Miracle-dz/UniFAR-FTUs huggingface dataset:
Different Catechol-O-Methyl Transferase Inhibitors in Parkinson's Disease: A Bayesian Network Meta-Analysis

Parkinson's disease (PD) is a common, chronic, progressive, debilitating neurodegenerative disease. The current levodopa treatment requires the addition of other drugs, such as catechol-O-methyl transferase (COMT) inhibitors, to alleviate motor fluctuations in advanced PD. Therefore, a theoretical reference for treatment is urgently needed. In this study, an appropriate search strategy was used to screen eligible studies on different drugs to treat patients with PD from the Embase, PubMed, and Cochrane Library. The publication dates were from January 1990 to June 2021. We integrated eligible randomized controlled trials, and statistical analysis was performed on three kinds of effectiveness outcomes and two types of safety outcomes. We assessed the average difference or odds ratio between each drug and placebo and summarized them as the average and 95% confidence interval (CI), respectively. In terms of efficacy, entacapone (mean difference [MD], 0.64 h; 95% CI, 0.29–1.0), opicapone (MD, 0.92 h; 95% CI, 0.35–1.5), and tolcapone (MD, 3.2 h; 95% CI, 2.1–4.2) increased patients' total ON-time compared to placebo. Tolcapone (MD, −100 mg; 95% CI −160 to −45) reduced the total daily dose of levodopa therapy. None of these three drugs was found to have statistical significance in mean change from baseline in UPDRS part III scores when compared with others. In terms of safety, tolcapone (MD, 3.8; 95% CI, 2.1–6.8), opicapone (MD, 3.7; 95% CI, 2–7.2), and entacapone (MD, 2.2; 95% CI, 1.5–3.3) increased the number of cases of dyskinesia compared to placebo. Entacapone (MD, 1.7; 95% CI, 1.3–2.2) and tolcapone (MD, 4.3; 95% CI, 1.3–15) were more likely to cause adverse events than placebo. In conclusion, opicapone showed higher efficiency and fewer safety problems in five indicators we selected when compared with the other two drugs.
Progress in the Application of Carbon Dots-Based Nanozymes

As functional nanomaterials with simulating enzyme-like properties, nanozymes can not only overcome the inherent limitations of natural enzymes in terms of stability and preparation cost but also possess design, versatility, maneuverability, and applicability of nanomaterials. Therefore, they can be combined with other materials to form composite nanomaterials with superior performance, which has garnered considerable attention. Carbon dots (CDs) are an ideal choice for these composite materials due to their unique physical and chemical properties, such as excellent water dispersion, stable chemical inertness, high photobleaching resistance, and superior surface engineering. With the continuous emergence of various CDs-based nanozymes, it is vital to thoroughly understand their working principle, performance evaluation, and application scope. This review comprehensively discusses the recent advantages and disadvantages of CDs-based nanozymes in biomedicine, catalysis, sensing, detection aspects. It is expected to provide valuable insights into developing novel CDs-based nanozymes.
Combined Therapy With Avastin, a PAF Receptor Antagonist and a Lipid Mediator Inhibited Glioblastoma Tumor Growth

