Fire is a significant threat to human life and civil infrastructures. Builders and architects are hankering for safer and sustainable alternatives of concrete that do not compromise with their design intent or fire safety requirements. The aim of the present work is to improve the residual compressive performance of concrete in the post-fire exposure, by incorporating by-products from urban residues. Based on sustainability and circular economy motivations, the attention is focused on rubber tire fly ash, aged brick powder, and plastic (PET) bottle residuals used as partial sand replacement. The selected by-products from urban residues are used for the preparation of Cement-Based Composites (CBCs) in two different proportions (10 % and 15 %). The thermal CBC behaviour is thus investigated under realistic fire scenarios (i.e., Direct Flame (DF) for 1 hour (1h)), by following the ISO 834 standard provisions, but necessarily resulting in non-uniform thermal exposure for the cubic specimens. The actual thermal exposure is further explored with a Finite Element (FE) model, giving evidence of thermal boundaries effects. The post-fire residual compressive strength of heated concrete and CBC samples is hence experimentally derived, and compared to unheated specimens in ambient conditions. From the experimental study, the enhanced post-fire performance of CBCs with PET bottle residual is generally found superior to other CBCs or concrete. The structure-property relation is also established, with the support of Scanning Electron Microscopy (SEM) micrographs. Based on existing empirical models of literature for the prediction of the compressive or residual compressive strength of standard concrete, newly developed empirical relations for both concrete and CBCs are assessed.

The main objective of this study is to develop a Hapke photometric model that is suited for Chang’E-1 (CE-1) Interference Imaging Spectrometer (IIM) data. We first divided the moon into three areas including ‘maria’, ‘new highland’ and old ‘highland’ with similar photometry characteristic based on the Hapke parameters of the moon derived from Lunar Reconnaissance Orbiter Camera (LROC) Wide Angle Camera (WAC) multispectral data. Then, we selected the sample data in the ‘maria’ area and obtained a new set of Hapke model’s parameters that can best fit these data. Result shows that photometric correction using Hapke model with these new derived parameters can eliminate the effect of variations in viewing and luminating geometry, especially ‘opposition surge’, more efficiently than the empirical model. The corrected mosaic shows no significant artifacts along the tile boundaries, and more detailed information of the image can be exhibited due to a better correction of ‘opposition surge’ at small phase angle (g <15°).

The effectiveness of immunotherapy for cervical adenocarcinoma (CA) has not been demonstrated yet. It may be possible for us to use programmed cell death 1 (PD-1), programmed cell death-ligand 1 (PD-L1), and CD8 as biomarkers of response to immune therapy in CA patients. In the present study, we aimed to investigate whether the expression levels of PD-1, PD-L1, and CD8 can predict the prognosis of CA patients and their response to ICI therapy. The levels of the PD-1, PD-L1, and CD8 proteins were analyzed by immunohistochemical analysis from formalin-fixed, paraffin-embedded tumor samples. The correlation between the expression levels and patient prognosis was analyzed by the Kaplan–Meier method and univariate and multivariate Cox proportional hazard regression model. We observed a significant inverse-correlation between the PD-1 and CD8 expression (p=0.001, chi square test). We also found a significant inverse-correlation between the PD-L1 and CD8 expression (p=0.027). The overall survival was significantly worse in patients with positive PD-1 expression (p=0.027). Similarly, the progression-free survival was also worse (p=0.087). Our results demonstrate that a high level of PD-1 expression is associated with a poor prognosis in CA patients. Further research is necessary to identify the molecular mechanisms that mediate this association.

Knowledge of the spatio-temporal occurrence of avalanche activity is critical for avalanche forecasting and hazard mapping. We present a near-real time automatic avalanche monitoring system that outputs detected avalanche polygons within roughly 10 min after Sentinel- 1 SAR data download. Our avalanche detection algorithm has an average probability of detection of 67.2 % with a false alarm rate averaging 45.9, with maximum POD's over 85 % and minimum FAR's of 24.9 % compared to manual detection of avalanches. The high variability in performance stems from the dynamic nature of snow in the Sentinel-1 data. After tuning parameters of the detection algorithm, we processed five years of Sentinel-1 images acquired over a 150 x 100 km large area in Northern Norway, with the best setup. Compared to a dataset of field-observed avalanches, 77.3 % were manually detectable. Using these manual detections as benchmark, the avalanche detection algorithm achieved an accuracy of 79 % with high POD's in cases of medium to large wet snow avalanches. For the first time, we can present a dataset of spatiotemporal avalanche activity over several winters from a large region. This unique dataset allows for research into the relationship between avalanche activity and triggering meteorological factors, mapping of avalanche prone areas and near-real time avalanche activity monitoring to assist public avalanche forecasting. Currently, the Norwegian Avalanche Warning Service is using our processing system for pre-operational use in three regions in Norway.

Aim: The purpose of this examination is determining predictors to oral health behaviors predict in Iranian students in district 1 Tehran based on the health belief model with added commitment to plan construct. Methods: This cross-sectional study were randomly selected conducted on 351 eligible four grade female students in the first district of Tehran, Iran in 2017. The random Multi‑stage random cluster sampling method was used to recruit students. The inclusion criteria were being graded, four female students (aged 9-11 years), or education at the fourth grade of one of the elementary schools studied in the first district of Tehran and, The health of the student from a physical and psychological of view. Logistic regression analysis was used to identify the variables that predict oral health behaviors. To assess the predictors of oral health behaviors, all the expanded Health Belief Model constructs with the construct of “Commitment to Plan of Action” from “Health Promotion Model were examined as risk factors to see if they influence on the probability of brushing behavior and dental floss behavior occurrence and were interpreted through odds ratio (OR). SPSS version 19 was used to analyze the data. Results: Totally 308 four grade female students with mean age of 9.32 ± 0.81 years old took part in the study. The total 31.8% of the students reported that they were brushing behavior less than twice a day and 55.2% students claimed, use of dental floss behavior once a week or less than once a day. The results indicated that perceived self-efficacy (OR=1.46, 95% CI=0.57-3.78, P<0.001), Commitment to plan (OR=1.13, 95% CI=1.04-1.23, P<0.001) and Cues to action (OR=1.42, 95% CI=1.14–1.76, P=0.002) were the significant predicting variables which is the key factor of brushing twice a day, and use of dental floss once a day or more (OR=1.02, 95% CI=0.23-3.53, P=0.003). Conclusion: This study has shown the effectiveness of the health belief model with added commitment to plan construct to predict oral health behavior in female students. So, it seems that the model as a framework for designing training programs to improve students to improve oral health behavior can be used.

The inhibition of heat shock protein 90 (Hsp90) a molecular chaperone for multiple oncogenic client proteins is considered as a promising approach to overcome radioresistance. Since most Hsp90 inhibitors activate HSF-1 that induces the transcription of cytoprotective and tumor-promoting stress proteins such as Hsp70 and Hsp27, a combined approach consisting of HSF-1 knockdown (k.d.) and Hsp90 inhibition was investigated. A specific HSF-1 k.d. was achieved in H1339 lung cancer cells using RNAi-Ready pSIRENRetroQ vectors with puromycin resistance. The Hsp90 inhibitor NVP-AUY922 was evaluated at low concentrations - ranging from 1-10nM - in control and HSF-1 k.d. cells. Protein expression (i.e., Hsp27/Hsp70, HSF-1, pHSF-1) and transcriptional activity was assessed by Western blot analysis and luciferase assays and radiosensitivity was measured by proliferation, apoptosis (Annexin V, active caspase 3), clonogenic cell survival, alkaline comet, γH2AX, 53BP1 and Rad51 foci assays. The k.d. of HSF-1 resulted in a significant reduction of basal and NVP-AUY922-induced Hsp70/Hsp27 expression levels. A combined approach consisting of HSF-1 k.d. and low concentrations of the Hsp90 inhibitor NVP-AUY922 potentiates radiosensitization which involves an impaired homologous recombination mediated by Rad51. Our findings are key for clinical applications of Hsp90 inhibitors with respect to adverse hepatotoxic effects.

HIV treatment strategies against viral enzymes are continuously hampered by viral drug resistance. Recent findings show that viral substrate Gag contributes to HIV-1 Protease Inhibitor (PI) resistance, leading to demands for new strategies in HIV treatment where Gag is recognized as a drug target. To successfully target Gag, there is a need of in-depth understanding of the Gag polyprotein and the effects of Gag mutations. Here, we propose new strategies in designing novel Gag inhibitors against existing and novel emerging Gag mutations via a structural understanding of the Gag-Protease relationship in PI resistance. In this review, we discuss the role of both novel and previously reported mutations, revealing insights to how they aid in PI resistance, and how new Gag inhibitors can be designed.

Lung adenocarcinoma with EGFR-TKI (epidermal growth factor receptor-tyrosine kinase inhibitor) resistance was reported to harbor higher ability of invasion and migration than those sensitive to EGFR-TKI, but the function of MMPs (matrix metalloproteinases) has not been explored in EGFR-TKI resistant lung adenocarcinoma. In this study, the correlation between immunohistochemical status of MMP-1 and clinicopathological factors were analyzed in 89 lung adenocarcinoma. We performed microarray, migration assay and invasion assay using EGFR-TKI sensitive cell lines and EGFR-TKI resistant cell lines. To clarify the mechanism of MMP-1 induction, we treated lung adenocarcinoma cells with EGF and rapamycin, performed phosphorylation antibody array and analyzed the correlation between MMP-1 expression and EGFR or mTOR (mammalian target of rapamycin) pathway. As a result, we firstly demonstrated that MMP-1 played an important role in migration and invasion abilities of EGFR-TKI resistant lung adenocarcinoma, and that mTOR pathway could be associated with an induction of MMP-1. We demonstrated the significant positive correlation between MMP-1 status in lung adenocarcinoma cells and the history of smoking, and the subtype of invasive mucinous adenocarcinoma. In conclusion, This study provides insights into the development of a possible alternative therapy manipulating MMP-1 and mTOR signaling pathway in EGFR-TKI resistant lung adenocarcinoma.

Many studies, which try to analyze conditions for debris flow development, ignore the type of initiation. Therefore this paper deals with the following questions: What type of hydro-mechanical triggering mechanisms for debris flows can we distinguish in upstream channels of debris flow prone gullies? Which are the main parameters controlling the type and temporal sequence of these triggering processes and what is their influence on the meteorological thresholds for debris flow initiation? A series of laboratory experiments were carried out in a flume, 8 m long and with a width of 0.3 m. to detect the conditions for different types of triggering mechanisms. The flume experiments show a sequence of hydrological processes triggering debris flows, namely erosion and transport by intensive overland flow and by infiltrating water causing failure of channel bed material. On the basis of these experiments an integrated hydro-mechanical model was developed, which describes Hortonian and Saturation overland flow, maximum sediment transport, through flow and failure of bed material. The model was calibrated and validated using process indicator values measured during the experiments in the flume. Virtual model simulations, carried out in a schematic hypothetical source area of a catchment show that slope angle and hydraulic conductivity of the bed material determine the type and sequence of these triggering processes. It was also clearly demonstrated that the type of hydrological triggering process and the influencing geometrical and hydro-mechanical parameters may have a great influence on rainfall intensity-duration threshold curves for the start of debris flows.

The dengue virus (DENV) is an arbovirus belonging to the Flaviviridae family; the species comprises four antigenically distinct serotypes (DENV–1, DENV–2, DENV–3, and DENV–4), which are further subdivided into genotypes. The virus is transmitted to humans through mosquito bites, primarily from the Aedes spp. genus. Dengue is endemic in various parts of the world, including tropical and subtropical regions of Asia, Latin America, Africa, and Oceania. In Brazil, the state of Tocantins, located in north-central Brazil, has experienced a significant number of arboviral disease cases, particularly dengue. This study aimed to monitor DENV circulation within the state by conducting full genome sequencing of viral genomes recovered from 61 patients between June 2021 and July 2022. During this period, both DENV-1 and DENV-2 serotypes were identified. Our findings confirm the circulation of DENV serotypes 1 and 2 in Tocantins, affecting males and females equally, with younger age groups (4 to 43 years old) being the most susceptible. Phylogenetic analysis revealed that the circulating viruses belong to DENV–1 genotype V American and DENV–2 genotype III Southeast Asian/American. The Bayesian analysis of DENV-1 Genotype V sequenced here is closely related to genomes previously sequenced in the state of São Paulo. Regarding DENV-2 genotype III genomes, these are clustered in a distinct, well-supported subclade, along with previously reported isolates from the states of Goiás and São Paulo. In both cases, our results suggest that multiple introductions of these genotypes occurred in the Tocantins state. This observation highlights the significant impact of major population centers in Brazil on virus dispersion, including other Latin-American countries and the USA. In the SNP analysis, DENV-1 displayed 122 distinct missense mutations, while DENV-2 had 44, with significant mutations predominantly occurring in the envelope and NS5 proteins. The analyses performed here reveal the concomitant circulation of distinct DENV-1 and -2 genotypes in some Brazilian states, underscoring the dynamic evolution of the DENV and the ongoing significance of surveillance efforts in supporting public health policies.

The human T-cell leukemia virus type 1 (HTLV-1) is the only known human oncogenic retrovirus. HTLV-1 can cause a cancer called adult T-cell leukemia/lymphoma (ATL). The virus is transmitted through body fluids of infected individuals, primarily breast milk, blood, and semen. At least 5–10 million people in the world are infected with HTLV-1. In addition to ATL, HTLV-1 infection can also cause HTLV-I-associated myelopathy (HAM /TSP). ATL is characterized by low viral ex-pression and poor prognosis. The oncogenesis triggered by HTLV-1 is extremely complex and the molecular mechanisms are not fully understood. However, viral regulatory proteins Tax and HTLV-1 bZIP factor (HBZ) have been shown to play key roles in the transformation of HTLV-1-infected T cells. Moreover, several studies have shown that the final fate of HTLV-1-infected transformed T cell clones is the result of a complex interplay of HTLV-1 oncogenic protein expression with cellular transcription factors that subvert the cell cycle and disrupt reg-ulated cell death, thereby exerting their transforming effects. This review provides updated in-formation on the mechanisms underlying the transforming action of HTLV-1 and the potential therapeutic targets to combat ATL.

The prognosis of patients with recurrent or metastatic of the head and neck squamous-cell carcinoma (HNSCC) refractory to platinum-based chemotherapy is severe and, consequently, the identification of therapeutic options for this category of patients is a priority. Nivolumab, an anti- programmed cell death protein 1 (anti-PD-1) monoclonal antibody, has been approved for the treatment of recurrent or metastatic HNSCC after platinum-based therapy progressing. We present the early experience of two academic center including diagnostic, clinical, biological, therapeutic and outcomes characteristics of head and neck cancer (HNC) patients treated with Nivolumab. The purpose of the study is to identify certain peculiarities and to report them compared to the data from the literature in order to generate some hypotheses that coud constitute criteria for the selection of cases with maximum benefit to immunotherapy. Analyzing the data obtained from 18 patients treated in Emergency County Hospital Craiova, "Saint Nectarie" Oncological Hospital Craiova and Euroclinic Oncological Center Iasi January 2020 and March 2023 it could be hypothesized that lower nadir values of neutrophil to lymphocyte ratio (<3.5) and the adition of intensive regimens of chemotherapy and radiotherapy could justify a favorable response in terms of progression free survival (PFS) during immunotherapy with Nivolumab. To our knowledge, the study included the first two cases of second primary malignancy (SPM) in the head neck region treated with Nivolumab. The reported data support a possible benefit of the sequential administration of radiotherapy, immunotherapy for SPM cases. Higher positive dynamic of neutrophil to lymphocyt ratio (NLR) could be associated with worst outcome during immunotherapy. All study observations including the role of infections and antibiotic treatment as well as the possible biomarker value of NLR variation during immunotherapy should be investigated in multicenter clinical trials.

