Miracle-dz/UniFAR-FTUs huggingface dataset:
Hyperoxia Provokes Time- and Dose-Dependent Gut Injury and Endotoxemia and Alters Gut Microbiome and Transcriptome in Mice

Background: Oxygen therapy usually exposes patients to hyperoxia, which induces injuries in the lung, the heart, and the brain. The gut and its microbiome play key roles in critical illnesses, but the impact of hyperoxia on the gut and its microbiome remains not very clear. We clarified the time- and dose-dependent effects of hyperoxia on the gut and investigated oxygen-induced gut dysbiosis and explored the underlying mechanism of gut injury by transcriptome analysis. Methods: The C57BL/6 mice were randomly divided into the control group and nine different oxygen groups exposed to hyperoxia with an inspired O2 fraction (FiO2) of 40, 60, and 80% for 24, 72, and 168 h (7 days), respectively. Intestinal histopathological and biochemical analyses were performed to explore the oxygen-induced gut injury and inflammatory response. Another experiment was performed to explore the impact of hyperoxia on the gut microbiome by exposing the mice to hyperoxia (FiO2 80%) for 7 days, with the 16S rRNA sequencing method. We prolonged the exposure (up to 14 days) of the mice to hyperoxia (FiO2 80%), and gut transcriptome analysis and western blotting were carried out to obtain differentially expressed genes (DEGs) and signaling pathways related to innate immunity and cell death. Results: Inhaled oxygen induced time- and dose-dependent gut histopathological impairment characterized by mucosal atrophy (e.g., villus shortening: 80% of FiO2 for 24 h: P = 0.008) and enterocyte death (e.g., apoptosis: 40% of FiO2 for 7 days: P = 0.01). Administered time- and dose-dependent oxygen led to intestinal barrier dysfunction (e.g., endotoxemia: 80% of FiO2 for 72 h: P = 0.002) and potentiated gut inflammation by increasing proinflammatory cytokines [e.g., tumor necrosis factor alpha (TNF-α): 40% of FiO2 for 24 h: P = 0.003)] and reducing anti-inflammatory cytokines [Interleukin 10 (IL-10): 80% of FiO2 for 72 h: P < 0.0001]. Hyperoxia induced gut dysbiosis with an expansion of oxygen-tolerant bacteria (e.g., Enterobacteriaceae). Gut transcriptome analysis identified 1,747 DEGs and 171 signaling pathways and immunoblotting verified TLR-4, NOD-like receptor, and apoptosis signaling pathways were activated in oxygen-induced gut injury. Conclusions: Acute hyperoxia rapidly provokes gut injury in a time- and dose-dependent manner and induces gut dysbiosis, and an innate immune response is involved in an oxygen-induced gut injury.
Multimodal Imaging Technology Effectively Monitors HER2 Expression in Tumors Using Trastuzumab-Coupled Organic Nanoparticles in Patient-Derived Xenograft Mice Models

Trastuzumab is a monoclonal antibody targeting human epidermal growth factor 2 (HER2), which has been successfully used in the treatment of patients with breast cancer and gastric cancer; however, problems concerning its cardiotoxicity, drug resistance, and unpredictable efficacy still remain. Herein, we constructed novel organic dopamine–melanin nanoparticles (dMNs) as a carrier and then surface-loaded them with trastuzumab to construct a multifunctional nanoprobe named Her-PEG-dMNPs. We used micro-PET/CT and PET/MRI multimodality imaging to evaluate the retention effect of the nanoprobe in HER2 expression in gastric cancer patient-derived xenograft (PDX) mice models after labeling of the radionuclides 64Cu or 124I and MRI contrast agent Mn2+. The nanoprobes can specifically target the HER2-expressing SKOV-3 cells in vitro (3.61 ± 0.74 vs. 1.24 ± 0.43 for 2 h, P = 0.002). In vivo, micro-PET/CT and PET/MRI showed that the 124I-labeled nanoprobe had greater contrast and retention effect in PDX models than unloaded dMNPs as carrier (1.63 ± 0.07 vs. 0.90 ± 0.04 at 24 h, P = 0.002), a similarity found in 64Cu-labeled Her-PEG-dMNPs. Because 124I has a longer half-life and matches the pharmacokinetics of the nanoparticles, we focused on the further evaluation of 124I-Her-PEG-dMNPs. Furthermore, immunohistochemistry staining confirmed the overexpression of HER2 in the animal model. This study developed and validated novel HER2-specific multimodality imaging nanoprobes for quantifying HER2 expression in mice. Through the strong retention effect of the tumor site, it can be used for the promotion of monoclonal antibody treatment effect and process monitoring.
Influence of Polysaccharides From Polygonatum kingianum on Short-Chain Fatty Acid Production and Quorum Sensing in Lactobacillus faecis