Glioblastoma multiforme (GBM) is an aggressive, highly proliferative, invasive brain tumor with a poor prognosis and low survival rate. The current standard of care for GBM is chemotherapy combined with radiation following surgical intervention, altogether with limited efficacy, since survival averages 18 months. Improvement in treatment outcomes for patients with GBM requires a multifaceted approach due to the dysregulation of numerous signaling pathways. Recently emerging therapies to precisely modulate tumor angiogenesis, inflammation, and oxidative stress are gaining attention as potential options to combat GBM. Using a mouse model of GBM, this study aims to investigate Avastin (suppressor of vascular endothelial growth factor and anti-angiogenetic treatment), LAU-0901 (a platelet-activating factor receptor antagonist that blocks pro-inflammatory signaling), Elovanoid; ELV, a novel pro-homeostatic lipid mediator that protects neural cell integrity and their combination as an alternative treatment for GBM. Female athymic nude mice were anesthetized with ketamine/xylazine, and luciferase-modified U87MG tumor cells were stereotactically injected into the right striatum. On post-implantation day 13, mice received one of the following: LAU-0901, ELV, Avastin, and all three compounds in combination. Bioluminescent imaging (BLI) was performed on days 13, 20, and 30 post-implantation. Mice were perfused for ex vivo MRI on day 30. Bioluminescent intracranial tumor growth percentage was reduced by treatments with LAU-0901 (43%), Avastin (77%), or ELV (86%), individually, by day 30 compared to saline treatment. In combination, LAU-0901/Avastin, ELV/LAU-0901, or ELV/Avastin had a synergistic effect in decreasing tumor growth by 72, 92, and 96%, respectively. Additionally, tumor reduction was confirmed by MRI on day 30, which shows a decrease in tumor volume by treatments with LAU-0901 (37%), Avastin (67%), or ELV (81.5%), individually, by day 30 compared to saline treatment. In combination, LAU-0901/Avastin, ELV/LAU-0901, or ELV/Avastin had a synergistic effect in decreasing tumor growth by 69, 78.7, and 88.6%, respectively. We concluded that LAU-0901 and ELV combined with Avastin exert a better inhibitive effect in GBM progression than monotherapy. To our knowledge, this is the first study that demonstrates the efficacy of these novel therapeutic regimens in a model of GBM and may provide the basis for future therapeutics in GBM patients.
Redefining the Subsurface Biosphere: Characterization of Fungi Isolated From Energy-Limited Marine Deep Subsurface Sediment

The characterization of metabolically active fungal isolates within the deep marine subsurface will alter current ecosystem models and living biomass estimates that are limited to bacterial and archaeal populations. Although marine fungi have been studied for over fifty years, a detailed description of fungal populations within the deep subsurface is lacking. Fungi possess metabolic pathways capable of utilizing previously considered non-bioavailable energy reserves. Therefore, metabolically active fungi would occupy a unique niche within subsurface ecosystems, with the potential to provide an organic carbon source for heterotrophic prokaryotic populations from the transformation of non-bioavailable energy into substrates, as well as from the fungal necromass itself. These organic carbon sources are not currently being considered in subsurface energy budgets. Sediments from South Pacific Gyre subsurface, one of the most energy-limited environments on Earth, were collected during the Integrated Ocean Drilling Program Expedition 329. Anoxic and oxic sediment slurry enrichments using fresh sediment were used to isolate multiple fungal strains in media types that varied in organic carbon substrates and concentration. Metabolically active and dormant fungal populations were also determined from nucleic acids extracted from in situ cryopreserved South Pacific Gyre sediments. For further characterization of physical growth parameters, two isolates were chosen based on their representation of the whole South Pacific Gyre fungal community. Results from this study show that fungi have adapted to be metabolically active and key community members in South Pacific Gyre sediments and potentially within global biogeochemical cycles.
Two New M23 Peptidoglycan Hydrolases With Distinct Net Charge

Bacterial peptidoglycan hydrolases play an essential role in cell wall metabolism during bacterial growth, division, and elongation (autolysins) or in the elimination of closely related species from the same ecological niche (bacteriocins). Most studies concerning the peptidoglycan hydrolases present in Gram-positive bacteria have focused on clinically relevant Staphylococcus aureus or the model organism Bacillus subtilis, while knowledge relating to other species remains limited. Here, we report two new peptidoglycan hydrolases from the M23 family of metallopeptidases derived from the same staphylococcal species, Staphylococcus pettenkoferi. They share modular architecture, significant sequence identity (60%), catalytic and binding residue conservation, and similar modes of activation, but differ in gene distribution, putative biological role, and, strikingly, in their isoelectric points (pIs). One of the peptides has a high pI, similar to that reported for all M23 peptidases evaluated to date, whereas the other displays a low pI, a unique feature among M23 peptidases. Consequently, we named them SpM23_B (Staphylococcus pettenkoferi M23 “Basic”) and SpM23_A (Staphylococcus pettenkoferi M23 “Acidic”). Using genetic and biochemical approaches, we have characterized these two novel lytic enzymes, both in vitro and in their physiological context. Our study presents a detailed characterization of two novel and clearly distinct peptidoglycan hydrolases to understand their role in bacterial physiology.
Prenatal Diagnosis in a Fetus With X-Linked Recessive Chondrodysplasia Punctata: Identification and Functional Study of a Novel Missense Mutation in ARSE

