Miracle-dz/UniFAR-FTUs huggingface dataset:
Lysine Methylation Modulates the Interaction of Archaeal Chromatin Protein Cren7 With DNA

Cren7 and Sis7d, two chromatin proteins from Sulfolobus islandicus, undergo extensive methylations at multiple lysine residues to various extents. Whether this highly conserved protein serves an epigenetic role in the regulation of the structure and function of the chromosome remains unclear. In the present study, we show that methylation significantly affects Cren7, but not Sis7d, in the ability to bind DNA and to constrain negative DNA supercoils. Strikingly, methylated Cren7 was significantly less efficient in forming oligomers or mediating intermolecular DNA bridging. Single-site substitution mutation with glutamine reveals that methylation of the four lysine residues (K24, K31, K42, and K48) of Cren7 at the protein-DNA interface, which are variably conserved among Cren7 homologues from different branches of the Crenarchaeota, influenced Cren7-DNA interactions in different manners. We suggest that dynamic methylation of Cren7 may represent a potential epigenetic mechanism involved in the chromosomal regulation in crenarchaea.
Evaluation of a Simple Clinical Language Paradigm With Respect to Sensory Independency, Functional Asymmetry, and Effective Connectivity

The present study replicates a known visual language paradigm, and extends it to a paradigm that is independent from the sensory modality of the stimuli and, hence, could be administered either visually or aurally, such that both patients with limited sight or hearing could be examined. The stimuli were simple sentences, but required the subject not only to understand the content of the sentence but also to formulate a response that had a semantic relation to the content of the presented sentence. Thereby, this paradigm does not only test perception of the stimuli, but also to some extend sentence and semantic processing, and covert speech production within one task. When the sensory base-line condition was subtracted, both the auditory and visual version of the paradigm demonstrated a broadly overlapping and asymmetric network, comprising distinct areas of the left posterior temporal lobe, left inferior frontal areas, left precentral gyrus, and supplementary motor area. The consistency of activations and their asymmetry was evaluated with a conjunction analysis, probability maps, and intraclass correlation coefficients (ICC). This underlying network was further analyzed with dynamic causal modeling (DCM) to explore whether not only the same brain areas were involved, but also the network structure and information flow were the same between the sensory modalities. In conclusion, the paradigm reliably activated the most central parts of the speech and language network with a great consistency across subjects, and independently of whether the stimuli were administered aurally or visually. However, there was individual variability in the degree of functional asymmetry between the two sensory conditions.
Development of an Adeno-Associated Virus-Vectored SARS-CoV-2 Vaccine and Its Immunogenicity in Mice

Owing to the outbreak of the novel coronavirus (SARS-CoV-2) worldwide at the end of 2019, the development of a SARS-CoV-2 vaccine became an urgent need. In this study, we developed a type 9 adeno-associated virus vectored vaccine candidate expressing a dimeric receptor binding domain (RBD) of the SARS-CoV-2 spike protein (S protein) and evaluated its immunogenicity in a murine model. The vaccine candidate, named AAV9-RBD virus, was constructed by inserting a signal peptide to the N-terminus of two copies of RBD, spaced by a linker, into the genome of a type 9 adeno-associated virus. In vitro assays showed that HeLa cells infected by the recombinant AAV virus expressed high levels of the recombinant RBD protein, mostly found in the cell culture supernatant. The recombinant AAV9-RBD virus was cultured and purified. The genome titer of the purified recombinant AAV9-RBD virus was determined to be 2.4 × 1013 genome copies/mL (GC/mL) by Q-PCR. Balb/c mice were immunized with the virus by intramuscular injection or nasal drip administration. Eight weeks after immunization, neutralizing antibodies against the new coronavirus pseudovirus were detected in the sera of all mice; the mean neutralizing antibody EC50 values were 517.7 ± 292.1 (n=10) and 682.8 ± 454.0 (n=10) in the intramuscular injection group and nasal drip group, respectively. The results of this study showed that the recombinant AAV9-RBD virus may be used for the development of a SARS-CoV-2 vaccine.
Metabolome Analysis of Banana (Musa acuminata) Treated With Chitosan Coating and Low Temperature Reveals Different Mechanisms Modulating Delayed Ripening

