Interactive Hierarchical Timeline for Collaborative Text Negotiation in Historical Records.

Visualizing event timelines for collaborative text writing is an important application for navigating and understanding such data, as time passes and the size and complexity of both text and timeline increase. They are often employed by applications such as code repositories and collaborative text editors. In this paper, we present a visualization tool to explore historical records of writing of legislative texts, which were discussed and voted on by an assembly of representatives. Our visualization focuses on event timelines from text documents that involve multiple people and different topics, allowing for observation of different proposed versions of said text or tracking data provenance of given text sections, while highlighting the connections between all elements involved. We also describe the process of designing such a tool alongside domain experts, with three steps of evaluation being conducted to verify the effectiveness of our design.

Combinatory glycoengineering of monoclonal antibodies and its application in cancer therapy: a narrative review.

Background and Objective: The application of immunotherapy, especially in terms of recombinant monoclonal antibodies (mAbs), is a revolution in the pharmaceutical industry field. Glycosylation plays an essential role in the structures and functions of mAbs, which must be carefully monitored and designed throughout their entire lifespan to ensure safety and efficacy. This review aimed to summarize the current status of the glycoengineering of mAbs for providing reference for the pharmaceutical industry. The application of glycoengineering of mAbs in cancer therapy will also be discussed in this article. Methods: We searched the PubMed/MEDLINE database to identify studies published between 1970 and 2023 that investigated glycoengineering of recombinant mAbs and its applications. The major findings of these studies were summarized. Key Content and Findings: This article reviews the relationship between glycosylation profiles and antibody-dependent cell-mediated cytotoxicity (ADCC), complement-dependent cytotoxicity (CDC), shelf-life, and other properties of mAbs. Furthermore, the rational design of glycosylation profiles provides solutions to the unmet needs of new drug development and biosimilar manufacturers. This review also emphatically describes various feasible strategies to optimize the glycosylation pattern in biomanufacturing reported in recent years, especially the approaches of combinatory glycoengineering explored in this field. Finally, we share examples of glycoengineering of mAbs applied in cancer therapy. Conclusions: Glycan modifications have been achieved through genetic and metabolic glycoengineering. A better understanding of the interplay between cells and the exogenous environment help the combinatorial strategy for glycoengineering in precise control mode. Furthermore, new high-tech approaches for glycoengineering are leading biological engineering and biotherapeutics to a new stage.

Exploring the Intricate Nexus of Sarcopenia and Cognitive Impairment.

Sarcopenia, a group of skeletal muscle diseases with high prevalence in older adults, usually manifests as loss of muscle mass and strength, and/or physical performance decline. Cognitive impairment, defined as impaired function in one or more cognitive domains such as memory, language, computation, comprehension, executive, and visuospatial skills, affects the quality of life and social functioning of patients. Both sarcopenia and cognitive impairment are common geriatric syndromes, and the two disorders interact and influence each other. Declining muscle function accelerates cognitive impairment, and cognitive impairment in turn affects muscle strength. Potential common pathological mechanisms between the two include chronic inflammation, mitochondrial dysfunction and oxidative stress, and gut microbiota disorder. Additionally, neuroendocrine connections including testosterone, insulin, and growth factors have important effects on muscle and brain function. Recently, the development of applied metabolomics technologies has shown significant potential in uncovering shared biochemical pathways and exploring potential biomarkers. Exercise, nutritional, and cognitive interventions are significant as nonpharmacologic approaches in the treatment of sarcopenia and cognitive impairment. However, the specific mechanism of interaction between two diseases, biomarkers and effective therapeutic medications still has knowledge gaps that need to be further explored.

Concentration quenching inhibition and fluorescence enhancement in Eu3+-doped molybdate red phosphors with two-phase mixing.