X-Linked recessive chondrodysplasia punctata (CDPX1) is a rare skeletal dysplasia characterized by stippled epiphyses, brachytelephalangy, and nasomaxillary hypoplasia. CDPX1 is caused by function loss of arylsulfatase E (ARSE, also known as ARSL). Pathogenic mutations in ARSE are responsible for CDPX1 in newborns or adults; however, studies have not fully explored prenatal cases. In the current study, a novel missense mutation (c.265A > G) in ARSE was identified in a fetus with short limbs using whole-exome sequencing (WES). Bioinformatic analysis showed that the variant was pathogenic, and RT-qPCR, Western blot, and enzymatic assays were performed to further explore pathogenicity of the variant. The findings showed that the variant decreased transcription and protein expression levels and led to loss of enzymatic activity of the protein. The novel mutation c.265A > G in ARSE was thus the genetic cause for the phenotype presented by the fetus. The current study presents a prenatal case in Chinese population using functional analysis of ARSE, which helps the family to predict recurrence risks for future pregnancies and provides more information for understanding this rare condition. The findings show that WES is a feasible method for prenatal diagnosis of fetuses with CDPX1.
Increasing AZA-Accredited Zoo and Aquarium Engagement in Conservation

Conservation should be the higher purpose of any modern zoological facility and has consistently been a required element of accreditation by the Association of Zoos and Aquariums (AZA). Each year, AZA-accredited zoos and aquariums collectively commit considerable resources to conservation around the world, exceeding 150 million USD annually since 2011 and exceeding 231 million USD in 2019. Furthermore, with 195 million people visiting AZA-accredited zoos and aquariums each year, there is enormous opportunity to connect people to nature and engage them as agents of change. As AZA facilities continue to prioritize conservation-driven missions, their participation in field conservation has increased greatly. AZA SAFE: Saving Animals From Extinction (SAFE)® was established in 2014 to encourage greater collaboration of AZA members and their field partners to save species. The SAFE framework is dedicated to species recovery and based on conservation best practices. SAFE species programs develop 3-year action plans that build on established recovery plans, evaluate impact, and combine AZA facilities and visitors to increase resources for research, public engagement, communications, and conservation funding. Here we share preliminary outcomes of the SAFE program as they relate to programmatic measures of success to determine whether the framework 1) is useful for the AZA membership as measured by engagement and participation, and 2) increases conservation activity on behalf of targeted species as measured by the number of facilities supporting a species' conservation and financial investment. In this analysis we utilized data supported by the AZA Annual Report for Conservation and Science (ARCS) to demonstrate benefits of the SAFE framework and provide insights into future strategies to enhance conservation impact.
Characterization of Immune-Related Long Non-coding RNAs to Construct a Novel Signature and Predict the Prognosis and Immune Landscape of Soft Tissue Sarcoma