Polysaccharide is one of the main active ingredients of Polygonatum kingianum, which has been proven to regulate the balance of gut microbiota. For the first time, this study focused on the regulation of polysaccharides from Polygonatum kingianum (PS) on Lactobacillus faecis, a specific probiotic in the intestinal tract. PS effectively promoted the biomass, biofilm and acetic acid production in L. faecis 2-84, and enhanced quorum sensing (QS) signaling. The characteristics of gene sequence were analyzed using genomics approaches, and L. faecis 2-84 was found to encode 18 genes that are closely related to QS and 10 genes related to short-chain fatty acids (SCFAs). Additionally, transcriptome and proteome analysis demonstrated that PS could promote the QS system of L. faecis by enhancing the transcription of oppA gene and expression of oppD protein. PS also regulated the production and metabolism of SCFAs of L. faecis by upregulating the expression of ldh and metE gene and adh2 protein, and downregulating the expression of mvK gene. In conclusion, it was speculated that PS could affect intestinal SCFAs production by affecting the QS system and SCFAs production in L. faecis. The present study implied that PS might have a role in promoting the growth of intestinal probiotics, where the QS system and SCFAs might be two of the important mechanisms for the probiotic activity of PS.
Development and Application of EST-SSR Markers in Cephalotaxus oliveri From Transcriptome Sequences

Cephalotaxus oliveri is an endemic conifer of China, which has medicinal and ornamental value. However, the limited molecular markers and genetic information are insufficient for further genetic studies of this species. In this study, we characterized and developed the EST-SSRs from transcriptome sequences for the first time. The results showed that a total of 5089 SSRs were identified from 36446 unigenes with a density of one SSR per 11.1 kb. The most common type was trinucleotide repeats, excluding mononucleotide repeats, followed by dinucleotide repeats. AAG/CTT and AT/AT exhibited the highest frequency in the trinucleotide and dinucleotide repeats, respectively. Of the identified SSRs, 671, 1125, and 1958 SSRs were located in CDS, 3′UTR, and 5′UTR, respectively. Functional annotation showed that the SSR-containing unigenes were involved in growth and development with various biological functions. Among successfully designed primer pairs, 238 primer pairs were randomly selected for amplification and validation of EST-SSR markers and 47 primer pairs were identified as polymorphic. Finally, 28 high-polymorphic primers were used for genetic analysis and revealed a moderate level of genetic diversity. Seven natural C. oliveri sampling sites were divided into two genetic groups. Furthermore, the 28 EST-SSRs had 96.43, 71.43, and 78.57% of transferability rate in Cephalotaxus fortune, Ametotaxus argotaenia, and Pseudotaxus chienii, respectively. These markers developed in this study lay the foundation for further genetic and adaptive evolution studies in C. oliveri and related species.
Sex Reversal and Performance in Fitness-Related Traits During Early Life in Agile Frogs

Sex reversal is a mismatch between genetic sex (sex chromosomes) and phenotypic sex (reproductive organs and secondary sexual traits). It can be induced in various ectothermic vertebrates by environmental perturbations, such as extreme temperatures or chemical pollution, experienced during embryonic or larval development. Theoretical studies and recent empirical evidence suggest that sex reversal may be widespread in nature and may impact individual fitness and population dynamics. So far, however, little is known about the performance of sex-reversed individuals in fitness-related traits compared to conspecifics whose phenotypic sex is concordant with their genetic sex. Using a novel molecular marker set for diagnosing genetic sex in agile frogs (Rana dalmatina), we investigated fitness-related traits in larvae and juveniles that underwent spontaneous female-to-male sex reversal in the laboratory. We found only a few differences in early life growth, development, and larval behavior between sex-reversed and sex-concordant individuals, and altogether these differences did not clearly support either higher or lower fitness prospects for sex-reversed individuals. Putting these results together with earlier findings suggesting that sex reversal triggered by heat stress may be associated with low fitness in agile frogs, we propose the hypothesis that the fitness consequences of sex reversal may depend on its etiology.
Epigenetic Priming of Bladder Cancer Cells With Decitabine Increases Cytotoxicity of Human EGFR and CD44v6 CAR Engineered T-Cells

