Miracle-dz/UniFAR-FTUs huggingface dataset:
Role of Inflammatory Cytokines in COVID-19 Patients: A Review on Molecular Mechanisms, Immune Functions, Immunopathology and Immunomodulatory Drugs to Counter Cytokine Storm

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is a severe pandemic of the current century. The vicious tentacles of the disease have been disseminated worldwide with unknown complications and repercussions. Advanced COVID-19 syndrome is characterized by the uncontrolled and elevated release of pro-inflammatory cytokines and suppressed immunity, leading to the cytokine storm. The uncontrolled and dysregulated secretion of inflammatory and pro-inflammatory cytokines is positively associated with the severity of the viral infection and mortality rate. The secretion of various pro-inflammatory cytokines such as TNF-α, IL-1, and IL-6 leads to a hyperinflammatory response by recruiting macrophages, T and B cells in the lung alveolar cells. Moreover, it has been hypothesized that immune cells such as macrophages recruit inflammatory monocytes in the alveolar cells and allow the production of large amounts of cytokines in the alveoli, leading to a hyperinflammatory response in severely ill patients with COVID-19. This cascade of events may lead to multiple organ failure, acute respiratory distress, or pneumonia. Although the disease has a higher survival rate than other chronic diseases, the incidence of complications in the geriatric population are considerably high, with more systemic complications. This review sheds light on the pivotal roles played by various inflammatory markers in COVID-19-related complications. Different molecular pathways, such as the activation of JAK and JAK/STAT signaling are crucial in the progression of cytokine storm; hence, various mechanisms, immunological pathways, and functions of cytokines and other inflammatory markers have been discussed. A thorough understanding of cytokines’ molecular pathways and their activation procedures will add more insight into understanding immunopathology and designing appropriate drugs, therapies, and control measures to counter COVID-19. Recently, anti-inflammatory drugs and several antiviral drugs have been reported as effective therapeutic drug candidates to control hypercytokinemia or cytokine storm. Hence, the present review also discussed prospective anti-inflammatory and relevant immunomodulatory drugs currently in various trial phases and their possible implications.
The crystal structure of 1-methyl-2,4-dinitro-5-iodoimidazole, C4H3IN4O4

Abstract C4H3IN4O4, orthorhombic, Pbca (no. 61), a = 9.9513(6) Å, b = 11.3365(4) Å, c = 14.3295(12) Å, V = 1616.55(17) Å3, Z = 8, Rgt(F) = 0.0279, wRref(F2) = 0.0684, T = 105.6 K.
Mindfulness Buffers the Effect of Inauthenticity on Depression

Objectives Pressures in daily life limit one’s ability to be authentic and research shows that inauthenticity can be detrimental to mental health. Mindfulness is known to have a protective effect on mental health through an accepting and nonjudgmental stance. This study aimed to establish whether mindfulness buffers the relationship between inauthenticity and depression. Method A cross-sectional sample of employed individuals in New Zealand (n=301) completed an online survey assessing their levels of authenticity, mindfulness, and depression. Results Findings indicate that authenticity and mindfulness together explain 29% of variance in depression. In addition, mindfulness can buffer the negative impact of low authenticity on depression. Conclusion Inauthenticity is related to higher levels of depression, but mindfulness is able to buffer this impact. These findings imply that engaging in mindfulness practice may be beneficial for mental health when individuals experience reduced authenticity.
Increased early motivational response to food in adolescent anorexia nervosa revealed by magnetoencephalography

Abstract Background It remains unclear to what extent reduced nutritional intake in anorexia nervosa (AN) is a consequence of a reduced motivational response to food. Although self-reports typically suggest AN patients have a reduced appetitive response, behavioral and neurophysiological measures have revealed evidence for both increased and reduced attentional biases towards food stimuli. The mechanisms influencing food perception in AN, might be clarified using time-sensitive magnetoencephalography (MEG) to differentiate the early (more automatic processing) stages from the late (more controlled) stages. Methods MEG was recorded in 22 partially weight-restored adolescent AN patients and 29 age- and gender-matched healthy control (HC) participants during a rapid serial visual presentation paradigm using 100 high-calorie food, 100 low-calorie food, and 100 non-food pictures. Neural sources of event-related fields were estimated using the L2-Minimum-Norm method and analyzed in early (50–300 ms) and late (350–500 ms) time intervals. Results AN patients rated high-calorie food as less palatable and reported overall less food craving than HC participants. Nevertheless, in response to food pictures AN patients showed relative increased neural activity in the left occipito-temporal and inferior frontal regions in the early time interval. No group differences occurred in the late time interval. Conclusions MEG results speak against an overall reduced motivational response to food in AN. Instead, relative increased early food processing in the visual cortex suggests greater motivated attention. A greater appetitive response to food might be an adaptive mechanism in a state of undernourishment. Yet, this relative increased food processing in AN was no longer present later, arguably reflecting rapid downregulation.
The impact of resveratrol on skin wound healing, scarring, and aging

