Miracle-dz/UniFAR-FTUs huggingface dataset:
An optimized mode of interferon intermittent therapy help improve HBsAg disappearance in chronic hepatitis B patients

Background To investigate the effect of intermittent interferon therapy mode on the disappearance of hepatitis B surface antigen (HBsAg) in chronic hepatitis B (CHB) patients. Methods This is a retrospective cohort study in CHB patients who were suspended from pegylated interferon α (PEG-IFNα) therapy due to a plateau in HBsAg decline during the initial treatment period, and resumed interferon therapy after an interval of 3–6 months. Patients received entecavir or tenofovir during the interval period. Hepatitis B virus (HBV) virological and serological indexes, clinical biochemical indexes, and blood routine tests were performed at the baseline and every 3 months during follow-up of initial interferon treatment. A functional cure was analyzed as a primary outcome. Results A total of 304 patients treated with intermittent PEG-IFNα were included in the statistical analysis, including 215 men and 89 women, aged 37.97 ± 8.53 years, and 73 hepatitis B e antigen (HBeAg)-negative and 231 HBeAg positive patients. In total 59 patients (19.41%) achieved HBsAg disappearance through the initial, intermittent, and retreatment of PEG-IFNα treatment, of whom 43 patients (14.14%) achieved HBsAg seroconversion. Early HBsAg response to initial treatment was significantly associated with HBsAg response at 12 and 24 weeks of retreatment. After the intermission period, the incidence of HBsAg disappearance in patients with early HBsAg response in the retreatment period was 43.87%. The baseline HBsAg and 12-week HBsAg response in the retreatment period had higher predictive value than the initial treatment HBsAg response. Conclusion The initial, intermittent, and retreatment mode of interferon can help to improve the HBsAg disappearance rate in CHB patients. Clinical trial registration [www.ClinicalTrials. gov], identifier [NCT04028856].
Analysis of the absorbed constituents and mechanism of liquidambaris fructus extract on hepatocellular carcinoma

Background: Hepatocellular carcinoma (HCC) refers to one of the top 10 cancers in terms of morbidity and mortality globally, seriously influencing people’s lives. First recorded in Compendium of Materia Medica, liquidambaris fructus (LF) generates definite anti-liver tumor effect. However, its effective substances and mechanism remain to be elucidated. Methods: Serum pharmacochemistry and UPLC-QTOF-MS technologies were employed to explore the plasma of rats after intragastric administration of liquidambaris fructus extract (LFE) in order to find the active ingredients. Subsequently, DEN-induced rat liver cancer model was established with the purpose of investigating the anti-tumor activity of LFE from physiological, pathological and biochemical aspects. Finally, non-target metabonomics combined with q-PCR and Western blot methods were adopted for revealing the mechanism. Results: Totally 11 prototype blood transfused ingredients, including imperatorin and phellopterin were detected. LFE presents excellent impact on enhancing the quality of life, prolonging the life cycle, reducing inflammatory reaction, protecting hepatocytes, improving body immunity and killing liver tumor cells. Altogether 82 endogenous differential metabolites were found in metabonomics, suggesting that LFE can treat HCC by acting on key targets of PTEN/PI3K/Akt pathway and fatty acid metabolism. Further research also verified that LFE can upregulate the relative expression levels of PTEN, PDCD4, Caspase 9, Caspase 3, Bax and Bad as well as lower the relative expression levels of PI3K, AKT, VEGFA and Bcl-2. Conclusion: This study revealed the pharmacodynamic material basis of LFE in the treatment of HCC, and from the perspective of metabolomics proved that the effects of inhibiting the growth of tumor cells, promoting tumor cell apoptosis, reducing inflammatory reaction, protecting hepatocytes, improving the survival state of tumor rats, and prolonging the life cycle are related to its impact on PTEN/PI3K/Akt, fatty acid metabolism and other key signal pathways.
Nitric oxide–an antidote to seed aging modifies meta-tyrosine content and expression of aging-linked genes in apple embryos