Banana (Musa acuminata) is one of the most important crop plants consumed in many countries. However, the commercial value decreases during storage and transportation. To maintain fruit quality, postharvest technologies have been developed. Storage at low temperature is a common method to prolong the shelf life of food products, especially during transportation and distribution. Another emerging approach is the use of chitosan biopolymer as an edible coating, which can extend the shelf life of fruit by preventing moisture and aroma loss, and inhibiting oxygen penetration into the plant tissue. Gas chromatography-mass spectrometry metabolite profiling of the banana ripening process was performed to clarify the global metabolism changes in banana after chitosan coating or storage at low temperature. Both postharvest treatments were effective in delaying banana ripening. Interestingly, principal component analysis and orthogonal projection to latent structure regression analysis revealed significant differences of both treatments in the metabolite changes, indicating that the mechanism of prolonging the banana shelf life may be different. Chitosan (1.25% w/v) treatment stored for 11 days resulted in a distinct accumulation of 1-aminocyclopropane-1-carboxylic acid metabolite, an important precursor of ethylene that is responsible for the climacteric fruit ripening process. Low temperature (LT, 14 ± 1°C) treatment stored for 9 days resulted in higher levels of putrescine, a polyamine that responds to plant stress, at the end of ripening days. The findings clarify how chitosan delays fruit ripening and provides a deeper understanding of how storage at low temperature affects banana metabolism. The results may aid in more effective development of banana postharvest strategies.
PEAC: An Ultrasensitive and Cost-Effective MRD Detection System in Non-small Cell Lung Cancer Using Plasma Specimen

Circulating tumor DNA (ctDNA), a tumor-derived fraction of cell-free DNA (cfDNA), has emerged as a promising marker in targeted therapy, immunotherapy, and minimal residual disease (MRD) monitoring in postsurgical patients. However, ctDNA level in early-stage cancers and postsurgical patients is very low, which posed many technical challenges to improve the detection rate and sensitivity, especially in the clinical practice of MRD detection. These challenges usually include insufficient DNA input amount, limit of detection (LOD), and high experimental costs. To resolve these challenges, we developed an ultrasensitive ctDNA MRD detection system in this study, namely PErsonalized Analysis of Cancer (PEAC), to simultaneously detect up to 37 mutations, which account for 70–80% non-small cell lung cancer (NSCLC) driver mutations from low plasma sample volume and enables LOD of 0.01% at a single-site level. We demonstrated the high performance achieved by PEAC on both cfDNA reference standards and clinical plasma samples from three NSCLC patient cohorts. For cfDNA reference standards, PEAC achieved a specificity of 99% and a sensitivity of 87% for the mutations at 0.01% allele fraction. In the second cohort, PEAC showed 100% concordance rate between ddPCR and Next-generation sequencing (NGS) among 29 samples. In the third cohort, 22 of 59 patients received EGFR TKI treatment. Among them, three in four patients identified low level actionable gene mutations only by PEAC had partial responses after targeted therapy, demonstrating high ctDNA detection ability of PEAC. Overall, the developed PEAC system can detect the majority of NSCLC driver mutations using 8–10 ml plasma samples, and has the advantages of high detection sensitivity and lower costs compared with the existing technologies such as ddPCR and NGS. These advantages make the PEAC system quite appropriate for ctDNA and MRD detection in early-stage NSCLC and postsurgical recurrence monitoring.
The Power of Microbiome Studies: Some Considerations on Which Alpha and Beta Metrics to Use and How to Report Results

