Miracle-dz/UniFAR-FTUs huggingface dataset:
PD-L1 Silencing in Liver Using siRNAs Enhances Efficacy of Therapeutic Vaccination for Chronic Hepatitis B

In chronic hepatitis B virus (HBV) infection, virus-specific T cells are scarce and partially dysfunctional. Therapeutic vaccination is a promising strategy to induce and activate new virus-specific T cells. In long-term or high-level HBV carriers, however, therapeutic vaccination by itself may not suffice to cure HBV. One reason is the impairment of antiviral T cells by immune checkpoints. In this study, we used small-interfering RNA (siRNA) in combination with a heterologous prime-boost therapeutic vaccination scheme (TherVacB) to interfere with a major immune checkpoint, the interaction of programmed death protein-1 (PD-1) and its ligand (PDL-1). In mice persistently replicating HBV after infection with an adeno-associated virus harboring the HBV genome, siRNA targeting PD-L1 resulted in a higher functionality of HBV-specific CD8+ T cells after therapeutic vaccination, and allowed for a more sustained antiviral effect and control of HBV in peripheral blood and in the liver. The antiviral effect was more pronounced if PD-L1 was down-regulated during prime than during boost vaccination. Thus, targeting PD-L1 using siRNA is a promising approach to enhance the efficacy of therapeutic vaccination and finally cure HBV.
Frailty among Older People during the First Wave of the COVID-19 Pandemic in The Netherlands

Restrictive measures due to the COVID-19 pandemic may cause problems in the physical, social, and psychological functioning of older people, resulting in increased frailty. In this cross-sectional study, we aimed to assess the prevalence and characteristics of frailty, to examine differences in perceived COVID-19-related concerns and threats between frail and non-frail people and to identify variables associated with frailty in the first wave of the COVID-19 pandemic, in Dutch older people aged ≥ 65 years. We used data from the Lifelines COVID-19 Cohort Study. The Groningen Frailty Indicator (GFI) was used, with a score ≥ 4 indicating frailty. Frailty was described per domain (i.e., physical, cognitive, social, and psychological). The association between demographic, health and lifestyle variables and frailty was determined with logistic regression analyses. Frailty was present in 13% of the 11,145 participants that completed the GFI. Most items contributing to a positive frailty score were found within the social domain, in the frail (51%) and the non-frail (59%) persons. For items related to concerns and threats, a significantly higher proportion of frail people reported being worried or feeling threatened. In conclusion, during Corona restrictions, prevalence of frailty was considerable in older people from the Northern Netherlands, with one in eight being frail. Frailty was characterized by social problems and frail people were more often worried and felt threatened by the COVID-19 pandemic.
Receiver–Coil Location Detection in a Dynamic Wireless Power Transfer System for Electric Vehicle Charging

Receiver position sensing is investigated in a dynamic wireless power transfer (DWPT) system for electric vehicle (EV) charging. Exploiting the peculiar behaviour of the resonator arrays input impedance, it is possible to identify the position of the receiver coil by exciting the first array resonator with a signal at a proper frequency and measuring the resulting current. An analytical expression of the input impedance of the resonator array coupled with the EV receiver coil placed in a generic position is provided; its sensitivity to different circuit parameters is also analysed. The outline of a simple and effective algorithm for the localization of the EV is proposed and applied to a test case.
The Heat Shock Protein 90 Inhibitor, AT13387, Protects the Alveolo-Capillary Barrier and Prevents HCl-Induced Chronic Lung Injury and Pulmonary Fibrosis