The objective of this study was to evaluate the potential benefits of feeding spray-dried porcine plasma (SDPP) to pigs infected with African swine fever virus (ASFV). Two groups of twelve weaned pigs each were fed with CONVENTIONAL or 8% SDPP enriched diets. Two pigs (trojans)/group) were injected intramuscularly with the pandemic ASFV (Georgia 2007/01) and comingled with the rest of the pigs (1:5 trojan:naïve ratio) to simulate a natural route of transmission. Trojans developed ASF and died within the first week after inoculation but contact pigs did not develop ASF, viremia or seroconversion. Therefore, three more trojans per group were introduced to optimize the ASFV transmission (1:2 trojan:naïve ratio). Blood, nasal and rectal swabs were weekly harvested and at end of the study, ASFV-target organs collected. After the second exposure, rectal temperature of conventionally fed contact pigs increased >40.5˚C while fever was delayed in the SDPP contact pigs. Additionally, PCR Ct values in blood, secretions and tissue samples were significantly lower (P<0.05) for CONVENTIONAL compared to SDPP contact pigs. Under these study conditions, contact exposed pigs fed SDPP had delayed ASFV transmission and reduced virus load, likely by enhanced specific T-cell priming after the first ASFV-exposure.

Therapeutic antibodies targeting immune checkpoints have shown limited efficacy in clinical trials in glioblastoma (GBM) patients. Ultrasound-mediated blood-brain barrier opening (UMBO) using low-intensity pulsed ultrasound improved drug delivery to the brain. We explored the safety and the efficacy of UMBO plus immune checkpoint inhibitors in preclinical models of GBM. A Blood-brain barrier (BBB) opening was performed using a 1 MHz preclinical ultrasound system in combination with 10µl/g microbubbles. Brain penetration of immune checkpoint inhibitors was determined, and immune cell populations were evaluated using flow cytometry. The impact of repeated treatments on survival was determined. In syngeneic GL261-bearing immunocompetent mice, we showed that UMBO safely and repeatedly open the BBB. BBB opening was confirmed visually and microscopically using Evans’s blue dye and magnetic resonance imaging. UMBO plus anti-PDL-1 was associated with a significant improvement of the overall survival compared to anti-PD-L1 alone. Using mass spectroscopy, we showed that the penetration of therapeutic antibodies can be increased when delivered intravenously compared to non-sonicated brains. Furthermore, we observed an enhancement of activated microglia percentage when combined with anti-PD-L1. Here, we report that the combination of UMBO and anti-PD-L1 dramatically increases GL261-bearing mice's survival compared to their counterparts treated with anti-PD-L1 alone. Our study highlights the BBB as a limitation to overcome to increase the efficacy of anti-PD-L1 in GBM and supports clinical trials combining UMBO and in GBM patients.

The presence of a non-structural protein 1 (NS1) in tick-borne encephalitis (TBE) vaccines and the possible induction of an NS1-specific immune response in vaccinated individuals remains a somewhat controversial topic. Previously, we detected the presence of NS1 in Encepur TBE vaccine by mass spectrometry and found the induction of NS1-specific IgG antibodies in mice vaccinated with FSME-Immun TBE vaccine. Here, in this follow-up study, we examined the dynamics and extent of the NS1-specific IgG response in mice vaccinated with these two vaccines in more detail and compared it with the IgG response to the whole virus (WV). Mice were vaccinated at two-week intervals with a total of six doses of each vaccine, and levels of IgG antibodies to TBE virus WV and NS1 were measured by ELISA after each dose. Both vaccines elicited a robust anti-WV IgG response after two doses. The Encepur vaccine did not elicit NS1-specific IgG even after all six doses. In contrast, FSME-Immun vaccine triggered production of NS1-specific IgG after four doses. The results indicate that FSME-Immun is the only vaccine that elicits an NS1-specific antibody response in mice. However, compared to WV-specific IgG, the NS1-specific response is weaker, and a higher number of doses is required to induce detectable levels of NS1-specific IgG antibodies.

Immune checkpoint blockade (ICB)-based therapy is revolutionizing cancer treatment by fostering successful immune surveillance and effector cell responses against various types of cancers. However, patients with HER2+ cancers are yet to benefit from this therapeutic strategy. Precisely, several questions regarding the right combination of drugs, drug modality, and effective dose recommendations pertaining to the use of ICB-based therapy for HER2+ patients remain unanswered. In this study, we use a mathematical modeling-based approach to quantify the growth inhibition of HER2+ breast cancer (BC) cell colonies (ZR75) when treated with anti-HER2; trastuzumab (TZ) and anti-PD-1/PD-L1 (BMS-202) agents. Our data show that a combination therapy of TZ and BMS-202 can significantly reduce the viability of ZR75 cells and trigger several morphological changes. The combination decreased the cell’s invasiveness along with altering several key pathways, such as Akt/mTor and ErbB2 compared to monotherapy. In addition, BMS-202 causes dose-dependent growth inhibition of HER2+ BC cell colonies alone, while this effect is significantly improved when used in combination with TZ. Based on the in-vitro monoculture experiments conducted, we argue that BMS-202 can cause tumor growth suppression not only by mediating immune response but also by interfering with the growth signaling pathways of HER2+ BC. Nevertheless, further studies are imperative to substantiate this argument and to uncover the potential crosstalk between PD-1/PD-L1 inhibitors and HER2 growth signaling pathways in breast cancer.

Vaccination against tick-borne encephalitis (TBE) is based on the use of formalin-inactivated, culture-derived whole-virus vaccines. Immune response following vaccination is primarily directed to the viral envelope (E) protein, the major viral surface antigen. In Europe, two TBE vaccines are available in adult and pediatric formulations, FSME-IMMUN® (Pfizer) and Encepur® (GlaxoSmithKline). Herein, we analyzed the content of these vaccines using mass spectrometry (MS). The MS analysis revealed that the Encepur vaccine contains not only proteins of the whole virus particle, but also viral non-structural protein 1 (NS1). MS analysis of the FSME-IMMUN vaccine failed due to the high content of human serum albumin used as a stabilizer in the vaccine. However, the presence of NS1 in FSME-IMMUN was confirmed by immunization of mice with six doses of this vaccine, which led to a robust anti-NS1 antibody response. NS1-specific western blot analysis detected anti-NS1 antibodies also in sera of humans who received multiple doses of either of these two vaccines; however, most vaccinees who received ≤3 doses were negative for NS1-specific antibodies. The contribution of NS1-specific antibodies to protection against TBE was demonstrated by immunization of mice with purified NS1 antigen, which led to a significant (p < 0.01) prolongation of the mean survival time after lethal virus challenge. This indicates that stimulation of anti-NS1 immunity by the TBE vaccines may increase their protective effect.

The present study is the second step (concerning the normal-diet restoration) of the our previous one (concerning the calcium-free diet) to determine whether the normal-diet restoration, with/without concomitant PTH(1-34) administration, can influence amounts and deposition sites of the total bone mass. Histomorphometric evaluations and immunohistochemical analysis for Sclerostin expression were conducted on the vertebral bodies and femurs in rat model. The final goals are: i) to define timing and manners of bone mass changes when calcium is restored in the diet; ii) to analyze the different involvement of the two bony architectures having different metabolism (i.e. trabecular versus cortical bone); iii) to verify the eventual role of PTH(1-34) administration. Results evidenced the greater involvement of the trabecular bone with respect to the cortical one, in answering to different calcium diet content, and the effect of PTH mostly in the recovery of trabecular bony architecture. The main findings emerged from the present study are: i) the importance of the interplay between mineral homeostasis and skeletal homeostasis in modulating and guiding bone answers to dietary/metabolic alterations and ii) the evidence that the more involved bony architecture is the trabecular one, the most susceptible to the dynamical balance of the two homeostases.

IL1RA intron 2 86-bp repeat and IL4 intron 3 70-bp repeat are VNTRs that have been associated with various diseases, but their role in obesity is elusive. The objective of this study was to investigate the association of IL1RA and IL4 VNTRs with obesity and adiposity in 315 Malaysian subjects (128 M/187 F; 23 Malays/251 ethnic Chinese/41 ethnic Indians). The allelic distributions of IL1RA and IL4 were significantly different among ethnicities, and the alleles were associated with total body fat (TBF) classes. Individuals with IL1RA I/II genotype or allele II had greater risk of having higher adiposity - even after controlling for ethnicity [Odds Ratio (OR) of I/II genotype = 12.21 (CI = 2.54, 58.79; p = 0.002); II allele = 5.78 (CI = 1.73, 19.29; p = 0.004)]. However, IL4 VNTR B2 allele was only significantly associated with overall adiposity status before adjusting for ethnicity [OR = 1.53 (CI = 1.04, 2.23; p = 0.03)]. TBF was also significantly higher in those with IL1RA II allele compared with I allele (31.79 ± 2.52 vs. 23.51 ± 0.40; p = 0.005). Taken together, IL1RA intron 3 VNTR seems to be a genetic marker for overall adiposity status in Malaysian subjects.

Oncogenic protein E6 from Human Papilloma Virus 16 (HPV-16) mediates the degradation of Membrane-associated guanylate kinase with inverted domain structure-1 (MAGI-1), throughout the interaction of its protein binding motif (PBM) with the Discs-large homologous regions 1 (PDZ1) domain of MAG1-1. Generic variation in the E6 gene that translates to changes in the protein’s amino acidic sequence modifies the interaction of E6 with the cellular protein MAGI-1. MAGI-1 is a scaffolding protein found at tight junctions of epithelial cells, where it interacts with a variety of proteins regulating signaling pathways. MAGI-1 is a multidomain protein containing two WW (rsp-domain-9), one guanylate kinase-like, and six PDZ domains. PDZ domains played an important role in the function of MAGI-1 and served as targets for several viral proteins including the HPV-16 E6. The aim of this work was to evaluate, with an in silico approach, employing molecular dynamics simulation and protein-protein docking, the interaction of the intragenic variants E-G350 (L83V), E-C188/G350 (E29Q/L83V), E-A176/G350 (D25N/L83V), E6-AAa (Q14H/H78Y/83V) y E6-AAc (Q14H/I27RH78Y/L83V) and E6-reference of HPV-16 with MAGI-1. We found that variants E-G350, E-C188/G350, E-A176/G350, AAa and AAc increase their affinity to our two models of MAGI-1 compared to E6-reference.

Knee osteoarthritis (KOA) is a progressive and multifactorial disease that leads to joint pain, muscle weakness, physical disability, and decreased quality of life. In KOA, hyaluronic acid (HA) quantity and molecular weight (MW) are decreased, leading to joint pain due to increased wear of the knee articular cartilage. Arthrogenic muscle inhibition, which is usually found in patients with KOA, is associated with joint inflammation, pain, and swelling, also causing muscle atrophy, primarily of the anterior thigh muscles, and hindering the rehabilitation process. The aim of our work was to determine if a single HA infiltration could minimize the effects of arthrogenic muscle inhibition in patients with KOA in the short term, using isokinetic dynamometry to evaluate the strength of the knee extensor and flexor muscles of the thigh. Thirty patients with KOA who underwent both clinical and isokinetic assessment, and that received a single injection of HA, were retrospectively included. Our results showed that a single intra-articular injection of HA significantly reduces pain and improves joint function at four weeks, while non-statistically significant improvements were observed for the reference isokinetic parameter (maximum torque) at both 90°/s and 180°/s. Further high-quality studies are necessary to confirm the results of our study.

Introduction: The World Health Organization (WHO) recommends visual inspection with acetic acid (VIA) for cervical cancer screening (CCS) in lower-resource settings; however, quality varies widely, and it is difficult to maintain a well-trained cadre of providers. The Smartphone-Enhanced Visual Inspection with Acetic acid (SEVIA) program was designed to offer secure sharing of cervical images and real-time supportive supervision to health care workers providing screening in semirural Tanzania, in order to improve quality and accuracy of visual assessment of the cervix for treatment. The purpose of this evaluation was to document early learnings from patients, providers, and higher-level program stakeholders, on barriers and enablers to program implementation. Methods: From September 9th to December 8th, 2016, observational activities and open-ended interviews were conducted with image reviewers (n= 5), providers (n=17), community mobilizers (n=14), patients (n=21), supervisors (n=4) and implementation partners (n=5) involved with SEVIA. Sixty-six interviews were conducted at 14 facilities, in all 5 of the program regions. Results SEVIA was found to be a highly regarded tool for the enhancement of CCS services in Northern Tanzania. Acceptability, adoption, appropriateness, feasibility, and coverage of the intervention were highly recognized. It appeared to be an effective means of improving good clinical practice among providers and fit seamlessly into existing roles and processes. Barriers to implementation included network connectivity issues, and community misconceptions and adoption of CCS more generally. Conclusion: SEVIA is a practical and feasible mobile health intervention and tool that easily integrated into the National CCS program to enhance quality of care. With the introduction of HPV DNA testing as a primary screening strategy for cervical cancer prevention in settings such as Tanzania, the role of a mobile health platform for program surveillance, tracking follow-up care, and quality assurance of visual assessment of the cervix for treatment (in women who test positive for high-risk HPV) further supports the importance of programs, such as SEVIA, in low resource contexts. Further expansion of the program, especially to rural areas where screening providers can benefit from virtual support for screening services through the use of the mobile App, could strengthen the delivery of services within the national cervical cancer prevention program.

Background: Multiple drug delivery systems obtained by loading nanoparticles (NPs) with different drugs with different physicochemical properties present a promising strategy to achieve synergistic effects between drugs or overcome undesired effects. This study aims to develop a new NP by loading Quercetin (Que) and valproic acid (VPA) onto chitosan. In this context, our study investigated the antioxidant activities of chitosan NPs loaded with single and dual drugs containing Que against oxidative stress. Method: The synthesis of single (Que or VPA) and dual-drug (Que and VPA) loaded chitosan NPs, characterization of the NPs, conducting in vitro antioxidant activity studies, and analysis of the cytotoxicity and antioxidant activity of the NPs in SH-SY5Y cell lines were performed. Result: The NP applications that protected cell viability to the greatest extent against H2O2-induced cell damage were, respectively, 96 µg/ml of Que-loaded chitosan NP (77.30%, 48 h), 2 µg/ml of VPA-loaded chitosan NP (70.06%, 24 h), 96 µg/ml of blank chitosan NP (68.31%, 48 h), and 2 µg/ml of Que and VPA-loaded chitosan NP (66.03%, 24 h). Conclusion: Our study establishes a successful paradigm in developing drug-loaded NPs, with uniform and homogeneous distribution of drugs onto NPs. Chitosan NPs loaded with both single and dual drugs possessing antioxidant activity were successfully developed.

