Miracle-dz/UniFAR-FTUs huggingface dataset:
Effects of oral anticoagulant therapy in patients with pulmonary diseases

Background To evaluate the effect of oral anticoagulants (OACs) therapy, including vitamin K antagonist (VKA) and direct oral anticoagulants (DOAC) in patients with pulmonary diseases. Methods Literature from PubMed, MEDLINE, and Cochrane Library were screened until June 2022. Studies assessing OACs for pulmonary hypertension (PH), pulmonary embolism (PE), pulmonary fibrosis (PF), or chronic obstructive pulmonary disease (COPD) were evaluated for inclusion. Results Our study indicated that in patients with PH, PE, and COPD, OACs could significantly reduce the mortality risk, and the effects of VKA and DOACs without statistical difference in reducing the risk of recurrent embolism events. In patients with sclerosis-associated pulmonary arterial hypertension (SSc-PAH) or idiopathic pulmonary fibrosis (IPF), vitamin K antagonist (warfarin) significantly increased the mortality risk, while DOACs were not. As for the safety outcome of OACs, existing studies indicate that compared with patients treated with warfarin, the users of DOAC have a lower risk of major bleeding, while there is no statistical significance between them in non-major bleeding events. In current guidelines, the anticoagulation regimen for patients with pulmonary disease has not been defined. The results of our study confirm that DOACs (apixaban, rivaroxaban, dabigatran, and edoxaban) are superior to VKAs in the efficacy and safety outcomes of patients with pulmonary disease. Conclusions Oral anticoagulant therapy brings benefits to patients with PH, PE, or COPD, while the anticoagulation regimen for patients with SSc-PAH or IPF requires serious consideration. Compared with VKA, DOAC is a non-inferior option for anticoagulation in pulmonary disease treatment. Further studies are still needed to provide more reliable evidence about the safety outcome of pulmonary disease anticoagulation.
Potential protective benefits of Schisandrin B against severe acute hepatitis in children during the COVID-19 pandemic based on a network pharmacology analysis

Aims: Reports of hepatitis in children during the coronavirus disease 2019 (COVID-19) pandemic garnered worldwide attention. The most probable culprits are adenovirus and severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). At present, the optimal symptomatic treatment consists of a combination of anti-COVID-19 and hepatitis symptom alleviators. Schisandrin B (SchB) has been known to have liver-protective properties for a long time, whereas anti-COVID-19 properties only recently have been discovered. In the case of COVID-19 with hepatitis of unknown origin, we used network pharmacology to explore the symptomatic therapy and protective effects of SchB. Main methods: The most probable protein targets of SchB were predicted in the SwissTargetPrediction database. The GeneCards, National Center for Biotechnology Information, and Online Mendelian Inheritance in Man databases were used to compile information on the diseases hepatitis, adenovirus, and SARS-CoV-2. Following the use of a Venn diagram viewer to identify intersection genes, we constructed a protein–protein interaction network and identified the core genes. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment, as well as molecular docking, were employed to highlight the mechanisms of SchB on hepatitis. Key findings: SchB contains 27 targets on adenovirus_hepatitis and 16 targets on SARS-CoV-2_hepatitis, with 12 shared genes. Both target populations clustered in viral infection and cancer pathways, as well as in processes such as kinase activity phosphatase, cell adhesion, and ATPase binding. These genes might be closely related to liver damage and membrane binding from adenovirus or SARS-CoV-2 infections. In addition, epidermal growth factor receptor, HSP90AA1, and MAPK1 were among the top five targets of both SchB SARS-CoV-2 hepatitis and SchB adenovirus hepatitis. Significance: SchB may target common protective targets and mechanisms against acute hepatitis caused by adenovirus or by SARS-CoV-2 in children during the COVID-19 pandemic. These findings indicate SchB’s potential as a treatment for hepatitis of unknown origin.
Climate factors determine the utilization strategy of forest plant resources at large scales

Plant functional traits are a representation of plant resource utilization strategies. Plants with higher specific leaf area (SLA) and lower leaf dry matter content (LDMC) exhibit faster investment-return resource utilization strategies. However, the distribution patterns and driving factors of plant resource utilization strategies at the macroscale are rarely studied. We investigated the relative importance of climatic and soil factors in shaping plant resource utilization strategies at different life forms in forests using data collected from 926 plots across 163 forests in China. SLA and LDMC of plants at different life forms (i.e., trees, shrubs, and herbs) differ significantly. Resource utilization strategies show significant geographical differences, with vegetation in the western arid regions adopting a slower investment-return survival strategy and vegetation in warmer and wetter areas adopting a faster investment-return survival strategy. SLA decreases significantly with increased temperature and reduced rainfall, and vegetation growing in these conditions exhibits conservative resource utilization. Mean annual precipitation (MAP) is a key climatic factor that controls the resource utilization strategies of plants at the macroscale. Plants use resources more conservatively as soil pH increases. The influence of climate and soil factors is coupled to determine the resource utilization strategies of plants occupying different life forms at the macroscale, but the relative contribution of each varies across life forms. Our findings provide a theoretical framework for understanding the potential impact of increasing global temperatures on plant resource utilization.
Primary and memory immune responses against rough Brucella canis are less robust compared to smooth B. abortus and B. melitensis following intratracheal infection in mice

