Miracle-dz/UniFAR-FTUs huggingface dataset:
Roles of the Non-Structural Proteins of Influenza A Virus

Influenza A virus (IAV) is a segmented, negative single-stranded RNA virus that causes seasonal epidemics and has a potential for pandemics. Several viral proteins are not packed in the IAV viral particle and only expressed in the infected host cells. These proteins are named non-structural proteins (NSPs), including NS1, PB1-F2 and PA-X. They play a versatile role in the viral life cycle by modulating viral replication and transcription. More importantly, they also play a critical role in the evasion of the surveillance of host defense and viral pathogenicity by inducing apoptosis, perturbing innate immunity, and exacerbating inflammation. Here, we review the recent advances of these NSPs and how the new findings deepen our understanding of IAV–host interactions and viral pathogenesis.
Enhanced Cycling Performance of Rechargeable Zinc–Air Flow Batteries Using Potassium Persulfate as Electrolyte Additive

Zinc–air batteries (ZABs) offer high specific energy and low-cost production. However, rechargeable ZABs suffer from a limited cycle life. This paper reports that potassium persulfate (KPS) additive in an alkaline electrolyte can effectively enhance the performance and electrochemical characteristics of rechargeable zinc–air flow batteries (ZAFBs). Introducing redox additives into electrolytes is an effective approach to promote battery performance. With the addition of 450 ppm KPS, remarkable improvement in anodic currents corresponding to zinc (Zn) dissolution and limited passivation of the Zn surface is observed, thus indicating its strong effect on the redox reaction of Zn. Besides, the addition of 450 ppm KPS reduces the corrosion rate of Zn, enhances surface reactions and decreases the solution resistance. However, excess KPS (900 and 1350 ppm) has a negative effect on rechargeable ZAFBs, which leads to a shorter cycle life and poor cyclability. The rechargeable ZAFB, using 450 ppm KPS, exhibits a highly stable charge/discharge voltage for 800 cycles. Overall, KPS demonstrates great promise for the enhancement of the charge/discharge performance of rechargeable ZABs.
The Association Between Delivery of Small-for-Gestational-Age Neonate and Their Risk for Long-Term Neurological Morbidity

Small-for-gestational-age (SGA) is defined as a birth weight below the 10th or below the 5th percentile for a specific gestational age and sex. Previous studies have demonstrated an association between SGA neonates and long-term pediatric morbidity. In this research, we aim to evaluate the possible association between small-for-gestational-age (SGA) and long-term pediatric neurological morbidity. A population-based retrospective cohort analysis was performed, comparing the risk of long-term neurological morbidities in SGA and non-SGA newborns delivered between the years 1991 to 2014 at a single regional medical center. The neurological morbidities included hospitalizations as recorded in hospital records. Neurological hospitalization rate was significantly higher in the SGA group (3.7% vs. 3.1%, OR = 1.2, 95% CI 1.1–1.3, p < 0.001). A significant association was noted between neonates born SGA and developmental disorders (0.2% vs. 0.1%, OR = 2.5, 95% CI 1.7–3.8, p < 0.001). The Kaplan-Meier survival curve demonstrated a significantly higher cumulative incidence of neurological morbidity in the SGA group (log-rank p < 0.001). In the Cox proportional hazards model, which controlled for various Confounders, SGA was found to be an independent risk factor for long-term neurological morbidity (adjusted hazard ratio( HR) = 1.18, 95% CI 1.07–1.31, p < 0. 001). In conclusion, we found that SGA newborns are at an increased risk for long-term pediatric neurological morbidity.
Interactions between Two Parasitoids of Tephritidae: Diachasmimorpha longicaudata (Ashmead) and Psyttalia cosyrae (Wilkinson) (Hymenoptera: Braconidae), under Laboratory Conditions