This study investigated the possible usage of beeswax oleogels instead of milk fat as a fat source in ice cream production and konjac gum as a stabilizer instead of salep. For this aim, 12 different ice cream samples were prepared using various fat and oil sources (milk fat and oleogel), stabilizers (salep and konjac gum), and emulsifiers (monoglyceride (MG), palsgaard (PG), and none emulsifier emulsifier-free (NE)). It was determined that the overrun ratio in ice cream samples containing milk fat was higher than in oleogel and the viscosity of the ice cream mix containing palsgaard and oleogel was greater than that of the other treatments (milk fat, MG, and NE). While the first dripping time of the samples with PG and konjac gum was longer compared to the samples without emulsifier (NE) and Monoglyceride (MG), the complete melting times of the samples were close to each other. Whereas the dissolution rate of the samples with salep was higher than that of konjac gum, the fat destabilization ratios of the samples with oleogel and konjac gum were lower than those of milk fat and salep. The fat destabilization ratio of samples containing PG as an emulsifier was statistically higher (p <0.01) than that of samples containing MG and NE. It was found that the unsaturated fatty acid (C18:1, C18:2, and C18:3) content of the samples containing oleogel was significantly higher (p <0.01) than that of the samples containing milk fat. However, butyric and caproic acids, which are aliphatic fatty acids, were found to be deficient in the samples to which oleogel was added instead of milk fat. As to the microscopic appearance, while water and oil particles were not homogeneously dispersed in the ice cream samples with oleogel, they were fully homogeneously dispersed in the milk fat-added ice cream samples. In addition, it was determined that panelists preferred the C samples (milk fat as fat source, salep and PG as emulsifier).Among the samples with added oleogel as oil source, they liked the J sample more (oleogel as fat source,conjak gum and none emulgator). Therefore, the C and J samples can be recommended for consumption

FMD is a highly contagious animal disease that occurs in cloven-hoofed animals including pigs. To prevent FMD, vaccines and adjuvants are used to induce an immune response, but it is not sufficient to show the effect of preventing viral infection. In this study, we conducted to evaluate the increasing effect of FMD vaccine SP antibody by administrating Zn-ASP to 100 pigs from three test pig farms with feed. FMD vaccine antibody titer and immunological index were analyzed using an enzyme-linked immunosorbent assay (ELISA) kit, and hematological and blood biochemical parameters were analyzed using an automatic blood analyzer. The titer of FMD vaccine SP antibody in the 0.2% Zn-ASP-administered group significantly increased compared to that in the positive control group only injected with FMD vaccine at 4 weeks after the first vaccination and at 4, 8 and 16 weeks after the second vaccination, respectively (p&lt;0.05). The FMD vaccine SP antibody positive rate was 100% until shipment. IFN-γ and IgA were significantly increased by Zn-ASP administration 4 weeks after the first vaccination and 4 weeks after the second vaccination (p&lt;0.05). On the other hand, serum AST, and CPK (p&lt;0.001) were significantly decreased by Zn-ASP. Our results show that the administration of Zn-ASP is effective in enhancing the antibody titer and immunity of the FMD vaccine by FMD vaccination, and it is thought that it can be used as an oral adjuvant (OrAd) to prevent viral diseases such as FMD.

Structural integrity is a crucial aspect of engineering components, particularly in the field of additive manufacturing (AM). Surface roughness is a vital parameter that significantly influences the structural integrity of additively manufactured parts. In this study, we present a comprehensive investigation into the relationship between surface roughness and structural integrity of Polyactic Acid (PLA) specimens produced through additive manufacturing. This research work focuses on the prediction of surface roughness of Additive Manufactured Polyactic Acid (PLA) specimens using eight different supervised machine learning regression-based algorithms. For the first time, Explainable AI techniques are employed to enhance the interpretability of the machine learning models. The eight algorithms used in this study are Support Vector Regression, Random Forest, XG Boost, Ada Boost, Catboost, Decision Tree, Extra Tree regressor, and Gradient Boosting regressor. The study analyzes the performance of these algorithms to predict the surface roughness of PLA specimens, while also investigating the impact of individual input parameters through Explainable AI methods. The experimental results indicate that the XG Boost algorithm outperforms the other algorithms with the highest coefficient of determination value of 0.9634. This value demonstrates that the XG Boost algorithm provides the most accurate predictions for surface roughness compared to other algorithms. The study also provides a comparative analysis of the performance of all the algorithms used in this study, along with insights derived from Explainable AI techniques.

Nanosized drug delivery systems (DDS) have been studied as a novel strategy against cancer due to their potential to simultaneously decrease drug inactivation and systemic toxicity and increase passive and/or active drug accumulation within the tumor(s). Triterpenes are plant-derived compounds with interesting therapeutic properties. Betulinic acid (BeA) is a pentacyclic triterpene which has great cytotoxic activity against different cancer types. Herein, we developed a nanosized protein-based DDS of bovine serum albumin (BSA) as the drug carrier combining two compounds: doxorubicin (Dox) and the triterpene BeA using an oil-water-like micro-emulsion method. Spectrophotometric assays were performed to determine protein and drug concentrations in the DDS. The biophysical properties of these DDS were characterized using dynamic light scattering (DLS) and circular dichroism (CD) spectroscopy confirming nanoparticle (NP) formation and drug loading into the protein structure, respectively. The encapsulation efficiency was 77% for Dox and 18% for BeA. More than 50% of both drugs were released within 24 h, at pH 6.8, while less drug was released at pH 7.4 in this time period. Co-incubation viability assays of Dox and BeA alone for 24 h demonstrated synergistic cytotoxic activity in the low μM range against the non-small cell lung carcinoma (NSCLC) A549 cells. Viability assays of the BSA(Dox+BeA) DDS demonstrated a higher synergistic cytotoxic activity than the two drugs with no carrier. Moreover, confocal microscopy analysis confirmed cellular internalization of the DDS and nucleus accumulation of the Dox. We determined the mechanism of action of the BSA(Dox+BeA) DDS, confirming S-phase cell cycle arrest, DNA damage, caspase cascade activation, and downregulation of the epidermal growth factor receptor (EGFR) expression. This DDS has the potential to synergistically maximize the therapeutic effect of Dox and diminish chemoresistance induced by EGFR expression using a natural triterpene against NSCLC.

Degraded soils causing from natural and human affects are universal in arid and semi-arid regions all over the world. Bentonite and humic acid (BHA) are increasingly being tested to remediate these degraded lands with potential benefits on crop production and soil health. The objective of this paper was to determine the residual effects four to five years after a one-time BHA application at six rates on (i) dynamic changes in soil properties, and (ii) oat crop productivity parameters, in a dryland farming ecosystem. With increasing rates of one-time BHA application, soil profile water storage displayed a piecewise linear increase plus plateau, whereas soil electrical conductivity, pH and bulk density were all reduced significantly (P < 0.05) in the 0-20 cm and 20-60 cm layers. The improved soil environments gave rise to an increased activity of soil enzymes urease, invertase and catalase that respectively reached the peak values of 97%, 37% and 32% at the rates of 21 to 24 Mg BHA ha-1. These conversely boosted soil nutrient turnover, leading to a 40% higher soil available P. Compared with the control treatment, application of BHA at the estimated optimum rate (roughly 24 Mg ha-1) increased grain yield by 20%, protein yield by 62%, water use efficiency by 41%, and partial factor productivity of N by 20%. Results of this study showed for the first time that a one-time BHA application would be a new and effective strategy to combat land degradation, drought, and promote a sustainable soil micro-ecological environment in dryland agroecosystem under a varying climate scenario.

Novel SARS-CoV-2, a bat based virus originated in Wuhan, China that caused a global pandemic in December, 2019 belongs to the Betacorona virus family and contains single stranded genome of ~29Kbp. The host cell invasion of SARS-CoV-2 is facilitated by interaction of C-Terminal Domain (CTD) of Spike (S) protein of virus and host ACE2 receptor in the presence of TMPRSS seine protease secreted by the host cell. In this study the mutation hotspots of S-protein will be identified and the impact of such mutation in the binding affinity will be studied. Additionally, the lead molecule which can bind to the mutated protein also will be identified. Multiple sequence alignment of the spike protein sequence of SARS-CoV-2 shows the number of single amino acid mutation hotspots such as L5F, R214L, R408I, G476S, V483A, H519Q, A520S, T572I, D614G and H655Y. Among these mutations D614G has 57.5% occurrence and G476S, V483A has 7.5% occurrence. The mutated proteins were modelled based on wild type homolog and docked to ACE2 receptor. When the mutated S protein is docked, the ∆G (binding free energy) value is very minimal in mutated protein showed the stability of variants. By the drug repurposing method, 1000 FDA approved drugs were virtually screened for its binding to RBD of S1 domain. Among these drugs Digitoxin, Gliquidone and Zorubicin Hcl binds to spike proteins with higher docking score (lesser than -8.5 Kcal/mol) to both wild type and mutants.

Background: While intimate feminine hygiene products are widely used by women as part of daily cleansing routines, little is known about how these products impact the vulvovaginal area and its microbiome stability. A novel gel wash containing lactic acid (pH 4.2) for external daily use was formulated to provide gentle cleansing, freshness, and antimicrobial protection to maintain a healthy balance of the vulvar skin area. This 4-week clinical study assessed tolerance of the gel wash when used on the external genital area and its effects on skin hydration, vulvar skin pH, and the vulvar microbiome. After a 7-day pre-study conditioning period, 36 healthy females in 3 balanced age groups (18-29, 30-44, and 45-55 years) used the gel wash to cleanse their external genital area (mons pubis and vulva) and entire body at least once per day for 28 days. The primary endpoint wasSkin tolerance of the gel wash was assessed by the gynecologist. Effects of the gel wash on vulvar skin microbiota were studied by performing bacterial 16S rRNA and fungal ITS microbial richness and diversity analysis. Results: Based on gynecologic assessment after 28 days of use, the gel wash showed acceptable tolerance, with no signs of increased dryness, redness, edema, itching, stinging, or burning. Use of the gel wash was associated with a significant increase in both short-term (single application) and longer-term (daily use for 28 days) skin moisturization. There was no significant change in vulvar skin pH over time with daily product use, and the gel wash did not significantly affect the natural vulvar microbiome species richness or diversity for bacteria or fungi. Conclusions: Results of the study showed that this new gel wash is a mild, moisturizing cleanser that does not harm and instead maintains the natural pH and microbial diversity of vulvar skin. To our knowledge, this was the first study to assess the effect of an antimicrobial feminine gel wash on the natural pH and vulvar microbiome habitat of the skin using bacterial 16S rRNA and fungal ITS genetic sequencing techniques, thereby providing a better understanding of the bacterial and fungal communities that inhabit the external vulvar area in healthy women.

Gymnema sylvestre is a pharmacological plant which has a rich source of bioactive compounds specifically gymnemic acid (GA) and phenolic compounds (PC) that used for pharmaceutical industries. Sources for naturally occurring bioactive compounds are limited, due to geographical and seasonal variations; on the other hand, it is commercially in demand. Biosynthesis of G. sylvestre phytochemicals through in vitro culture often enhanced by elicitation. The use of cell suspension cultures (CSC) has interested serious attention on the production of essential phytochemicals. The current study is aimed at improving the contents of GA and PC in G. sylvestre CSC using the copper oxide nanoparticles (CuO NPs). Callus was obtained on MS medium with 2.0 mg/L 2,4-dichlorophenoxyacetic acid (2,4-D), 0.1 mg/L kinetin (KIN), phytoagar (8.0 g/L), and sucrose (30 g/L). The above medium devoid of agar was used for the initiation of CSC. The CSC was treated with three levels of CuO NPs (1, 3 or 5 mg/L) to enhance the production of GA and PC. The greatest amount of GA (89.25 mg/g dry cell mass, DCM), total phenolic (245.10 mg/g), and flavonoid (4.57 mg/g) in CSC were achieved when G. sylvestre cells were treated for 48 h with 3 mg/L CuO NPs. Also, the biomedical potential (antioxidant, antidiabetic, anti-inflammatory, antibacterial, antifungal and anticancer activities) were also high in the CuO NPs (3 mg/L) treated CSC extracts of G. sylvestre. CuO NPs elicitation of CSC significantly increased production of GA (9-fold), and PC than non-elicited CSC in G. sylvestre.

The effects of orally administered lactic acid bacteria metabolites on the skin were studied using an atopic dermatitis-like murine model created by feeding mice with HR-AD. The lactic acid bacteria metabolites were obtained by inoculating 35 strains of 16 species of lactic acid bacteria into soy milk and culturing them. The atopic dermatitis-like murine model was created by feeding HR-1 mice HR-AD for 40 days. The skin condition of mice that were fed HR-AD worsened compared with normal mice, i.e., reduced water content in the stratum corneum, increased transepidermal water loss (TEWL), reduced ceramide AP content in the stratum corneum, and increased epidermis thickness. When mice that had been fed the HR-AD diet was administered a raw liquid of lactic acid bacteria metabolites orally, the measured values related to water content in the stratum corneum, TEWL, ceramide AP content in the stratum corneum, and epidermis thickness improved. To find out the active components for these effects, filtrate and residue from the raw liquid of lactic acid bacteria metabolites and lipid components extracted from the raw liquid were examined at the same time. Results showed that the water-soluble components or residue after filtration did not demonstrate effects but the raw liquid and the lipid fraction did. These findings suggest that lactic acid bacteria metabolites improve skin injury in an atopic dermatitis-like murine model.

The transient vanilloid receptor potential type 1 (TRPV1) regulates neuronal and vascular functions mediated by nitric oxide (NO) and by the calcitonin gene-related peptide (CGRP). Here we study the participation of TRPV1 in the regulation of myocardial injury caused by ischemia-reperfusion and in the regulation of NO, tetrahydrobiopterin (BH4), the cGMP pathway, CGRP, total antioxidant capacity (TAC), malondialdehyde (MDA) and phosphodiesterase-3 (PDE-3). Isolated hearts of Wistar rats were used (according to Langendorff) to study the effects of capsaicin (CS), capsazepine (CZ) and CZ+CS treatments. The hearts were divided into three subgroups; 1) perfusion, 2) ischemia and 3) ischemia-reperfusion. In all groups we studied cardiac work and levels of NO, cGMP, BH4, CGRP, TAC, MDA and PDE-3 in ventricular tissue. Western blots were used to determine the expressions of eNOS, iNOS and phosphorylated NOS (pNOS). Structural changes were determined by histological evaluation. CS prevented damage caused by ischemia-reperfusion by improving cardiac work and the levels of NO, cGMP, BH4, TAC and CGRP. TRPV1 and iNOS expression were increased under ischemic conditions, while eNOS and pNOS were not modified. We conclude that the activation of TRPV1 constitutes a therapeutic possibility to counteract the damage caused by ischemia and reperfusion by regulating the NO pathway through CGRP.

Farmers today are using biochemical treatments to improve their crop yields. Commercialized organic biostimulants exist in the form of pyroligneous acid generated by burning agricultural waste products. During the 2023 growing season we demonstrated that soil treatment with a commercial pyroligneous acid product, Coriphol™, manufactured by Corigin Solutions, Inc., stimulated plant growth and significantly improved yield with an optimal treatment dose of 2 gal./acre. In the present work we examined the effect of this treatment on soybean nutritional content using seed harvested from the 2023 season. Total mean seed protein content for untreated control plants was 32.26 ± 0.49% of dry mass and increased 10.8% to 35.64 ± 0.64% with treatment. This increase resulted in a net reduction in total free amino acid content although levels of the es-sential dietary amino acid, lysine, were boosted 6-fold. Total lipid content was unaffected by treatment with mean levels of 21.61 ± 0.70% of dry mass noted. Treatment, however, reduced saturated fatty acid content by roughly 40% while reducing the polyunsaturated content of linoleic acid in favor of the monounsaturated fatty acid, oleic acid. Finally, Coriphol™ treatment did not impact seed content of eight essential micronutrients including Na, Mg, K, Ca, Fe, Ni, Cu and Mo, but did significantly boost Zn and Mn levels. Altogether, these results demonstrate that soil treat-ment with the growth stimulant Coriphol™ has the potential to improve the dietary nutritional value of soybean.