Resveratrol is a well‐known antioxidant that harbours many health beneficial properties. Multiple studies associated the antioxidant, anti‐inflammatory, and cell protective effects of resveratrol. These diverse effects of resveratrol are also potentially involved in cutaneous wound healing, scarring, and (photo‐)aging of the skin. Hence, this review highlighted the most relevant studies involving resveratrol in wound healing, scarring, and photo‐aging of the skin. A systematic review was performed and the database PubMed was searched for suitable publications. Only original articles in English that investigated the effects of resveratrol in wound healing, scarring, and (photo‐)aging of the skin were analysed. The literature search yielded a total of 826 studies, but only 41 studies met the inclusion criteria. The included studies showed promising results that resveratrol might be a feasible treatment approach to support wound healing, counteract excessive scarring, and even prevent photo‐aging of the skin. Resveratrol represents an interesting and promising novel therapy regime but to confirm resveratrol‐associated effects, more evidence based in vitro and in vivo studies are needed.
Cobalt Regulates Activation of Camk2α in Neurons by Influencing Fructose 1,6-Bisphosphatase 2 Quaternary Structure and Subcellular Localization

Fructose 1,6-bisphosphatase 2 (Fbp2) is a gluconeogenic enzyme and multifunctional protein modulating mitochondrial function and synaptic plasticity via protein-protein interactions. The ability of Fbp2 to bind to its cellular partners depends on a quaternary arrangement of the protein. NAD+ and AMP stabilize an inactive T-state of Fbp2 and thus, affect these interactions. However, more subtle structural changes evoked by the binding of catalytic cations may also change the affinity of Fbp2 to its cellular partners. In this report, we demonstrate that Fbp2 interacts with Co2+, a cation which in excessive concentrations, causes pathologies of the central nervous system and which has been shown to provoke the octal-like events in hippocampal slices. We describe for the first time the kinetics of Fbp2 in the presence of Co2+, and we provide a line of evidence that Co2+ blocks the AMP-induced transition of Fbp2 to the canonical T-state triggering instead of a new, non-canonical T-state. In such a state, Fbp2 is still partially active and may interact with its binding partners e.g., Ca2+/calmodulin-dependent protein kinase 2α (Camk2α). The Fbp2-Camk2α complex seems to be restricted to mitochondria membrane and it facilitates the Camk2α autoactivation and thus, synaptic plasticity.
Amorphous NdIZO Thin Film Transistors with Contact-Resistance-Adjustable Cu S/D Electrodes

High-performance amorphous oxide semiconductor thin film transistors (AOS-TFT) with copper (Cu) electrodes are of great significance for next-generation large-size, high-refresh rate and high-resolution panel display technology. In this work, using rare earth dopant, neodymium-doped indium-zinc-oxide (NdIZO) film was optimized as the active layer of TFT with Cu source and drain (S/D) electrodes. Under the guidance of the Taguchi orthogonal design method from Minitab software, the semiconductor characteristics were evaluated by microwave photoconductivity decay (μ-PCD) measurement. The results show that moderate oxygen concentration (~5%), low sputtering pressure (≤5 mTorr) and annealing temperature (≤300 °C) are conducive to reducing the shallow localized states of NdIZO film. The optimized annealing temperature of this device configuration is as low as 250 °C, and the contact resistance (RC) is modulated by gate voltage (VG) instead of a constant value when annealed at 300 °C. It is believed that the adjustable RC with VG is the key to keeping both high mobility and compensation of the threshold voltage (Vth). The optimal device performance was obtained at 250 °C with an Ion/Ioff ratio of 2.89 × 107, a saturation mobility (μsat) of 24.48 cm2/(V·s) and Vth of 2.32 V.
Regional Difference in the Association between the Trajectory of Selenium Intake and Hypertension: A 20-Year Cohort Study