Simple Summary Wasps, generally referred to as “farmers friends” because of their ability to control devastating fruit flies, were imported from Hawaii and released in Kenya for the management of the invasive Oriental fruit fly Bactrocera dorsalis. It was noted that the introduced wasp had developed a liking for the native fruit fly species Ceratitis cosyra which already has a native wasp controlling it. We therefore undertook a study to understand the interaction of the introduced and native wasp on the invader Oriental and native fruit flies. Our results show that when the native wasp attacks the invader fruit fly, the wasp is killed because of the strong immune system of the oriental fruit fly. The good news is that the introduced wasp efficiently controls both the invader and the native fruit flies. We have discussed these findings based on various scientific principles which favor the co-existence of the two wasps without any detrimental effect on their survival. We have also suggested that more studies be conducted in open field conditions where both fruit flies occur in abundance and choices regarding which fruit fly species to attack are much wider. Abstract The braconid wasp, Diachasmimorpha longicaudata (Ashmead), was introduced in Kenya from Hawaii for classical biological control of the invasive tephritid, Bactrocera dorsalis Hendel. Following reports that D. longicaudata had formed new associations with Ceratitis cosyra, laboratory experiments were conducted to assess the interaction between the introduced and the native parasitoid of C. cosyra; Psyttalia cosyrae (Wilkinson) under three scenarios: B. dorsalis only, C. cosyra only and mixed populations of the two species. Parasitoids were introduced to the host as sole, sequential and simultaneous releases. Host searching and probing events were five times higher for D. longicaudata than P. cosyrae with both hosts. Total parasitism was highest (78%) when D. longicaudata was released alone on C. cosyra, compared to 20% for P. cosyrae released on the same host. Releases of P. cosyrae on B. dorsalis resulted in 0% parasitism, compared to 64% parasitism by D. longicaudata. Specific parasitism for P. cosyrae was three times higher when P. cosyrae was released first in sequential releases on C. cosyra compared to when it was released after D. longicaudata. These findings suggest that the two parasitoids can both suppress C. cosyra but B. dorsalis acts as a reproductive sink for P. cosyrae. Our findings should form the basis of field investigations where options are much wider for both parasitoids.
The Impact of a School-based, Nurse-delivered Asthma Health Education Program on Quality of Life, Knowledge, and Attitudes of Saudi Children with Asthma

ABSTRACT More than two million people have asthma in Saudi Arabia: 13% aged 6–10 years. Asthma is one of the most common childhood illnesses. Little has been explored about children’s ability to learn more about their own asthma in Saudi Arabia. The study was designed to assess the impact of a school-based, nurse-delivered asthma health education program on asthmatic children’s knowledge and attitude toward asthma, quality of life, anxiety level, and school absenteeism. A quasi-experimental, non-equivalent group, pretest–posttest design was used. The education program was developed from existing evidence. The Pediatric Asthma Quality of Life Questionnaire, Spence Anxiety Tool, Asthma Knowledge Questionnaire, and Asthma Attitude Questionnaire were employed for data collection. Intervention (n = 130) and control (n = 98) groups were drawn from 10 schools in Ha’il region, Saudi Arabia. Descriptive and inferential statistics were used to examine differences within and between groups. Knowledge of asthma increased significantly more in the intervention group than in the control group. Attitude toward asthma was not changed by the intervention. Anxiety scores reverted to pretest level by posttest II. The intervention group had significantly better total quality of life scores than the control group, and school absenteeism reduced significantly after the delivery of the program. It was concluded that the asthma education program impacted positively on students’ knowledge, quality of life, and school attendance. However, asthma education did not change attitudes toward the condition, and the impact on anxiety was not persistent. The results emphasize the benefits of the provision of health education directly to children. Asthma education should be integrated into the Saudi national child health program.
Bicuspid aortic valve and aortopathy: novel prognostic predictors for the identification of high-risk patients.

