Several studies report an impact of the neurotransmitter dopamine (DA) on human immune cells, with effects dependent on immune cell type addressed and their activation status. Another contributing factor appears to be sex, as sex-specific differences in the dopaminergic pathway are described in the neurological context as well as in autoimmune diseases. However, a deeper understanding of these differences in peripheral immune cells remains limited. In this study, we investigated the effects of dopaminergic stimulation on activation and cytokine secretion of peripheral blood mononuclear cells from women and men using flow cytometry, ELISA and multiplex assay. We found a B cell-driven downregulation in cytokine secretion of monocytes exclusively from women under physiological conditions. Moreover, B cells from men showed higher dopamine receptor (DR) expression, which was shown to be further increased by sex hormones only in men. In monocytes from women, an acute inflammatory stimulus via CpG combined with dopaminergic stimulation caused a switch to a proinflammatory phenotype, which was less pronounced in men. These novel findings in sex-specific responses to dopaminergic stimulation are crucial for understanding DA’s function in the healthy and activated immune system and provide evidence to treat DA-related pathologies in a sex-specific manner.

Accurate computational prediction of B-cell epitopes can greatly enhance biomedical research and rapidly advance efforts to develop therapeutics, monoclonal antibodies, vaccines, and immunodiagnostic reagents. Previous research efforts have primarily focused on the development of computational methods to predict linear epitopes rather than conformational epitopes, although the latter is much more biologically predominant. Several conformational B-cell epitope prediction methods have recently been published, but their predictive performances are weak. Here, we present a review of the latest computational methods and assess their performances on a diverse test set of 29 non-redundant unbound antigen structures. Our results demonstrate that ISPIPab outperformed all other methods. Finally, we suggest new strategies and opportu-nities to improve computational predictions of conformational B-cell epitopes.

Potential permanent magnet (Fe0.7Co0.3)2B has large saturation magnetization and high Curie temperature but a moderate magnetocrystalline anisotropy (MCA) and displays relatively low coercivity. One way to improve coercivity is to combine the contribution from magnetocrystalline- and magnetic shape anisotropy by preparing (Fe0.7Co0.3)2B nanowires. We study the effect of size, morphology, and surface defect on the hard magnetic properties of nanowires using micromagnetic simulation. The hard magnetic properties of (Fe0.7Co0.3)2B nanowire bonded magnet have been estimated, including the role of inter-wire magnetostatic interaction. By considering the existence of local reduction of MCA energy up to 30% on the surface layer of nanowires, the anisotropic bonded magnet with 65% vol. of (Fe0.7Co0.3)2B nanowires displays typical magnetic properties of remanence Br=8.4 kG, coercivity Hci=9.9 kOe, and maximum energy product (BH)m=17.8 MGOe. Developing effective technology for synthesizing nanowires and fabricating corresponding bonded magnets is promising for manufacturing practical magnets based on magnetic phase with relatively low or moderate MCA, such as (Fe0.7Co0.3)2B.

B-cell lymphomas (BCL) is the most frequent hematological cancer in dogs. Treatment typically consists of chemotherapy, with CHOP-based protocols. However, outcome remains generally poor, urging the exploration of new therapeutic strategies with a targeted approach. Myc tran-scription factor plays a crucial role in regulating cellular processes and its dysregulation is im-plicated in numerous human and canine malignancies, including canine BCL (cBCL). This study aims to evaluate the efficacy of indirectly inhibiting Myc in cBCL using BI2536 and MZ1 com-pounds in two in vitro models (CLBL-1 and KLR-1201). Both BI2536 and MZ1, alone and com-bined, affected cell viability in a significant concentration and time-dependent manner. Western Blot revealed an upregulation of PLK1 expression in both cell lines upon treatment with BI2536, in association with a reduction in c-Myc protein levels. Conversely, MZ1 led to a decrease in its primary target, BRD4, along with a reduction in c-Myc. Furthermore, BI2536, both alone and in combination with MZ1, induced larger transcriptomic changes in cells compared to MZ1 alone, primarily affecting MYC target genes and genes involved in cell cycle regulation. These data un-derscore the potential role of Myc as therapeutic target in cBCL, providing a novel approach to indirectly modulate this molecule.

(1) Background: Hepatitis B virus (HBV) viral load (VL) is useful in determining treatment eligibility, however, due to high costs associated with the test, hepatitis B e antigen (HBeAg) is recommended as a proxy for HBV VL in resource-limited settings. (2) Methods: We used 299 archived plasma samples with hepatitis B surface antigen (HBsAg), HBeAg, and HBV VL (cut-off of 20,000 IU/mL and 200,000 IU/mL) results from people living with human immunodeficiency virus (PLWH). HBeAg and HBV VL results were analyzed to evaluate the use of HBeAg to determine CHB treatment eligibility and qualification of HBV prevention of mother-to-child transmission (PMTCT) prophylaxis for the first time in Botswana. (3) Results: Approximately 70.8% and 87.5% of participants with HBeAg-positive serology had HBV viral loads ≥20,000 IU/mL and 200,000 IU/mL respectively. Using logistic regression, the odds of having a qualifying HBV VL for CHB treatment and PMTCT prophylaxis were respectively 55.5 and 110.4 times higher in participants with positive HBeAg serology indicating a statistically significant association between HBeAg status and HBV VL. (4) Conclusions: HBeAg detection may not always correlate with high HBV VL, warranting further research focusing on this association, and other biomarkers that correlate better with HBV VL.

Effects of the enzyme N-acetylgalactosamine-4-sulfatase (Arylsulfatase B, ARSB), which removes the 4-sulfate group at the non-reducing end of chondroitin 4-sulfate, on the expression of PD-L1 were determined and the underlying mechanism of PD-L1 expression elucidated. Initial experiments in human melanoma cells (A375) showed PD-L1 expression increased from 357 ± 31 to 796 ± 50 pg/mg protein (p

Hepatitis B and C are major health issues in developing countries such as Pakistan and Afghan-istan. The aim of this study was to determine the prevalence and effectiveness of a screening program for hepatitis B and C in a region with no existing programs, and to estimate their prev-alence in the general population in Khyber Pakhtunkhwa Province, Pakistan, as well as in Afghan refugees or migrants. A prospective cohort study was done in the general population of Peshawar and its adjacent districts, as well as migrants from neighboring provinces of Afghani-stan, who presented to our tertiary-care health facility. A Microsoft Excel registry was created for data collection, which were analyzed using IBM SPSS via descriptive analysis, normal distribution curve histograms, and chi-squared tests. A total of 9563 individuals were screened for hepatitis (5894 males and 3669 females), including Afghan migrants in Peshawar and surrounding districts. 876 individuals tested positive for hepatitis, with 538 positive for hepatitis B (383 males and 155 females) and 330 positive for hepatitis C (198 males and 134 females). Eight individuals had a hepatitis B and C co-infection. Among the study population, the prevalence rates were 2.2% for hepatitis B and 2.3% for hepatitis C, of which the Afghan migrants accounted for 2.7% and 0.5%, respectively. According to the gender-based distribution, hepatitis B was more prevalent in males, whereas there was no significant gender-based difference for hepatitis C. Our results highlight the need for a comprehensive approach to control hepatitis B and C in Pakistan and Afghanistan. Increased awareness, improved healthcare, and preventive measures such as screening and elimination programs to prevent severe liver diseases and eradicate hepatitis are necessary.

Inositol is a natural carbocyclic sugar that plays an essential role in regulating the vital cellular functions of plants and animals. Current research has explored methyl derivatives of inositol, reporting on their various biological activities, including antitumor, anti-inflammatory, and anti-osteoporosis activities. Our previous study demonstrated that L-quebrachitol, a methyl derivative of inositol, enhances osteoblastogenesis and bone formation; however, its effect on osteoclastogenesis remains unclear. Consequently, we aimed to investigate the effect of L-quebrachitol on the receptor activator of nuclear factor-κB ligand-induced osteoclastogenesis in pre-osteoclastic RAW 264.7 cells. The results revealed that L-quebrachitol suppressed RANK-mediated signalling, including nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and Fos proto-oncogene (cFOS) pathways, at both gene and protein levels. Moreover, the critical transcription factor for osteoclastogenesis, nuclear factor of activated T cells c1 (NFATc1), was downregulated. Inhibition of osteoclast-associated marker genes encoding proteolytic enzymes, such as tartrate-resistant acid phosphatase (TRAP), matrix metallopeptidase 9 (MMP-9), and cathepsin K, led to reduced formation of TRAP-positive multinucleated cells and resorption pits. These findings demonstrate the dose-dependent inhibitory effect of L-quebrachitol on osteoclastogenesis through the modulation of receptor activator of nuclear factor κB (RANK)-mediated signalling pathways. However, further exploration of L-quebrachitol's potential as a therapeutic approach for osteoporosis is warranted.