The effect of selenium on hypertension is inconclusive. We aimed to study the relationship between selenium intake and incident hypertension. Adults (age ≥20 years) in the China Health and Nutrition Survey were followed up from 1991 to 2011 (N = 13,668). The latent class modeling method was used to identify trajectory groups of selenium intake. A total of 4039 respondents developed hypertension. The incidence of hypertension was 30.1, 30.5, 30.6, and 31.2 per 1000 person-years among participants with cumulative average selenium intake of 21.0 ± 5.1, 33.2 ± 2.8, 43.8 ± 3.6, and 68.3 ± 25.2 µg/day, respectively. Region and selenium intake interaction in relation to hypertension was significant. In the multivariable model, cumulative intake of selenium was only inversely associated with the incident hypertension in northern participants (low selenium zone), and not in southern participants. Compared to selenium intake trajectory Group 1 (stable low intake), all three trajectory groups had a low hazard ratio for hypertension among the northern participants. However, Group 4 (high intake and decreased) showed an increasing trend of hypertension risk in the south. In conclusion, the association between selenium intake and the incidence of hypertension varied according to regions in China. In the low soil selenium zone, high selenium intake might be beneficial for hypertension prevention.
Preclinical development of plant‐based oral immune modulatory therapy for haemophilia B

Summary Anti‐drug antibody (ADA) formation is a major complication in treatment of the X‐linked bleeding disorder haemophilia B (deficiency in coagulation factor IX, FIX). Current clinical immune tolerance protocols are often not effective due to complications such as anaphylactic reactions against FIX. Plant‐based oral tolerance induction may address this problem, as illustrated by the recent first regulatory approval of orally delivered plant cells to treat peanut allergy. Our previous studies showed that oral delivery of plant cells expressing FIX fused to the transmucosal carrier CTB (cholera toxin subunit B) in chloroplasts suppressed ADA in animals with haemophilia B. We report here creation of the first lettuce transplastomic lines expressing a coagulation factor, in the absence of antibiotic resistance gene. Stable integration of the CTB‐FIX gene and homoplasmy (transformation of ˜10 000 copies in each cell) were maintained in both T1 and T2 generation marker‐free plants. CTB‐FIX expression in lyophilized leaves of T1 and T2 marker‐free plants was 1.0–1.5 mg/g dry weight, confirming that the marker excision did not affect antigen levels. Oral administration of CTB‐FIX to Sprague Dawley rats at 0.25, 1 or 2.5 mg/kg did not produce overt adverse effects or toxicity. The no‐observed‐adverse‐effect level (NOAEL) is at least 2.5 mg/kg for a single oral administration in rats. Oral administration of CTB‐FIX at 0.3 or 1.47 mg/kg either mixed in food or as an oral suspension to Beagle dogs did not produce any observable toxicity. These toxicology studies should facilitate filing of regulatory approval documents and evaluation in haemophilia B patients.
Hepatic Wnt1 Inducible Signaling Pathway Protein 1 (WISP-1/CCN4) Associates with Markers of Liver Fibrosis in Severe Obesity

Liver fibrosis is a critical complication of obesity-induced fatty liver disease. Wnt1 inducible signaling pathway protein 1 (WISP1/CCN4), a novel adipokine associated with visceral obesity and insulin resistance, also contributes to lung and kidney fibrosis. The aim of the present study was to investigate the role of CCN4 in liver fibrosis in severe obesity. For this, human liver biopsies were collected from 35 severely obese humans (BMI 42.5 ± 0.7 kg/m2, age 46.7 ± 1.8 y, 25.7% males) during bariatric surgery and examined for the expression of CCN4, fibrosis, and inflammation markers. Hepatic stellate LX-2 cells were treated with human recombinant CCN4 alone or in combination with LPS or transforming growth factor beta (TGF-β) and examined for fibrosis and inflammation markers. CCN4 mRNA expression in the liver positively correlated with BMI and expression of fibrosis markers COL1A1, COL3A1, COL6A1, αSMA, TGFB1, extracellular matrix turnover enzymes TIMP1 and MMP9, and the inflammatory marker ITGAX/CD11c. In LX-2 cells, the exposure to recombinant CCN4 caused dose-dependent induction of MMP9 and MCP1. CCN4 potentiated the TGF-β-mediated induction of COL3A1, TIMP1, and MCP1 but showed no interaction with LPS treatment. Our results suggest a potential contribution of CCN4 to the early pathogenesis of obesity-associated liver fibrosis.
Depression in midlife women attending a menopause clinic is associated with a history of childhood maltreatment