Hydrochloric acid (HCl) exposure causes asthma-like conditions, reactive airways dysfunction syndrome, and pulmonary fibrosis. Heat Shock Protein 90 (HSP90) is a molecular chaperone that regulates multiple cellular processes. HSP90 inhibitors are undergoing clinical trials for cancer and are also being studied in various pre-clinical settings for their anti-inflammatory and anti-fibrotic effects. Here we investigated the ability of the heat shock protein 90 (HSP90) inhibitor AT13387 to prevent chronic lung injury induced by exposure to HCl in vivo and its protective role in the endothelial barrier in vitro. We instilled C57Bl/6J mice with 0.1N HCl (2 µL/g body weight, intratracheally) and after 24 h began treatment with vehicle or AT13387 (10 or 15 mg/kg, SC), administered 3×/week; we analyzed histological, functional, and molecular markers 30 days after HCl. In addition, we monitored transendothelial electrical resistance (TER) and protein expression in a monolayer of human lung microvascular endothelial cells (HLMVEC) exposed to HCl (0.02 N) and treated with vehicle or AT13387 (2 µM). HCl provoked persistent alveolar inflammation; activation of profibrotic pathways (MAPK/ERK, HSP90); increased deposition of collagen, fibronectin and elastin; histological evidence of fibrosis; and a decline in lung function reflected in a downward shift in pressure–volume curves, increased respiratory system resistance (Rrs), elastance (Ers), tissue damping (G), and hyperresponsiveness to methacholine. Treatment with 15 mg/kg AT13387reduced alveolar inflammation, fibrosis, and NLRP3 staining; blocked activation of ERK and HSP90; and attenuated the deposition of collagen and the development of chronic lung injury and airway hyperreactivity. In vitro, AT13387 prevented HCl-induced loss of barrier function and AKT, ERK, and ROCK1 activation, and restored HSP70 and cofilin expression. The HSP90 inhibitor, AT13387, represents a promising drug candidate for chronic lung injury that can be administered subcutaneously in the field, and at low, non-toxic doses.
The New Treatment Methods for Non-Hodgkin Lymphoma in Pediatric Patients

Simple Summary Non-Hodgkin lymphoma is one of the most frequently occurring hematologic diseases in the world. Current drugs and therapies have improved outcomes for patients with lymphoma, but there is still a need to identify novel medications for treatment-resistant cases. The aim of this review is to gather the latest findings on non-Hodgkin lymphoma in children, including genetic approaches, the application of therapy, the available treatment options, and resistance to medications. Abstract One of the most common cancer malignancies is non-Hodgkin lymphoma, whose incidence is nearly 3% of all 36 cancers combined. It is the fourth highest cancer occurrence in children and accounts for 7% of cancers in patients under 20 years of age. Today, the survivability of individuals diagnosed with non-Hodgkin lymphoma varies by about 70%. Chemotherapy, radiation, stem cell transplantation, and immunotherapy have been the main methods of treatment, which have improved outcomes for many oncological patients. However, there is still the need for creation of novel medications for those who are treatment resistant. Additionally, more effective drugs are necessary. This review gathers the latest findings on non-Hodgkin lymphoma treatment options for pediatric patients. Attention will be focused on the most prominent therapies such as monoclonal antibodies, antibody–drug conjugates, chimeric antigen receptor T cell therapy and others.
Mechanisms Controlling Carbon Sinks in Semi‐Arid Mountain Ecosystems

Feedbacks between the intertwined water and carbon cycles in semi‐arid mountain ecosystems can introduce large uncertainties into projections of carbon storage. In this study, we sought to understand the influence of key mechanisms on carbon balances, focusing on an ecosystem whose complex terrain and large interannual variability in precipitation adds to its vulnerability to warming. We applied a dynamic vegetation‐ecosystem model (Lund‐Potsdam‐Jena General Ecosystem Simulator) to simulate water‐carbon interactions in the 104,512 km2 Mediterranean‐climate ecosystems of California's Sierra Nevada for 1950–2099. Our 48 scenarios include a combination of carbon dioxide (CO2) increase, air temperature change, and varying plant rooting depths. We found that with warming (+2 and +5°C), water limitations on growth and enhanced soil respiration reduce carbon storage; however, CO2 fertilization and associated enhanced water‐use efficiency offset this loss. Using the 4 km model resolution to capture steep mountain precipitation gradients, plus accounting for the several meters of actual root‐accessible water storage in the region, were also important. With warming accompanied by CO2 fertilization our projections show that the Sierra Nevada sequestering at least 200 Tg (2 kg m−2) carbon, versus carbon loss with warming alone. The increase reflects coniferous forests growing at high elevations, and some increase in broadleaved forests at low‐to‐intermediate elevations. Importantly, uncertainty in fire disturbance could shift our finding from carbon sink to source. The improved mechanistic understanding of these feedbacks can advance modeling of carbon‐water interactions in mountain‐ecosystem under a warmer and potentially drier climate.
Increasing Role of Targeted Immunotherapies in the Treatment of AML