Background Treatment of B-cell malignancies with CD19-directed chimeric antigen receptor (CAR) T-cells marked a new era in immunotherapy, which yet has to be successfully adopted to solid cancers. Epigenetic inhibitors of DNA methyltransferases (DNMTi) and histone deacetylases (HDACi) can induce broad changes in gene expression of malignant cells, thus making these inhibitors interesting combination partners for immunotherapeutic approaches. Methods Urothelial carcinoma cell lines (UCC) and benign uroepithelial HBLAK cells pretreated with the DNMTi decitabine or the HDACi romidepsin were co-incubated with CAR T-cells directed against EGFR or CD44v6, and subsequent cytotoxicity assays were performed. Effects on T-cell cytotoxicity and surface antigen expression on UCC were determined by flow cytometry. We also performed next-generation mRNA sequencing of inhibitor-treated UCC and siRNA-mediated knockdown of potential regulators of CAR T-cell killing. Results Exposure to decitabine but not romidepsin enhanced CAR T-cell cytotoxicity towards all UCC lines, but not towards the benign HBLAK cells. Increased killing could neither be attributed to enhanced target antigen expression (EGFR and CD44v6) nor fully explained by changes in the T-cell ligands PD-L1, PD-L2, ICAM-1, or CD95. Instead, gene expression analysis suggested that regulators of cell survival and apoptosis were differentially induced by the treatment. Decitabine altered the balance between survival and apoptosis factors towards an apoptosis-sensitive state associated with increased CAR T-cell killing, while romidepsin, at least partially, tilted this balance in the opposite direction. Knockdown experiments with siRNA in UCC confirmed BID and BCL2L1/BCLX as two key factors for the altered susceptibility of the UCC. Conclusion Our data suggest that the combination of decitabine with CAR T-cell therapy is an attractive novel therapeutic approach to enhance tumor-specific killing of bladder cancer. Since BID and BCL2L1 are essential determinants for the susceptibility of a wide variety of malignant cells, their targeting might be additionally suitable for combination with immunotherapies, e.g., CAR T-cells or checkpoint inhibitors in other malignancies.
Patient Uptake, Experiences, and Process Evaluation of a Randomized Controlled Trial of Internet-Based Cognitive Behavioral Therapy for Tinnitus in the United States

Introduction: An internet-based cognitive behavioral therapy (ICBT) offers a way to increase access to evidence-based tinnitus care. To increase the accessibility of this intervention, the materials were translated into Spanish to reach Spanish as well as English speakers. A clinical trial indicated favorable outcomes of ICBT for tinnitus for the population of the United States. In view of later dissemination, a way to increase the applicability of this intervention is required. Such understanding is best obtained by considering the perspectives and experiences of participants of an intervention. This study aimed to identify the processes that could facilitate or hinder the clinical implementation of ICBT in the United States. Methods: This study evaluated the processes regarding enrolment, allocation, intervention delivery, the outcomes obtained, and the trial implementation. The study sample consisted of 158 participants who were randomly assigned to the experimental and control group. Results: Although the recruitment was sufficient for English speakers, recruiting the Spanish participants and participants belonging to ethnic minority groups was difficult despite using a wide range of recruitment strategies. The allocation processes were effective in successfully randomizing the groups. The intervention was delivered as planned, but not all the participants chose to engage with the materials provided. Compliance for completing the outcome measures was low. The personal and intervention factors were identified as barriers for the implementation whereas the facilitators included the support received, being empowering, the accessibility of the intervention, and its structure. Conclusion: An understanding regarding the factors contributing to the outcomes obtained, the barriers and facilitators of the results, engagement, and compliance were obtained. These insights will be helpful in preparing for the future dissemination of such interventions. Clinical Trial Registration: www.ClinicalTrials. gov, identifier: NCT04004260. Registered on 2 July 2019.
A Two-step Strategy for High-Value-Added Utilization of Rapeseed Meal by Concurrent Improvement of Phenolic Extraction and Protein Conversion for Microbial Iturin A Production