Infant hepatitis B vaccine coverage in China is high, with over 95% of infants immunized; however, high vaccine coverage can often mask low timeliness. The vaccination interval between the second and third dose is not clearly defined by immunization guidelines in China. This retrospective cohort study assessed the time interval distribution of hepatitis B vaccination among a cohort of randomly selected live births from Centers for Disease Control and Prevention across four provinces or municipalities in China between January 2017 and December 2021. Among the infants analyzed, 163,224 received the first dose of hepatitis B vaccine with 146,905 (90.0%) and 135,757 (83.2%) infants receiving the second and third doses, respectively. A total of 132,577 (90.2%) infants received the second dose between 28–61 days after the first dose. Of the 119,437 (88.0%) infants that completed the hepatitis B series between 61–214 days after the second dose, 87,067 (64.1%) infants were vaccinated with the third dose between 151–180 days after the second dose. The time interval distribution for the three doses of hepatitis B vaccine varied across the four provinces or municipalities (P<0.001). Of the 58,077 infants who completed the hepatitis B vaccine series, 36,377 (62.6%) infants used the same type of hepatitis B vaccine for all three doses. Overall, the timeliness of hepatitis B vaccination for infants was lower than expected, with regional disparities observed. This highlights the need for improved timeliness through the introduction of a defined timeframe for the last two doses of vaccine, and training for obstetricians and related personnel.

Cathepsins (Caths) are lysosomal proteases that participate in various physiological and pathological processes. Accumulating evidence suggests that cathepsins play a multifaceted role in radiotherapy response. Firstly, cathepsins contribute to the remodelling of the tumor microenvironment by degrading extracellular matrix components, promoting angiogenesis, and facilitating tumor invasion and metastasis. Their proteolytic activity influences the tumor's response to radiation by affecting oxygenation, nutrient availability, and immune cell infiltration within the tumor microenvironment. Furthermore, cathepsins have been implicated in DNA damage repair processes, including non-homologous end joining and homologous recombination. Cathepsin-mediated DNA repair mechanisms can promote radioresistance in cancer cells, limiting the efficacy of radiotherapy. Additionally, cathepsins have been associated with the activation of prosurvival signalling pathways, such as PI3K/Akt and NF-κB, which can confer resistance to radiation-induced cell death. Radiotherapy plays a crucial role in the treatment of various malignancies. However, the effectiveness of radiotherapy can be limited by intrinsic or acquired resistance mechanisms in cancer cells. In recent years, there has been growing interest in understanding the role of cathepsins, a family of proteases, in modulating the response of tumor cells to radiotherapy. In this study, we shed light on the regulation and expression of cathepsin B in colon carcinoma cell line (Caco-2) before and after exposure to radiation were investigated. Radiation-induced upregulation of cathepsin B in dose-independent manner. Proteolytic inhibition of cathepsin B by cathepsin B specific inhibitor CA074 has increased the cytotoxic effect of ionizing irradiation in caco-2 cells. Similar results were also obtained after cathepsin B knockout by CRISPR CAS9. These results showed that cathepsin B could contribute to ionizing radiation resistance and abolishing of cathepsin B either by inhibition its proteolytic activity or expression has increased in caco-2 cells susceptibility to ionizing irradiation.

Our concern was to obtain a biocomposite material with improved properties of the constituent materials (poly(lactic- co-glycolic acid) (PLGA) and zinc–boron (Zn–B) complex) in accordance with the novelties in the field of delivery systems for therapeutic agents which lately redefine the importance of biopolymer nanocomposites with PLGA (biodegradable composites). The advantages of such a biomaterial target the health system, being easy to obtain, through a cost-effective method. The water/oil/water double emulsion method also allows the adjustment of the synthesis parameters, to maximize the degree of Zn–B complex encapsulation. The morphological aspects of the samples (size, shape, porosity) were established by scanning electron microscopy (SEM). Particle size distribution (by volume and by number) was determined by direct light scattering (DLS). For all the synthesized materials, the observed morphology was typical for PLGA, spherical one. The particle size distribution showed that depending on the synthesis conditions, the particles can be obtained with diameters between 10–450 nm range and the value of the zeta potential (ZP) shows that the particles have electronegative surface charge, which offers a favorable perspective on the phenomena of aggregation, flocculation, dispersion. It was observed, applying the design of experiments (DoE), that the size of the particles increased with increasing amounts of PLGA and polyvinyl alcohol (PVA) in the formulation, while ZP increased with higher PLGA and smaller PVA. The encapsulation efficiency was determined by ultra-high performance liquid chromatography/mass spectrometry (UHPLC/MS).

Hepatitis B e antigen (HBeAg) is a marker of wild-type hepatitis B virus replication. In resource-limited countries where access to enzyme-linked immunosorbent assay (ELISA) remains a challenge, rapid diagnostic tests (RDT) constitute a good alternative. The HBeAg status is employed to evaluate eligibility for antiviral therapy and to prevent the transmission of hepatitis B from mother to child (PMTCT). The objective of this study was to assess the diagnostic performance of the SD-Bioline®HBeAg RDT commonly used for detecting HBeAg in laboratories in Burkina Faso. The sample panel used was collected from HBsAg positive patients received in the laboratory for the detection of HBeAg with the rapid test. The samples were retested for HBeAg using the VIDAS HBe/Anti-HBe enzyme-linked fluorescent assay (ELFA) (Gold standard). Then, the viral load (VL) of HBV DNA was determined using the GENERIC HBV CHARGE VIRLAE kit (GHBV-CV). The diagnostic performances of the SD-Bioline®HBeAg and its agreement with the gold standard were calculated with their 95% confidence intervals. 340 sera obtained from HBsAg positive patients were included in this evaluation Compared to the VIDAS HBe/Anti-HBe ELFA test, the sensitivity (Se) and specificity (Sp) of the SD-Bioline®HBeAg test were 33.3% and 97.9% respectively. The concordance between the two tests was 0.42. Depending on the viral load, the Se and Sp varied from 8.8% and 98.3% for a VL < 2,000 IU/mL to 35.5% and 98.4% for a VL > 2,000,000 IU/mL. The results showed a low Sensibility of the SD-Bioline®HBeAg RDT test, indicating that its use is inappropriate for the clinical management of HBV-infected patients. They also highlight the urgent need to develop HBeAg rapid tests with better sensitivities.

The supramolecular based macrocyclic amphiphiles have attracted great attention in the field of drug delivery due to their unique self-assembling nature. Therefore, these macrocycles are used as nanocarriers for the delivery of poor water soluble drugs, and also for those which have lower permeability, and cannot cross the barrier to reach the desired site. Herein, we design and synthesized a new supramolecular amphiphilic macrocycle to overcome these problems. The macrocycle was synthesized in two steps. In first step 4-hydroxybenzaldehyde was treated with 1-bromotetradecane to obtain a derivatized product which was then treated with resorcinol to cyclize and get calix(4)resorcinarene based supramolecular amphiphilic macrocycle. The synthesized macrocycle and intermediate products were characterized by Mass spectrometry, IR and 1H-NMR spectroscopic techniques. The amphiphile was screened for biocompatibility studies, vesicles formation, and then Amphotericin-B was loaded in the supramolecular amphiphile based vesicles and was characterized for shape, size, homogeneity, surface charge, drug entrapment, in-vitro release profile and stability through atomic force microscopy (AFM), Zetasizer, HPLC and FT-IR. Amp-B loaded macrocycle based vesicles were investigated for in-vivo bioavailability in rabbits. The synthesized macrocycle was nontoxic in cancer cells, hemo-compatible and safe in mice. The drug-loaded macrocycle based vesicles appeared spherical, nano-ranged, and homogeneous in size with negative surface charge and were able to load an increased amount of drug. The vesicles are stable upon storage and when incubated with gastric simulated fluid. Amp-B increased oral bioavailability was achieved when delivered in synthesized macrocycle based vesicles. These results point out that the synthesized supramolecular amphiphile is an efficient nanocarrier to enhance the oral bioavailability of lipophilic drugs

(1) Background: The intermediate-depth seismicity in the Vrancea region (Romania) is characterized by localized and persistent earthquake activity that culminates about two or three times in a century with the occurrence of a large event (M 6.5). Here we have revisited some important seismicity characteristics, using earthquake catalog data spanning two different time periods: 2005 – 2013 and 1960 – 2000. (2) Methods: we have determined the b-value of the frequency-magnitude distribution of earthquakes, using a maximum likelihood procedure, and estimated the parameter to quantify anomalous seismicity rate decreases and increases. (3) Results: by using data from the first period, we have confirmed the existence of a decreased b-value in the deepest part of the seismogenic zone; by using data from the second period, we have statistically confirmed the seismic quiescence that preceded the occurrence of the 1977 M7.4 Vrancea earthquake. (4) Conclusions: the decreased b-value has been interpreted either in terms of an increased lithostatic stress with depth or as an indicator of the depth range where the next major Vrancea earthquake may occur. The time variation of the seismicity parameter may reveal anomalous seismic quiescence and increased earthquake rates that may precede the occurrence of large earthquakes.