In this study, unlike conventional methods for producing vanadium (3.5+) electrolyte by VOSO4 and V2O5, a batch-type hydrothermal reactor was used to produce a vanadium (3.5+) electrolyte for vanadium redox flow batteries through a reduction reaction. The starting material, V2O5, was mixed with different concentrations of citric acid (0.8M, 1.2M, 1.6M, 2.0M) as reducing agent and stirred using a hot plate at 90°C for 60 minutes to achieve complete dispersion in the solution. The resulting solution was then subjected to a hydrothermal reduction reaction in a furnace at 150°C for 24 hours to produce vanadium (3.5+). The mixed state of the produced vanadium (3+) and vanadium (4+) was confirmed using UV-vis spectroscopy. Electrochemical properties were investigated through CV analysis, confirming that the optimal concentration was 1.6M. Charge and discharge experiments were conducted to compare the current efficiency, energy efficiency, and voltage efficiency of the electrolyte prepared by the hydrothermal reduction process and the electrolyte prepared by VOSO4. As a result, the electrolyte produced through the hydrothermal reduction process showed improved performance in all efficiencies. The results shows that vanadium (3.5+) electrolyte could be easily produced through a reaction process using citric acid.

The article presents data on research of processes of obtaining concentrated phosphoric acid from Karatau phosphate rock. The research of purification of wet-process phosphoric acid by the method of liquid extraction with organic solvents is given. The influence of magnesium salts and sulfuric acid as impurities on the distribution factor of phosphoric acid is determined. It is shown that with increasing the initial concentration of phosphoric acid from 5.38 to 25.61% P2O5, the distribution factor at 25°C increases from 0.178 to 0.436 for n-butyl alcohol, from 0.06 to 0.183 for isoamyl alcohol, and from 0.120 to 0.320 for tributyl phosphate. Increasing the temperature from 25 to 60°C had little or no effect on the distribution factor. It was determined that the distribution factors of phosphoric acid depend on the initial concentration of phosphoric acid in the presence of sulfuric acid. It is shown that phosphoric acid is extracted better with n-butanol. Extraction of phosphoric acid with n-butanol on the principle of counterflow with subsequent azeotropic distillation of the solvent allows to obtain relatively pure and highly concentrated (56-63% of P2O5) phosphoric acid. The process of dehydration of phosphoric acid in the presence of sulfuric acid in the mixture was studied.

The present study aimed to evaluate the effect of the citric acid on the properties of solid pine wood, which were submitted to thermomechanical treatment. A preliminary test was performed in a previous study to evaluate the influence of different temperatures of pressing and concentrations of citric acid over the physical properties of wood. After choosing the best treatments (170°C and 5% and 10% of citric acid) it was evaluated the effect of these on the chemical properties (SEM, FTIR and pH), on the density profile using an X-ray microtomography, and on the resistance to ageing through abrasion test. The result of the chemical analysis allowed to observe an increase of the presence of ester functional groups, as well as a better coverage and higher acidity of the surface. The density profile technique allowed to observe the formation of peaks of density on the surface where the acid was applied. Lastly, it was also possible to verify an increase in the resistance to abrasion because of the application of the citric acid.

Bisphosphonates (BPs) are successfully used to cure a number of bone diseases characterized by metabolic osteopenia, such as Osteoporosis, or neoplastic osteolysis, such as Multiple Myeloma and Bone Metastases. These drugs exert their therapeutic effect inducing a systemic osteoclast depletion that, in turn, is responsible for a reduced bone resorption. Unfortunately, in addition to their beneficial activity, BPs can also determine a frightening side effect known as Osteonecrosis of the Jaw (ONJ). It is generally believed that the inability of osteoclasts to get rid of inflamed / necrotic bone tissue represents the main physio-pathological aspect of ONJ. In principle, a therapeutic strategy able to elicit a local re-activation of osteoclast production could counteract ONJ and promote the healing of its lesions. We have previously demonstrated that Magnesium (Mg) is a powerful inducer of osteoclast differentiation. Using a model of Vitamin D3 – dependent osteoclastogenesis, based on the U937 cell line, here we show that, surprisingly, this property of Mg is greatly enhanced by the presence of Zoledronic Acid (ZA), chosen for our study because it is the most effective among BPs. This finding allow us to hypothesize that Mg might play an important role in the topical therapy of ONJ.

A series of alpha,omega-bis(o-methoxyphenyl)arenes were prepared through Suzuki-Miyaura coupling reactions of dibromoarenes with o-methoxyphenyl boronic acid. P2O5-CH3SO3H-mediated direct polycondensation of alpha,omega-bis(o-methoxyphenyl)arenes with trans-1,4-cyclohexanedicarboxylic acid proceeded regioselectively to afford 1,4-cyclohexanediyl-containing aromatic polyketones. The resulting aromatic polyketones have high Tg and excellent solubility in typical organic solvents. In addition, the polyketone films fabricated by solution casting method are more colorless and transparent than those without cyclohexanediyl units.

The aim of this systematic scoping review was to provide scientific evidence on the efficacy and methods of application of hyaluronic acid in the coverage of gingival recessions in terms of recession depth (RD) reduction, clinical attachment level (CAL) gain, probing depth (PD). An electronic search of the literature on the main databases was conducted. Initially, 405 articles were identified. Finally, 4 studies were included after the review process. It was not possible to perform a meta-analysis of the articles selected because of the differences among the surgical treatments and commercial formulations and compositions of hyaluronic acid. Both randomized controlled trials in this research examined Recession Type 1 gingival treated with coronally advanced flap. Recessions were treated with either modified coronally advanced tunnel or laterally closed tunnel combined with subepithelial connective tissue graft and hyaluronic acid (HA) in all case series. The studies analyzed no significant variation was found in PD variable. The results of RD reduction are in accordance with the literature. Modifications of CAL are connected to variations of RD. HA seems to improve the clinical outcomes of the described surgical treatment.

Lithium-sulfur (Li-S) battery has been regarded as an important candidate for the next-generation energy storage system due to its high theoretical capacity (1675 mAh g-1) and high energy density (2600 Wh kg-1). However, the shuttle effect of polysulfide seriously affects the cycling stability of the Li-S battery. Here, a novel Fe3C decorated folic acid-derived graphene-like N-doped carbon sheet (Fe3C@N-CS) was successfully prepared as the polysulfide catalyst to modify the separator of Li-S battery. The porous layered structures can successfully capture polysulfide as a physical barrier, and the encapsulated Fe3C catalyst can effectively trap and catalyze the conversion of polysulfide, thus accelerating the redox reaction kinetics. Together with the highly conductive networks, the cell with Fe3C@N-CS modified separator evinces superior cycling stability with 0.06% capacity decay per cycle at 1 C rate over 500 cycles and excellent specific capacity with an initial capacity of 1260 mAh g-1 at 0.2 C. Besides, at a high sulfur loading of 4.0 mg cm-2, the batteries also express superb cycle stability and rate performance.

γ-Aminobutyric acid (GABA) plays an important role in plant development and postharvest properties of fruits. However, studies on regulation of kiwifruit ripening by GABA are scarce. Here, we evaluted physicochemical characters and the expression profile of genes related to ripening in hardy kiwifruit treated with exogenous GABA compared to control during postharvest storage period. The results showed that (1) exogenous GABA treatment not only improved the fruit quality but also inhibited respiration rate and ethylene production, as well as reduced the enzyme activities of ACC oxidase (ACO) and ACC synthase (ACS), via down-regulating the expression of AaACO1 and AaACO3, AaACS1 and AaACS2 during kiwifruit storage period; (2) on the one hand, overexpression of AaGAD1 or AaGAD4 gene which is involved in GABA biosynthesis inhibited ethylene production by reducing the enzyme activities of ACO and ACS, whereas silencing of AaGAD1 or AaGAD4 gene led to the reverse effect. On the other hand, overexpression of AaGAD1 or AaGAD4 decreased the expression levels of AaACO1 and AaACO3, AaACS1 and AaACS2, whereas silencing of AaGAD1 or AaGAD4 gene increased the expression levels of these four genes. Above all, our findings demonstrate that exogenous GABA treatment could improve the storage quality and extend the shelf life of kiwifruit, Additionally, the content of GABA was participated in the regulation of ethylene biosynthesis at the molecular level.

Targeted therapies with antiangiogenic drugs (e.g., sunitinib) and immune checkpoint inhibitors (e.g., anti-PD-1 antibodies) are the standard of care for patients with metastatic renal cell carcinoma. Although these treatments improve patient survival, they are rarely curative. We previously hypothesized that advanced cancers might be treated without drugs by using artificial diets in which the levels of specific amino acids (AAs) are manipulated. In this work, after showing that AA manipulation induces selective anticancer activity in renal cell carcinoma cells in vitro, we evaluated the anticancer activity of 17 artificial diets in a challenging animal model of renal cell carcinoma. The model was stablished by injecting murine renal cell carcinoma (Renca) cells into the peritoneum of immunocompetent BALB/cAnNRj mice. Mice survival was markedly improved when their normal diet was replaced with our artificial diets. Mice fed a diet lacking six AAs (diet T2) lived longer than mice treated with sunitinib or anti-PD-1 immunotherapy; several animals lived very long or were cured. Controlling the levels of several AAs (e.g., cysteine, methionine and leucine) and lipids was important for the anticancer activity of the diets. Additional studies are needed to further evaluate the therapeutic potential of this simple and inexpensive anticancer strategy.

In horses, there is an increasing interest in developing long-lasting drug formulations, with bi-opolymers as viable carrier alternatives in addition to their use as scaffolds, suture threads, screws, pins, and plates for orthopedic surgeries. This communication focuses on the prolonged biocompatibility and biodegradation of PLA, prepared by hot pressing at 180 ºC. Six samples were implanted subcutaneously on the lateral surface of the neck of one horse. The polymers remained implanted for 24 to 57 weeks. Physical examination, plasma fibrinogen, and the mechanical noci-ceptive threshold (MNT) were performed. After 24, 28, 34, 38, and 57 weeks, the materials were removed for histochemical analysis using hematoxylin-eosin and scanning electron microscopy (SEM). There were no essential clinical changes. MNT decreased after the implantation procedure, returning to normal after 48h. A foreign body response was observed by histopathologic evalua-tion up to 38 weeks. At 57 weeks, no polymer or fibrotic capsules were identified. SEM showed surface roughness suggesting a biodegradation process, with an increase in the average pore di-ameter. As in the histopathological evaluation, it was not possible to detect the polymer 57 weeks after implantation. PLA showed biocompatible degradation and these findings may contribute to future research in the biomedical area.

Background: Acute intermittent porphyria (AIP) is caused by haploinsufficiency of porphobilin-ogen deaminase (PBGD) enzymatic activity. Acute attacks occur in response to fasting and altera-tions in glucose metabolism, insulin resistance and mitochondrial turnover may be involved in AIP pathophysiology. Therefore, we investigated the metabolic pathways in PBGD-silenced hepatocytes and assessed the efficacy of an insulin-mimic, the α-lipoic acid (α-LA) as a potential therapeutic strategy. Methods: HepG2 cells were transfected with a siRNA targeting PBGD (siPBGD). Cells were cul-tured with low glucose concentration to mimic fasting and exposed to α-LA alone or with glu-cose. Results: At baseline, siPBGD cells showed lower expression of genes involved in glycolysis and mitochondrial dynamics along with reduced total ATP levels. Fasting further unbalanced gly-colysis by inducing ATP shortage in siPBGD cells and activated DRP1, which mediates mito-chondrial separation. Consistently, siPBGD cells in fasted state showed the lowest protein levels of Complex IV which belong to the oxidative phosphorylation (OXPHOS) machinery. α-LA up-regulated glycolysis and prompted ATP synthesis and triglyceride secretion, thus possibly providing energy fuels to siPBGD cells by improving glucose utilization. Finally, siPBGD exposed to α-LA plus glucose raised mitochondrial dynamics, OXPHOS activity and energy production. Conclusions: α-LA-based therapy may ameliorate glucose metabolism and mitochondrial dys-functions in siPBGD hepatocytes. Keywords: AIP, PBGD, glucose metabolism, mitobiogenesis, α-lipoic acid

A multilevel factorial design of 23 with 12 experiments was developed for the preparation of cellulose nanocrystals (CNC) from Agave tequilana Weber var. Azul bagasse. The studied parameters were acid type (H2SO4 and HCl), acid concentration (60 and 65 wt% for H2SO4, 2 and 8N for HCl) temperature (40 and 60°C for H2SO4, 50 and 90°C for HCl), and hydrolysis time (40, 55 and 70 min for H2SO4, 30, 115 and 200 min for HCl). The obtained CNC were physical and chemically characterized using dynamic light scattering (DLS), atomic force microscopy (AFM), Fourier-transform infrared spectroscopy (FT-IR), X-ray photoelectron spectroscopy (XPS), and X-ray diffraction (XDR) techniques. The size and morphology of A. tequilana CNC strongly depend on the acid type and hydrolysis parameters. The shortest CNC were obtained with H2SO4 (65 wt%, 40 °C, and 70 min) had a length of 137 ± 68 nm, width 33 ± 7 nm, and height 9.1 nm, whereas the shortest CNC obtained with HCl (2 N, 50 °C and 30 min) had a length of 216 ± 73 nm, width 69 ± 17 nm, and height 8.9 nm. CNC prepared from H2SO4 resulted shorter and thinner than those obtained with HCl. The total sulfate groups content in CNC obtained with H2SO4 increase with time agree to CSG=aebt, and increases with temperature and acid concentration.

Various techniques have been used to “clean-up” industrial phosphoric acid: precipitation, flotation, activated charcoal or clay treatment. To address membrane processes potential in phosphoric acid clarification process, this study explores the advantage of membrane techniques as new route for phosphoric acid clarification in an eco-efficient way through the use of “regenerated spent membrane”. Regeneration of the spent membranes was performed on of 0.15 m2 active area regeneration. These membrane samples were used to study the phosphoric acid clarification at a laboratory scale. They were immersed in an oxidizer for at most seven days. The samples were characterized systematically before immersion in an oxidant media. In this study, the potential to regenerate spent membranes and application of this media to clarify the 29% P2O5 phosphoric acid was demonstrated. This study shows, by tests that the reverse osmosis (RO) membranes achieve an abatement of 70% and 65% for solids and organic materials, respectively. These positive results will pave the way for implementing these membranes phosphoric acid treatment process. Moreover, besides being economically advantageous, the use of the spent membrane is likely an environmentally friendly route (no waste, no organic solvent and effluent to be regenerated later on).

This study deals with computational analysis of dominant fatty acid ethyl esters characterized from the biodiesel produced from waste beef tallow by means of KOH catalyzed ethanol based transesterification. Ethyl palmitate, Ethyl Oleate, Ethyl Stearate and Ethyl Myristate were identified as dominant fatty acid esters and were computed for molecular analysis in Gaussian 09 software using Density Functional Theory (B3LYP method) with 6-31G* as basis set. Geometric parameters were in accordance with existing experimental values and population analysis exhibited negative charge for oxygen atoms, both positive & negative charge for carbon atoms in all ester molecules. The molecular dipole moment was higher for unsaturated ester molecule and quadruple moment proposed electronic dislocation in X+Y direction. Also, energy gap decreased slightly with increasing carbon chain but reduced drastically with increase in unsaturation. Electrostatic potential mapping displayed negative electrostatic potential for oxygen atoms in ester linkage of all ester molecules.