Brucella canis is the cause of canine brucellosis, a globally distributed, zoonotic pathogen which primarily causes disease in dogs. B. canis is unique amongst the zoonotic Brucella spp. with its rough lipopolysaccharide, a trait typically associated with attenuation in gram-negative bacteria. Unfortunately, no vaccine is available against B. canis, and vaccine development is hampered by a limited understanding of the immune response required to combat it and the course of infection following a physiologically relevant, mucosal route of inoculation. To address these concerns and analyze the impact of the rough phenotype on the immune response, we infected mice intratracheally with rough B. canis or smooth B. melitensis or B. abortus. Bacterial colonization and histologic lesions were assessed in systemic target organs as well as locally in the lungs and draining mediastinal lymph node. Mice were also reinfected with Brucella following antibiotic treatment and cytokine production by T lymphocytes in the lung and spleen was assessed by flow cytometry to investigate the memory immune response. Despite its rough phenotype, B. canis established a persistent infection at the same level of colonization as the smooth strains. However, B. canis induced significantly less granulomatous inflammation in the spleen as well as a lack of bronchial-associated lymphoid tissue (BALT) hyperplasia in the lungs. These differences coincided with increased IL-10 and decreased IFN-γ in the spleen of B. canis-infected mice. Previous exposure to all Brucella strains provided protection against colonization following secondary challenge, although induction of IFN-γ by T lymphocytes was seen only in the lungs during B. canis infection while the smooth strains induced this cytokine in the spleen as well. Neither Brucella strain induced significant polyfunctional T lymphocytes, a potential immunomodulatory mechanism that appears to be independent of lipopolysaccharide phenotype.
Oxidative stress: An essential factor in the process of arteriovenous fistula failure

For more than half a century, arteriovenous fistula (AVFs) has been recognized as a lifeline for patients requiring hemodialysis (HD). With its higher long-term patency rate and lower probability of complications, AVF is strongly recommended by guidelines in different areas as the first choice for vascular access for HD patients, and its proportion of application is gradually increasing. Despite technological improvements and advances in the standards of postoperative care, many deficiencies are still encountered in the use of AVF related to its high incidence of failure due to unsuccessful maturation to adequately support HD and the development of neointimal hyperplasia (NIH), which narrows the AVF lumen. AVF failure is linked to the activation and migration of vascular cells and the remodeling of the extracellular matrix, where complex interactions between cytokines, adhesion molecules, and inflammatory mediators lead to poor adaptive remodeling. Oxidative stress also plays a vital role in AVF failure, and a growing amount of data suggest a link between AVF failure and oxidative stress. In this review, we summarize the present understanding of the pathophysiology of AVF failure. Furthermore, we focus on the relation between oxidative stress and AVF dysfunction. Finally, we discuss potential therapies for addressing AVF failure based on targeting oxidative stress.
Analytical results for phase bunching in the pendulum model of wave-particle interactions

Radiation belt electrons are strongly affected by resonant interactions with cyclotron-resonant waves. In the case of a particle passing through resonance with a single, coherent wave, a Hamiltonian formulation is advantageous. With certain approximations, the Hamiltonian has the same form as that for a plane pendulum, leading to estimates of the change at resonance of the first adiabatic invariant I, energy, and pitch angle. In the case of large wave amplitude (relative to the spatial variation of the background magnetic field), the resonant change in I and its conjugate phase angle ξ are not diffusive but determined by nonlinear dynamics. A general analytical treatment of slow separatrix crossing has long been available and can be used to give the changes in I associated with “phase bunching,” including the detailed dependence on ξ, in the nonlinear regime. Here we review this treatment, evaluate it numerically, and relate it to previous analytical results for nonlinear wave-particle interactions. “Positive phase bunching” can occur for some particles even in the pendulum Hamiltonian approximation, though the fraction of such particles may be exponentially small.
Global spectrum of USH2A mutation in inherited retinal dystrophies: Prompt message for development of base editing therapy