Marine seaweeds are nature’s largesse resource in human well-being. Seaweed’s contribution to the food industry is being widened for its rich source of essential vitamins, minerals, and PUFA. ‘Nori’ is a dried sheet of red seaweed Porphyra sp. used to make ‘sushi’ a renowned cuisine in Japan, and other Southeast Asian countries. In this present study, commercial-grade ‘Nori’ was extracted and fractionated with different solvents, and subjected to evaluate the cytotoxic activity on human ovarian tetracarcinoma cells (PA1). As a result, the ethyl acetate fraction was found effective in inhibiting the proliferation of human ovarian cancer cells with an IC50 value of 41.1 µg/mL. The main component responsible for anticancer activity was determined as a sesquiterpene lactone Tatridin B (3h-cyclodeca[b]furan-2-one, 4,9-dihydroxy-6-methyl-3,10-dimethylene-). Moreover, it was found effective in inhibiting NSD2, an important and recently proposed biomarker for several types of cancer. This is a hitherto report on the presence of this compound in ‘Nori’ showing potent anticancer activity on human ovarian tetracarcinoma (PA1).

In this review paper, the occurrence in the plant kingdom and the biological activities associated to two specific phenyl-ethanoid glycosides i.e., leucosceptoside A and leucosceptoside B, were shown and discussed. This is the first work ever done on such subject. Analysis of the literature data clearly indicates that leucosceptoside A is much more common in plants and exerts many more biological activities than leucosceptoside B even if this also presents some important elements. All of this was widely discussed in this paper.

For the Philippines, a country exposed to multiple natural hazards like severe wind, sustainable development includes resiliency. Severe wind hazard is brought by tropical cyclones in the Western Pacific, known as typhoons, that frequent the Philippines. Therefore, adequately evaluating the wind hazard and its impact is crucial for sustainable building design. Acknowledging the impacts of climate change on said hazards would require adaptation to its consequences which necessitate a deeper understanding on the changing behavior of typhoons in recent years. For this study, detailed wind information from the Japan Meteorological Agency from 1977-2021, the Holland-B parameter, and the radius of maximum wind speed for each typhoon, are determined for simulation of the regional cyclonic wind field. The analysis of the Holland-B parameters, which represent the steepness of the pressure gradient and tropical cyclone convection, suggest that the Holland-B parameters have been increasing since 2011. The regional wind fields caused by the typhoons also suggest an increasing trend in severe wind hazard. Seasonality for the location of severe wind hazard is also observed, with the Southern Philippines experiencing an increase (decrease) during the Northeast (Southwest) Monsoon season, and the Northern Philippines experiencing an increase (decrease) during the Southwest (Northeast) Monsoon season.

B lymphocyte development has two DNA recombination processes: V(D)J recombination of the immunoglobulin (Igh) gene variable region and class switching of the Igh constant regions from IgM to IgG, IgA, or IgE. V(D)J recombination is required for successful maturation of B cells from pro-B to pre-B to immature-B and then to mature B cells in the bone marrow. CSR occurs outside of the bone marrow when mature B cells migrate to peripheral lymphoid organs, such as spleen and lymph nodes. Both V(D)J recombination and CSR depend on an “open chromatin” state that makes DNA accessible to specific enzymes, recombination activating gene (RAG), and activation-induced cytidine deaminase (AID). Acetyltransferases GCN5 and PCAF possess redundant functions acetylating histone H3 lysine 9 (H3K9). Here, we generated a mouse model that lacks both GCN5 and PCAF in B cells. We found that double-deficient mice possess low levels of mature B cells in the bone marrow and peripheral organs, an accumulation of pro-B cells in bone marrow, and reduced CSR levels. We conclude that both GCN5 and PCAF are required for B cell development in vivo.

To investigate the photosynthetic change characteristics of mango leaves under enhanced UV-B radiation, adult ‘Tainong No. 1’ mango (Mangifera indica) trees were treated (N=nine individuals) with simulated enhanced UV-B radiation [24 and 96 kJ/(m2·d)] in the field, and the photochemical reactions, activities of key enzymes in carbon assimilation, and the expression of genes were observed. The results showed that compared with the control, there was a decrease in tree yield and nutritional flavor quality of the fruits under the 96 kJ/(m2·d) treatment, while no significant changes were observed under 24 kJ/(m2·d). After 20 or 40 days, leaves’ net photosynthetic rate (Pn), stomatal conductance (Sc), transpiration rate (Tr), intercellular CO2 concentration (Ci), and chlorophyll a/b under exposure to 96 kJ/(m2·d) of UV-B were significantly lower than in the control, whereas chlorophyll a, chlorophyll b, carotenoids, Hill reaction activity, photochemical quenching coefficient (qP), and Rubisco activities were significantly higher. By contrast, the Hill activity and Rubisco activity under 24 kJ/(m2·d) were significantly higher than the control, while Pn, Sc, Tr, Ci, and the content of photosynthetic pigments were similar to the control. The expression of gene coding the Rubisco big subunit (rbcL) was inhibited by the 96 kJ/(m2·d) treatment. We conclude that stomatal limitation was directly induced by 96 kJ/(m2·d), resulting in the inhibition of photosynthesis and the reduction in yield and deterioration of the quality of mango.

Diffuse large B cell lymphoma (DLBCL), the most frequent type of non-Hodgkin lymphoma in adulthood, remains challenging clinical issues. Despite enhanced remission rates can be achieved, there are one-third of patients who will not respond to current treatment or will relapse with resistant disease, necessitating ongoing efforts on effective treatment strategies and agents. The vacuole H+-ATPase inhibitor bafilomycin A1 is broadly used to block late stage of autophagy flux at high concentration. In this study, we show that, to our surprise, bafilomycin A1 effectively inhibited and killed DLBCL cells at nanomolar concentrations (5nM). Bafilomycin A1 targeted cell cycle regulators cyclin D1 and cyclin E2 to induce cell cycle arrest in G0/G1 phase. Meanwhile, it induced caspase-dependent apoptosis with concomitant cleaved caspase-3 and Parp. Furthermore, we found that bafilomycin A1 inhibited autophagy flux at both early and late stages of the autophagy flux through activating ERK and mammalian target of rapamycin signaling, as well as by inhibiting the degradation of autolysosomes. We speculated that bafilomycin A1 as autophagy inhibitor might enhance the effect of DLBCL chemotherapeutic drug rituximab. Accordingly, our results provided evidence that the combination of bafilomycin A1 with rituximab enhanced the inhibition of DLBCL cells notably. Taken together, our data suggest that bafilomycin A1 may be a promising candidate drug in the therapy of diffuse large B cell lymphoma.

As air traffic demand grows, robust, data-driven anomaly detection methods are required to ensure that aviation systems become safer and more efficient. The terminal airspace is identified as the most critical airspace for both individual flight-level and system-level safety and efficiency. As such, developing data-driven anomaly detection methods to analyze terminal airspace operations is paramount. With the expansion of ADS-B technology, open-source flight tracking data has become more readily available to enable larger-scale analyses of aircraft operations. This paper makes a distinction between spatial metrics in ADS-B trajectory data and energy metrics derived from ADS-B trajectory data. Motivated by the limited number of approaches that simultaneously consider both spatial and energy metrics, this paper introduces the concepts of spatial anomalies and energy anomalies. In particular, it proposes a novel, unified framework for detection of spatial and energy anomalies in ADS-B trajectory data (and associated derived metrics). The framework consists of three main parts - a data processing procedure, a spatial anomaly detection method, and an energy anomaly detection method. The framework is demonstrated utilizing four months of ADS-B trajectory data associated with arrivals at San Francisco International Airport, and the relationship between the spatial and energy anomalies in this terminal airspace is explored. The results that stem from the implementation of this framework indicate that if an aircraft is spatially not conforming to an identified set of air traffic flows representing standard spatial operations, then this aircraft is more likely to experience non-conformance to standard operations in its energy metrics. Aviation operators, such as air traffic controllers, may benefit from this observation, as it may factor into decision-making in instances where there is the potential to instruct an aircraft to spatially deviate from standard operations. Additionally, this research revealed underlying differences between trajectories that are spatially nominal yet energy-anomalous and those trajectories that are spatially anomalous and energy-anomalous. Focusing solely on energy anomaly detection does not provide insight into potential spatial-related decisions that may have been made to result in off-nominal energy behavior.