Human mesenchymal stem cells (hMSCs) constitute of cells having potential of self-renewal and proliferation and are commonly isolated from bone marrow aspirates of large bones. The osteogenic potential of these stem cells has been extensively exploited by scientists during the last many years for the biological evaluation of synthetic scaffolds with applications in tissue engineering. Current work aimed to synthesize N-arylhydrazone derivatives of orotic acid and their evaluation as stimulators of human mesenchymal stem cells. Some of the analogs show good to moderate proliferation rate.

Catalytic upgrading of bio-based platform molecules is one of promising approaches for biomass valorization. However, most solid catalysts are thermally and/or chemically unstable and difficult to prepare. In this study, a stable organic phosphonate-hafnium solid catalyst (PPOA-Hf) was synthesized, and acid-base bifunctional sites were found to play a cooperative role in the cascade transfer hydrogenation and cyclization of ethyl levulinate (EL) to γ-valerolactone (GVL). Under relatively mild reaction conditions of 160 ºC for 6 h, EL was completely converted to GVL in a good yield of 85%. The apparent activation energy was calculated to be 53 kJ/mol, which was lower than other solid catalysts for the same reaction. In addition, the PPOA-Hf solid catalyst did not significantly decrease its activity after five recycles, and no evident leaching of Hf was observed, indicating its high stability and potential practical application.

Acid lime [Citrus aurantifolia (Christm.) Swingle] is a fruit crop, enriched with high commercial value and is cultivated in 60 out of 75 districts representing all geographical landscapes of Nepal. Lack of high yielding cultivars is probably one of the main reason for its extremely reduced productivity which warrants a deep understanding of genetic diversity in existing germplasm. Hereby, we aim to access the genetic diversity of acid lime germplasm cultivated at 3-different ecological gradients of eastern Nepal employing PCR-based Inter-Simple Sequence Repeats markers (ISSR). Altogether, 21 polymorphic ISSR markers were used to assess the genetic diversity in 60 acid lime cultivars sampled from different geographical locations. Analysis of binary data matrix was performed on the basis of bands obtained, scoring of the data was done accordingly, and principal coordinate analysis and phenogram were constructed using different computer algorithms. ISSR profiling yielded 234 amplicons, of which 87.18% were found to be polymorphic. The number of amplified fragments ranged from 7-18 with amplicon size ranging from 250-3200 bp. The NTSYS based Cluster analysis using UPGMA algorithm taking Dice Similarity coefficient separated 60 accessions into 2-major and 3-minor clusters. The genetic diversity analysis revealed the highest for Terai and the lowest for High-hill zone. Cluster I comprised of accessions from High-hill and Mid-hill regions revealing the close genetic relationship, whereas cluster II comprised of accessions from all three agro-ecological zones and the exotic varieties. Furthermore, our results revealed the accessions harvested from different geographical gradients were not genetically distinct, but highest diversity was observed in Terai accessions in comparison to the regions belonging to the High and Mid-hills. Thus, our data indicate that the ISSR provides a better option for evaluating the genetic diversity of Nepalese Acid Lime cultivars and furnished significant information, assisting parental selection in current and future breeding programs and germplasm conservation which ultimately may help to provide a technological breakthrough for the farmers of the developing country like Nepal.

The effects of simulated acid rain (SAR) on the photosynthetic performance of subtropical coniferous species have not been thoroughly investigated. In this study, we treated two coniferous species, Pinus massoniana (PM) and Cunninghamia lanceolata (CL), with SAR and then analyzed photosynthetic activities via the simultaneous measurement of prompt fluorescence(PF), delayed fluorescence(DF), and modulated reflection at 820 nm(MR820). Following the low-pH SAR treatment, the I–P phase of the OJIP curves of PM and CL decreased significantly and then the K-band and L-band were detectable. The delayed fluorescence for both PM and CL decreased as the pH of the SAR solution decreased, with a more significant decrease in the I1 peak than in the I2 peak. According to the MR820 curve, the exposure to SAR stress inhibited the rapid decrease and slow increase in the MR820 transients of PM and CL. The gradients of the decreasing and increasing phases were lower for CL than for PM at pH 2.5. In addition, SAR decreased the light energy captured per unit area (ABS/CSm) and the quantum yield of electron transfer per unit area (ETO/CSm), but it increased the accumulation of QA−, thereby decreasing primary photochemical efficiency (TRO/CSm, φPO). These changes in photosystem II (PSII) resulted in a decrease in the maximum quantum yield of PSII (Fv/Fm) and the performance index (PIABS). Moreover, PSII was protected from thylakoid membrane photodamages through the increase in heat dissipation per unit area (DIO/CSm) in response to SAR. The increase in δRO as the pH of the SAR solution decreased was observed for PM, but not for CL. Considered together, the study findings suggest that SAR treatments can decrease chlorophyll contents and damage the OEC in PM and CL, which obstructs the transfer of electrons on the donor and acceptor sides of PSII. However, PM is better able to withstand SAR stress than CL, likely because of the activation of a protective mechanism (reflected by the change in δRO). Therefore, in coniferous forest areas severely affected by acid rain, CL may need to be protected more than PM.

Tyrosyl-DNA phosphodiesterase 1 (Tdp1) is an important DNA repair enzyme and one of the causes of tumor resistance to topoisomerase 1 inhibitors such as topotecan. Inhibitors of this Tdp1 in combination with topotecan may improve the effectiveness of therapy. In this work, we synthesized usnic acid derivatives, which are hybrids of its known derivatives - tumor sensitizers to topotecan. New compounds inhibit Tdp1 in the micromolar and submicromolar concentration range; some of them enhance the effect of topotecan on the metabolic activity of cells of various lines according to the MTT test. One of the new compounds (compound 7) not only sensitizes Krebs-2 and Lewis carcinomas of mice to the action of topotecan, but also normalizes the state of the peripheral blood of mice, which is disturbed in the presence of a tumor. Thus, the synthesized substances may be the prototype of a new class of additional therapy for cancer.

The changes in consumer lifestyles have raised awareness of the variety of food options and packaging technologies. Active and smart packaging represents an innovative technology that serves to enhance the safety and quality of products. Smart packaging, as a subset of this technology, entails the integration of additives into packaging materials, thereby facilitating the preservation or extension of product quality and shelf life. This technological approach stimulates a heightened demand for safer food products with prolonged shelf life. Active packaging predominantly relies on the utilization of natural active substances. Therefore, the combination of active substances has a significant impact on the characteristics of active packaging particularly on polymeric blend like Polylactic acid (PLA) as a matrix. So, This review will summarize and explains how the addition of natural active agents influenced the properties related to the performance of active packaging through systematic analysis, providing new insights about the relationship between the types of active agents on physical-mechanical properties, bacterial colony reduction, and applications in foods packaging such as meat, fish, fruit, and vegetables. Through their integration, the market for active and smart packaging systems is expected to have a bright future.

The seasonal variation in fatty acids and minerals concentrations was investigated through the analysis of Pecorino Romano cheese samples collected in January, April, and June. A fraction of samples contained missing values in their fatty acid profile. Probabilistic Principal component analysis coupled with Linear Discriminant Analysis was employed to classify cheese samples on a production season basis while accounting for missing data and quantifying the missing Fatty acids concentration for the sample in which they were absent. The levels of rumenic acid, vac-cenic acid and omega-3 compounds were positively correlated with the spring season, while the length of the saturated fatty acids increased throughout the production seasons. Concerning the classification performances, the optimal number of principal components (i.e., 5) achieved an ac-curacy in cross-validation equal to 98 %. Then, when the model was tasked to impute the lacking Fatty acid concentration values, the optimal number of principal components resulted in an R2 value in cross-validation of 99.53%

Lambertianic acid (LA) is a biologically active compound from the leaves of Pinus koraiensis. In the present study, apoptotic mechanisms of LA plus TNF-related apoptosis-inducing ligand (TRAIL) were elucidated in non-small cell lung cancer cells (NSCLCs). Cytotoxicity assay, flow cytometry, immunoprecipitation and Western blotting were performed. Here, combined treatment of LA and TRAIL increased cytotoxicity, sub-G1 population and cleaved poly (ADP-ribose) polymerase (PARP) and caspase3/8/9 in A549 and H1299 cells compared to LA or TRAIL alone. Furthermore, combined treatment of LA and TRAIL significantly decreased anti-apoptotic proteins such as B-cell lymphoma 2 (Bcl-2), Fas-like inhibitor protein (FLIP) and X-linked inhibitor of apoptosis protein (XIAP) and enhanced the activation of pro-apoptotic proteins Bid compared to LA or TRAIL alone. In addition, combined treatment of LA and TRAIL upregulated the expression of Death receptor 4 (DR4) and downregulated phosphorylation of nuclear factor kappa-light-chain-enhancer of activated B cells (p-NF-B), inhibitory protein of kB family (p-IB) and FLIP in A549 and H1299 cells along with disrupted binding of XIAP with caspase3 or NF-B. Overall, these findings suggest that lambertianic acid enhances TRAIL-induced apoptosis via inhibition of XIAP/NF-B in TRAIL resistant NSCLCs.

Locoregional anaesthetic techniques are invaluable for providing multimodal analgesia for painful surgical procedures. This prospective, randomised study describes a nerve stimulator-guided bra-chial plexus blockade (BPB) in rabbits undergoing orthopaedic surgery in comparison to systemic lidocaine. Premedication was provided with intramuscular (IM) medetomidine, fentanyl and midazolam. Anaesthesia was induced (propofol IV) and maintained with isoflurane. Nine rabbits received a lidocaine BPB (2%; 0.3 ml kg-1), and eight received lidocaine constant rate infusion (CRI) (2 mg kg-1 IV, followed by 100 µg kg-1 minute-1). Rescue analgesia was provided with Fentanyl IV. Carprofen was administered at the end of surgery. Post-operative pain was determined using the Rabbit Grimace Scale (RGS) and a composite pain scale. Buprenorphine was administered accord-ing to pain score for two hours after extubation. Rabbits were filmed during the first two hours to measure distance travelled and behaviours. Food intake and faeces output were compared. Every rabbit in CRI required intraoperative rescue analgesia compared to no rabbits in BPB. How-ever, rabbits in both groups had similar pain scores and there was no difference in administration of postoperative analgesia. There were no significant differences in food intake or faeces produc-tion over 18 hours, and no significant differences in distance travelled, or behaviours examined during the first two hours. BPB seems superior for intraoperative analgesia. Postoperatively both groups were comparable.

This study examines the influences of live streaming servicescape on Chinese consumers' luxury purchase intention. Interestingly, for the sample without luxury purchase experience, the mediating effect of the perceived value of luxury goods is significant but effect of consumer trust is not. For the sample with luxury purchase experience, the result of mediating effect is just the opposite. The interaction between conspicuous consumption and live streaming servicescape plays a certain role in regulating the perceived value of luxury goods. These results show that luxury brands can adopt innovation in the live streaming servicescape for different types of consumers to promote live streaming marketing. This study enriches the servicescape theory of live streaming.

This study investigated how positive (e.g., incentives) and negative (e.g., restrictions) reinforcement used in vaccination promotional messages and trust in government impact parental vaccine perceptions and decisions on vaccinating their children during a large-scale infectious disease crisis. Two hundred and eighty-six parents of unvaccinated teens participated in a 2 (reinforcement: positive vs. negative) × 2 (trust in government: high vs. low) between-subjects experimental survey. Positive reinforcement (e.g., gift cards for the vaccinated) was more effective for parents with low trust in the government to improve their attitudes and intentions toward child vaccination, while parents with high trust in the government were unaffected by reinforcement types. To the best of our knowledge, this study is among the first to examine the effects of both positive and negative reinforcement on vaccination perceptions and behavioral intentions through a controlled experiment and is the first study to do so in a large-scale infectious disease crisis setting. This research is expected to help public health professionals better prepare for and manage virus-induced public health crises in the future.

Keywords: Red meat; Processed meat; poultry; dairy; mortality

In commercial terms, Virgin Olive Oil (VOO) is considered an exceptional food of excellent sensory and nutritional quality, for its taste and genuine odour and, as well as for its bioactive compounds, of a great interest for the health. This quality can be affected by oxidative degradation, chemical as well as enzymatic (activity of oxidative endogenous enzymes from polyphenol oxidase and peroxidase olive fruit type), of essential components during extraction and conservation of VOO. In the bibliography, the reduction of oxygen during the malaxation process and the storage of the oil has been studied in different ways. However, research about the reduction of oxygen in the crushing of olive fruit, malaxation of the paste and/or both at the same time in “real extraction condition” is scarce. The reduction of oxygen has been compared to control conditions (concentration of atmospheric oxygen of 21%). Batches of 200 kg of olive fruit, Picual cultivar, were used and the following treatments were applied: Control (21% O2 Mill - 21% O2 Mixer), “IM-NM”: Inerted milling -Normal malaxation (6.5% O2 Mill-21% O2 Mixer), “NM-IM”: Normal milling-Inerted malaxation (21% O2 Mill-4 % O2 Mixer) and “IM-IM”: Inerted milling-Inerted malaxation (5.5% O2 Mill-10% O2 Mixer). The parameters of commercial quality covered by Regulation: free acidity, peroxide value and absorbency in ultra-violet (k 232 and k270) did not suffer any change in relationship to the control, the oils belong to the comercial category of “Extra virgin olive oil”. The phenolic compounds are involved in the distinctive bitter and purgent taste and, their healthy properties and their oxidative stability, increased with the downsizing amounts of oxygen regarding control and the IM-NM, NM-IM and IM-IM treatments with an average of 4, 10 and 20 %, respectively. By contrast, total volatile compounds decrease between a 10-20 % in all oxygen reduction treatments. The volatile compounds arising from lipoxygenase pathway, which are responsable for the green and fruity notes of VOO, also decreased their concentration with the treatments, between 15-20%. The results show how the reduction of oxygen in the milling and malaxation stages of olive fruit can modulate the content of phenols, volatile compounds, carotenoids and chlorophyll pigments of the VOO avoiding the degradation of compound with sensorial and nutritional interest.

Background: Implant surface topography is a key element in achieving osseointegration. Nanostructured surfaces have shown promising results in accelerating and improving bone healing around dental implants. The main objective of the present clinical and histological study is to compare, at 4 and 6 weeks, (w) bone-to-implant contact in implants having either machined surface (MAC), SLA medium roughness surface or a Nanostructured Calcium-Incorporated sur-face (XPEED®). Methods: 35 mini-implants with 3 different surface treatments (XPEED® (n=16) – SLA (n=13) – Machined (n=6), were placed in the posterior maxilla of 11 patients then, retrieved at either 4 or 6w in a randomized split-mouth study design. Results: The BIC rate measured at 4 and 6w respectively, was: 16.8 % (±5.0) and 29.0 % (±3.1) for MAC surface; 18.5 % (±2.3) and 33.7 % (±3.3) for SLA surface; 22.4 % (±1.3) and 38.6 % (±3.2) for XPEED® surface. In all types of in-vestigated surfaces, the time factor appeared to significantly increase the BIC rate (p < .05). XPEED® surface showed a significantly higher values when compared to both SLA and MAC values at 4w (p < .05). Also, at 6w, both roughened surfaces (SLA and XPEED® ) showed signifi-cantly higher values (p < .05) than turned surface (MAC). Conclusion: Nanostructured Calcium titanate coating is able to enhance bone deposition around implants at early healing stages.