AIMS Bicuspid aortic valve (BAV) may be complicated by aortic aneurysms and dissection. This study aimed to evaluate the prognostic efficacy of markers from cardiac imaging, as well as genetic and new biomarkers, to early predict aortic complications. METHODS AND RESULTS We re-evaluated after a mean time of 48 ± 11 months 47 BAV patients who had undergone previous echocardiography for evaluation of aortic stiffness and 2D aortic longitudinal strain (LS) (by speckle-tracking analysis), and who had given a blood sample for the assessment of a single-nucleotide polymorphism of elastin gene (ELN rs2 071307) and quantification of elastin soluble fragments (ESF). Surgical treatment of aortic aneurysm/dissection was the primary endpoint, and an aortic dimension increase (of one or more aortic segments) ≥1 mm/year was the secondary endpoint. Nine patients underwent surgical treatment of ascending aorta (AA) aneurysms. Out of the 38 patients who did not need surgical intervention, 16 showed an increase of aortic root and/or AA dimension ≥1 mm/year. At multivariate Cox regression analysis, an impaired AA LS was an independent predictor of aortic surgery [P = 0.04; hazard ratio (HR) 0.961; 95% confidence interval (CI) 0.924-0.984] and aortic dilatation (P = 0.007; HR 0.960; 95% CI 0.932-0.989). An increased quantity of ESF was correlated (P = 0.015) with the primary endpoint at univariate Cox regression analysis but it did not keep statistical significance at multivariate analysis. CONCLUSION In BAV patients, impairment of elastic properties of the AA, as assessed by 2D LS, is an effective predictor of aortic complications.
Point mutation in CD19 facilitates immune escape of B cell lymphoma from CAR-T cell therapy

Background Tumor relapse due to mutation in CD19 can hinder the efficacy of chimeric antigen receptor (CAR)-T cell therapy. Herein, we focused on lymphoma patients whose B cells exhibited a point mutation in CD19 of B cells after CAR-T cell infusion. Methods The CAR-T and CD19+ B cells from peripheral blood or bone marrow were assessed using flow cytometry. Genome sequencing was conducted to identify the molecular characteristics of CAR-T and CD19+ B cells from pre-relapse and postrelapse samples. CD19 in CARs comprising single chain fragments variable (scFV) antibody with FMC63 or 21D4 was constructed. The cytotoxic efficacy of CAR-T cells was also evaluated via in vitro and in vivo experiments. Results A patient with high-grade B cell lymphoma exhibited complete response, but the lymphoma relapsed in her left breast at 6 months after CD19 CAR (FMC63)-T cell infusion. A mutation was found in exon 3 of CD19 (p.163. R-L) in malignant B cells of the patient. In two lymphoma patients who exhibited resistance to CAR-T cell therapy, a mutation was detected in exon 3 of CD19 (p.174. L-V). Functional analysis revealed that FMC63 CAR-T cells exhibited antitumor ability against wild-type CD19+ cells but were unable to eradicate these two types of mutated CD19+ cells. Interestingly, 21D4 CAR-T cells were potentially capable of eradicating these mutated CD19+ cells and exhibiting high antitumor capacity against CD19+ cells with loss of exon 1, 2, or 3. Conclusions These findings suggest that point mutation can facilitate immune escape from CAR-T cell therapy and that alternative CAR-T cells can effectively eradicate the mutated B cells, providing an individualized therapeutic approach for lymphoma patients showing relapse.
[Structure-activity-relationship study of the new anticancer drug lycobetaine (AT-1840)].

Lycobetaine (AT-1840), developed by our institute, is a new chemotherapeutic agent with relatively high percentage of remission on the treatment of ovary cancer and stomach cancer; no remarkable changes in blood picture, EKG and GPT, were observed. Early examination of the structure activity relationship of lycobetaine gave the following results: 1. A potential betaine and a methylenedioxy group in this compound may be critical for exhibiting antitumor activity; 2. Fission of the five membered ring of lycobetaine will not affect its antitumor activity. In order to see whether the distance between the phenolic oxygen and quaternary nitrogen affects its antitumor activity, compounds 7a～c, 8a～b were synthesized and screened against tumor in mice bearing EAC Preliminary experimental results showed that among the open ring analogs of lycobetaine, 7a, 7b and 8d possessed marked antitumor activity and 7c did not. The results indicate that changes in the distance of the betaine in lycobetaine obviously influence its antitumor activity.
Live Cell Microscopy of Murine Polyomavirus Subnuclear Replication Centers