Background: Hepatocellular carcinoma (HCC) is one of most common cancers with a high mortality rate. HBV/HCV infection is an important risk factor to trigger HCC. Therefore, developing serum biomarkers for early diagnosis is crucial to prolong survival in HCC patients. Methods: An antibody array technology was utilized to detect serum from 20 HBV-related HCC patients, 20 chronic hepatitis B patients and 20 normal population, whose results were further validated by ELISA. Results: Both antibody array and ELISA showed that ten growth factors (SCF R, GDF-15, HGF, FGF-4, IGFBP-1, PIGF, GH, GDNF, BDNF and IGF-1) were significantly differential in HCC patients when compared to the non-HCC population. Among these growth factors, the levels of SCF R, GDF-15, HGF, GH and IGF-1 showed significant correlation with hepatitis B and its severity, indicating that these growth factors may promote HCC progression by an HBV-specific mechanism. A therapy targeting these growth factors in hepatitis B patients may help to prevent the development of HCC. FGF4 and GH were found, for the first time, to be upregulated in HCC, suggesting that these two growth factors may serve as novel serum biomarkers for the early diagnosis of HCC. Conclusion: The combined detection of all the differential growth factors may improve the diagnostic accuracy of HCC.

Non-homologous end-joining (NHEJ) is a DNA repair pathway required to detect, process, and ligate DNA double-stranded breaks (DSBs) throughout the cell cycle. The NHEJ pathway is necessary for V(D)J recombination in developing B and T lymphocytes. During NHEJ, Ku70 and Ku80 form a heterodimer that recognizes DSBs and promotes recruitment and function of downstream factors PAXX, MRI, DNA-PKcs, Artemis, XLF, XRCC4, and LIG4. Mutations in several known NHEJ genes result in severe combined immunodeficiency (SCID). Inactivation of Mri, Paxx or Xlf in mice results in normal or mild phenotype, while combined inactivation of Xlf/Mri, Xlf/Paxx, or Xlf/Dna-pkcs leads to late embryonic lethality. Here, we describe three new mouse models. We demonstrate that deletion of Trp53 rescues embryonic lethality in mice with combined deficiencies of Xlf and Mri. Furthermore, Xlf^-/-Mri^-/-Trp53^+/- and Xlf^-/-Paxx^-/-Trp53^+/- mice possess reduced body weight, severely reduced mature lymphocyte counts, and accumulation of progenitor B cells. We also report that combined inactivation of Mri/Paxx results in live-born mice with modest phenotype, and combined inactivation of Mri/Dna-pkcs results in embryonic lethality. Therefore, we conclude that XLF is functionally redundant with MRI and PAXX during lymphocyte development in vivo. Moreover, Mri genetically interacts with Dna-pkcs and Paxx.

The outbreak of the 2019 Novel Coronavirus (2019-nCoV) has rapidly spread from Wuhan, China to multiple countries, causing staggering number of infections and deaths. A systematic profiling of the immune vulnerability landscape of 2019-nCoV is lacking, which can bring critical insights into the immune clearance mechanism, peptide vaccine development, and antiviral antibody development. In this study, we predicted the potential of all the 2019-nCoV viral proteins to induce class I and II MHC presentation and form linear antibody epitopes. We showed that the enrichment for T cell and B cell epitopes is not uniform on the viral genome, with several focused regions that generate abundant epitopes and may be more targetable. We showed that genetic variations in 2019-nCoV, though fewer for the moment, already follow the pattern of mutations in related coronaviruses, and could alter the immune vulnerability landscape of this virus, which should be considered in the development of therapies. We create an online database to broadly share our research outcome. Overall, we present an immunological resource for 2019-nCoV that could significantly promote both therapeutic development and mechanistic research.

Despite a considerable body of published research on Hepatitis B in Bangladesh, researchers continue to lament the lack of reliable information about Hepatitis B epidemiology. The present review aims to provide a comprehensive survey of the literature with particular focus on a number of epidemiological questions, as well as a commentary on the trends of Hepatitis B research as it has taken place in Bangladesh. The key themes to emerge from this review are: first, beyond noting a declining trend, it is difficult to provide conclusive estimates about Hepatitis B prevalence in the general population of Bangladesh. The majority of the studies, even the ones conducted on apparently healthy populations, fail to be adequately representative for the reasons explored in the article. Secondly, Hepatitis B in Bangladesh is sharply stratified across sociodemographic lines, which speaks to the role of awareness and risk exposure in Hepatitis B prevalence. Third, more research on occult infection rates is required to estimate the extent of risk posed by the current blood donation screening program, which relies exclusively on Hepatitis B surface antigen as a biomarker. The same considerations apply for the comparative importance of vertical vs. horizontal transmission, and prevalence among particular risk groups like healthcare workers with high occupational exposure. Finally, while recent studies do allow us, albeit with some ambiguity, to draw conclusions about distribution of Hepatitis B genotypes in Bangladesh, there needs to be an added emphasis on molecular epidemiology. It is hoped that the present review, the first of its kind in Bangladesh, will serve as an up-to-date summary of the course Hepatitis B epidemiology research in Bangladesh has taken thus far, as well as crucial gaps to address going forward.

Background: Dual function tail tubular proteins (TTP) belonging to the lytic bacteriophages are the interesting group of biologically active enzymes. Surprisingly, apart from their structural function, they are also polysaccharide hydrolyzes destroying bacterial extracellular components. One of the representatives of this group is TTPB from Klebsiella pneumoniae phage – KP32. TTPB hydrolyzes exopolysaccharide (EPS) of Klebsiella pneumoniae and Enterococcus faecalis strain. This depolymerizing feature was associated with the activity to prevent bacterial biofilm formation. TTPB can inhibit biofilm formation by K. pneumoniae, Enterobacter cloacae, Staphylococcus aureus, Enterococcus faecalis and Pseudomonas aeruginosa strains. Moreover, synergistic activity with antibiotic action has been observed, most likely due to depolymerases’ facilitation of contact of antibiotic with bacterial cells. Methods: TTPB was overexpressed in E coli system, purified and tested towards the bacterial strains using agar overlay method. The hydrolytic activity of TTPB was performed using EPSs of K. pneumoniae PCM2713 and E. cloacae ATCC 13047 as the substrates. Next, we determined the reducing sugar (RS) levels in the TTPB/EPS mixtures, regarding the RS amount obtained after acidic hydrolysis. The antibiofilm activity of TTPB has been set down on bacterial biofilm using a biochemical method. Finally, we have demonstrated the synergistic activity of TTPB with kanamycin. Results: For the first time, the hydrolytic activity of TTPB towards bacterial EPSs has been shown. TTPB releases about a half of the whole RS amount of EPSs belonging to K. pneumoniae PCM 2713 and E. cloacae ATCC 13047 strains. 1.12 µM of the phage protein reduces biofilm of both strains by over 60%. Destroying the bacterial biofilm the phage protein improves the antibiotic action increasing kanamycin effectiveness up to four times.

A new synthetic approach to polyfunctional hexahydropyrrolo[3,4-b]pyrroles was developed based on cyclization of N-arylbromomaleimides with aminocrotonic acid esters. A highly chemo- and stereoselective reaction is a Hantzsch-type domino process, involving the steps of initial nucleophilic C-addition or substitution and subsequent intramolecular nucleophilic addition without recyclyzation of imide cycle.