The prognostic value of inflammatory indices such as absolute monocyte count (AMC) has been a subject of interest in recent prostate cancer (PCa) literature, while hemoglobin concentration (HGB) has been recognized as a survival factor in castration-resistant metastatic prostate cancer, but its value remains unclear in localized disease. The aim of this study was to test the prognostic value of these two simple and inexpensive biomarkers for survival based on a cohort of 1016 patients treated with primary radiotherapy and androgen deprivation therapy for localized or locally advanced intermediate- or high-risk PCa. Complete survival data was available for all cases based on the National Cancer Registry with a median observation time of 120 months (IQR 80.9-144.7). Missing blood test data were supplemented using the Nearest Neighbor Imputation, and the Cox proportional hazards regression model was used for analysis. The median age was 68.8 years (IQR 63.3-73.5). The five-year overall survival was 82.8%, and 508 patients were alive at the time of analysis. The median time between blood tests and the first day of radiotherapy was 6 days (IQR 0-19). HGB (p = 0.009) and AMC (p = 0.003) were independent prognostic factors for survival, along with age, ISUP Grade Group, clinical T stage and maximum PSA concentration. The study demonstrated that HGB and AMC can be useful biomarkers for overall survival in patients treated with radiotherapy for localized intermediate- or high-risk PCa.

The importance of antibodies in health care and the biotechnology research and development demands not only knowledge of their experimental structures at high resolution, but also practical implementation of this knowledge for both effective and efficient design and production of antibody for its use in both medical and research applications. While the experimental wet-lab approach is usually costly, laborious and time-consuming, computational (dry-lab) approaches, in spite of their intrinsic limitations in comparison with its experimental (wet-lab) counterpart, provide a cheaper and faster alternative option. For the first time, this article reports a comprehensive set of structural electrostatic features extracted from experimentally determined antigen-antibody-related structures, including especially those structural electrostatic features at the interfaces of all experimentally determined antigen-antibody complex structures as of February 29, 2020, to facilitate effective and efficient machine learning-based computational antibody design using currently available experimental structures inside Protein Data Bank.

Surgical knots are sequences of half-knots (H) or half-hitches (S), defined by their number of throws, by an opposite or similar rotation compared with the previous one and for half-hitches, whether sliding (s) or blocking (b). Opposite rotation results in (more secure) symmetric (s) knots, similar rotation in asymmetric (a) knots, and changing active and passive ends has the same effect as changing rotation. Loop security is the force to keep tissue together after a first half-knot or sliding half-hitches. With polyfilament sutures H2, H3, SSs and SSsSsSs have a loop security of 10, 18, 28 and 48 Newton (N), respectively. With monofilament sutures, they are only 7, 16, 18 and 25N. Since many knots can reorganise, the definition of knot security as the force at which the knot opens or the suture breaks should be replaced by the clinically more relevant percentage of clinically dangerous and insecure knots. Secure knots with polyfilament sutures require a minimum of 4 or 5 throws, but the risk of destabilisation is high. With monofilament sutures, only 2 symmetric+4 asymmetric blocking half-hitches are secure. In conclusion, half-hitch sequences are recommended since mandatory for monofilament sutures, adding flexibility for loop security with less risk of destabilisation.

The study aimed to assess the prevalence and correlates of hazardous, harmful or dependent alcohol use (HHDA) and drug use among persons 15 years and older in South Africa. In a national cross-sectional 2017 survey, 39,210 persons 15 years and older (Median=34 years) responded to a questionnaire on substance and health variables. Logistic regression was used to assess the determinants of HHDA and any drug use. Results indicate that (10.3%) engaged HHDA, 16.5% among males and 4.6% among females, and past 3-month drug use was 8.6%, 13.3% among males and 4.1% among females. In adjusted logistic regression analysis, among men, middle age (25-34 year olds), higher education, urban residence, drug use, and psychological distress were positively and Indian or Asian and White population groups were negatively associated with HHDA. Among women, middle age (25-34 year olds), Coloureds, residing on rural farms and urban areas, drug use and psychological distress were positively and older age (55 years and older), and Indians or Asians were negatively associated with HHDA. In adjusted logistic regression analysis, among men, having Grade 8-11 education, Coloureds, being unemployed, and HHDA were positively and middle and older age (25 years and older) and being a student or learner were negatively associated with past 3-month any drug use. Among women, Coloureds, Indians or Asians, and HHDA were positively and older age (45 years and older) was negatively associated with past 3-month and drug use. About one in ten participants engaged HHDA and any drug use, and several sociodemographic and health indicators were identified associated with HHDA and any drug use.

Glioblastoma is a solid, infiltrating and the most frequent highly malignant primary brain tumor. Our aim was to find the prognostic value of mutations of IDH1, MGMT, EGFR, p53, ATRX, Ki67 genes and the correlation between sex, age, presenting with seizures, number of interventions, extent of resection with Overall Survival (OS), Progression Free Survival (PFS) and Karnofsky performance status (KPS) score. A randomized retrospective analysis of 122 patients treated by a single operator at Sapienza University of Rome, was carried out. After surgery patients followed standard treatment Stupp protocol [6]. Exclusion criteria were: patients with primitive brainstem and spinal cord gliomas and patients who underwent partial resections (resection < 90%) and cases of brain biopsy exclusively for diagnostic purposes. Statistical analysis with a simultaneous regression model was carried on by SPSS 25 ® (IBM) program. Results showed statistically significant survival increase in four groups: 1) patients treated with gross total resection (p< 0.03); 2) patients with methylated MGMT promoter (p<0.005); 3) patients with non EGFR amplification or EGFRvIII mutation (p<0.035); 4) mutated IDH1/IDH2 (p<0.0161). Higher survival rates (but not statistically significant) were observed also in patients with: age < 75 years, Ki 67 <10%, lesions in non eloquent areas, ATRX gene mutation and presentation with seizures.

Emollients are valued ingredients of many cosmetic products and medical devices used to support the treatment and prevention of many skin diseases. Despite the fact that they are one of the oldest cosmetic ingredients, raw materials as well as new recipe solutions are constantly being sought, the main goal of which is to obtain products with the most favorable physicochemical properties while improving the hydration of the stratum corneum and softening and smoothing the skin. This article presents the results of physicochemical tests of selected emollients: natural [Macadamia Integrifolia Seed Oil, Ricinus Communis Seed Oil, Prunus Amygdalus Dulcis, Vitis Vinifera (Grape) Seed Oil], semi-synthetic Caprylic/Capric Triglyceride and synthetic (Octyldodecanol, Dicaprylyl Carbonate, Dibutyl Adipate). Then, recipes for cosmetic oils were developed, differing in the type and concentration of emollients used. The obtained formulations were subjected to physicochemical tests (dynamic viscosity, surface tension, wetting angle, color assessment) and selected parameters of the epidermal barrier function (skin hydration and lubrication) were assessed. By appropriately selecting the type and concentration of emollients in the cosmetic oil recipe, it is possible to obtain products with the appropriate ability to spread on the skin, form a uniform protective layer on the skin and remain on the skin for a sufficiently long time. The observed improvement in skin hydration and the level of lubrication after using formulations containing mixtures of natural and semi-synthetic/synthetic emollients confirms that both groups of these raw materials can be components of cosmetic body oil recipes with an emollient effect, and the products themselves constitute an important element of the care of skin affected by the disease process.

Mycoplasma synoviae (MS) is a highly contagious bacteria that can cause significant harm in commercial poultry populations while not prevented. Rapid detection of its presence in a flock is crucial from the perspective of animals' health and economic income. Authors propose spectral measurements strongly backed up by the AI data processing algorithms for classifying egg origin: from healthy hens or MS-infected ones. The newest obtained classification factors are F-scores for white eggshells 99% and for brown eggshells 99%—all data used for classification were taken by the portable multispectral fibre-optics reflectometer.

Background: The conformation of the recipient site for an inlay graft presents an increased contact with the parent bone compared to the onlay graft. This might favor bone growth within the inlay compared to the onlay grafts. Hence, the objective of this study was to compare bone incorporation and remodeling process of xenogeneic en bloc grafts, placed using two bone grafting techniques, i.e., onlay vs. inlay. Methods: In this prospective, randomized, split-mouth study (test and control sides in the same animal), two bone grafting techniques were comparatively evaluated on the lateral aspect of the rabbit mandibles. One side was prepared with perforations (onlay site), whereas the other side was prepared with trephines and drills to obtain a wide (7 mm) standardized recipient site (inlay site). A xenogeneic bone block was fixed in the center with a titanium screw in both sides of the mandible and covered with a collagen membrane. Two healing periods were applied in the study: 2 and 10 weeks of healing. Results: after 2 weeks of healing, the mean percentage of new bone was 10.4% and 23.3% at the onlay and inlay grafts, respectively (p=0.022). After 10 weeks of healing, new bone increased to 13.2% and 25.4%, respectively (p=0.080). In this period of healing, the inlay grafts presented new bone percentage &gt;20% in all regions examined while the onlay graft presented a lower percentage in the most external regions of the graft. Conclusion: The percentage of new bone increased faster and was higher in the inlay compared to the onlay grafts. The composition of the grafts allowed new bone to reach the most peripheral regions in both graft groups, even though it was higher in the inlay group. A marginal closure of the defects by newly formed bone was observed in the inlay group.

The rapid introduction of DAAs has revolutionized the treatment of chronic HCV infection, however some concerns have been arose about their early and long term safety in real life settings. Therefore, these drugs achieve a robust and sustained virological response in a short duration of treatment, being a quick winning option, but, what then? At now an extensive follow-up in real life settings does not exist particularly on HCC occurrence as recently suggested in a Cochrane review . In this regard from February 2015 to December 2017 a group of 5 Hospital and Academic Centers in Southern Italy (Campania Region) managed an observational, prospective, real-life study on efficacy and safety of DAAs treatment schedule enrolling 1022 consecutive HCV patients treated with IFN-free DAAs regimens being followed-up for 24 months. Our preliminary data on the first 360 patients out of 1022 whose completed at least 66 weeks follow-up, based on clinical, laboratory and expert ultrasonography every three months, showed an SVR in 342 out 360 (95%) patients of which 9 had a new diagnosed HCC (2.63%). Specifically HCC developed in mean after 16,2 months after end of treatment as one or more nodules (2-3 cm in mean) with an increase in alpha-fetoprotein 10 x u.n.v (n.v. <15 UI/mL) in patients with F4 fibrosis staging at the time of treatment enrolment. In conclusion, in view of our findings and literature evidences, regular clinical, laboratory and expert ultrasonography follow-up should carefully performed also on these patients and the current Faster, Higher, Stronger approach to the new antivirals development should strongly be revisited in the light of possible late adverse events like HCC occurrence and the relative economic impact on health care system cost.

The concept of an economy that is circular and without the need for material or energy input has an irresistible appeal to those who have recognized that planetary boundaries exist and that resources are not unlimited. Thus, in the public discourse its narrative outperforms other lines of arguments when it comes to keeping radical critics of destructive extractivism and the growth imperative in check and averting the uptake of diverging opinions by larger segments of the population and government bodies. Moreover, the myth of a circular economy has the additional benefit that it can win over parts of the environmental movement that dread radical and transformative change, particularly in the urban milieus of a middle-class that enjoys the privileges of the current social order. In this paper I argue that the circular economy narrative tends to hinder the necessary systemic transformation while entailing a wide range of specific measures that deserve to be recognized for their merit.

Drought stress has been considered a major problem in coffee crops, and the higher occurrence of unpredictable environmental events has highlighted the vulnerability of agricultural systems. Several reports have indicated selenium (Se) as a plant biostimulant against environmental stress, including drought. The effects of Se in plants are related to the modulation of enzymatic activity, energetics and osmoprotectants plant content, and nutrient balance in plants. However, investi-gating the effective time of Se application is crucial for better understanding its effects on coffee plants, a drought-sensitive crop. This study aimed to investigate the role of Se supply in improving drought tolerance in coffee seedlings while also evaluating the best timing for Se application. Five times of Se foliar application were assessed during induced drought stress by PEG-6000 using the day of imposing stress as a default, plus two control treatments: i) with osmotic stress and without Se; ii) without osmotic stress and Se. The treatments were compared with both control treatments. Results demonstrated that the osmotic stress (OS) promoted mild stress in the coffee plants, as ex-pected. Plants under stress showed reduced GR and SOD activity compared with the non-stressed ones, and the OS induces starch degradation, which is potentialized by Se foliar supply, mainly when Se is applied before inducing the stress. The decline in the starch content might be considered a strategy to provide energy to coffee seedlings. The seedlings that received foliar Se application 8 days before the stress exhibited higher CAT, APX, and SOD than those that did not receive OS nor Se application. The results obtained in this study suggest that the previous Se foliar spray is more effective than the Se supply after OS to overcome the adverse condition. On the other hand, the post-stress application seems to impose extra stress on the plants, leading them to reduce the water potential.

Introduction. Covid-19 faced the world with serious health and socioeconomic issues. At the very beginning of the pandemics, the vaccine was considered by health authorities and the medical community the only way to curb the spread of the virus. One of the measures that have been proposed to increase vaccinations was the mandatory policy. The purpose of this study was to compare determinants of voluntary and mandatory vaccination among students of Albanian University. Methodology: This cross-sectional study by means of an online survey, was conducted among students enrolled in the private University “Albanian University”, Tirana, Albania during the last week of winter semester 7-14 Feb 2022. Results: 878 students participated in this study, among them 612 (69.7%) were females, 266 (30%) were males. 506 (57%) of the participants were enrolled in Medical Sciences (MS), 372(42.3%) were Non-Medical Science (Non-MS) group. 773 (88%) was vaccinated against Covid-19, 105 (11.8%) were not vaccinated. 466 (53%) reported voluntary vaccination, 412 (46.9%) reported mandatory vaccination. Among students that vaccinated voluntary 266 (57%) were from MS group, 200(42.9%) from Non-MS group. 237(57.5%) of students in mandatory vaccination group were from MS group, 175 (42.4%) from Non-MS. Conlusion. Vaccine safety and efficacy were hindering factors of vaccination. Also, based on the results of this study, the students felt encouraged to vaccinate by the academic staff. This clearly demonstrates that the staff does not lack the skills to enhance stu-dents' knowledge about the risk of infectious diseases and the importance of vaccination. Therefore, to influence as much as possible students’ attitude toward vaccination, comprehensive educational programs including modification of existing curricula should be considered.

Patients under immunosuppressive therapy for kidney diseases or on maintenance hemodialysis are more susceptible to infection than the general population since loss of renal function per se was an immunocompromised condition. Of relevance, CT imaging plays a crucial role in the detection and management of pulmonary infectious diseases. We hence presented diverse CT findings of pulmonary infections in the above said patients collected during our arduous work against a wide range of pathogens including klebsiella pneumoniae, staphylococcus aureus, candida parapsilosis, aspergillus, cryptococcus, mucor, pneumocystis carinii, cytomegalovirus, mycobacterium and nocardia. Notably, the pulmonary pathological changes were either primary pneumonia or secondary to the catheter-associated bloodstream infection. For a descriptive purpose, pulmonary manifestations of Wegener’s granuloma, lung cancer and diffuse alveolar hemorrhage/infection in vasculitis were also examined. As such, we retrospectively elaborated most likely CT features of each individual pathogen and briefly covered the differential diagnosis as well. Arguably, combination of pattern recognition with knowledge of the clinical setting could make a presumptive diagnosis and early treatment even more convenient. From the experience of first-line nephrologists, our work could make a substantial contribution to the expeditious and efficacious management of pulmonary infections in the pertinent patient population.