Short-term (3 h) treatment of embryos isolated from accelerated aged apple seeds (Malus domestica Borkh.) with nitric oxide (NO) partially reduced the effects of aging. The study aimed to investigate the impact of the short-term NO treatment of embryos isolated from apple seeds subjected to accelerated aging on the expression of genes potentially linked to the regulation of seed aging. Apple seeds were artificially aged for 7, 14, or 21 days. Then, the embryos were isolated from the seeds, treated with NO, and cultured for 48 h. Progression of seed aging was associated with the decreased transcript levels of most of the analyzed genes (Lea1, Lea2a, Lea4, Hsp70b, Hsp20a, Hsp20b, ClpB1, ClpB4, Cpn60a, Cpn60b, Raptor, and Saur). The role of NO in the mitigation of seed aging depended on the duration of the aging. After 7 and 14 days of seed aging, a decreased expression of genes potentially associated with the promotion of aging (Tor, Raptor, Saur) was noted. NO-dependent regulation of seed aging was associated with the stimulation of the expression of genes encoding chaperones and proteins involved in the repair of damaged proteins. After NO application, the greatest upregulation of ClpB, Pimt was noted in the embryos isolated from seeds subjected to 7-day long accelerated aging, Hsp70b, Hsp70c, and Cpn in the embryos of seeds aged for 14 days, and Lea2a in the embryos of seeds after 21 days of aging. We also demonstrated the increased meta-tyrosine concentration depending or in respect the progression of artificial aging, and the NO-induced increased phenylalanine content in seeds artificially aged for 21 days. In the NO-treated embryos of seeds aged for 7 and 21 days, the level of tyrosine was almost doubled compared to the aged tissue. Our data confirmed the usage of meta-tyrosine as a marker of seed aging and indicated that the increased meta-tyrosine/tyrosine ratio could be related to the loss of seed viability.
A Comparison of MRI Quantitative Susceptibility Mapping and TRUST-Based Measures of Brain Venous Oxygen Saturation in Sickle Cell Anaemia

In recent years, interest has grown in the potential for magnetic resonance imaging (MRI) measures of venous oxygen saturation (Yv) to improve neurological risk prediction. T2-relaxation-under-spin-tagging (TRUST) is an MRI technique which has revealed changes in Yv in patients with sickle cell anemia (SCA). However, prior studies comparing Yv in patients with SCA relative to healthy controls have reported opposing results depending on whether the calibration model, developed to convert blood T2 to Yv, is based on healthy human hemoglobin (HbA), bovine hemoglobin (HbBV) or sickle hemoglobin (HbS). MRI Quantitative Susceptibility Mapping (QSM) is an alternative technique that may hold promise for estimating Yv in SCA as blood magnetic susceptibility is linearly dependent upon Yv, and no significant difference has been found between the magnetic susceptibility of HbA and HbS. Therefore, the aim of this study was to compare estimates of Yv using QSM and TRUST with five published calibration models in healthy controls and patients with SCA. 17 patients with SCA and 13 healthy controls underwent MRI. Susceptibility maps were calculated from a multi-parametric mapping acquisition and Yv was calculated from the mean susceptibility in a region of interest in the superior sagittal sinus. TRUST estimates of T2, within a similar but much smaller region, were converted to Yv using five different calibration models. Correlation and Bland-Altman analyses were performed to compare estimates of Yv between TRUST and QSM methods. For each method, t-tests were also used to explore group-wise differences between patients with SCA and healthy controls. In healthy controls, significant correlations were observed between QSM and TRUST measures of Yv, while in SCA, there were no such correlations. The magnitude and direction of group-wise differences in Yv varied with method. The TRUST-HbBV and QSM methods suggested decreased Yv in SCA relative to healthy controls, while the TRUST-HbS (p < 0.01) and TRUST-HbA models suggested increased Yv in SCA as in previous studies. Further validation of all MRI measures of Yv, relative to ground truth measures such as O15 PET and jugular vein catheterization, is required in SCA before QSM or TRUST methods can be considered for neurological risk prediction.
Cryo-electron tomography related radiation-damage parameters for individual-molecule 3D structure determination