Rapeseed meal (RSM) is a major by-product of oil extraction from rapeseed, consists mainly of proteins and phenolic compounds. The use of RSM as protein feedstock for microbial fermentation is always hampered by phenolic compounds, which have antioxidant property with health-promoting benefits but inhibit bacterial growth. However, there is still not any good process that simultaneously improve extraction efficiency of phenolic compounds with conversion efficiency of protein residue into microbial production. Here we established a two-step strategy including fungal pretreatment followed by extraction of phenolic compounds. This could not only increase extraction efficiency and antioxidant property of phenolic compounds by about 2-fold, but also improve conversion efficiency of protein residue into iturin A production by Bacillus amyloliquefaciens CX-20 by about 33%. The antioxidant and antibacterial activities of phenolic extracts were influenced by both total phenolic content and profile, while microbial feedstock value of residue was greatly improved because protein content was increased by ∼5% and phenolic content was decreased by ∼60%. Moreover, this two-step process resulted in isolating more proteins from RSM, bringing iturin A production to 1.95 g/L. In conclusion, high-value-added and graded utilization of phenolic extract and protein residue from RSM with zero waste is realized by a two-step strategy, which combines both benefits of fungal pretreatment and phenolic extraction procedures.
Deep-Learning-Based Natural Language Processing of Serial Free-Text Radiological Reports for Predicting Rectal Cancer Patient Survival

Most electronic medical records, such as free-text radiological reports, are unstructured; however, the methodological approaches to analyzing these accumulating unstructured records are limited. This article proposes a deep-transfer-learning-based natural language processing model that analyzes serial magnetic resonance imaging reports of rectal cancer patients and predicts their overall survival. To evaluate the model, a retrospective cohort study of 4,338 rectal cancer patients was conducted. The experimental results revealed that the proposed model utilizing pre-trained clinical linguistic knowledge could predict the overall survival of patients without any structured information and was superior to the carcinoembryonic antigen in predicting survival. The deep-transfer-learning model using free-text radiological reports can predict the survival of patients with rectal cancer, thereby increasing the utility of unstructured medical big data.
Trace Metal Lead Exposure in Typical Lip Cosmetics From Electronic Commercial Platform: Investigation, Health Risk Assessment and Blood Lead Level Analysis

Lead (Pb) in lipstick products has become an increasing concern, which can cause safety problems to human body directly with diet. To investigate the Pb exposure and potential health risk level of typical popular lip cosmetics in Chinese e-commerce market, Python crawler was introduced to identify and select 34 typical popular lip cosmetics, including 12 lipsticks, 13 lip glosses, and 9 lip balms. And then this study used ICP-MS to determine the content of Pb. Furthermore, the ingestion health risk assessment method issued by United States Environmental Protection Agency (USEPA) and Monte Carlo simulation algorithm were applied to assess the probabilistic health risks of adults exposure. Finally, taking the possible exposure of children contacting with lip products, the health risk assessment of children blood Pb was carried out. The results showed that the concentration of Pb in lip products ranged from 0 to 0.5237 mg/kg, which was far lower than the limit set by various countries. The probabilistic non-carcinogenic risks and carcinogenic risks were 4.93 ×10−7~2.82 ×10−3 and 1.68 ×10−12~9.59 ×10−9, respectively, which were in an acceptable level. The results of blood Pb assessment suggested that the Pb content of lip cosmetics had no obvious influence on blood Pb concentration of children, and background Pb exposure is the main factor affecting children's blood Pb level (BLL). Overall, the samples of lip products are selected by Python crawler in this study, which are more objective and representative. This study focuses on deeper study of Pb, especially for the health risk assessment of blood Pb in children exposed to lip products. These results perhaps could provide useful information for the safety cosmetics usage for people in China and even the global world.
Bioinformatics on the Road: Taking Training to Students and Researchers Beyond State Capitals