Food waste is one of the greatest challenge to sustainability in developed and developing countries. In the former, food waste is concentrated in the final part of the chain. Too Good To Go is a digital platform aimed to prevent food waste, where consumers can buy magic boxes from different outlets containing food products that are approaching their end-of-life. However, the mechanism of the platform enable the outlets to publish their offering much in advance of the pick-up time, raising the question whether the food sold on the platform is effectively a leftover or a planned production. Our empirical study gathers data from over 1200 outlets in Rome on the Too Good To Go platform.

The aim of this study is to empirically examine the link between foreign direct investment (FDI) and domestic investment (DI) in South Africa over the period of 41 years (1975-2016). Accurately, it attempts to determine whether FDI crowds in or crowds out DI in South Africa. DI is sub-divided into private domestic investment (credit to domestic private sector) and public corporation investment (state owned enterprises). We used the Autoregressive Distributed Lag-Error Correction Model (ARDL-ECM) technique to ascertain long run and short run effects concurrently after establishing that the variables were stationary (using the PP test). The results of the unit root test shows that all variables are integrated of order zero I(0) or integrated of order one I(1), indicating that the series of variables are stationary in the level or first difference form. The findings revealed that variables are cointegrated in the long run. The ARDL model found a negative link between FDI and domestic investment. The result implies that FDI crowds out domestic investment. Moreover, the long run estimate revealed that domestic investment is crowded in by government investment expenditure (GINV). Other findings uncovered that, GDP crowds out private domestic investment while crowding in public corporation investment. Moreover, the long run estimate revealed that domestic investment is crowded in by gross domestic savings (SAV). On the other hand, the real exchange rate (EXCR) crowds out private domestic investment while crowding in public corporation investment. Trade openness (TRA) crowds out domestic investment. Additionally, the short run estimate uncovered that private domestic investment is crowded out by FDI, EXCR, and TRA whereas GINV, GDP and SAV is crowding in private domestic investment. Other findings discovered that, in the short run, public corporation investment is crowded out by FDI, GDP, EXCR and TRA, while GINV and SAV crowd in public corporation investment. The CUSUM confirms that the models are structurally firmness.

This review asks some hard questions about what the enigmatic graphoglyptid trace fossils are, documents some of their early fossil record from the Ediacaran-Cambrian transition and explores the idea that they may not have been fossils at all. Most researchers have considered the Graphoglyptida to have had a microbial-farming mode of life similar to that proposed for the fractal Ediacaran Rangeomorpha. This begs the question “What are the Graphoglyptida if not the Rangeomorpha persevering” and if so then “What if…?”. This provocative idea has at its roots some fundamental questions about how to distinguish burrows sensu-stricto from the external molds of endobenthic sediment displacive organisms.

Cannabis (Cannabis Sativa L.) is now legally produced in many regions worldwide. Cannabis flourishes under high light intensities (LI); making it an expensive commodity to grow in controlled environments, despite its exceptionally high market value. It is commonly believed that cannabis secondary metabolite levels may be enhanced both by increasing LI and by exposing crops to ultraviolet radiation (UV). However, there is sparse scientific evidence to guide cultivators. Therefore, the impact of LI and UV on yield and quality must be elucidated to enable cultivators to optimize their lighting protocols. We explored the effects of LI, ranging from 350 to 1400 μmol m^-2 s^-1 and supplemental UV spectra on cannabis yield and potency. There were no spectrum effects on inflorescence yield, but harvest index under UVA+UVB was reduced slightly (1.6%) vs. the control. Inflorescence yield increased linearly from 19.4 to 57.4 g/plant and harvest index increased from 0.565 to 0.627, as LI increased from 350 to 1400 μmol m^-2 s^-1. Although there were no UV spectrum effects on total equivalent Δ⁹-tetrahydrocannabinol (T-THC) content in leaves, the neutral form, THC, was 30% higher in UVA+UVB vs. control. While there were no LI effects on inflorescence T-THC content, the content of the acid form (THCA) increased by 20% and total terpenes content decreased by 20% as LI increased from 350 to 1400 μmol m^-2 s^-1. High LI can substantially increase cannabis yield and quality, but we found no commercially-relevant benefits of adding supplemental UV radiation to indoor cannabis production.

The implications of urban revitalization, gentrification, and residential migration have attracted widespread interest and ongoing debate among scholars across a range of disciplines. While a significant body of literature explores race and class interactions within urban gentrifying neighborhoods, few have examined the environments that await those displaced by this process. This study explores the social and political impact of urban gentrification and class stratification within the black community by examining responses of black middle class residents in Prince George’s County, MD to the growing in-migration of low-income and minority residents from Washington, DC. Drawing on data from the U.S. Census Bureau, a multi-neighborhood sample of ninety-five black middle class residents of Prince George’s County, and informal interviews with subject-area experts, this study explores how race and class shape residential decisions and their impact on residential mobility initiatives. Residents responded to a 26-item survey that covered demographic information, political and community engagement, and their attitudes and beliefs about the poor, changes in their community, and racial unity and responsibility. Findings from cross tabulations and binary logistic regression indicate that lower middle class residents are the most likely to resist in-migration by exiting their communities and/or voting against proposals to create affordable housing options. Core and upper middle class residents were the most likely to stay in their neighborhoods despite increases in low-income migration, to vote in support of policies to create affordable housing options and to believe their responsibility to poor blacks could include sharing residential space.

Many stable water dispersions of various chemical compositions containing bioactive chemical compounds: copper silicate, titanium dioxide and zinc oxide (and other auxiliary substances) were developed and fabricated - they were used for preparation of thin hybrid coatings having very good antimicrobial properties against gram negative bacteria (Escherichia coli), gram positive bacteria (Staphylococcus aureus) and yeast fungus (Candida albicans). Polyester (PES) nonwovens were modified by dip-coating, and PES and cotton fabrics - by dip-coating and coating methods.

Phosphorus deficiency highly interferes with plant growth and development. Plants respond to the persistent P deficiency by coordinating the expression of genes involved in the alleviation of the stress. Promoters of phosphate transporter genes are of great choice for the development of genetically modified plants with enhanced phosphate uptake abilities, which improve crop yields in phosphate-deficient soils. In our previous study, the sugarcane phosphate transporter PHT1;2 gene, showed a significantly high expression under salinity stress. In this study, the Erianthus arundinaceus EaPHT1;2 gene was isolated and characterized using various in-silico tools. The deduced 542 amino acid residues have 10 transmembrane domains, with a molecular weight and isoelectric point of 58.9 kDa and 9.80, respectively. They displayed 71–96% similarity with Arabidopsis thaliana, Zea mays, and Saccharum hybrid. To elucidate the function of the 5’ regulatory region, the 1.1kb promoter was isolated and validated in tobacco transgenics under Pi stress. The EaPHT1;2 promoter activity was detected using the β-glucuronidase (GUS) assay. While the EaPHT1;2 promoter showed 3 to 4.2-fold higher expression than the most widely used CaMV35S promoter. The 5’ deletion analysis with and without 5’UTR regions, revealed that a small size 374 bp fragment with the highest promoter activity among 5′ truncated fragments, which was 2.7 and 4.2 times higher than the well-used CaMV35S promoter under normal and Pi-deprivation conditions, respectively. The strong and short promoter of EaPHT1;2 with 374 bp showed significant expression in low Pi-stress conditions and it could be a valuable source for the development of stress-tolerant transgenic crops

Porcine parvovirus (PPV) 1 is a major causative pathogen of reproductive failure, and porcine circovirus (PCV) 2 is an etiological pathogen causing PCV-associated and PCV diseases worldwide. PPV2–6 and PCV3 were recently identified as newly emerging viruses with unknown pathogeneses. However, little is known of PPV1–6 and PCV3 effects or their co-infections with PCV2. In this study, we examined 926 samples (272 aborted pig fetuses and 654 pig lung tissues) from domestic pig farms for the presence of PPV1–6 or PCV3 and for PCV2 co-infection with these seven viruses. The prevalence of PPV and PCV was significantly greater in lung tissue samples than aborted pig fetus samples. PPV3–6 were detected for the first time in Korean domestic pigs. Co-infection rates with PCV2 and other viruses were significantly higher in abattoir samples than that in aborted pig fetus samples. Concurrent infections are more common than single infection in pig population and nu-merous infectious pathogens such as PPV and PCV2 can impact the respiratory diseases. Fur-thermore, Korean PPV1 strain (PPV1-82) was identical to the virulent PPV-27a strain in this respect. Our results describe, for the first time the prevalence of PPV1–6 and PCV3 infections and their co-infection rates with PCV2 in Korean domestic pigs.

The ongoing evolution of severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) has resulted in the recent emergence of a highly divergent variant of concern (VOC) defined as Omicron or B.1.1.529. This VOC is of particular concern because it has the potential to evade most therapeutic antibodies and has undergone a sustained genetic evolution, resulting in the emergence of five distinct sub-lineages. However, the evolutionary dynamics of initially identified Omicron BA.1 and BA.2 sub-lineages remain poorly understood. Herein, we combined Bayesian phylogenetic analysis, mutational profiling, and selection pressure analysis to track virus genetic changes that drive the early evolutionary dynamics of the Omicron. Based on the Omicron dataset chosen for the improved temporal signals and sampled globally between November 2021 and January 2022, most recent common ancestor (tMRCA) and substitution rates for BA.1 were estimated to be 18 September 2021 (95% highest posterior density (HPD) 04 August – 22 October 2021) and 1.435×10-3 (95% HPD = 1.021×10-3 – 1.869×10-3) substitution/site/year, respectively, whereas 03 November 2021 (95% highest posterior density (HPD) 26 September – 28 November 2021) and 1.074×10-3 (95% HPD = 6.444×10-4 – 1.586×10-3) substitution/site/year for BA.2 sub-lineage. The findings of this study suggest that the Omicron BA.1 and BA.2 sub-lineages originated independently and evolved over time. Furthermore, we identified multiple sites in spike protein undergoing continued diversifying selection that may alter the neutralization profile of BA.1. This study shed light on the ongoing global genomic surveillance and Bayesian molecular dating analyses to better understand the evolutionary dynamics the virus and, as a result, mitigate the impact of emerging variants on public health.

Providing data on usage patterns is key to assessing the reduced-risk potential of novel tobacco and nicotine products at a population level. We performed a nationwide cross-sectional survey of the general population in Japan to assess usage patterns after the introduction of tobacco heating products (THPs). Eligible participants were Japanese residents, aged 20 years or older who consented to complete the survey. Individuals living in institutions were excluded. A three-stage probability sampling method was applied that was geographically stratified by street blocks proportionate to population density. Respondents self-reported patterns of product use and reasons for THP use. Complete responses were available from 5,306 individuals, of whom 933.5 (17.6%) were current users, 984.2 (18.5%) were former users and 3388.4 (63.9%) were never users of tobacco products. Cigarettes were used by 14.6% of current tobacco product users and THPs by 5.3%. Cigarettes and THPs were used exclusively by 64.5% and 12.2%, respectively, and both were used by 12.7%. The most common reasons reported for THP use were perceived reduction in harm to self and others compared to cigarettes. While the prevalence of cigarette use in Japan is decreasing, THPs seem to be increasingly used as long-term alternatives to cigarette smoking.

Background: Previous data indicate a role of IL-1 and IL-1RA imbalance in bladder carcinoma (BC) and inhibition of IL-1 signaling might be considered a treatment option. Objective: To assess expression patterns and the prognostic role of IL-1ß and IL-1RA in invasive BC and to evaluate their interaction with AKT signaling and proliferation. Design, Setting, and Participants: The study included two independent cohorts of n=92 and n=102 patients who underwent radical cystectomy for BC. Specimen from BC and benign urothelium (n=22 and n=39) were processed to a tissue microarray and immunohistochemically stained for IL-1ß, IL-1RA, AKT and Ki-67. Expression scores were correlated to clinical variables and Ki-67 and AKT expression. Outcome measurements and statistical analysis: Association with outcome was assessed using Wilcoxon Kruskal-Wallis tests, Chi-square tests or linear regression, dependent on the variable’s category. Kaplan–Meier and Cox proportional hazard analyses were used to estimate recurrence-free (RFS), cancer-specific (CSS) and overall survival (OS). Results: Both, IL-1ß and IL-1RA were significantly overexpressed in invasive BC compared to benign urothelium in both cohorts (p&lt;0.005). IL-1ß was associated with vascular invasion (210 vs. 183, p&lt;0.02), lymphatic invasion (210 vs. 180, &lt;0.05) and G3 cancer (192 vs. 188, &lt;0.04). Survival analysis revealed favorable RFS, CSS, and OS in case of high IL-1ß expression (p&lt;0.02, &lt;0.03 and &lt;0.006, respectively). Multivariate analyses revealed an independent impact of (low) IL1ß expression on RFS, CSS and OS. IL-1ß and IL-1ß/IL-1RA ratio were positively correlated to AKT expression (p&lt;0.05 and &lt;0.01, respectively). Additionally, high expression of Ki-67 (&gt;15%) correlated with higher levels of IL-1β (p=0.01). Conclusions: Overexpression of IL-1ß and IL-1RA is frequently found in BC, with a prognostic significance observed for IL-1ß protein expression. The observed link between the IL-1ß / IL-1RA axis and AKT signaling may indicate possible autophagy activation processes beside the known tumor-promoting effects of AKT.

The well-known equations for the process of powder compaction (PCP) in a rigid die published over the period from the beginning of the last century to the present are considered. Most of the considered equations are converted into the dependence of the densification pressure on the relative density. The equations were analyzed and their ability to describe PCP was assessed by determining the coefficient of determination when approximating experimental data on the compaction of various powders. It is shown that most of the equations contain two constants, the values of which are determined by fitting the mathematical dependence to the experimental curve. Such equations are able to describe PCP with high accuracy in the case of compaction of powders up to a relative density of 0.9-0.95. It is also shown that different equations can describe PCP in the range of density change from the initial to 0.9 with the same and sufficiently high accuracy, but when the process of compaction is extrapolated to higher values of density, the curves diverge. This indicates the importance of equations that can unambiguously describe PCP to a relative density equal to or close to 1.0. For an adequate description of PCP to a relative density greater than 0.95, equations containing three or four constants have proven themselves well.

The involvement of NK and other cytotoxic cells is considered the first defense' line against cancer. However, a significant lack of information prevails on the possible roles played by factors considered characteristic of primitive cells, such as c-kit and Sca-1, in activating these cells, particularly in melanoma models subjected to treatments with substances under investigation, such as the case of norcantharidin. In this study, B16F1 murine melanoma cells were used to induce tumors in DBA/2 mice, estimating the proportions of NK and iNKT cells, the presence of activation (CD107a+) and primitive/activation (c-kit+/Lya6A+) markers, some tumor parameters, such as the presence of mitotic bodies, nuclear factor area, NK and iNKT cell infiltration in the tumor, infiltrated tumor area, and infiltrating lymphocyte count at 10x and 40x in specimens treated with pentoxifylline, norcantharidin and the combination of both drugs. Possible correlations were estimated with Pearson's correlation analysis. Despite having demonstrated multiple correlations, it should be noted that immaturity/activation markers were related to these cells' activation. At the tumor site, iNKT cells are the ones that exert the cytotoxic potential on tumor cells, but they are confined to specific sites in the tumor. Due to the higher number of interactions of natural killer cells with tumor cells, it is concluded that the most effective treatment was PTX at 60 mg/kg + NCTD at 0.75 mg/kg.