Red phosphor plays a crucial role in improving the quality of white light illumination and backlight displays. However, significant challenges remain to enhance red emission intensity in different matrix materials. Herein, a class of two-phase mixing red phosphors of NaIn1-x(MoO4)2:xEu3+ (NIMO:xEu3+) has been successfully prepared by the traditional high-temperature solid-state reaction method. The coordination environment, phase structure, excitation and emission spectra, fluorescence kinetics, and temperature-dependent luminescence properties of the system have been studied comprehensively. It is worth mentioning that the red emission intensity continues to increase with the increased Eu3+ doping concentration, and the fluorescence lifetimes remain unchanged. These extraordinary phenomena mainly stem from the special concentration quenching mechanism in such two-phase mixing material, namely, the increased lattice interface barriers from Eu six-coordinated units and Eu eight-coordinated units can effectively block the non-radiation by enlarging the average distance between luminescent centers. The improved fluorescence thermal stability and suppressed non-radiative transition rate in NIMO:40%Eu3+ sample are further proving regulatory role of lattice interface barriers. In addition, a warm white light-emitting diode (LED) is successfully fabricated, exhibiting Commission Internationale de l'Eclairage (CIE) coordinates of (0.343, 0.335), a color rendering index (CRI) of 92.1, and a correlated color temperature (CCT) of 5013 K, showing significant application prospects for high-quality lighting devices.

Visualizing Historical Book Trade Data: An Iterative Design Study with Close Collaboration with Domain Experts.

The circulation of historical books has always been an area of interest for historians. However, the data used to represent the journey of a book across different places and times can be difficult for domain experts to digest due to buried geographical and chronological features within text-based presentations. This situation provides an opportunity for collaboration between visualization researchers and historians. This paper describes a design study where a variant of the Nine-Stage Framework [46] was employed to develop a Visual Analytics (VA) tool called DanteExploreVis. This tool was designed to aid domain experts in exploring, explaining, and presenting book trade data from multiple perspectives. We discuss the design choices made and how each panel in the interface meets the domain requirements. We also present the results of a qualitative evaluation conducted with domain experts. The main contributions of this paper include: 1) the development of a VA tool to support domain experts in exploring, explaining, and presenting book trade data; 2) a comprehensive documentation of the iterative design, development, and evaluation process following the variant Nine-Stage Framework; 3) a summary of the insights gained and lessons learned from this design study in the context of the humanities field; and 4) reflections on how our approach could be applied in a more generalizable way.

Advances About Immunoinflammatory Pathogenesis and Treatment in Diabetic Peripheral Neuropathy.

Most diabetic patients develop diabetic peripheral neuropathy (DPN). DPN is related to the increase of inflammatory cells in peripheral nerves, abnormal cytokine expression, oxidative stress, ischemia ,and pro-inflammatory changes in bone marrow. We summarized the progress of immune-inflammatory mechanism and treatment of DPN in recent years. Immune inflammatory mechanisms include TNF-α, HSPs, PARP, other inflammatory factors, and the effect of immune cells on DPN. Treatment includes tricyclic antidepressants and other drug therapy, immune and molecular therapy, and non-drug therapy such as exercise therapy, electrotherapy, acupuncture, and moxibustion. The pathogenesis of DPN is complex. In addition to strictly controlling blood glucose, its treatment should also start from other ways, explore more effective and specific treatment schemes for various causes of DPN, and find new targets for treatment will be the direction of developing DPN therapeutic drugs in the future.

Multiple analytical methods for identification and quality evaluation of Fritillariae Thunbergii Bulbus based on biological single molecules by high-performance liquid chromatography.

Quantitative analysis for biological single molecules in Fritillariae Thunbergii Bulbus and identification method by chemometrics was established by using high-performance liquid chromatography. Amino acids, nucleosides, and nucleobases were quantitatively analyzed, and 11 peaks were selected for species identification. A Common pattern was established for chemometrics, and then similarity analysis, principal component analysis, and hierarchical cluster analysis heatmap were applied, and the results indicated that species were ideally identified from the adulterants as Fritillariae Cirrhosae Bulbus. This evaluation method was valuable for further quality control to select the characteristic components.

Combination with Chemometrics and Quantification for Quality Evaluation and Variety Identification of Flos Chimonanthi Praecocis by HPLC.

Flos Chimonanthi Praecocis (FCP) is one of the popular traditional Chinese medicines, which have been widely used in China. Inconspicuous appearance differences are disadvantageous for identification, and it is difficult to evaluate the quality of FCP using the current methods. In this article, a simple method that combined chemometrics and quantitative analysis was established. The samples were obtained from three typical varieties for fingerprint analysis by high-performance liquid chromatography. Contents of rutin and quercetin were determined, and then a common pattern with 16 characteristic peaks was applied for principal component analysis, similarity analysis, and the hierarchical cluster analysis heatmap (HCA heatmap) to characterize the similarity and differences among samples for identification. Furthermore, seven characteristics peaks with higher loading values were selected for chemometrics analysis after dimensionality reduction to reduce analytical difficulty, and the new common pattern showed the similar identification effects. Overall, combination with chemometrics and quantitative analysis would provide a useful and simple method for quality control of FCP in the future.