Abstract A growing body of literature has suggested that the perimenopause and the early postmenopausal years are associated with an increased risk of experiencing symptoms of depression and the development of first-onset and recurrent episodes of major depressive disorder. Multiple risk factors have been identified, including stressful life events and lower socioeconomic status, as well as early life adversity. The objective of the current study was to characterize the influence of early life childhood maltreatment and incident depression among women experiencing bothersome menopausal symptoms. Participants were recruited from two university-affiliated specialty clinics caring for women with bothersome menopausal symptoms. Assessments included the Childhood Trauma Questionnaire (CTQ), the Center for Epidemiological Studies – Depression (CES-D) scale and the Greene Climacteric Scale. Findings from this cross-sectional study indicate that adverse childhood experiences, as measured using the CTQ, were highly prevalent among women seeking care for bothersome menopausal symptoms (66%). Further, a greater score on the CTQ was significantly associated with higher CES-D scores, as well as with a greater burden of menopausal symptoms, after adjusting for confounding. Our findings lend support to the growing body of literature suggesting that early life stress affects mental health well into adulthood.
Lateral Habenula 5-HT2C Receptor Function Is Altered by Acute and Chronic Nicotine Exposures

Serotonin (5-HT) is important in some nicotine actions in the CNS. Among all the 5-HT receptors (5-HTRs), the 5-HT2CR has emerged as a promising drug target for smoking cessation. The 5-HT2CRs within the lateral habenula (LHb) may be crucial for nicotine addiction. Here we showed that after acute nicotine tartrate (2 mg/kg, i.p.) exposure, the 5-HT2CR agonist Ro 60-0175 (5–640 µg/kg, i.v.) increased the electrical activity of 42% of the LHb recorded neurons in vivo in rats. Conversely, after chronic nicotine treatment (6 mg/kg/day, i.p., for 14 days), Ro 60-0175 was incapable of affecting the LHb neuronal discharge. Moreover, acute nicotine exposure increased the 5-HT2CR-immunoreactive (IR) area while decreasing the number of 5-HT2CR-IR neurons in the LHb. On the other hand, chronic nicotine increased both the 5-HT2CR-IR area and 5-HT2CR-IR LHb neurons in the LHb. Western blot analysis confirmed these findings and further revealed an increase of 5-HT2CR expression in the medial prefrontal cortex after chronic nicotine exposure not detected by the immunohistochemistry. Altogether, these data show that acute and chronic nicotine exposure differentially affect the central 5-HT2CR function mainly in the LHb and this may be relevant in nicotine addiction and its treatment.
Structure and Development of the Legume-Rhizobial Symbiotic Interface in Infection Threads

The intracellular infection thread initiated in a root hair cell is a unique structure associated with Rhizobium-legume symbiosis. It is characterized by inverted tip growth of the plant cell wall, resulting in a tunnel that allows invasion of host cells by bacteria during the formation of the nitrogen-fixing root nodule. Regulation of the plant-microbial interface is essential for infection thread growth. This involves targeted deposition of the cell wall and extracellular matrix and tight control of cell wall remodeling. This review describes the potential role of different actors such as transcription factors, receptors, and enzymes in the rearrangement of the plant-microbial interface and control of polar infection thread growth. It also focuses on the composition of the main polymers of the infection thread wall and matrix and the participation of reactive oxygen species (ROS) in the development of the infection thread. Mutant analysis has helped to gain insight into the development of host defense reactions. The available data raise many new questions about the structure, function, and development of infection threads.
Lean Body Mass and Muscle Cross-Sectional Area Adaptations Among College Age Males with Different Strength Levels across 11 Weeks of Block Periodized Programmed Resistance Training