Acute myeloid leukemia (AML) is the most common acute leukemia in adults. The standard of care in medically and physically fit patients is intensive induction therapy. The majority of these intensively treated patients achieve a complete remission. However, a high number of these patients will experience relapse. In patients older than 60 years, the results are even worse. Therefore, new therapeutic approaches are desperately needed. One promising approach in high-risk leukemia to prevent relapse is the induction of the immune system simultaneously or after reduction of the initial tumor burden. Different immunotherapeutic approaches such as allogenic stem cell transplantation or donor lymphocyte infusions are already standard therapies, but other options for AML treatment are in the pipeline. Moreover, the therapeutic landscape in AML is rapidly changing, and in the last years, a number of immunogenic targets structures eligible for specific therapy, risk assessment or evaluation of disease course were determined. For example, leukemia-associated antigens (LAA) showed to be critical as biomarkers of disease state and survival, as well as markers of minimal residual disease (MRD). Yet many mechanisms and properties are still insufficiently understood, which also represents a great potential for this form of therapy. Therefore, targeted therapy as immunotherapy could turn into an efficient tool to clear residual disease, improve the outcome of AML patients and reduce the relapse risk. In this review, established but also emerging immunotherapeutic approaches for AML patients will be discussed.
Tung Oil Thermal Treatment Improves the Visual Effects of Moso Bamboo Materials

Color is one of the most important characteristics of a material’s appearance, which affects the additional value of bamboo and psychological feelings of users. Previous studies have shown that the dimensional stability, mildew resistance and durability of bamboo were improved after tung oil thermal treatment. In this study, the effects of tung oil thermal treatment on bamboo color at different temperatures and durations of time were investigated. The results show that the lightness (L*) of bamboo decreased as the tung oil temperature or duration of time increased. The red–green coordinates (a*) and color saturation (C*) of bamboo were gradually increased as the tung oil temperature rose from 23 °C to 160 °C, while the a* and C* were gradually decreased when the temperature continued to rise from 160 °C to 200 °C. There was no significant difference in the yellow–blue coordinates (b*) of bamboo when the duration was prolonged from 0.5 h to 3 h with tung oil thermal treatment at 140 °C. Eye movement data show that the popularity of bamboo furniture was significantly improved at 23–100 °C and slightly improved at 160–180 °C with tung oil treatment. Therefore, tung oil thermal treatment plays a positive role in improving visual effects and additional value of bamboo.
In vitro acaricidal activity of Piper tuberculatum against Rhipicephalus (Boophilus) microplus

ABSTRACT Rhipicephalus (Boophilus) microplus has a strong impact on bovine health. The aim of this study was to evaluate the in vitro acaricidal activity of Piper tuberculatum extracts on R. (Boophilus) microplus ticks obtained from cattle. The adult immersion test (AIT) was used to estimate the inhibition of oviposition. Moreover, the larval package test (LPT) was performed. P. tuberculatum extracts at 100 mg/ml showed a mortality of 78% after 24 h in adult ticks, reaching 100% at 9 days. Moreover, the mortality rate was signiﬁcantly diﬀerent (p˂0.001) among the tested groups at 11 days. Probit regression analysis showed that the mean lethal concentration (LC50) of P. tuberculatum extracts was 20.30 mg/ml after 24 h. On day 11, there were signiﬁcant diﬀerences in oviposition rate among the groups, with 56% oviposition in the control group, whereas no oviposition was observed (p˂0.01) in the groups treated with P. tuberculatum at 100 mg/ml. In the LPT, high mortality (56.00%) was found in the group treated with P. tuberculatum (50 mg/ml), whereas the control group had 2.67% (p˂0.01). The use of P. tuberculatum extracts (100 mg/ml) was highly eﬀective as an acaricide, reaching a high mortality rate in adult R. microplus ticks.
Rapid Nontranscriptional Effects of Calcifediol and Calcitriol