Enzymatic degradation of organic pollutants is a new and promising remediation approach. Peroxidases are one of the most commonly used classes of enzymes to degrade organic pollutants. However, it is generally assumed that all peroxidases behave similarly and produce similar degradation products. In this study, we conducted detailed studies of the degradation of a model aromatic pollutant, Sulforhodamine B dye (SRB dye), using two peroxidases—soybean peroxidase (SBP) and chloroperoxidase (CPO). Our results show that these two related enzymes had different optimum conditions (pH, temperature, H₂O₂ concentration...etc.) for efficiently degrading SRB dye. High-performance liquid chromatography and LC-mass spectrometry analyses confirmed that both SBP and CPO transformed the SRB dye into low molecular weight intermediates. While most of the intermediates produced by the two enzymes were the same, the CPO treatment produced at least one different intermediate. Furthermore, toxicological evaluation using lettuce (Lactuca sativa) seeds demonstrated that the SBP-based treatment was able to eliminate the phytotoxicity of SRB dye, but the CPO-based treatment did not. Our results show, for the first time, that while both of these related enzymes can be used to efficiently degrade organic pollutants, they have different optimum reaction conditions and may not be equally efficient in detoxification of organic pollutants.

Lamin A, B and C, the nuclear intermediate-filament proteins, play a role in epigenetic regulation. While Lamin B is expressed in all nucleated cells studied, Lamin A/C are transcribed in most somatic cell types except mature B lymphocytes. Since Epstein-Barr virus (EBV), a human gammaherpesvirus, is associated with tumorigenic processes and is known to alter the epigenotype of its host cells, we studied the expression of the LMNA gene and its epigenetic marks in EBV-carrying human lymphoid cell lines. We observed a high lamin A/C mRNA and protein expression in EBV-immortalized lymphoblastoid cell lines (LCLs) and in group III Burkitt lymphoma (BL) lines where hypomethylated first exons were observed with activating histone marks. In most cell lines with low promoter activity a highly methylated first exon could be detected. Our data showed that methylation of the first exon of LMNA was associated with the downregulation of LMNA expression whereas euchromatic histone marks were enriched at active LMNA promoters in EBV-immortalized LCLs. These data suggest a role for viral latency products to activate LMNAp in EBV-infected latency type III B cells in vitro. Expression of lamin A/C may contribute to the establishment of activated B cell phenotype that needs further explorations.

This article explores the use of vegetation indices (VIs) in remote sensing for estimating standing wood volume and volume increments in forest ecosystems. The study investigates the correlations between various VIs and wood volume across different forest stand age classes, focusing on the effectiveness of commonly used indices such as Squared Ratio Simple Red Edge (SQSR) and Red-Edge Ratio Vegetation Index (RERVI), as well as other typical indicators including Enhanced Vegetation Index (EVI), Red-Edge EVI (RE-EVI), and Green Normalized Difference Vegetation Index (GNDVI). Additionally, the analysis considers a pair of indicators based on blue and near-infrared channels, resembling the Blue-normalized Difference Vegetation Index (BNDVI). The research reveals that quadratic and power-law models of SQSR and RERVI demonstrate higher correlations (>0.40) with wood volume, especially in younger forest stands (>0.80). Furthermore, the study highlights the potential of NDII and NDWI indices for estimating volume increments in certain classes of forest stands (0.70). However, correlations vary across different forest stand classes, suggesting the need for further investigation into the reliability of VIs for monitoring wood volume and volume increments in forest ecosystems. Overall, this research contributes to the understanding of the applicability of VIs in remote sensing for forest management and ecosystem monitoring.

Chemosensory proteins (CSP) are found in the olfactory sensory organs (antennae and maxillary palps) and/or gustatory sensory organs (labellum and legs) and long been accepted to function through binding ‘odorants’. Yet, the same CSPs are also expressed in many tissues other than olfactory and gustatory organs, such as gut, brain, fat body, wing, epidermis, corpora allata, pheromone gland, prothoracic gland, etc. In this review, we suggested the rename “chemosensory protein (CSP)” to “4 Cysteines Soluble Protein (4CSP). To support our idea, we reviewed CSPs from several aspects: their primary sequences, existence of CSP in insects, hexapods, and bacteria, expression during development and in other tissues, evolution of CSP genes, genomic mining, their ancestral functions and lipoid binding, function outside the chemosensory/binding aspect, their intracellular function, and from structure to function. The scope of the review per se is broad, and this is especially true given the volume of data that has been gathered on CSP expressed in ways that are not consistent with the olfactory paradigm. We discuss the Mp10 story in aphids, our research on insecticide resistance, and other lipid transport and immunity-related processes. There is substantial evidence to support the non-chemosensory aspects of CSPs, which is where the majority of discussions lean. There are still very few, if any, statements outlining the aspects of CSPs’ chemosensory properties, specifically how they activate olfactory receptor neurons (ORNs). We present an analysis showing a stronger correlation between them and the actin complex family proteins, mucins, and translation initiation factors. An additional argument is the existence of CSPs outside of insects. Therefore, strong arguments in favor of renaming chemosensory proteins are becoming evident here, outweighing the drawbacks.

This is a brief critique of the functions—particularly olfactory functions—specified for the “Chemosensory Protein” (CSPs) molecule family. On the basis of these proteins’ presence in the sensory antennal lymph of locusts, odor chemosensory ligand binding functions have been hypothesized. According to this hypothesis, the entire protein molecule superfamily is referred to as “CSPs”. However, new information and developments in the field of CSP molecular research, such as the expression of CSP genes in the gut, brain, fat body, epidermis, and pheromone gland, as well as gene expression profiling from most early developmental stages—that is, CSP expression well in advance of the appearance of chemical sense nerve cells—strongly suggest that the protein molecule has other roles that are unrelated to chemosensing. Moreover, CSPs are found in bacterial microbial prokaryote organisms in addition to insects. Thus, we examine the molecule’s name, definition, RNA editing, protein structure, lipid binding properties, DNA interaction, and evolutionary characteristics in brief before referring to this protein family as “Chemosensory Proteins”. This article tries to compel and discuss the most recent information as a way to rename this protein family. Because of its highly conserved molecular distinctive feature (four adjacent cysteines), we propose renaming “CSPs” as “4CSPs” (4 Cysteines Soluble Proteins).

We investigate the cosmological evolution of the universe for a spatially flat FLRW background space within the context of $f(T,B)$ gravity, which is a recently formulated teleparallel theory that connects both $f(T)$ and $f(R)$ gravity under suitable limits. The analysis has been done by focusing on four different $f(T,B)$ cosmological models corresponding to various choices of scale factor, namely emergent, logamediate, and intermediate. In addition to this, we also assume a power-law-like function of $f(T,B)$ gravity. The reconstruction of $f(T,B)$ gravity has been done by considering the Holographic Ricci Dark Energy(HRDE) (a particular case of a highly generalized holographic dark energy given in Nojiri et al. in General Relativity and Gravitation, 38, pp.1285-1304,2006) as the background fluid. We analyze the equation of state parameters and the squared speed of sound for the reconstructed models. Finally, we conducted the thermodynamical analysis for each reconstructed model. The generalised second law of thermodynamics(GSLT) is valid for the four different $f(T,B)$ cosmological models.

We explored an extension of the Cauchy-Riemann equations to the algebra of treons, recently described by Alejandro Bermejo, whose elements are ordered 3-tuples. We leveraged the isomorphism between the algebra of treons and algebra B, and deduced the Cauchy-Riemann equations for the algebra of treons, establishing the necessary conditions for analyticity in this algebraic structure. This work significantly broadened our horizons in complex analysis and introduced new possibilities for applications across various fields of advanced mathematics.

In this work, zinc oxide (ZnO)/ granular activated carbon (GAC) composites at different ZnO concentration (0.25M-ZnO@GAC, 0.5M-ZnO@GAC, and 0.75M-ZnO@GAC) were prepared by an in-situ hydrothermal method and demonstrated synergistic photocatalytic degradation and ad-sorption of Rhodamine B (RhB). The thermal stability, morphological structure, elemental com-position, crystallographic structure, and textural properties of developed catalysts were charac-terized by thermal gravimetric analysis (TGA/DTG), scanning electron microscopy equipped with energy dispersive-x-ray (SEM-EDS), x-ray diffraction (XRD), and Brunauer–Emmett–Teller (BET) analysis. Successful loading of ZnO onto GAC was confirmed by SEM-EDS and XRD analysis. The BET surface areas of GAC, 0.25M-ZnO@GAC, 0.5M-ZnO@GAC, and 0.75M-ZnO@GAC were 474 m2/g, 450 m2/g, 453 m2/g, and 421 m2/g, respectively. The decrease in GAC could be attributed to the successful loading of ZnO on the GAC surface. Notably, 0.5M-ZnO@GAC exhibited the best photocatalytic degradation efficiency of 82% and 97% under UV-A and UV-C light over 120 min, attributed to improved crystallinity and visible light absorption. The photocatalytic degradation parameters revealed that lowering the RhB concentration, raising the catalyst dosage and pH be-yond the point of zero charge (PZC) would favor the RhB degradation. Photocatalytic reusability was demonstrated over 5 cycles. Scavenger tests revealed that the hydroxyl radicals (•OH), su-peroxide radicals (O2−•), and photoinduced hole (h+) radicals play a major role during the RhB degradation process. Based on the TOC results, the RhB mineralization efficiency of 79.1% was achieved by 0.5M-ZnO@GAC. Additionally, GAC exhibited a strong adsorptive performance towards RhB with adsorption capacity and RhB removal of 487.1 mg/g and 99.5% achieved within 90 min equilibrium time. The adsorption characteristics were best described by pseu-do-second-order kinetics, suggesting chemical adsorption. This research offers a new strategy for the development of effective photocatalyst materials with potential for wider wastewater treat-ment applications.