To understand the dynamic structure–function relationship of soft- and biomolecules, the determination of the three-dimensional (3D) structure of each individual molecule (nonaveraged structure) in its native state is sought-after. Cryo-electron tomography (cryo-ET) is a unique tool for imaging an individual object from a series of tilted views. However, due to radiation damage from the incident electron beam, the tolerable electron dose limits image contrast and the signal-to-noise ratio (SNR) of the data, preventing the 3D structure determination of individual molecules, especially at high-resolution. Although recently developed technologies and techniques, such as the direct electron detector, phase plate, and computational algorithms, can partially improve image contrast/SNR at the same electron dose, the high-resolution structure, such as tertiary structure of individual molecules, has not yet been resolved. Here, we review the cryo-electron microscopy (cryo-EM) and cryo-ET experimental parameters to discuss how these parameters affect the extent of radiation damage. This discussion can guide us in optimizing the experimental strategy to increase the imaging dose or improve image SNR without increasing the radiation damage. With a higher dose, a higher image contrast/SNR can be achieved, which is crucial for individual-molecule 3D structure. With 3D structures determined from an ensemble of individual molecules in different conformations, the molecular mechanism through their biochemical reactions, such as self-folding or synthesis, can be elucidated in a straightforward manner.
TEVAR and EVAR, the unknown knowns of the cardiovascular hemodynamics; and the immediate and long-term consequences of fabric material on major adverse clinical outcome

This review discusses the impact of endovascular aneurysm repair on cardiovascular (CV) hemodynamics and the role of stent-graft material, i.e., polytetrafluoroethylene (PTFE) vs. polyester in post-procedural outcomes. Endovascular aneurysm repair has been widely employed in the last decades for thoracic and abdominal aneurysm repair. However, aortic endografts are stiff and alter the native flow hemodynamics. This failure to simulate the native aorta could lead to added strain on the heart, manifesting as increased left ventricular strain, higher pulse pressure, and congestive heart failure later. This could result in adverse CV outcomes. Also, evidence is mounting to support the implication of stent-graft materials, i.e., PTFE vs. polyester, in adverse post-procedural outcomes. However, there is an absence of level one evidence. Therefore, the only way forward is to plan and perform a randomised controlled trial to demonstrate the alterations in the CV hemodynamics in the short and long run and compare the available stent-graft materials regarding procedural and clinical outcomes. We believe the best solution, for now, would be to reduce the stented length of the aorta. At the same time, in the longer term, encourage continuous improvement in stent-graft materials and design.
Assessment and correlates of autistic symptoms in Schizophrenia Spectrum Disorders measured with the PANSS Autism Severity Score: A systematic review

Schizophrenia Spectrum Disorders (SSD) and Autism Spectrum Disorders (ASD) are considered separate entities, but the two spectra share important similarities, and the study of these areas of overlap represents a field of growing scientific interest. The PANSS Autism Score (PAUSS) was recently developed specifically to assess autistic symptoms in people living with SSD reliably and quickly. The aims of the present systematic review were to provide a comprehensive assessment of the use of the PAUSS scale in available literature and to systematically analyze cognitive, functional and neurobiological correlates of autistic symptoms measured with this instrument in SSD. The systematic literature search included three electronic databases (PubMed, Scopus and PsycINFO) as well as a manual search in Google Scholar and in reference lists of included papers. Screening and extraction were conducted by at least two independent reviewers. Out of 213 identified records, 22 articles referring to 15 original studies were included in the systematic review. Studies were conducted in several different countries by independent groups, showing consistent scientific interest in the use of the scale; most works focused on cognitive and functional correlates of ASD symptoms, but some also considered neurobiological features. Results of included studies showed that autistic symptoms in people with SSD are consistently associated with worse cognitive performance, especially in the social cognition domain, and with worse psychosocial functioning. However, the presence of autistic symptoms appears to also have a protective role, particularly on functioning, in subjects with more severe psychotic symptoms. Further exploring the impact of autistic symptoms could be of significant scientific and clinical interest, allowing the development of tailored interventions to improve treatment for people living with SSDs.
Recent advances of the mammalian target of rapamycin signaling in mesenchymal stem cells

Mammalian target of rapamycin (mTOR) is a serine/threonine kinase involved in a variety of cellular functions, such as cell proliferation, metabolism, autophagy, survival and cytoskeletal organization. Furthermore, mTOR is made up of three multisubunit complexes, mTOR complex 1, mTOR complex 2, and putative mTOR complex 3. In recent years, increasing evidence has suggested that mTOR plays important roles in the differentiation and immune responses of mesenchymal stem cells (MSCs). In addition, mTOR is a vital regulator of pivotal cellular and physiological functions, such as cell metabolism, survival and ageing, where it has emerged as a novel therapeutic target for ageing-related diseases. Therefore, the mTOR signaling may develop a large impact on the treatment of ageing-related diseases with MSCs. In this review, we discuss prospects for future research in this field.
Non-canonical DNA/RNA structures associated with the pathogenesis of Fragile X-associated tremor/ataxia syndrome and Fragile X syndrome