Purpose Mutation in the USH2A gene is the most common cause of inherited retinal dystrophy (IRD), including non-syndromic retinitis pigmentosa (RP) and Usher syndrome II (USH2). Gene editing and therapy targeting USH2A, especially the hotspot region, would benefit a large proportion of IRD patients. In this study, we comprehensively analyzed the genetic spectrum of the USH2A gene, aiming to identify global hot spot mutations in USH2A-related IRDs and differences in hot spot regions across continents. Materials and methods A retrospective USH2A-related IRD study was conducted, including our IRD cohort, and reported USH2A studies worldwide. Results A total of 3,972 mutated USH2A alleles of approximately 1,935 patients were collected from 33 cohort studies worldwide, containing 102 alleles of 51 patients in our IRD cohort. Mutations in exon 13 were the most common, reaching 18.4% globally and a higher frequency of 22% in America, 19.2% in Europe, and a lower 12% in East Asia. Pathogenic mutations that affected 10 of the 72 exons of USH2A, exon 2, exon 13, exon 41–43, exon 50, exon 54, exon 57, exon 61, and exon 63 in total were responsible for half of global USH2A mutant alleles. With base editors including adenine base editor (ABE), cytidine base editor (CBE), and glycosylase base editor (GBE), 76.3% of single nucleotide variations (SNVs) and 58% of all mutations in USH2A are correctable. Meantime, four novel pathogenic mutations were revealed in our IRD cohort, p. (Val1130Cysfs*72), p. (Ala2139fs*14), p. (Gly4139Arg), and p. (Val4166Cysfs*7). Conclusion In this study, we revealed four novel mutations, expanding the spectrum of USH2A mutations, and importantly presented global hotspot exons and mutations of USH2A as well as the proportion of SNVs that can be restored by different base editors, providing a perspective for exploring high-efficiency and broader-reaching gene editing and gene therapies.
Conditions affecting the association of general trait-anxiety with the ERN-Ne

The ERN-Ne of the event-related potential indicates error monitoring. Even though enlarged ERN-Ne amplitudes have often been related to higher anxiety scores, a recent meta-analysis provided very small effect sizes for the association of trait-anxiety with the ERN-Ne. Conditions modulating this association were investigated in the present study: (1) The generality of the trait-anxiety factor, (2) gender, and (3) experimental conditions, i.e., worry induction and error aversiveness. Participants (48% men) completed a flanker task. Worries were induced before the task by giving participants (n = 61) a bogus feedback claiming their responses were slower than the average responses of participants, whereas other participants (n = 61) got the feedback that they responded as fast as other participants. Aversiveness of errors was varied by playing sinus tones after too slow responses in one part of the task (no-scream condition) and aversive screams after too slow responses in another part (scream condition). Increased ERN-Ne amplitudes of response time errors occurred for individuals higher on trait-anxiety in the condition with induced worries and screams. A multiple group model for women and men indicated that women are more sensitive to conditions altering the association of trait-anxiety with the ERN-Ne.
Examining the moderating role of technostress and compatibility in EFL Learners’ mobile learning adoption: A perspective from the theory of planned behaviour

Mobile English learning has multiple advantages and brings enormous benefits to EFL learners. However, not everyone adopts it, and the determinants of learners’ adoption intention have not yet been investigated fully. This study aimed to better understand learners’ adoption by employing the theory of planned behaviour (TPB) in conjunction with the influences of technostress and compatibility. Based on existing literature, a research model was proposed and verified with a sample of 409 undergraduates from a Chinese university. The results indicated that in the context of mobile English learning: (a) Individuals with higher adoption intention are more likely to engage in mobile English learning with higher frequency (b = 0.473, P < 0.001) and longer duration (b = 0.330, P < 0.001); (b) Individuals’ attitude toward mobile English learning (b = 0.171, P < 0.05), perceived behavioural control (b = 0.221, P < 0.001), subjective norms (b = 0.237, P < 0.05), and compatibility (b = 0.443, P < 0.001) are significantly positively associated with their adoption intention; (c) Compatibility is the strongest predictor of adoption intention (b = 0.443, P < 0.001) and negatively moderates the effect of subjective norms on adoption intention (b = –0.103, P < 0.005); (d) The influence of technostress on the adoption intention of mobile English learning is not significant (b = –0.041, P > 0.05). Practical implications related to mobile English learning were discussed.
Paternal alcohol exposures program intergenerational hormetic effects on offspring fetoplacental growth

Hormesis refers to graded adaptive responses to harmful environmental stimuli where low-level toxicant exposures stimulate tissue growth and responsiveness while, in contrast, higher-level exposures induce toxicity. Although the intergenerational inheritance of programmed hormetic growth responses is described in plants and insects, researchers have yet to observe this phenomenon in mammals. Using a physiologically relevant mouse model, we demonstrate that chronic preconception paternal alcohol exposures program nonlinear, dose-dependent changes in offspring fetoplacental growth. Our studies identify an inverse j-shaped curve with a threshold of 2.4 g/Kg per day; below this threshold, paternal ethanol exposures induce programmed increases in placental growth, while doses exceeding this point yield comparative decreases in placental growth. In male offspring, higher paternal exposures induce dose-dependent increases in the placental labyrinth layer but do not impact fetal growth. In contrast, the placental hypertrophy induced by low-level paternal ethanol exposures associate with increased offspring crown-rump length, particularly in male offspring. Finally, alterations in placental physiology correlate with disruptions in both mitochondrial-encoded and imprinted gene expression. Understanding the influence of ethanol on the paternally-inherited epigenetic program and downstream hormetic responses in offspring growth may help explain the enormous variation observed in fetal alcohol spectrum disorder (FASD) phenotypes and incidence.
Raloxifene Stimulates Estrogen Signaling to Protect Against Age- and Sex-Related Intervertebral Disc Degeneration in Mice