Background Since sequencing techniques have become less expensive, larger sample sizes are applicable for microbiota studies. The aim of this study is to show how, and to what extent, different diversity metrics and different compositions of the microbiota influence the needed sample size to observe dissimilar groups. Empirical 16S rRNA amplicon sequence data obtained from animal experiments, observational human data, and simulated data were used to perform retrospective power calculations. A wide variation of alpha diversity and beta diversity metrics were used to compare the different microbiota datasets and the effect on the sample size. Results Our data showed that beta diversity metrics are the most sensitive to observe differences as compared with alpha diversity metrics. The structure of the data influenced which alpha metrics are the most sensitive. Regarding beta diversity, the Bray–Curtis metric is in general the most sensitive to observe differences between groups, resulting in lower sample size and potential publication bias. Conclusion We recommend performing power calculations and to use multiple diversity metrics as an outcome measure. To improve microbiota studies, awareness needs to be raised on the sensitivity and bias for microbiota research outcomes created by the used metrics rather than biological differences. We have seen that different alpha and beta diversity metrics lead to different study power: because of this, one could be naturally tempted to try all possible metrics until one or more are found that give a statistically significant test result, i.e., p-value < α. This way of proceeding is one of the many forms of the so-called p-value hacking. To this end, in our opinion, the only way to protect ourselves from (the temptation of) p-hacking would be to publish a statistical plan before experiments are initiated, describing the outcomes of interest and the corresponding statistical analyses to be performed.
Systems Analysis Reveals Contraceptive-Induced Alteration of Cervicovaginal Gene Expression in a Randomized Trial

Hormonal contraceptives (HCs) are vital in managing the reproductive health of women. However, HC usage has been linked to perturbations in cervicovaginal immunity and increased risk of sexually transmitted infections. Here, we evaluated the impact of three HCs on the cervicovaginal environment using high-throughput transcriptomics. From 2015 to 2017, 130 adolescent females aged 15–19 years were enrolled into a substudy of UChoose, a single-site, open-label randomized, crossover trial (NCT02404038) and randomized to injectable norethisterone–enanthate (Net-En), combined oral contraceptives (COC), or etonorgesterol/ethinyl–estradiol–combined contraceptive vaginal ring (CCVR). Cervicovaginal samples were collected after 16 weeks of randomized HC use and analyzed by RNA-Seq, 16S rRNA gene sequencing, and Luminex analysis. Participants in the CCVR arm had a significant elevation of transcriptional networks driven by IL-6, IL-1, and NFKB, and lower expression of genes supporting epithelial barrier integrity. An integrated multivariate analysis demonstrated that networks of microbial dysbiosis and inflammation best discriminated the CCVR arm from the other contraceptive groups, while genes involved in epithelial cell differentiation were predictive of the Net-En and COC arms. Collectively, these data from a randomized trial represent the most comprehensive “omics” analyses of the cervicovaginal response to HCs and provide important mechanistic guidelines for the provision of HCs in sub-Saharan Africa.
Dosimetric Evaluation of Incidental Irradiation to the Internal Mammary Chain After Surgery in Breast Cancer Patients

Background and Purpose The low rate of internal mammary node (IMN) recurrence was attributed to systemic therapy and internal mammary chain (IMC) coverage by the tangential fields of irradiation. This study aimed to evaluate the incidental irradiation dose to the IMC in breast cancer patients after surgery and to estimate the clinical predictive parameters affecting the magnitude of the IMC. Materials and Methods A total of 138 patients treated with postmastectomy radiotherapy and 210 patients undergoing radiotherapy after breast-conserving surgery (BCS) in our hospital were retrospectively analyzed. The mean dose (Dmean) to the IMC and the first to third intercostal spaces of IMC levels (ICS1–3) were evaluated. We evaluated the IMC coverage according to the type of surgery and whether the ipsilateral supraclavicular fossa (SCF) was included in the irradiation field. Results The incidental radiation dose to the IMC was 29.69 Gy, and the dose delivered to the IMC, ICS1, and ICS2 showed a greater coverage in the modified radical mastectomy (MRM) group when compared with the BCS group (32.85 vs. 27.1 Gy, 26.6 vs. 12.5 Gy, 34.63 vs. 30.42 Gy). The dose delivered to ICS3 showed no difference between the MRM and BCS groups (37.41 vs. 36.24 Gy). Furthermore, 131 patients (37.64%) received radiotherapy to the chest wall and ipsilateral SCF. In the univariate analysis, both surgery type and SCF irradiation were parameters affecting the Dmean of incidental radiation to the IMC (r = −0.179, P = 0.001; r = −0.175, P = 0.001). In the multivariate analysis, surgery type was the only correlative factor that affected incidental radiation dose to the IMC (r = –3.534, P = 0.000). Conclusion The real influencing factor of incidental dose to the IMC was the surgery form rather than the accession of SCF irradiation.
Recruitment of LC3 by Campylobacter jejuni to Bacterial Invasion Site on Host Cells via the Rac1-Mediated Signaling Pathway