During polyomavirus (PyV) infection, host proteins localize to subnuclear domains, termed viral replication centers (VRCs), to mediate viral genome replication. Although the protein composition and spatial organization of VRCs have been described using high-resolution immunofluorescence microscopy, little is known about the temporal dynamics of VRC formation over the course of infection. We used live cell fluorescence microscopy to analyze VRC formation during murine PyV (MuPyV) infection of a mouse fibroblast cell line that constitutively expresses a GFP-tagged replication protein A complex subunit (GFP-RPA32). The RPA complex forms a heterotrimer (RPA70/32/14) that regulates cellular DNA replication and repair and is a known VRC component. We validated previous observations that GFP-RPA32 relocalized to sites of cellular DNA damage in uninfected cells and to VRCs in MuPyV-infected cells. We then used GFP-RPA32 as a marker of VRC formation and expansion during live cell microscopy of infected cells. VRC formation occurred at variable times post-infection, but the rate of VRC expansion was similar between cells. Additionally, we found that the early viral protein, small TAg (ST), was required for VRC expansion but not VRC formation, consistent with the role of ST in promoting efficient vDNA replication. These results demonstrate the dynamic nature of VRCs over the course of infection and establish an approach for analyzing viral replication in live cells.
Emotion regulation deficits mediate childhood sexual abuse effects on stress sensitization and depression outcomes

Abstract Child sexual abuse (CSA) is a notable risk factor for depressive disorders. Though multiply determined, increased sensitivity to stress (stress sensitization) and difficulty managing distress (emotion regulation) may reflect two pathways by which CSA confers depression risk. However, it remains unclear whether stress sensitization and emotion regulation deficits contribute to depression risk independently or in a sequential manner. That is, the frequent use of maladaptive emotion regulation responses and insufficient use of those that attenuate distress (adaptive emotion regulation) may lead to stress sensitization. We tested competing models of CSA, stress sensitization, and emotion regulation to predict depression symptoms and depressive affects in daily life among adults with and without histories of CSA. Results supported a sequential mediation: CSA predicted greater maladaptive repertoires that, in turn, exacerbated the effects of stress on depression symptoms. Maladaptive responses also exacerbated the effects of daily life stress on contemporaneous negative affect (NA) levels and their increase over time. Independent of stress sensitization, emotion regulation deficits also mediated CSA effects on both depressive outcomes, though the effect of maladaptive strategies was specific to NA, and adaptive responses to positive affect. Our findings suggest that emotion regulation deficits and stress sensitization play key intervening roles between CSA and risk for depression.
Monoclonal full-length antibody against TAR DNA binding protein 43 reduces related proteinopathy in neurons

Amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD), 2 incurable neurodegenerative disorders, share the same pathological hallmark named TDP43 (TAR DNA binding protein 43) proteinopathy. This event is characterized by a consistent cytoplasmic mislocalization and aggregation of the protein TDP43, which loses its physiological properties, leading neurons to death. Antibody-based approaches are now emerging interventions in the field of neurodegenerative disorders. Here, we tested the target specificity, in vivo distribution, and therapeutic efficacy of a monoclonal full-length antibody, named E6, in TDP43-related conditions. We observed that the antibody recognizes specifically the cytoplasmic fraction of TDP43. We demonstrated its ability in targeting large neurons in the spinal cord of mice and in reducing TDP43 mislocalization and NF-κB activation. We also recognized the proteasome as well as the lysosome machineries as possible mechanisms used by the antibody to reduce TDP43 proteinopathy. To our knowledge, this is the first report showing the therapeutic efficacy and feasibility of a full-length antibody against TDP43 in reducing TDP43 proteinopathy in spinal neurons of an ALS/FTLD mouse model.
Auxin Homeostasis and Distribution of the Auxin Efflux Carrier PIN2 Require Vacuolar NHX-Type Cation/H+ Antiporter Activity

The Arabidopsis vacuolar Na+/H+ transporters (NHXs) are important regulators of intracellular pH, Na+ and K+ homeostasis and necessary for normal plant growth, development, and stress acclimation. Arabidopsis contains four vacuolar NHX isoforms known as AtNHX1 to AtNHX4. The quadruple knockout nhx1nhx2nhx3nhx4, lacking any vacuolar NHX-type antiporter activity, displayed auxin-related phenotypes including loss of apical dominance, reduced root growth, impaired gravitropism and less sensitivity to exogenous IAA and NAA, but not to 2,4-D. In nhx1nhx2nhx3nhx4, the abundance of the auxin efflux carrier PIN2, but not PIN1, was drastically reduced at the plasma membrane and was concomitant with an increase in PIN2 labeled intracellular vesicles. Intracellular trafficking to the vacuole was also delayed in the mutant. Measurements of free IAA content and imaging of the auxin sensor DII-Venus, suggest that auxin accumulates in root tips of nhx1nhx2nhx3nhx4. Collectively, our results indicate that vacuolar NHX dependent cation/H+ antiport activity is needed for proper auxin homeostasis, likely by affecting intracellular trafficking and distribution of the PIN2 efflux carrier.
Costimulatory Effect of Rough Calcium Phosphate Coating and Blood Mononuclear Cells on Adipose-Derived Mesenchymal Stem Cells In Vitro as a Model of In Vivo Tissue Repair