Background: Increasing evidence has demonstrated that immune-related long non-coding RNAs (irlncRNAs) are critically involved in tumor initiation and progression and associated with the prognosis of various cancers. However, their role in soft tissue sarcoma (STS) remains significantly uninvestigated. Materials and Methods: Gene expression profiles were extracted from The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) for the identification of irlncRNAs. Univariate analysis and modified least absolute shrinkage and selection operator (LASSO) penalized regression analysis were employed to determine differently expressed irlncRNA (DEirlncRNA) pairs of prognostic value, and subsequently, a risk signature based on DEirlncRNA pairs was established. Furthermore, Kaplan–Meier analysis and the area under the receiver operating characteristic curve (AUC) were used to assess survival differences and the predictive accuracy of the risk signature, respectively. Lastly, the correlation of irlncRNAs with immune characteristics and chemosensitivity in patients with STS were further investigated. Results: A total of 1088 irlncRNAs were identified, and 311 irlncRNAs were distinguished as DEirlncRNAs. A total of 130 DEirlncRNA pairs were further identified as prognostic markers, and 14 pairs were selected for establishing a risk signature. The irlncRNA-based risk signature functioned as an independent prognostic marker for STS. Compared with the patients in the high-risk group, those in the low-risk group exhibited a better prognosis and were more sensitive to several chemotherapeutic agents. In addition, the irlncRNA-based risk signature was significantly associated with immune scores, infiltrating immune cells, and the expression of several immune checkpoints. Conclusion: In conclusion, our data revealed that the irlncRNA-based risk signature resulted in reliable prognosis, effectively predicted the immune landscape of patients with STS and was significantly correlated with chemosensitivity, thus providing insights into the potential role of irlncRNAs as prognostic biomarkers and novel therapeutic targets for STS.
α-Hemolysin-Aided Oligomerization of the Spike Protein RBD Resulted in Improved Immunogenicity and Neutralization Against SARS-CoV-2 Variants

The increase in confirmed COVID-19 cases and SARS-CoV-2 variants calls for the development of safe and broad cross-protective vaccines. The RBD of the spike protein was considered to be a safe and effective candidate antigen. However, the low immunogenicity limited its application in vaccine development. Herein, we designed and obtained an RBD heptamer (mHla-RBD) based on a carrier protein-aided assembly strategy. The molecular weight of mHla-RBD is up to 450 kDa, approximately 10 times higher than that of the RBD monomer. When formulated with alum adjuvant, mHla-RBD immunization significantly increased the immunogenicity of RBD, as indicated by increased titers of RBD-specific antibodies, neutralizing antibodies, Th2 cellular immune response, and pseudovirus neutralization activity, when compared to RBD monomer. Furthermore, we confirmed that RBD-specific antibodies predominantly target conformational epitopes, which was approximately 200 times that targeting linear epitopes. Finally, a pseudovirus neutralization assay revealed that neutralizing antibodies induced by mHla-RBD against different SARS-CoV-2 variants were comparable to those against the wild-type virus and showed broad-spectrum neutralizing activity toward different SARS-CoV-2 variants. Our results demonstrated that mHla-RBD is a promising candidate antigen for development of SARS-CoV-2 vaccines and the mHla could serve as a universal carrier protein for antigen design.
CDT1 Is a Novel Prognostic and Predictive Biomarkers for Hepatocellular Carcinoma

Objective Hepatocellular carcinoma (HCC) is one of the most common malignant tumors endangering human health and life in the 21st century. Chromatin licensing and DNA replication factor 1 (CDT1) is an important regulator of DNA replication licensing, which is essential for initiation of DNA replication. CDT1 overexpression in several human cancers reportedly leads to abnormal cell replication, activates DNA damage checkpoints, and predisposes malignant transformation. However, the abnormal expression of CDT1 in HCC and its diagnostic and prognostic value remains to be elucidated. Methods TCGA, ONCOMINE, UALCAN, HCCDB, HPA, Kaplan-Meier plotter, STRING, GEPIA, GeneMANIA, and TIMER were conducted for bioinformatics analysis. CDT1 protein expression was evaluated by immunohistochemistry in HCC tissues through a tissue microarray. qRT-PCR, western blot and a cohort of functional experiments were performed for in vitro validation. Results In this study, we discovered remarkably upregulated transcription of CDT1 in HCC samples relative to normal liver samples through bioinformatic analysis, which was further verified in clinical tissue microarray samples and in vitro experiments. Moreover, the transcriptional level of CDT1 in HCC samples was positively associated with clinical parameters such as clinical tumor stage. Survival, logistic regression, and Cox regression analyses revealed the significant clinical prognostic value of CDT1 expression in HCC. The receiver operating characteristic curve and nomogram analysis results demonstrated the strong predictive ability of CDT1 in HCC. Kyoto Encyclopedia of Genes and Genomes and gene set enrichment analyses indicated that CDT1 was mainly associated with the cell cycle, DNA repair, and DNA replication. We further demonstrated the significant correlation between CDT1 and minichromosome maintenance (MCM) family genes, revealing abnormal expression and prognostic significance of MCMs in HCC. Immune infiltration analysis indicated that CDT1 was significantly associated with immune cell subsets and affected the survival of HCC patients. Finally, knockdown of CDT1 decreased, whereas overexpression of CDT1 promoted the proliferation, migration, invasion of HCC cells in vitro. Conclusions Our study findings demonstrate the potential diagnostic and prognostic significance of CDT1 expression in HCC, and elucidate the potential molecular mechanism underlying its role in promoting the occurrence and development of liver cancer. These results may provide new opportunities and research paths for targeted therapies in HCC.
Versatile Dynamic Motion Generation Framework: Demonstration With a Crutch-Less Exoskeleton on Real-Life Obstacles at the Cybathlon 2020 With a Complete Paraplegic Person