Campylobacter jejuni is a leading cause of food-borne disease worldwide. The pathogenicity of C. jejuni is closely associated with the internalization process in host epithelial cells, which is related to a host immune response. Autophagy indicates a key role in the innate immune system of the host to exclude invasive pathogens. Most bacteria are captured by autophagosomes and degraded by autophagosome-lysosome fusion in host cells. However, several pathogens, such as Salmonella and Shigella, avoid and/or escape autophagic degradation to establish infection. But autophagy involvement as a host immune response to C. jejuni infection has not been clarified. This study revealed autophagy association in C. jejuni infection. During infection, C. jejuni activated the Rho family small GTPase Rac1 signaling pathway, which modulates actin remodeling and promotes the internalization of this pathogen. In this study, we found the LC3 contribution to C. jejuni invasion signaling via the Rac1 signaling pathway. Interestingly, during C. jejuni invasion, LC3 was recruited to bacterial entry site depending on Rac1 GTPase activation just at the early step of the infection. C. jejuni infection induced LC3-II conversion, and autophagy induction facilitated C. jejuni internalization. Also, autophagy inhibition attenuated C. jejuni invasion step. Moreover, Rac1 recruited LC3 to the cellular membrane, activating the invasion of C. jejuni. Altogether, our findings provide insights into the new function of LC3 in bacterial invasion. We found the interaction between the Rho family small GTPase, Rac1, and autophagy-associated protein, LC3.
Initial Development and Psychometric Evidence of Physical Education Grit Scale (PE-Grit)

Background Grit is a key concept in positive psychology and educational science. The construct measures two related constructs that are interest and effort. Several instruments have been developed to measure this construct in professional and educational contexts, but no tools have been developed considering specific contexts such as physical education and sport. Objectives The objective of this study is to develop and test a measurement scale to assess Grit in the context of physical education and sport. Methods Two exploratory (Phase 1) and confirmatory (Phase 2) samples were administered the 16-item PE-Grit scale in Arabic. In addition, the confirmatory sample also was administered the R-SPQ-2F two-factor learning approaches scale. The factor structure was examined first by exploratory factor analysis on the first sample and then by confirmatory factor analysis on the second sample. Reliability testing was performed by checking internal consistency simultaneously by the three indices: McDonald's ω, Cronbach's α and Gutmann's λ6. Concurrent validity was checked by Pearson's correlation between the PE-Grit and the two dimensions of the SPQ-2F. Results After the exploratory factor analysis, which identified the factors and gave a preliminary validation of the designed instrument, confirmatory factor analysis was performed on three hierarchical models to be able to identify the best fitting model. A third-order hierarchical model with two physical and academic components each formed by interest and effort presented the best fit indices: chi X2 = 192.95 (p < 0.01), and the X2/DF = 1.36; GFI = 0.99; AGFI = 0.99; CFI and TLI close to 1; RMSEA = 0.025. In addition, McDonald's ω, internal consistency, and Gutmann's λ6 ranged from 0.78 to 0.86 for all four scale dimensions. Conclusion The PE-Grit scale displays adequate factor structure, good reliability, and acceptable concurrent validity and can be administered to assess Grit in physical education and sport students.
An Empirical Study on the Evaluation of Emotional Complexity in Daily Life