Clematis Florida (CF) is a folk medicinal herb in the southeast of China, which is traditionally used for treating osteoarticular diseases. However, the mechanism of action remains unclear. The present study used network pharmacology and experimental validation to explore the mechanism of CF in the treatment of rheumatoid arthritis (RA). Liquid chromatography-mass spectrometry (LC-MS/MS) identified 50 main compounds of CF, then the targets of them were obtained from TCMSP, ETCM, ITCM and Swiss TargetPrediction databases. RA disease related targets were obtained from DisGenet, OMIM and GeneCards databases. 99 overlapped targets were obtained using Venn diagram. The protein-protein interaction network (PPI)、the compound-target network (CT) and the compound-potential target genes-signaling pathways network (CPS) were built and analyzed. The results showed that the core compounds were screened as oleanolic acid, oleic acid, ferulic acid, caffeic acid, and syringic acid. And the core therapeutic targets were identified as PTGS2 (COX-2), MAPK1, NF-κB1, TNF, RELA by network pharmacology analysis, which belong to the MAPK signaling pathway and NF-κB signaling pathway. The animal experiments indicated that topical application of CF showed significant anti-inflammatory activity in mice model of xylene-induced ear edema and strong analgesic effect on acetic acid-induced withing. Furthermore, in the rat model of adjuvant arthritis (AA), topical administration of CF could alleviate toe swelling and ameliorate joint damage. The elevation of serum content of IL-6, COX-2, TNF-α, IL-1β, and RF caused by adjuvant arthritis were reduced by CF treatment. Western blotting tests showed that CF may exert regulation on the ERK and NF-κB pathway. The results provided a new perspective for the topical application of CF on RA.

Bacillus subtilis is a model organism used to study molecular processes in Gram-positive bacteria. Sigma factor B, which associates with RNA polymerase, is one of the transcriptional regulators involved in the cell’s response to environmental stress. Experiments have proven that the amounts of free σB (SigB) are controlled by a system of anti- (RsbW) and anti-anti-sigma (RsbV) factors expressed from the same operon as SigB. Moreover, the phosphorylation state of RsbV is controlled by phosphatases RsbP and RsbU, which directly dephosphorylates RsbV. A set of chemical equations describing the network controlling the levels of free SigB was converted to a set of differential equations quantifying the dynamics of the network. The solution of these equations allowed the simulation of the kinetic behavior of the network and its components under real conditions. In this study, the time series of protein expression measured by mass spectrometry were utilized to investigate the role of the phosphatases RsbU/RsbP in transmitting the environmental signal. Additionally, the influence of kinetic constants and the amounts of other network components on the functioning of the network was investigated. A comparison with the same simulation performed using transcriptomic dataset showed that while the time series between the proteomic and transcriptomic datasets) are not correlated, the results are the same. This indicates that when modeling is done within one dataset, it does not matter whether the data come from the mRNA or protein level. In summary, the computational results based on experimental data provide quantitative insight into the functioning of the SigB-dependent circuit and offer a template for the quantitative study of similar systems.

One characteristic of mammalian species is their capacity to produce and secrete milk from their mammary glands to feed and provide vital nutrients for the growth of their offspring. Even though mammary glands provide the same function in different species, their development, shape, and structure can vary according to their reproductive and ecological adaptations. Reproduction studies are important for cetacean conservation because they provide essential information to assess the dynamics of populations and species, particularly in relation to the management of animals under human care. A vast majority of literature on the female cetacean reproductive anatomy and physiology has focused on the ovaries, which can be used to infer life history characteristics, or genital diseases and anomalies. However, literature regarding the morphology, physiology, and developmental pattern of their mammary glands is scarce, with few anatomical and histological descriptions in species such as baleen whales; and more recently it has been assessed with the use of ultrasound in finless porpoises (Neophocaena asiaeorientalis). The aim of this review is to describe the current diagnostic tools applied in human and veterinary medicine to assess the mammary glands and how marine mammal medicine could benefit from these tools to evaluate the mammary glands in free-ranging and captive cetaceans. With the use of imaging techniques such as B-mode ultrasound, non-invasive studies could be performed to assess the mammary tissues, as what has been done to characterize the morphology of other organs in cetaceans, such as the reproductive tract of Indo-Pacific bottlenose dolphins under human care. By understanding and revising the current diagnostic tools to assess the mammary gland of humans and domestic animals, such as ultrasonography, it might be possible to determine which techniques could be applied by marine mammal veterinarians to enhance the evaluation of the cetacean mammary gland morphology and physiology.

The use of edible films has become a topic of great interest in the food and environmental sectors, due to their potential to prevent food deterioration and their biodegradability. In this context, this study aimed to develop and characterize edible films based on camu-camu residue, gelatin and glycerol, evaluating their solubility, thermal, degradability, antioxidant and water vapor permeability properties of the gelatin matrix. This is the first study incorporating camu-camu into a gelatin and glycerol matrix. The films produced with the incorporation of camu-camu residue proved to be manageable and soluble, with the presence of some non-soluble residues, providing a shine and a well-presented appearance. In the biodegradation results the samples 03 and 04 appeared to degrade the most, being two of the three most affected samples in the triplicate. The films showed degradation modifications from the third day of the experiment. In the germination and plant growth analysis, Sample 04 showed satisfactory development compared to other samples, making it the sample with the best overall result in the analyses. These results demonstrate that the produced materials have potential for food packaging applications.

Abstract: (1) Background: We determined the prevalence of hepatitis B virus (HBV) amongst people without human immunodeficiency virus (HIV) in rural and peri-urban areas in Botswana. (2) Methods: We screened hepatitis B surface antigen (HBsAg) from archived plasma samples of people without HIV (n=2135) randomly selected from the Botswana Combination Prevention Program (BCPP) (2013–2018). We sequenced 415 bp of the surface region using BigDye sequencing chemistry. (3) Results: The median age of participants was 31 (IQR: 24–46) and 64% (1360/2135) were female. HBsAg prevalence was 4.0% (86/2135) [95% CI: 3.3 – 4.9]) and ranged between 0%–9.2%. Older participants (>35 years) had increased odds of HBsAg positivity (OR: 1.94; 95% CI: [1.32–2.86]; p = 0.001. Thirteen samples were sequenced and 7 (53.8%) were genotype A, 3 (23.1%) were genotype D and genotype E each. Clinically significant mutations were identified in the surface region, but no classic drug resistance mutations were identified. (4) Conclusions: We report an HBV prevalence of 4.0% (95% CI 3.3 – 4.9) among people without HIV in rural and pe-ri-urban communities in Botswana with varying rates in different communities. A comprehen-sive national HBV program is required in Botswana to guide HBV prevention, testing and management.

Background: Despite their generally favorable prognosis, hepatic fibrosis remains a possible complication for hepatitis B virus (HBV) inactive carriers. This study aimed to estimate the prevalence of significant fibrosis and associated risk factors among Omani HBV inactive carriers. Methods: A retrospective study was conducted of 200 Omani HBV inactive carriers visiting a tertiary hospital in Muscat, Oman, between January 2017 and December 2018. Significant fibrosis (stage F2 or higher) was identified using two-dimensional shear-wave elastography. Baseline clinical, laboratory, and radiological data were analyzed to determine associations. Results: Of the total sample, 106 patients (53%) were male, and the mean age was 44.6 ± 9.3 years. The prevalence of significant fibrosis was 20% (n = 40). Male gender (p = 0.007), age ≥60 years (p = 0.024), and fatty changes in liver ultrasound (p = 0.044) were found to be independent factors for significant fibrosis. Conclusion: the prevalence of significant fibrosis was relatively high among a sample of Omani HBV inactive carriers, with several sociodemographic and clinical risk factors identified. Periodic assessment of liver function is needed for patients with these risk factors; moreover, routine biochemical parameters could be useful predictors of disease prognosis. Further research is recommended to substantiate these findings.