Protective effects of berberine against doxorubicin-induced cardiotoxicity in rats by inhibiting metabolism of doxorubicin.

1. The clinical use of doxorubicin, an effective anticancer drug, is severely hampered by its cardiotoxicity. Berberine, a botanical alkaloid, has been reported to possess cardioprotective and antitumor effects. In this study, we investigated the cardioprotective effect of berberine on doxorubicin-induced cardiotoxicity and the effect of berberine on the metabolism of doxorubicin. 2. Adult male Sprague-Dawley rats were administered doxorubicin in the presence or absence of berberine for 2 weeks. Administration of berberine effectively prevented doxorubicin-induced body weight reduction and mortality in rats. 3. Berberine reduced the activity of myocardial enzymes, including aspartate aminotransferase (AST), creatine kinase (CK), CK isoenzyme (CK-MB) and lactate dehydrogenase (LDH). Echocardiographic examination further demonstrated that berberine effectively ameliorated cardiac dysfunction induced by doxorubicin. 4. Berberine inhibited the metabolism of doxorubicin in the cytoplasm of rat heart and reduced the accumulation of doxorubicinol (a secondary alcohol metabolite of doxorubicin) in heart. 5. These data showed that berberine alleviated the doxorubicin-induced cardiotoxicity in rats via inhibition of the metabolism of doxorubicin and reduced accumulation of doxorubicinol selectively in hearts.

[Construction of miR-508-5P lentiviral vector and its targeted effect on S-phase kinase-associated protein-2 gene].

OBJECTIVE: To construct a lentiviral vector overexpressing miR-508-5p and verify its targeted regulating effect on S-phase kinase-associated protein-2 (SKP2) gene. METHODS: The stem-loop structure RNA of miR-508-5p was obtained by chemical synthesis and cloned into the linearized pSicoR plasmid. The positive recombinants, which had been identified by restriction enzyme digestion and DNA sequencing method, were transfected into HEK293T cells. Meanwhile, the potential target gene of SKP2-3'UTR, which was complementary with miR-508-5p, was obtained and cloned into the linearized pMIR-Report plasmid. The targeted effect of miR-508-5p on SKP2 gene was verified by the relative luciferase activity measurement, Western blotting and real-time PCR. RESULTS: The PCR, restriction enzyme digestion and DNA sequencing analysis demonstrated that the recombinant plasmids of pSicoR-miR-508-5p and pMIR-Report-SKP2 3'-UTR were constructed successfully. And it was showed that over-expression of miR-508-5p suppressed the mRNA and protein expression level of SKP2 significantly (P<0.05); and suppression of miR-508-5p expression increased the mRNA and protein expression level of SKP2 significantly (P<0.05). CONCLUSION: We have successfully constructed the lentiviral vector containing miR-508-5p gene. MiR-508-5p can suppress SKP2 gene expression by targeting the specific sequence of SKP2-3'UTR.

MicroRNA-149 negatively regulates TLR-triggered inflammatory response in macrophages by targeting MyD88.

MicroRNAs (miRNAs) have been shown to be important regulators of TLR signaling pathway at the post-transcriptional level. In this study, the potential role of miR-149 was explored in murine alveolar macrophage RAW264.7 cells. Our results demonstrated a dynamic change of the expressions of miR-149 expression and MyD88 in macrophage RAW264.7 upon Mycobacterium bovis Bacillus Calmette-Guerlin (BCG) infection or lipopolysaccharide (LPS) stimulation. The presence of BCG or LPS dynamically reduced the miR-149 expression, along with a substantially striking increase of MyD88 expression in these cells. More importantly, overexpression of miR-149 in RAW264.7 cells was associated with a significant decrease of MyD88 protein expression, as well as a reduced production of inflammatory mediator NF-κB 1, TNF-α and IL-6 in response to BCG infection or LPS stimulation. Further studies using immunoblotting assay against anti-MyD88 antibody and microRNA targeting luciferase reporter assay revealed that miR-149 was able to directly target the 3'-UTR of MyD88 mRNA and post-transcriptionally regulated MyD88 protein expression. These data suggested that miR-149 might be a key player of immune modulator for TLR/MyD88 signaling pathway in macrophages, which may through a mechanism of negatively regulating MyD88-dependent Toll-like receptors signaling pathway.