Lewis acid zeolites play an important role in industrially important green reactions closely related to fine chemicals and biomass conversion. Titanium-doped TS-1 zeolite is a milestone Lewis acid zeolite, which widely uses in industrially significant green oxidation processes with hydrogen peroxide as an oxidant under mild conditions. TS-1 Zeolites are normally synthesized in basic condition under hydrothermal treatment. Up to now, it is still not successful to synthesize active TS-1 Lewis acid zeolite by using inorganic alkali, e.g. NaOH or KOH as base, which are cheaper and more stable compared with quaternary ammonium hydroxide or organic amines used in the traditional synthesis. Here, inorganic base of NaOH was firstly employed in synthesizing active TS-1 zeolites. The crucial factor was the control of adverse effects of sodium cations on the incorporation of active titanium cations. A higher catalytic activity could be achieved by further reducing the size of the TS-1 crystal by seed-added strategy, which could approach the catalytic activity of commercial catalyst while the production cost was much lower than the commercial TS-1 catalysts, indicating great commercial potential and the possibility of preparing other cheap Lewis acid catalysts by using inorganic alkali.

Apoptosis under severe hypoxia is induced through p53 phosphorylation and HIF-1α-dependent p53 accumulation via ATR activation by DNA damage response (DDR) activation through replication stress. We previously demonstrated that the topoisomerase I catalytic inhibitor, 3EZ, 20Ac-ingenol, specifically induced apoptosis in Jeko-1 and Panc-1 cells, both of which are cell lines that show cyclin D1 overexpression. After progression to the S phase facilitated by nuclear cyclin D1, in the presence of 3EZ, 20Ac-ingenol, an intra S phase checkpoint was induced in ATR activation as part of replication stress-induced DDR. In this study, we examined whether 3EE, 20Ac-ingenol induces a higher degree of p53 phosphorylation and additional HIF-1α and p53 accumulation in response to replication stress-induced DDR activation under the hypoxic condition than under the normoxic condition by controlling ATR activation. 3EE, 20Ac-ingenol induced p53 activation and HIF-1α-dependent p53 accumulation through cooperative ATR activation via induced DDR with the hypoxia in Panc-1 cells. The Jeko-1 cells showed slight HIF-1α accumulation under hypoxia, but this was not decreased by 3EE, 20Ac-ingenol, so that the cells remained resistant to hypoxia. 3EE, 20Ac-ingenol induces an intricate interplay between p53 and HIF-1α accumulation via ATR activations that results in high p53 accumulation, which advanced transient expression and early disappearance of HIF-1?. The strong p53 accumulation and consequent PTEN activation also decreased HIF-1α accumulation and PD-L1 expression, which resulted in intense apoptosis.

C-C chemokine receptor 9 (CCR9) is a receptor for C-C-chemokine ligand 25 (CCL25). CCR9 is crucial in the chemotaxis of immune cells and inflammatory responses. Moreover, CCR9 is highly expressed in tumors including several solid tumors and T-cell acute lymphoblastic leukemia. Several preclinical studies have shown that anti-CCR9 monoclonal antibodies (mAbs) exert antitumor activity. Therefore, CCR9 is an attractive target for tumor therapy. In this study, we conducted the epitope mapping of an anti-mouse CCR9 (mCCR9) mAb, C9Mab-24 (rat IgG2a, kappa), using a 1 × alanine (1 × Ala) and 2 × alanine (2 × Ala)-substitution method via enzyme-linked immunosorbent assay. We first performed the 1 × Ala-substitution method using one alanine-substituted peptides of the mCCR9 N-terminus (amino acids 1-19). C9Mab-24 did not recognize two peptides (F14A and F17A), indicating that Phe14 and Phe17 are critical for C9Mab-24-binding to mCCR9. Furthermore, we conducted the 2 × Ala-substitution method using two consecutive alanine-substituted peptides of the mCCR9 N-terminus, and showed that C9Mab-24 did not react with four peptides (M13A–F14A, F14A–D15A, D16A–F17A, and F17A–S18A), indicating that 13-MFDDFS-18 is involved in C9Mab-24-binding to mCCR9. Overall, combining, the 1 × Ala or 2 × Ala scanning methods could be useful for understanding for target-antibody interaction.

Pre-eclampsia is a hypertension disorder during pregnancy, significantly affects maternal morbidity and mortality worldwide. A Case-control research was done on 100 pregnant mothers as respondents: 50 case (pre-eclampsia) and 50 control groups (healthy pregnant mothers). Selected case the following characteristics: were patients that visited the Syamrabu Bangkalan Public Hospital; were third-generation Madura natives; aged between 20-40 years old; had a gestational age of over 20mgg; had blood pressure above 140/90mmHg; and single pregnancies. Control had the following characteristics: were healthy pregnant women without pre-eclampsia or chronic hypertension; were third-generation Madura natives; had a gestational age of over 20mgg; aged between 20-40 years; and without pregnancy complications. The results showed of those with PE, 45 had the AA genotype (homozygote) (90%), five had AC (heterozygote) (8%) and one had CC (homozygote) (2%). As for those without PE, 33 had the AA genotype (homozygote) (73.3%), 11 had AC (heterozygote) (26.7%), none had CC (homozygote) (0%). PE and non-PE cases mostly had the AA genotype (homozygote) and A alleles. AT1R 1166 A/C polymorphism was found to be a significant risk factor for pre-eclampsia, while potassium level had no significant effect on it. Meaning further research is needed on different ethnicities and races.

The problem of fluid dynamics can be greatly simplified if, for every point in space, the strain-rate tensor is diagonalized. This tensor is introduced into the Navier-Stokes equations via material law and divergence of the stress tensor. This article shows that local SO(3)xU(1) gauge fields can be used to locally diagonalize the diffusion components of the strain-rate tensor. The gauge fields resulting from the connection can be interpreted as convection components of the flow, they show properties of quasiparticles and can be interpreted as elementary vortices. Thus, the proposed approach not only offers new insights for the solution and situative simplification of the Navier-Stokes equations, it also uncovers hidden symmetries within the flow convection, allowing - depending on boundary conditions - further interpretation.

Tapping panel dryness (TPD) syndrome is a complex disease of Rubber tree (Hevea brasiliensis L.) which causes cessation of latex drainage upon tapping of rubber tree. Rubber tree virus (RTV1) was identified as a novel pathogen associated with rubber tree and a potential causal agent of TPD. RTV1 is a monopartite RNA virus that is linear, non-enveloped and has a single-stranded (ss) positive RNA genome of approximately 6081 nucleotides and is composed of two major open reading frames (ORFs), ORF1 (polyprotein), and ORF2 (movement protein. This study aimed to investigate the possibility of rubber genome encoded tree microRNAs (miRNAs) as novel therapeutic targets against RTV1 using in silico algorithms. Mature rubber tree miRNAs are retrieved from the miRBase database and are used for hybridization of RTV1 using five different five different computational algorithms including miRanda, RNA22, RNAhybrid and psRNATarget. A total of eleven common rubber tree miRNAs were identified based on consensus genomic positions. The consensus of four algorithms predicted the hybridization sites of hbr-miR396a and hbr-miR398 at common locus positions 6676, 1840 respectively. To validate the prediction, secondary structures of the consensual rubber tree miRNAs and free energy of duplex binding were calculated using the RNAfold and RNAcofold algorithms respectively. We created a plot between rubber tree miRNAs and RTV1 ORFs by using Circos algorithm. In this study, we predicted eleven consensual rubber tree miRNAs. Among these miRNAs, hbr-miR398 was identified as the most effectual miRNA that may target the ORF1 gene of the RTV1 genome. The predicted data will be important in the development of rubber trees resistant to RTV1.

Multiple myeloma (MM) is characterized by the malignant proliferation of monoclonal plasma cells in the bone marrow with an elevation in monoclonal paraprotein, renal impairment, hypercalcemia, lytic bony lesions, and anemia. Immune cells and associated cytokines play a significant role in MM growth, progression, and dissemination. While some cytokines and their clinical significance are well described in MM biology, others remain relatively unknown. The aim of the present study was to assess the impact of pretreatment serum levels of 27 selected cytokines on progression-free survival (PFS) and overall survival (OS) in MM patients before first-line therapy with bortezomib-based regimens. Serum cytokine levels were assayed with a Bio-Rad Bio-Plex Pro Human Cytokine 27-Plex Assay on the MAGPIX Multiplex Reader and the Bio-Plex® 200 System (Bio-Rad) including IL-1β, IL-1Ra, IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IL-9, IL-10, IL-12, IL-13, IL-15, IL-17, Eotaxin, FGF, G-CSF, GM-CSF, IFN-γ, IP-10, MCP-1, MIP-1α, MIP-1β, PDGF-BB, RANTES, TNF-α, and VEGF. A total of 61 MM patients were examined. Most patients received a bortezomib, cyclophosphamide and dexamethasone (VCD) chemotherapy regimen. In the final multivariate model, IL-13 cytokine level (HR 0.1411, 95% CI: 0.0240-0.8291, p = 0.0302), and ASCT (HR 0.3722, 95% CI: 0.1826-0.7585, p=0.0065) significantly impacted PFS. Furthermore, ASCT (HR 0.142, 95% CI: 0.046-0.438, p=0.0007), presence of bone disease at diagnosis (HR 3.826, 95% CI: 1.471-9.949, p=0.0059) and two cytokine levels- IL-1Ra (HR 1.017, 95% CI: 1.004-1.030, p= 0.0091) and IL-4 (HR 0.161, 95% CI: 0.037-0.698, p = 0.0147) were independent predictors of OS. Three clusters of MM patients were identified with different cytokine profiles. In conclusion, serum pretreatment levels of IL-13 and IL-4 are predictors of better PFS and OS, respectively, whereas IL-1Ra pretreatment levels negatively impact OS in MM patients treated with bortezomib-based chemotherapy. Cytokine signature profile may have a potential influence on the outcome of patients treated with bortezomib.

New series of compounds containing both heterocycle moieties and pseudo-symmetric hydroxyethylamine core were obtained using a simple synthetic path that can provide a library of compounds in few steps and high yields. Furthermore, diversity-oriented synthesis was studied to change different functionalities according to needs. The in vitro inhibition activity against recombinant HIV-1 protease was evaluated. A beneficial effect of this class of compounds can be obtained either for the presence of a bis-benzyl group into the core and for the heterocyclic moiety in P1, specifically the indole ring. Docking analysis was also reported.

The SnRK gene family is a key regulator playing an important role in plant stress response by phosphorylating the target protein to regulate the signalling pathways. The function of SnRK gene family has been reported in many species but is limited to Triticum asetivum. In this study, SnRK gene family in the wheat genome was identified and its structural characteristics were described. One hundred forty-seven SnRK genes distributed across 21 chromosomes were identified in the Triticum aestivum genome and categorised into three subgroups (SnRK1/2/3) based on phylogenetic analyses and domain types. The gene intron-exon structure and protein-motif composition of SnRKs were similar within each subgroup but different amongst the groups. Gene duplication between the wheat, Arabidopsis, rice and barley genomes was also investigated in order to get insight into the evolutionary aspects of the TaSnRK family genes. SnRK genes showed differential expression patterns in leaves, roots, spike, and grains. Redundant stress-related cis-elements were also found in the promoters of 129 SnRK genes and their expression levels varied widely following drought, ABA and light regulated elements. In particular, TaSnRK2.11 had higher and increased expression under the abiotic stresses and can be a candidate gene for the abiotc stress tolerance. The findings will aid in the functional characterization of TaSnRK genes for further research.

Whereas a vast literature exists on satellite-based mapping of rice paddy fields in Asia, where most of the global production takes place, little has been produced so far that focuses on the European context. Detection and mapping methods that work well in the Asian context will not offer the same performances in Europe, where different seasonal cycles, environmental contexts, and rice varieties make distinctive features dissimilar to the Asian case. In this context, water management is a key clue; watering practices are distinctive for rice with respect to other crops, and within rice there exist diverse cultivation practices including organic and non-organic approaches. In this paper, we focus on satellite-observed water management to identify rice paddy fields cultivated with a traditional agricultural approach. Building on established research results, and guided by the output of experiments on real-world cases, a new method for analysing time series of Sentinel-1 data has been developed, which can identify traditional rice fields with a high degree of reliability. This work is a part of a broader initiative to build space-based tools for collecting additional pieces of evidence to support food chain traceability; the whole system will consider various parameters, whose analysis procedures are still at their early stages of development.

DR2B and DR2C extracts, from peel of commercially and physiologically ripe eggplants, were studied for the antioxidative cytoprotective properties and anti-HSV-1 activity, in line with the evidence that several antioxidants can impair viral replication by maintaining reducing conditions into the host cells. The antioxidative cytoprotective effects against tBOOH-induced damage was assessed in Caco2 cells, while the antiviral activity was studied in Vero cells; phenolic and anthocyanin fingerprint was characterized by integrated phytochemical methods. Results highlighted different compositions of the extracts, with chlorogenic acid and delphinidin-3-rutinoside as the major constituents; other peculiar phytochemicals were also identified. DR2C resulted able to partly counteract the tBOOH-induced cytotoxicity, with a remarkable lowering of lactate metabolism under both normoxia and hypoxia. DR2B and DR2C reduced ROS production, possessed scavenging and chelating properties. Interestingly, DR2C increased intracellular GSH levels. Furthermore, DR2C inhibited the HSV-1 replication when added for 24 h after viral adsorption, as also confirmed by the reduction of many viral proteins expression. Since DR2C was able to reduce NOX4 expression during HSV-1 infection, its antiviral activity may be correlated to its antioxidant properties. Although further studies are needed to better characterize DR2C activity, the results suggest this extract as a promising new anti-HSV-1 agent.

The aim of this study was to examine oxidative stress and low level of alpha-1-antitrypsin (A1AT) in primary Sjögren's syndrome (pSS), and evaluate the associated autoreactivity against unmodified and their 4-hydroxy-2-nonenal (HNE)-modified peptides with pSS. Two differentially expressed proteins, alpha-1-acid glycoprotein 1 (A1AG1) and A1AT, exhibited 2-fold differences, and their HNE modifications were identified by depleted-albumin and immunoglobulin G (IgG) serum protein, in-solution digestion, in-gel digestion, and nano-LC-MS/MS from pSS patients and age-matched healthy controls (HCs). Furthermore, levels of proteins, confirmation of HNE modifications, HNE-protein adducts and autoreactivity against unmodified and their HNE-modified peptides were further validated. Levels of the HNE-protein adduct and A1AG1 were significantly higher in pSS patients than HCs, but levels of A1AT were significantly lower in pSS patients compared to HCs. Only the HNE modification of A1AT was confirmed. Further, concentrations of anti-A1AT^50-63 IgG and anti-A1AT^50-63 HNE IgA were significantly lower in pSS patients than HCs. Our study suggests that elevated HNE-protein adduct, oxidative stress, level [odds ratio (OR) 4.877, p = 0.003], lowered A1AT level (OR 3.910, p = 0.010) and a decreased level of anti-A1AT^50-63 IgG (OR 3.360, p = 0.010) showed an increased risk in pSS patients compared to HCs, respectively.