ABO incompatibility is not considered a contraindication for hematopoietic stem cell transplantation (HSCT). Approximately 30% of transplants from related donors and up to 50% of transplants from unrelated donors are ABO-incompatible. The immuno-hematologic investigationsmay evaluate donor/recipient ABO mismatch and anti-A/B isohemoagglutinins (IHAs) titration in pre-HSCT phase. Immediate hemolysis or delayed complications (passenger lymphocyte syndrome and pure red cell aplasia) can appear post-HSCT. Some preventive treatmentstake into consideration the manipulation of the product and decision-making algorithms based on the titration of IHAs in the recipient with clinical protocols for the removal/reduction of IHAs through plasma exchange or immunoadsorption procedures. Currently, the best approach in the managementof ABO-incompatibletransplant is not defined in expert consensus documents or with solid evidence. In addition, the methods for IHAs titration are not standardized. The transfusion strategy must consider both the blood group systems of the recipient and the donor until the RBC engraftment and the confirmed ABO conversion (forward and reverse typing) on two consecutive and independent samples. Therefore, ABO incompatibility in the HSCT is an important immuno-hematologic challenge and request all necessary preventive measures including the appropriate selection of ABO blood components for transfusion.

Chondrocytes maintain the normal morphological structure and physiological function of articular cartilage. However, the increased expression of inflammatory mediators and matrix-degrading enzymes in chondrocytes can promote ECM degradation, consequently disrupting the physiological function of articular cartilage and ultimately leading to the onset of osteoarthritis (OA). Usnic acid (UA), an extract derived from plants, possesses multiple bioactive properties including anti-inflammatory and antioxidant effects. Hence, this study aims to explore the molecular mechanisms underlying its protective effects in an in vitro simulated model of OA in rat chondrocytes. In vivo experiments encompassed three groups: Control, Model, and Usnic acid (50 mg/kg), with sample extraction following 12 weeks of administration. Pathological alterations in articular cartilage were evaluated using Safranin O-fast green staining. Immunohistochemistry (ICH) analysis was employed to assess the expression of matrix degradation-related markers. The levels of serum cytokines were quantified via ELISA assays. In this study, primary rat chondrocytes were employed as the experimental subject. After a 24-hour treatment period, culture supernatants, total RNA, total protein, and nuclear protein were extracted from the different chondrocyte groups. ELISA and qPCR methods were used to measure levels of IL-6, TNF-α, and PGE2. WB and qPCR were employed to assess levels of p65, p-p65, IκBα, p-IκBα, Nrf2, HO-1, NQO1 ADAMTS-4, MMP-1, MMP-3, MMP-13, INOS, COX-2, and COL2A1. IF analysis was performed to examine Nrf2, p-p65 and COL2A1. Results: (1) In vivo, intraperitoneal injection of usnic acid (50mg/kg) can alleviate pathological changes in articular cartilage and the levels of inflammatory and oxidative-related matrix in the serum. (2) UA reduced the level of inflammatory cytokines in IL-1β-induced chondrocytes supernatant. (3) UA can produce anti-inflammatory and antioxidant effects and inhibit chondrocytes matrix degradation through the Nrf2 and NF-κB pathways. (3) The mechanism by which UA exerts a protective role in chondrocytes is mediated by Nrf2 Conclusion: UA inhibits the expression of chondrocyte matrix degradation-related components through Nrf2 mediated Nrf2 pathway and NF-κB pathway, promotes the production of protective substances, and ultimately exerts a protective effect on chondrocytes.

The biological conservation measures factor (B) in the Chinese Soil loss Equation (CSLE) model is one of the main components in evaluating soil erosion, and the accurate calculation of B factor at the regional scale is fundamental in predicting regional soil erosion and the dynamic changes. In this study, we developed an optimal computational procedure for estimating and mapping the B factor in the Google Earth Engine (GEE) cloud computing environment using multiple data sources through data suitability assessment and image fusion. Taking the Yanhe River Basin in the Loess Plateau of China as an example, we evaluated the availability of daily precipitation data (CHIRPS, ERA5, and PERSIANN-CDR data) against the data at national meteorological stations. We estimated the B factor from Sentinel-2 data and proposed a new method, namely trend migration method, to patch the missing values in Sentinel-2 data using three other remote sensing data (MOD09GA, Landsat-7, Landsat-8). We then calculated and mapped the B-factor in Yanhe River Basin based on rainfall erosivity, vegetation coverage, and land use types. The results show that the ERA5 precipitation dataset outperforms the CHIRPS and PERSIANN-CDR data in estimating rainfall erosivity and rainfall, and it can be utilized as an alternative data source for meteorological stations in soil erosion modeling. Compared to the harmonic analysis of time series (HANTS), the trend migration method proposed in this study is more suitable for patching the missing parts of Sentinel-2 data. The restored high-resolution Sentinel-2 data fit nicely with the 10-m resolution land use data, enhancing the B factor calculation accuracy from the region to the spot level. The B factor computation procedure developed in this study is applicable to various river basin and regional scales for regional soil erosion monitoring.

The Hepatitis B virus, chronically infects over 240 million persons worldwide. The Hepatitis B vaccine is 90% effective in preventing perinatal transmission if the first dose is given within the first 24 hours of life followed by a minimum of 2 subsequent doses. In October 2021, Antigua and Barbuda, through it’s only public hospital - the Sir Lester Bird Medical Centre, instituted a hospital based Hepatitis B vaccine birth dose policy. Timely birth dose coverage was 72% and total birth dose coverage 81%. 10.5% of parents refused the hepatitis b – birth dose, of which 76% either felt uncomfortable or preferred to wait. 100% of babies born before arrival received timely vaccine administration, likewise 100% of Hepatitis B exposed babies were vaccinated, with 83% of them receiving the Hepatitis B Immunoglobulin. A maternal Hepatitis B surface antigen result was available for 90.4% of mothers. Barriers to timely birth dose administration included vaccination hesitancy, gaps in healthcare worker knowledge, and the consistent supply of Hepatitis B vaccine. Instituting a quality improvement team, health information system, robust educational efforts, and addressing barriers will make achieving the WHO programmatic targets of eliminating mother to child transmission of hepatitis B by 2030 possible.

Diffuse large B-cell lymphoma (DLBCL) is an aggressive and biologically heterogeneous disease. Approximately 40% of patients with DLBCL will experience disease relapse or will be refractory to first line chemoimmunotherapy. In recent years there have been several new therapeutic agents approved for the treatment of relapsed/refractory (R/R) DLBCL. These agents include anti-CD19 chimeric antigen receptor T-cell therapies (CAR T-cells) and monoclonal antibodies as polatuzumab and tafasitamab. Nevertheless, despite the high efficacy of all these new therapies, there are still patients who do not respond or relapse, representing an unmet clinical need. This review describes new promising therapies that are under investigation to treat R/R DLBCL.

Background: The intrauterine and early extrauterine development represents a “window of opportunity” in the immunological development. The underlying mechanisms are still poorly understood. The aim of this study was to provide reference values B cell subpopulations in cord blood of term newborns, juveniles and in adults to find the spectrum of their physiological age-related variation. Methods: In this study, we used flow cytometry to evaluate human B lymphocytes and subpopulations in cord blood (n = 10), in peripheral blood from healthy juveniles aged 1 to 17 years (n=20) and from donors aged 24 to 62 years (n = 10). Results: Our findings showed increasing frequencies of IgM memory B cells, class-switched memory B cells, marginal zone B cells and plasmablasts, from cord blood to peripheral blood of juveniles and adults. In con-trast, the percentage of naïve B cells was higher in newborns than in juveniles and adults. The frequencies of were similar in cord blood and peripheral blood of adults. Interestingly, transitional B cells frequencies were similar in cord blood and adults but significantly lower in juveniles. Conclusions: The frequencies of circulating B cell subpopulation are subject to considerable changes during on-togeny, reflecting overlying effects of maturation and of the acquisition of an adaptive immune memory.