Classically, a secosteroid hormone, vitamin D, has been implicated in calcium and phosphate homeostasis and has been associated with the pathogenesis of rickets and osteomalacia in patients with severe nutritional vitamin D deficiency. The spectrum of known vitamin D-mediated effects has been expanded in recent years. However, the mechanisms of how exactly this hormone elicits its biological function are still not fully understood. The interaction of this metabolite with the vitamin D receptor (VDR) and, subsequently, with the vitamin D-responsive element in the region of specific target genes leading to the transcription of genes whose protein products are involved in the traditional function of calcitriol (known as genomic actions). Moreover, in addition to these transcription-dependent mechanisms, it has been recognized that the biologically active form of vitamin D3, as well as its immediate precursor metabolite, calcifediol, initiate rapid, non-genomic actions through the membrane receptors that are bound as described for other steroid hormones. So far, among the best candidates responsible for mediating rapid membrane response to vitamin D metabolites are membrane-associated VDR (VDRm) and protein disulfide isomerase family A member 3 (Pdia3). The purpose of this paper is to provide an overview of the rapid, non-genomic effects of calcifediol and calcitriol, whose elucidation could improve the understanding of the vitamin D3 endocrine system. This will contribute to a better recognition of the physiological acute functions of vitamin D3, and it could lead to the identification of novel therapeutic targets able to modulate these actions.
Conventional and Atypical Deep Penetrating Nevus, Deep Penetrating Nevus-like Melanoma, and Related Variants

Simple Summary Atypical deep penetrating nevus (DPN) is a unique skin tumor with an uncertain biologic/metastatic potential that may be difficult to distinguish from DPN (an indolent lesion) and DPN-like melanoma (an aggressive lesion) based on the results of histomorphologic analysis and commonly employed molecular studies such as fluorescence in situ hybridization and comparative genomic hybridization alone. Herein, we review the clinical, histomorphological, immunohistochemical, molecular, and cytogenetic characteristics of the DPN spectrum of lesions to try to better understand the prognosis of these lesions and possible treatment approaches. Abstract Deep penetrating nevus (DPN) is an uncommon acquired melanocytic lesion with a distinct histopathological appearance that typically behaves in an indolent manner. The lesion is characterized by a symmetrical proliferation of epithelioid to spindled melanocytes associated with abundant melanophages and wedge-shaped extension to the deep reticular dermis and subcutis. Pronounced cytologic atypia and mitotic figures are usually absent, which helps distinguish DPN from melanoma with a deep penetrating growth pattern. Recently, the concept of atypical DPN has been proposed for lesions that demonstrate borderline histomorphologic features and may be associated with lymph node deposits but lack the copy number aberrations typical of melanoma by either fluorescence in situ hybridization or comparative genomic hybridization. While most of these lesions have a favorable clinical course, rare lesions may progress to melanoma. In this review, we summarize the current literature on atypical DPNs with uncertain behavior/metastatic potential and outline the characteristics that distinguish these lesions from conventional DPN and melanoma with DPN-like features.
Geographic Variability of Biologically Active Compounds, Antioxidant Activity and Physico-Chemical Properties in Wild Bilberries (Vaccinium myrtillus L.)

The aim of this study was to characterize the variation in biologically active compounds, antioxidant activity and physico-chemical properties in naturally grown bilberries gathered from different sites in Northern Europe. The variability in the biologically active compounds, antioxidant capacity and physico-chemical properties, as well as the development of tools for the authenticity and quality control of wild bilberries (V. myrtillus L.) in different geographical locations was evaluated. The berries of bilberries were handpicked during the summers of 2019 and 2020 during the time periods when they are typically harvested for commercial purposes in Northern Europe (Norway (NOR), Finland (FIN), Latvia (LVA) and Lithuania (LTU)). Berries from locations in NOR were distinguished by their higher mean TPC (791 mg/100 g FW, average), whereas the mean TPC of samples from the most southern country, LTU, was the lowest (587 mg/100 g FW). The TPC of bilberries ranged from 452 to 902 mg/100 g FW. The TAC values of investigated bilberry samples varied from 233 to 476 mg/100 g FW. A high positive correlation was found between TPC and antioxidant activity of the bilberry samples (R = 0.88 and 0.91 (FRAP and ABTS assays, respectively)), whereas the correlation between TAC and antioxidant activity was lower (R = 0.65 and 0.60). There were variations in the TPC and TAC values of investigated berries, suggesting that genotype also affects the TPC and TAC in berries. In 2020, the pH values and TSS contents of berries were significantly lower than in 2019. To the best of our knowledge, this is the first comprehensive reported evaluation of the biologically active compounds in wild bilberries from different Northern European countries using one laboratory-validated method.
The Relationship between the Testicular Blood Flow and the Semen Parameters of Rams during the Selected Periods of the Breeding and Non-Breeding Seasons

