improving the effect of HS on meat quality of livestock and provides a new direction for the prevention of obesity caused by HS.

Background: Although studies have reported an increased risk for cognitive disorders in Hashimoto's thyroiditis (HT) patients, even in the euthyroid state, the mechanisms involved remain unclear. The hippocampus is a classic brain region associated with cognitive function, among which the formation of long-term potentiation (LTP) in the Schaffer collateral-CA1 pathway plays an important role in the process of learning and memory. Therefore, this study established a euthyroid HT model in mice and investigated whether and how HT itself has the ability to trigger LTP alterations accompanied by learning and memory abnormality. Methods: An experimental euthyroid HT model was established in NOD mice through immunization with porcine thyroglobulin (Tg). Morris water maze was measured to determine mice spatial learning and memory. We investigated the effect of HT on synaptic transmission and high-frequency stimulation-induced LTP in the Schaffer collateral-CA1 synapse of mice hippocampus in vivo. Then, animals were sacrificed for thyroid-related parameter measure as well as detection of cellular and molecular events associated with the induction of LTP. Results: HT mice showed intrathyroidal lymphocyte infiltration and rising serum thyroid autoantibody levels accompanied by normal thyroid function. The HT mice had poorer performance in Morris water maze than controls. These alterations were mirrored by abnormalities in synaptic plasticity in the Schaffer collateral-CA1 synapses of the hippocampus in vivo. The integrity of the synaptic structure is the premise for the production of LTP. As detected by transmission electron microscopy, the ultrastructure of synapse and astrocyte in the hippocampus were impaired in euthyroid HT mice. Additionally, Western blot and real-time polymerase chain reaction analyses confirmed that in HT mice, GS, GLAST, and GLT-1, key elements in glutamate-glutamine circulation located in astrocyte, were downregulated, accompanied by elevated levels of glutamate in the hippocampus, which impaired the material basis for LTP induction. NMDR2B expression in the hippocampus was also downregulated. Conclusion: HT can induce damage of LTP in the hippocampal Schaffer collateral-CA1 pathway in the euthyroid state, and this can be attributed, at least partly, to astrocytes impairment, which may underlie the deleterious effects of HT itself on hippocampal-dependent learning and memory function.