Fragile X-associated tremor/ataxia syndrome (FXTAS) and fragile X syndrome (FXS) are primary examples of fragile X-related disorders (FXDs) caused by abnormal expansion of CGG repeats above a certain threshold in the 5′-untranslated region of the fragile X mental retardation (FMR1) gene. Both diseases have distinct clinical manifestations and molecular pathogenesis. FXTAS is a late-adult-onset neurodegenerative disorder caused by a premutation (PM) allele (CGG expansion of 55–200 repeats), resulting in FMR1 gene hyperexpression. On the other hand, FXS is a neurodevelopmental disorder that results from a full mutation (FM) allele (CGG expansions of ≥200 repeats) leading to heterochromatization and transcriptional silencing of the FMR1 gene. The main challenge is to determine how CGG repeat expansion affects the fundamentally distinct nature of FMR1 expression in FM and PM ranges. Abnormal CGG repeat expansions form a variety of non-canonical DNA and RNA structures that can disrupt various cellular processes and cause distinct effects in PM and FM alleles. Here, we review these structures and how they are related to underlying mutations and disease pathology in FXS and FXTAS. Finally, as new CGG expansions within the genome have been identified, it will be interesting to determine their implications in disease pathology and treatment.
Pressure induced dynamical instabilities in body center cubic crystals

Large-scale atomistic simulations of shock-wave propagation in single crystals exhibit large anisotropies in the elastic-plastic and solid-liquid transitions. Characteristic of this type of simulations are the large strains at which the crystal yields plastically, regardless of crystal orientation. At these large strains, uniaxial deformations, such as those produced in planar shock loading generate dynamical instabilities. We have investigated the directional anisotropy of the elastic limit in bcc crystals, in particular Tantalum (Ta), employing molecular dynamics (MD) simulations. We show that the elastic plastic transition in BCC defect-free crystals is caused by the appearance of soft-phonon modes and not via homogenous nucleation of extended defects.
Enhancing Natural Killer Cell-Mediated Cancer Immunotherapy by the Biological Macromolecule Nocardia rubra Cell-Wall Skeleton

The biological macromolecule Nocardia rubra cell-wall skeleton (Nr-CWS) has well-established immune-stimulating and anti-tumor activities. However, the role of Nr-CWS on natural killer (NK) cells remains unclear. Here, we explore the function and related mechanisms of Nr-CWS on NK cells. Using a tumor-bearing model, we show that Nr-CWS has slightly effect on solid tumor. In addition, using a tumor metastasis model, we show that Nr-CWS suppresses the lung metastasis induced by B16F10 melanoma cells in mice, which indicates that Nr-CWS may up-regulate the function of NK cells. Further investigation demonstrated that Nr-CWS can increase the expression of TRAIL and FasL on spleen NK cells from Nr-CWS treated B16F10 tumor metastasis mice. The spleen index and serum levels of TNF-α, IFN-γ, and IL-2 in B16F10 tumor metastasis mice treated with Nr-CWS were significantly increased. In vitro, the studies using purified or sorted NK cells revealed that Nr-CWS increases the expression of CD69, TRAIL, and FasL, decreases the expression of CD27, and enhances NK cell cytotoxicity. The intracellular expression of IFN-γ, TNF-α, perforin (prf), granzyme-B (GrzB), and secreted TNF-α, IFN-γ, IL-6 of the cultured NK cells were significantly increased after treatment with Nr-CWS. Overall, the findings indicate that Nr-CWS could suppress the lung metastasis induced by B16F10 melanoma cells, which may be exerted through its effect on NK cells by promoting NK cell terminal differentiation (CD27lowCD11bhigh), and up-regulating the production of cytokines and cytotoxic molecules.
ZAT10 plays dual roles in cadmium uptake and detoxification in Arabidopsis