In Brazil, training capable bioinformaticians is done, mostly, in graduate programs, sometimes with experiences during the undergraduate period. However, this formation tends to be inefficient in attracting students to the area and mainly in attracting professionals to support research projects in research groups. To solve these issues, participation in short courses is important for training students and professionals in the usage of tools for specific areas that use bioinformatics, as well as in ways to develop solutions tailored to the local needs of academic institutions or research groups. In this aim, the project “Bioinformática na Estrada” (Bioinformatics on the Road) proposed improving bioinformaticians’ skills in undergraduate and graduate courses, primarily in the countryside of the State of Pará, in the Amazon region of Brazil. The project scope is practical courses focused on the areas of interest of the place where the courses are occurring to train and encourage students and researchers to work in this field, reducing the existing gap due to the lack of qualified bioinformatics professionals. Theoretical and practical workshops took place, such as Introduction to Bioinformatics, Computer Science Basics, Applications of Computational Intelligence applied to Bioinformatics and Biotechnology, Computational Tools for Bioinformatics, Soil Genomics and Research Perspectives and Horizons in the Amazon Region. In the end, 444 undergraduate and graduate students from higher education institutions in the state of Pará and other Brazilian states attended the events of the Bioinformatics on the Road project.
Identification and Characterization of Nine Novel X-Chromosomal Short Tandem Repeats on Xp21.1, Xq21.31, and Xq23 Regions

The application of X-chromosomal short tandem repeats (X-STRs) has been recognized as a powerful tool in complex kinship testing. To support further development of X-STR analysis in forensic use, we identified nine novel X-STRs, which could be clustered into three linkage groups on Xp21.1, Xq21.31, and Xq23. A multiplex PCR system was built based on the electrophoresis. A total of 198 unrelated Shanghai Han samples along with 168 samples from 43 families was collected to investigate the genetic polymorphism and forensic parameters of the nine loci. Allele numbers ranged from 5 to 12, and amplicon sizes ranged from 146 to 477 bp. The multiplex showed high values for the combined power of discrimination (0.99997977 in males and 0.99999999 in females) and combined mean exclusion chances (0.99997918 and 0.99997821 in trios, 0.99984939 in duos, and 0.99984200 in deficiency cases). The linkage between all pairs of loci was estimated via Kosambi mapping function and linkage disequilibrium test, and further investigated through the family study. The data from 43 families strongly demonstrated an independent transmission between LGs and a tight linkage among loci within the same LG. All these results support that the newly described X-STRs and the multiplex system are highly promising for further forensic use.
Characterization of microRNA Profiles in Pasteurella multocida-Infected Rabbits and Identification of miR-29-5p as a Regulator of Antibacterial Immune Response

Pasteurella multocida is the pathogenic agent for a variety of severe diseases in livestock, including rabbits. MicroRNAs (miRNAs) participate in the immune response to the pathogen. Distinct miRNA expression patterns were explored in rabbit lung by small-RNA deep sequencing to assess dysregulated miRNAs during P. multocida infection. Totally, 571 miRNAs were screened, of which, 62 were novel, and 32 exhibited differential expression (DE). Of the 32 known DE-miRNAs, 13 and 15 occurred at 1 day and 3 days post-infection (dpi); and ocu-miR-107-3p and ocu-miR-29b-5p were shared between the two time points. Moreover, 7,345 non-redundant target genes were predicted for the 32 DE-miRNAs. Putative target genes were enriched in diverse GO and KEGG pathways and might be crucial for disease resistance. Interestingly, upregulation of ocu-miR-29-5p suppresses P. multocida propagation and downregulates expression of epithelial membrane protein-2 (EMP2) and T-box 4 (TBX4) genes by binding to their 3′ untranslated region in RK13 cells. Thus, ocu-miR-29-5p may indirectly inhibit P. multocida invasion by modulating genes related to the host immune response, such as EMP2 and TBX4.
Nyström Regularization for Time Series Forecasting

This paper focuses on learning rate analysis of Nystr\"{o}m regularization with sequential sub-sampling for $\tau$-mixing time series. Using a recently developed Banach-valued Bernstein inequality for $\tau$-mixing sequences and an integral operator approach based on second-order decomposition, we succeed in deriving almost optimal learning rates of Nystr\"{o}m regularization with sequential sub-sampling for $\tau$-mixing time series. A series of numerical experiments are carried out to verify our theoretical results, showing the excellent learning performance of Nystr\"{o}m regularization with sequential sub-sampling in learning massive time series data. All these results extend the applicable range of Nystr\"{o}m regularization from i.i. d. samples to non-i.i. d. sequences.