Lower-limb exoskeletons are a promising option to increase the mobility of persons with leg impairments in a near future. However, it is still challenging for them to ensure the necessary stability and agility to face obstacles, particularly the variety that makes the urban environment. That is why most of the lower-limb exoskeletons must be used with crutches: the stability and agility features are deferred to the patient. Clinical experience shows that the use of crutches not only leads to shoulder pain and exhaustion, but also fully occupies the hands for daily tasks. In November 2020, Wandercraft presented Atalante Evolution, the first self-stabilized and crutch-less exoskeleton, to the powered exoskeleton race of the Cybathlon 2020 Global Edition. The Cybathlon aims at promoting research and development in the field of powered assistive technology to the public, contrary to the Paralympics where only participants with unpowered assistive technology are allowed. The race is designed to represent the challenges that a person could face every day in their environment: climbing stairs, walking through rough terrain, or descending ramps. Atalante Evolution is a 12 degree-of-freedom exoskeleton capable of moving dynamically with a complete paraplegic person. The challenge of this competition is to generate and execute new dynamic motions in a short time, to achieve different tasks. In this paper, an overview of Atalante Evolution system and of our framework for dynamic trajectory generation based on the direct collocation method will be presented. Next, the flexibility and efficiency of the dynamic motion generation framework are demonstrated by our tools developed for generating the important variety of stable motions required by the competition. A smartphone application has been developed to allow the pilot to choose between different modes and to control the motion direction according to the real situation to reach a destination. The advanced mechatronic design and the active cooperation of the pilot with the device will also be highlighted. As a result, Atalante Evolution allowed the pilot to complete four out of six obstacles, without crutches. Our developments lead to stable dynamic movements of the exoskeleton, hands-free walking, more natural stand-up and turning moves, and consequently a better physical condition of the pilot after the race compared to the challengers. The versatility and good results of these developments give hope that exoskeletons will soon be able to evolve in challenging everyday-life environments, allowing patients to live a normal life in complete autonomy.
Multilevel Attention Residual Neural Network for Multimodal Online Social Network Rumor Detection

In recent years, with the rapid rise of social networks, such as Weibo and Twitter, multimodal social network rumors have also spread. Unlike traditional unimodal rumor detection, the main difficulty of multimodal rumor detection is in avoiding the generation of noise information while using the complementarity of different modal features. In this article, we propose a multimodal online social network rumor detection model based on the multilevel attention residual neural network (MARN). First, the features of text and image are extracted by Bert and ResNet-18, respectively, and the cross-attention residual mechanism is used to enhance the representation of images with a text vector. Second, the enhanced image vector and text vector are concatenated and fused by the self-attention residual mechanism. Finally, the fused image–text vectors are classified into two categories. Among them, the attention mechanism can effectively enhance the image representation and further improve the fusion effect between the image and the text, while the residual mechanism retains the unique attributes of each original modal feature while using different modal features. To assess the performance of the MARN model, we conduct experiments on the Weibo dataset, and the results show that the MARN model outperforms the state-of-the-art models in terms of accuracy and F1 value.