Simple Summary There is a rising demand for sheep products such as meat, wool, and milk. Within the sheep flock, rams are the most valuable animals as they represent 50% of the genetics of every sheep flock. To improve productivity, monitoring of the rams’ semen quality allows breeders to maximize fertility. This study aimed to introduce the advanced semen evaluation tests and evaluate the correlations between the parameters of the basic and advanced semen evaluation tests and the dynamics of testicular blood flow. Semen was collected from eighteen rams, and a pulse wave Doppler examination was conducted in three routine ram examination periods in Poland: before the breeding season (BBS), during the breeding season (BS), and after the breeding season (ABS). Routine and advanced semen analysis, including computer-assisted sperm analysis (CASA), sperm chromatin dispersion test (SCD), and motile sperm organelle morphology examination (MSOME), were conducted. In Doppler ultrasonography, the peak systolic velocity (PSV), end-diastolic velocity (EDV), resistive index (RI), and pulsatility index (PI) were calculated. The high-quality semen was derived during BS, whereas BBS semen demonstrated high sperm abnormalities related to sperm cells DNA fragmentation and vacuolization. The features of higher sperm abnormalities correlated with an increase in RI, PI, and EDV, respectively. Abstract The study aimed to conduct advanced semen evaluation tests during routine ram examination periods in the breeding and non-breeding seasons and to investigate their correlation with the dynamics of testicular blood flow. Semen was collected from eighteen rams, and pulse wave Doppler examination before (BBS), during (BS), and after the breeding season (ABS). Routine and advanced semen analysis, including computer-assisted sperm analysis (CASA), sperm chromatin dispersion test (SCD), and motile sperm organelle morphology examination (MSOME), were conducted. In Doppler ultrasonography, the peak systolic velocity (PSV), end-diastolic velocity (EDV), resistive index (RI), and pulsatility index (PI) were calculated. In BS period, high sperm concentration (p < 0.0001) and total sperm number/ejaculate (p = 0.008) were noted. During the BBS period, a low percentage of forwarding motility (p = 0.017) and high sperm abnormalities (p = 0.005) were found. Also during this period, both SCD and MSOME revealed high sperm DNA fragmentation (p < 0.0001) and signs of vacuolization (Grade II-IV, p < 0.05). The advanced features of higher sperm abnormalities (Grade IV of MSOME) correlated with an increase RI (ρє <0.60;0.61>) and PI (ρє <0.46;0.52>), whereas the basic percentage of sperm abnormalities correlated with the EDV (ρє <0.44;0.73>) value. One may conclude that the current preliminary study requires further research concerning the monthly examination of a ram to provide full yearly characteristics of the relation between advanced semen evaluation tests and the dynamics of testicular blood flow.
Storage Effect on Phenolic Compounds and Antioxidant Activity of Nephelium lappaceum L. Extract

Preparation of potential antioxidant extracts with less process for storing in a long period is preferable. N. lappaceum rind, well known as a promising source of phenolic antioxidants agricultural residue, was employed to prepare crude extracts by different solvents. The phenolic content, flavonoid content, antioxidant, and anti-tyrosinase activities of the extracts were evaluated. The stability of the potential extract was then assessed for phenolic content and antioxidant activity under various storage conditions. The extractive yields of crude phenolic extract ranged from 16.61 to 28.78%. The ethanolic extract of N. lappaceum rind exhibited potential antioxidant activities and contained a high amount of phenolics and flavonoid contents. The extract remained with a high amount of the phenolic content (up to 88.79%) and retained its antioxidant property under various temperatures (4, 25, and 45 °C) after the first week of the storage period. The results suggest that phenolic content and antioxidant activity of N. lappaceum rind extract, as a nutraceutical or anti-aging ingredients in cosmetics, could be stored at a temperature from 4 °C to 45 °C with or without oxygen exposure at least for 16 weeks.