Emotional complexity means diversity, universality, and differentiation of individual emotions. This research consisted of two studies to demonstrate the constitution of the emotional complexity. In Study 1, the participants were asked to use 10 emotional words to record the variation of emotions over 30 days in daily life. In Study 2, the experimental materials were enriched. The participants were required to note the emotions with the Positive and Negative Affect Schedule in a 3-day holiday—all the individuals in the two studies needed to record the most important emotional event. As a result, the youth experienced complex emotions every day. Emotional complexity indicators included covariation index (r), component index (Cpc and Cunshared), granularity index (Ge, Gp, and Gn), and variability index (Vp and Vn). A four-factor model reflected a good model fit, with 𝜒2/df = 0.33, CFI = 1.00, TLI = 1.03, RMSEA = 0.000 (0.00, 0.20), SRMR = 0.003, including positive differentiation, covariation of positive affect and negative affect, negative differentiation, and emotional variation. These indicators may reflect the complex experiences in everyday life. The results shed light on the emotional experience that can change greatly within 1 day and on episodes of emotional disruption resulting from an important event coupled with excessive excitement or extreme tension.
Development and Validation of a Machine Learning-Based Radiomics Model on Cardiac Computed Tomography of Epicardial Adipose Tissue in Predicting Characteristics and Recurrence of Atrial Fibrillation

Purpose This study aimed to evaluate the feasibility of differentiating the atrial fibrillation (AF) subtype and preliminary explore the prognostic value of AF recurrence after ablation using radiomics models based on epicardial adipose tissue around the left atrium (LA-EAT) of cardiac CT images. Method The cardiac CT images of 314 patients were collected wherein 251 and 63 cases were randomly enrolled in the training and validation cohorts, respectively. Mutual information and the random forest algorithm were used to screen for the radiomic features and construct the radiomics signature. Radiomics models reflecting the features of LA-EAT were built to differentiate the AF subtype, and the multivariable logistic regression model was adopted to integrate the radiomics signature and volume information. The same methodology and algorithm were applied to the radiomic features to explore the ability for predicting AF recurrence. Results The predictive model constructed by integrating the radiomic features and volume information using a radiomics nomogram showed the best ability in differentiating AF subtype in the training [AUC, 0.915; 95% confidence interval (CI), 0.880–0.951] and validation (AUC, 0.853; 95% CI, 0.755–0.951) cohorts. The radiomic features have shown convincible predictive ability of AF recurrence in both training (AUC, 0.808; 95% CI, 0.750–0.866) and validation (AUC, 0.793; 95% CI, 0.654–0.931) cohorts. Conclusions The LA-EAT radiomic signatures are a promising tool in the differentiation of AF subtype and prediction of AF recurrence, which may have clinical implications in the early diagnosis of AF subtype and disease management.
USP30: Structure, Emerging Physiological Role, and Target Inhibition

Ubiquitin-specific protease 30 (USP30) is a deubiquitinating enzyme (DUB) belonging to the USP subfamily, which was found localized in the mitochondrial outer membrane and peroxisomes owing to its unique transmembrane domain. Structural study revealed that USP30 employed a unique catalytic triad and molecular architecture to preferentially cleave the Lys6 linked ubiquitin chains. USP30 plays an essential role in several cellular events, such as the PINK1/Parkin-mediated mitophagy, pexophagy, BAX/BAK-dependent apoptosis, and IKKβ–USP30–ACLY-regulated lipogenesis/tumorigenesis, and is tightly regulated by post-translational modification including phosphorylation and mono-ubiquitination. Dysregulation of USP30 is associated with a range of physiological disorders, such as neurodegenerative disease, hepatocellular carcinoma, pulmonary disorders, and peroxisome biogenesis disorders. Nowadays, scientists and many biopharmaceutical companies are making much effort to explore USP30 inhibitors including natural compounds, phenylalanine derivatives, N-cyano pyrrolidines, benzosulphonamide, and other compounds. For the treatment of pulmonary disorders, the study in Mission Therapeutics of USP30 inhibitor is already in the pre-clinical stage. In this review, we will summarize the current knowledge of the structure, regulation, emerging physiological role, and target inhibition of USP30, hoping to prompt further investigation and understanding of it.