Estrogen agonist raloxifene is an FDA-approved treatment of osteoporosis in postmenopausal women, which may also be a promising prophylactic for painful intervertebral disc (IVD) degeneration. Here, we hypothesized that 1) aging and biological sex contribute to IVD degeneration by reducing estrogen signaling and that 2) raloxifene stimulates estrogen signaling to protect against age- and sex-related IVD degeneration in mice. 2.5-month-old (male and female) and 22.5-month-old (female) C57Bl/6J mice were subcutaneously injected with raloxifene hydrochloride 5x/week for 6 weeks (n = 7–9/grp). Next, female mice were ovariectomized (OVX) or sham operated at 4 months of age and tissues harvested at 6 months (n = 5–6/grp). Advanced aging and OVX increased IVD degeneration score, weakened IVD strength, reduced estrogen receptor-α (ER-α) protein expression, and increased neurotransmitter substance P (SP) expression. Similar to aging and compared with male IVDs, female IVDs were more degenerated, mechanically less viscoelastic, and expressed less ER-α protein, but unlike the effect induced by aging or OVX, IVD mechanical force was greater in females than in males. Therapeutically, systemic injection of raloxifene promoted ER-α protein to quell these dysregulations by enlarging IVD height, alleviating IVD degeneration score, increasing the strength and viscoelastic properties of the IVD, and reducing IVD cell expression of SP in young-adult and old female mice. Transcriptionally, injection of raloxifene upregulated the gene expression of ER-α and extracellular matrix-related anabolism in young-adult and old IVD. In vertebra, advanced aging and OVX reduced trabecular BV/TV, whereas injection of raloxifene increased trabecular BV/TV in young-adult and old female mice, but not in young-adult male mice. In vertebra, advanced aging, OVX, and biological sex (females > males) increased the number of SP-expressing osteocytes, whereas injection of raloxifene reduced the number of SP-expressing osteocytes in young-adult female and male mice and old female mice. Overall, injection of estrogen agonist raloxifene in mice normalized dysregulation of IVD structure, IVD mechanics, and pain-related SP expression in IVD cells and osteocytes induced by aging and biological sex. These data suggest that, in addition to bone loss, raloxifene may relieve painful IVD degeneration in postmenopausal women induced by advanced age, biological sex, and estrogen depletion.
Integration of RNA-seq and ATAC-seq identifies muscle-regulated hub genes in cattle

As the main product of livestock, muscle itself plays an irreplaceable role in maintaining animal body movement and regulating metabolism. Therefore, it is of great significance to explore its growth, development and regeneration to improve the meat yield and quality of livestock. In this study, we attempted to use RNA-seq and ATAC-seq techniques to identify differentially expressed genes (DEGs) specifically expressed in bovine skeletal muscle as potential candidates for studying the regulatory mechanisms of muscle development. Microarray data from 8 tissue samples were selected from the GEO database for analysis. First, we obtained gene modules related to each tissue through WGCNA analysis. Through Gene Ontology (GO) functional annotation, the module of lightyellow (MElightyellow) was closely related to muscle development, and 213 hub genes were screened as follow-up research targets. Further, the difference analysis showed that, except for PREB, all other candidate hub genes were up-regulated (muscle group vs. other-group). ATAC-seq analysis showed that muscle-specific accessible chromatin regions were mainly located in promoter of genes related to muscle structure development (GO:0061061), muscle cell development (GO:0055001) and muscle system process (GO:0003012), which were involved in cAMP, CGMP-PKG, MAPK, and other signaling pathways. Next, we integrated the results of RNA-seq and ATAC-seq analysis, and 54 of the 212 candidate hub genes were identified as key regulatory genes in skeletal muscle development. Finally, through motif analysis, 22 of the 54 key genes were found to be potential target genes of transcription factor MEF2C. Including CAPN3, ACTN2, MB, MYOM3, SRL, CKM, ALPK3, MAP3K20, UBE2G1, NEURL2, CAND2, DOT1L, HRC, MAMSTR, FSD2, LRRC2, LSMEM1, SLC29A2, FHL3, KLHL41, ATXN7L2, and PDRG1. This provides a potential reference for studying the molecular mechanism of skeletal muscle development in mammals.