The block periodization training paradigm has been shown to produce enhanced gains in strength and power. The purpose of this study is to assess resistance training induced alterations in lean body mass and cross-sectional area using a block periodization training model among individuals (n = 15) of three differing strength levels (high, moderate and low) based on one repetition maximum back squat relative to body weight. A 3 × 5 mixed-design ANOVA was used to examine within-and between-subject changes in cross-sectional area (CSA), lean body mass (LBM), lean body mass adjusted (LBMadjusted) and total body water (TBW) over an 11-week resistance training program. LBMadjusted is total body water subtracted from lean body mass. The ANOVA revealed no statistically significant between-group differences in any independent variable (p > 0.05). Within-group effects showed statistically significant increases in cross-sectional area (p < 0.001), lean body mass (p < 0.001), lean body mass adjusted (p ˂ 0.001) and total body water (p < 0.001) from baseline to post intervention: CSA: 32.7 cm2 ± 8.6; 36.3 cm2 ± 7.2, LBM: 68.0 kg ± 9.5; 70.6 kg ± 9.4, LBMadjusted: 20.4 kg ± 3.1; 21.0 kg ± 3.3 and TBW: 49.8 kg ± 6.9; 51.7 kg ± 6.9. In conclusion, the results of this study suggest subjects experienced an increase in both lean body mass and total body water, regardless of strength level, over the course of the 11-week block periodized program. Gains in lean body mass and cross-sectional area may be due to edema at the early onset of training.
Presence of donor specific HLA class 2 antibodies (DSA class 2) is associated with development of graft fibrosis more than 10 years after liver transplantation–a retrospective single center study

Here the impact of donor specific human leukocyte antigen (HLA) class 2 antibodies (DSA cl 2) on long term outcome after liver transplantation (LT) was investigated. Altogether 156 (44 pediatric and 112 adult) LT recipients were included in the study. Graft fibrosis was assessed by liver elastography and biopsy. DSA cl 2 were determined by Luminex technology. 46% of LT recipients were positive for DSA cl 2 after a median follow‐up of 15 years. In the multivariate analysis DSA cl 2 were significantly associated with immunosuppressive monotherapy (OR 5.42; 95% CI: 1.02–28.90; p = .048). Compared to DSA cl 2 negative patients, positive recipients had significantly more graft fibrosis based on the liver stiffness (mean 9.4 ± 9.0 kPa vs. 6.5 ± 6.3 kPa; p < .002) and fibrosis stages determined by liver elastography (p = .016) and the performed liver biopsies (p = .002). Also, a significantly higher incidence of chronic rejections (11% vs. 2%; p = .045) and graft losses (6% vs. 0%; p = .043) were found. In the multivariate regression analysis DSA cl 2 were significantly associated with graft fibrosis (OR 4.57; 95% CI 1.59–13.10; p = .005). So, these data suggest that development of DSA cl 2 occurs more often with immunosuppressive monotherapy and may ultimately result in chronic rejection and graft fibrosis.
Temporal Trend of ST131 Clone among Urinary Escherichia coli Isolates in the Community: A Taiwan National Surveillance from 2002 to 2016

Sequence type (ST) 131 is a multidrug-resistant pandemic lineage of E. coli responsible for extraintestinal infections. Few surveillance data of ST131 included all antimicrobial-susceptible and -resistant isolates or focused on community-acquired urinary tract infection (UTI). From a population-based surveillance pool of 2997 outpatient urine E. coli isolates, 542 were selected for detection of ST131 based on ciprofloxacin and/or cefotaxime resistance. Pulsed-field gel electrophoresis (PFGE) was performed on all ST131 isolates to further determine their relatedness. The estimated overall ST131 prevalence in this community UTI cohort increased from 11.2% (in 2002–2004), 12.2% (in 2006–2008), 13.6% (in 2010–2012), to 17.4% in 2014–2016 (p < 0.01). In the ciprofloxacin-resistant/cefotaxime-resistant group, ST131 increased from 33.3% in 2002–2004 to 72.1% in 2014–2016 (p < 0.01). In the ciprofloxacin-resistant/cefotaxime-susceptible group, ST131 was found in 24.3% overall without significant increase in its prevalence over time. PFGE showed emergence of a cluster of ciprofloxacin-resistant/cefotaxime-resistant ST131 carrying Gr. 1 CTX-M ESBL in 2014–2016, especially 2016. Multivariate analysis revealed that age (≥65 y.o) and ciprofloxacin resistance were independent factors associated with ST131. This longitudinal surveillance showed that ciprofloxacin-resistant/cefotaxime-susceptible ST131 has been circulating in the community since 2002 but ciprofloxacin-resistant/cefotaxime-resistant ST131 increased rapidly in the later years.