Calcium phosphate (CaP) materials do not always induce ectopic vascularization and bone formation; the reasons remain unclear, and there are active discussions of potential roles for post-implantation hematoma, circulating immune and stem cells, and pericytes, but studies on adipose-derived stem cells (AMSCs) in this context are lacking. The rough (average surface roughness Ra = 2–5 µm) scaffold-like CaP coating deposited on pure titanium plates by the microarc oxidation method was used to investigate its subcutaneous vascularization in CBA/CaLac mice and in vitro effect on cellular and molecular crosstalk between human blood mononuclear cells (hBMNCs) and AMSCs (hAMSCs). Postoperative hematoma development on the CaP surface lasting 1–3 weeks may play a key role in the microvessel elongation and invasion into the CaP relief at the end of the 3rd week of injury and BMNC migration required for enhanced wound healing in mice. Satisfactory osteogenic and chondrogenic differentiation but poor adipogenic differentiation of hAMSCs on the rough CaP surface were detected in vitro by differential cell staining. The fractions of CD73+ (62%), CD90+ (0.24%), and CD105+ (0.41%) BMNCs may be a source of autologous circulating stem/progenitor cells for the subcutis reparation, but allogenic hBMNC participation is mainly related to the effects of CD4+ T cells co-stimulated with CaP coating on the in vitro recruitment of hAMSCs, their secretion of angiogenic and osteomodulatory molecules, and the increase in osteogenic features within the period of in vivo vascularization. Cellular and molecular crosstalk between BMNCs and AMSCs is a model of effective subcutis repair. Rough CaP surface enhanced angio- and osteogenic signaling between cells. We believe that preconditioning and/or co-transplantation of hAMSCs with hBMNCs may broaden their potential in applications related to post-implantation tissue repair and bone bioengineering caused by microarc CaP coating.
Clinical and demographic characteristics of people who smoke versus inject crystalline methamphetamine in Australia: Findings from a pharmacotherapy trial.

INTRODUCTION AND AIMS There has been a rapid increase in smoking crystalline methamphetamine in Australia. We compare the clinical and demographic characteristics of those who smoke versus inject the drug in a cohort of people who use methamphetamine. DESIGN AND METHODS Participants (N = 151) were dependent on methamphetamine, aged 18-60 years, enrolled in a pharmacotherapy trial for methamphetamine dependence, and reported either injecting (n = 54) or smoking (n = 97) methamphetamine. Measures included the Timeline Followback, Severity of Dependence Scale, Amphetamine Withdrawal Questionnaire, Craving Experience Questionnaire and the Brief Psychiatric Rating Scale (symptoms of depression, hostility, psychosis and suicidality). Simultaneous regression was used to identify independent demographic correlates of smoking methamphetamine and to compare the clinical characteristics of participants who smoked versus injected. RESULTS Compared to participants who injected methamphetamine, those who smoked methamphetamine were younger and less likely to be unemployed, have a prison history or live alone. Participants who smoked methamphetamine used methamphetamine on more days in the past 4 weeks than participants who injected methamphetamine (26 vs. 19 days, P = 0.001); they did not differ significantly in their severity of methamphetamine dependence, withdrawal, craving or psychiatric symptoms (P > 0.05). After adjustment for demographic differences, participants who smoked had lower craving [b (SE) = -1.1 (0.5), P = 0.021] and were less likely to report psychotic symptoms [b (SE) = -1.8 (0.7), P = 0.013] or antidepressant use [b (SE) = -1.1 (0.5), P = 0.022]. DISCUSSION AND CONCLUSIONS Smoking crystalline methamphetamine is associated with a younger less marginalised demographic profile than injecting methamphetamine, but a similarly severe clinical profile.