Cadmium (Cd) is a harmful heavy metal that is risky for plant growth and human health. The zinc-finger transcription factor ZAT10 is highly conserved with ZAT6 and ZAT12, which are involved in Cd tolerance in plants. However, the definite function of ZAT10 in Cd tolerance remains uncertain. Here, we demonstrated that ZAT10 negatively regulated Cd uptake and enhanced Cd detoxification in Arabidopsis. The expression of ZAT10 in plants is induced by Cd treatment. The zat10 mutant plants exhibited a greater sensitivity to Cd stress and accumulated more Cd in both shoot and root. Further investigations revealed that ZAT10 repressed the transcriptional activity of IRT1, which encodes a key metal transporter involved in Cd uptake. Meanwhile, ZAT10 positively regulated four heavy metal detoxification-related genes: NAS1, NAS2, IRT2, and MTP3. We further found that ZAT10 interacts with FIT, but their regulatory relationship is still unclear. In addition, ZAT10 directly bound to its own promoter and repressed its transcription as a negative feedback regulation. Collectively, our findings provided new insights into the dual functions of ZAT10 on Cd uptake and detoxification in plants and pointed to ZAT10 as a potential gene resource for Cd tolerance improvement in plants.
Inhibition of peripheral chemoreceptors improves ventilatory efficiency during exercise in heart failure with preserved ejection fraction − a role of tonic activity and acute reflex response

Peripheral chemoreceptors (PChRs) play a significant role in maintaining adequate oxygenation in the bloodstream. PChRs functionality comprises two components: tonic activity (PChT) which regulates ventilation during normoxia and acute reflex response (peripheral chemosensitivity, PChS), which increases ventilation following a specific stimulus. There is a clear link between augmented PChS and exercise intolerance in patients with heart failure with reduced ejection fraction. It has been also shown that inhibition of PChRs leads to the improvement in exercise capacity. However, it has not been established yet: 1) whether similar mechanisms take part in heart failure with preserved ejection fraction (HFpEF) and 2) which component of PChRs functionality (PChT vs. PChS) is responsible for the benefit seen after the acute experimental blockade. To answer those questions we enrolled 12 stable patients with HFpEF. All participants underwent an assessment of PChT (attenuation of minute ventilation in response to low-dose dopamine infusion), PChS (enhancement of minute ventilation in response to hypoxia) and a symptom-limited cardiopulmonary exercise test on cycle ergometer. All tests were placebo-controlled, double-blinded and performed in a randomized order. Under resting conditions and at normoxia dopamine attenuated minute ventilation and systemic vascular resistance (p = 0.03 for both). These changes were not seen with placebo. Dopamine also decreased ventilatory and mean arterial pressure responses to hypoxia (p < 0.05 for both). Inhibition of PChRs led to a decrease in V˙E/V˙CO2 comparing to placebo (36 ± 3.6 vs. 34.3 ± 3.7, p = 0.04), with no effect on peak oxygen consumption. We found a significant relationship between PChT and the relative decrement of V˙E/V˙CO2 on dopamine comparing to placebo (R = 0.76, p = 0.005). There was a trend for correlation between PChS (on placebo) and V˙E/V˙CO2 during placebo infusion (R = 0.56, p = 0.059), but the relative improvement in V˙E/V˙CO2 was not related to the change in PChS (dopamine vs. placebo). We did not find a significant relationship between PChT and PChS. In conclusion, inhibition of PChRs in HFpEF population improves ventilatory efficiency during exercise. Increased PChS is associated with worse (higher) V˙E/V˙CO2, whereas PChT predicts an improvement in V˙E/V˙CO2 after PChRs inhibition. This results may be meaningful for patient selection in further clinical trials involving PChRs modulation.
How Your Sense of Touch Can Change Your Brain

Your brain can be divided into various areas, one of which is responsible for your sense of touch. This part of your brain can be divided into even smaller areas that communicate with each body part. We can use a special map of the human body, called a sensory homunculus, to help us understand the various sizes of these parts of the brain. We will explain how this map was created and tell you about research showing how these brain areas can change. One study showed that brain areas can be recycled, meaning that the brain areas that no longer receive messages from the body can be used by other functioning brain areas. Another study showed that these changes can even occur within a single day! These studies can help scientists to better understand the brain and to help people who have problems with the sense of touch.