Prolonged fatigue is associated with non-pathological causes, and lacks an established therapeutic approach. The current study is aimed at assessing the efficacy of a new food supplement (Improve® Response) based on a chemically characterized pomegranate extract and hydro-soluble vitamins (B complex and C). UHPLC-HRMS analysis of pomegranate extract showed the presence of 59 compounds, with gallotannins and ellagitannins being the most abundant phytochemicals. For the clinical study, 58 subjects were randomized into two groups, 1 and 2 (n = 29, each), which received either the food supplement or placebo. The effects of the food supplement against fatigue were assessed via validated questionnaires, recorded at time intervals t0 (at baseline), t1 (after 28 days), t2 (56 days), and t3 (after follow-up) in combination with the analysis of biochemical markers at t0 and t2. Fatigue Severity Scale (FSS) questionnaire scores were significantly decreased at the t2 and t3 time intervals in subjects treated with the food supplements, while the effect of the food supplement on a 12-Item Short Form Survey (SF-12) was not considerable. Moreover, the food supplement did not significantly affect biochemical parameters associated with fatigue and stressed conditions. This study shows that the food supplement tested reduces prolonged fatigue following two months supplementation in healthy subjects with mild prolonged fatigue.

Background: Tetanus is an acute, fatal disease caused by exotoxins released from Clostridium tetani during infections. A protective humoral immune response can be induced by vaccinations with pediatric and booster combinatorial vaccines that contain inactivated tetanus neurotoxin (TeNT) as a major antigen. Although some epitopes in NeNT have been described using various ap-proaches, a comprehensive list of its antigenic determinants that are involved with immunity have not been elucidated. To that end, a high resolution analysis of the linear B-cell epitopes in NeNT was performed using antibodies generated in vaccinated children. Methods: Two hundred sixty-four peptides that cover the entire coding sequence of TeNT protein were prepared in situ on a cellulose membrane by SPOT synthesis and probed with sera from children vaccinated (ChVS) with a triple DTP-vaccine to map continuous B-cell epitopes that were further characterized and validated by immunoassays. Results: Forty-three IgG epitopes were identified. Four (TT-215-218) were chemically synthesized as Multiple Antigen Peptides (MAPs) and used in peptide ELISAs to screen post-pandemic DTP vaccinations. The assay displayed a high performance with high sensitivity (99.99%) and specificity (100%). Conclusions: The complete map of linear IgG epitopes induced by vaccination with inactivated TeNT highlights three key epitopes involved in the ef-ficacy of the vaccine. Antibodies against epitope TT-8/G can block enzymatic activity, and those against epitopes TT-40/G and TT-42/G can interfere with TeNT binding to neuronal cell receptors. We further show that four of the epitopes identified can be employed in peptide ELISAs to assess vaccine coverage. Overall, the data suggest a set of select epitopes to engineer new, directed vaccines

In this work Cu2O nanoparticles (NPs) were created in-situ on graphene functionalized with Thermomyces lanuginosus lipase (G@TLL) where site-oriented supported TLL acted as template and binder in the presence of copper salt by tailorable synthesis under mild conditions, producing a heterogeneous catalyst. Cu2O NPs was confirmed by XRD and XPS. The TEM microscopy showed that the nanoparticles were homogeneously distributed over the G@TLL surface with sizes of 53 nm and 165nm. This G@TLL-Cu2O hybrid was successfully used in the degradation of toxic organic compounds such as trichloroethylene (TCE) and Rhodamine B (RhB). In the case of TCE, the hybrid presented a high catalytic capacity, degrading 60 ppm of product in 60 min in aqueous solution and room temperature without the formation of other toxic subproducts. In addition, a TOF value of 7.5 times higher than the unsupported counterpart (TLL-Cu2O) was obtained, demonstrating the improved catalytic efficiency of the system in the solid-phase. The hybrid also presented an excellent catalytic performance for the degradation of Rhodamine B (RhB) obtaining a complete degradation (48ppm) in 50 min in in aqueous solution and room temperature and with the presence of a green oxidant as H2O2.

Hepatitis B virus (HBV) is a major global health challenge. Emerging evidence suggests that poor knowledge and stigma are impacting HBV control efforts in sub-Saharan Africa (SSA), however their role is not well understood. We conducted a cross-sectional study of adults aged ≥ 18 years in a community and pharmacy setting in Freetown, Sierra Leone. A structured questionnaire was used to assess knowledge, stigmatizing attitudes, and health-seeking behaviors regarding HBV. Logistic regression was used to identify predictors of HBV knowledge and related stigma. A total of 306 adult participants were enrolled (50.7% male, 7.5% HBV positive and 11.7% vaccinated). Overall, 52.2% had comprehensive HBV knowledge and 49.3% expressed a stigmatizing attitude towards people with HBV. Notwithstanding, 72.2% stated they would receive the HBV vaccine if offered, 80.4% would take anti-HBV medication and 78.8% would be willing to attend clinic regularly. Comprehensive HBV knowledge was associated with HBV positive status (aOR 4.41; p = 0.029) and being vaccinated against HBV (aOR 3.30; p = 0.034). HBV-related stigma was associated with secondary or higher level of education (aOR 2.36; p < 0.001), good HBV knowledge (aOR 2.05; p = 0.006) and pharmacy setting (aOR 1.74, p = 0.037). These findings suggest that education and stigma reduction may benefit HBV elimination efforts in SSA.

Retinitis pigmentosa-59 (RP59) is a rare, recessive form of RP, caused by mutations in the gene encoding DHDDS (dehydrodolichyl diphosphate synthase). DHDDS forms a heterotetrameric complex with Nogo-B Receptor (NgBR; gene NUS1) to form a cis-prenyltransferase (CPT) enzyme complex, which is required for synthesis of dolichol, which in turn is required for protein N-glycosylation as well as other glycosylation reactions in eukaryotic cells. Herein, we review the published phenotypic characteristics of RP59 models extant, with an emphasis on their ocular phenotypes, based primarily upon knock-in of known RP59-associated DHDDS mutations as well as cell type- and tissue-specific knockout of DHDDS alleles in mice. We also briefly review findings in RP59 patients with retinal disease and other patients with DHDDS mutations causing epilepsy and other neurologic disease. We discuss these findings in the context of addressing “knowledge gaps” in our current understanding of the underlying pathobiology mechanism of RP59, as well as their potential utility for developing therapeutic interventions to block the onset, or to dampen the severity or progression, of RP59.

Superantigens are unconventional antigens which recognise immune receptors outside the usual binding sites e.g. complementary determining regions (CDRs), to elicit a response within the target cell. T-cell superantigens crosslink T-cell receptors and MHC Class II molecules on antigen-presenting cells, leading to lymphocyte recruitment, induction of cytokine storms and T-cell anergy or apoptosis among many other effects. B-cell superantigens, on the other hand, bind immunoglobulin receptors on B-cells affecting opsonisation, IgG-mediated phagocytosis, and drive B-cells into apoptosis. Here, through a review of the structural basis for recognition of immune receptors by superantigens, we show that their binding interfaces share specific physicochemical characteristics when compared with other protein-protein interaction complexes. Given that antibody-binding superantigens have been exploited extensively in industrial antibody purification, these observations could facilitate further protein engineering to optimize the use of superantigens in this and other areas of biotechnology.

Recent evidence has highlighted the critical role of memory cells in maintaining lifelong food allergies, thereby identifying these cells as therapeutic targets. IgG⁺ memory B cells replenish pools of IgE-secreting cells upon allergen exposure, which contract thereafter due to the short lifespan of tightly regulated IgE-expressing cells. Advances in the detection and highly dimensional analysis of allergen-specific B and T cells from allergic patients have provided insight on their phenotype and function. The newly identified Th2A and Tfh13 populations represent a leap in our understanding of allergen-specific T cell phenotypes, though how these populations contribute to IgE memory responses remains poorly understood. Within, we discuss the mechanisms by which memory B and T cells are activated, integrating knowledge from human systems and fundamental research. We then focus on memory reactivation; specifically, on the pathways of secondary IgE responses. Throughout, we identify areas of future research which will help identify immunotargets for a transformative therapy for food allergy.

Non-coding RNAs (ncRNAs) comprise a diverse class of non-protein coding transcripts that regulate critical cellular processes associated with cancer. Advances in RNA-sequencing (RNA-Seq) have led to the characterization of non-coding RNA expression across different types of human cancers. Through comprehensive RNA-Seq profiling, a growing number of studies demonstrate that ncRNAs, including long non-coding RNA (lncRNAs) and microRNAs (miRNA), play central roles in progenitor B-cell Acute Lymphoblastic Leukemia (B-ALL) pathogenesis. Furthermore, due to their central roles in cellular homeostasis and their potential as biomarkers, the study of ncRNAs continues to provide new insight into the molecular mechanisms of B-ALL. This article reviews the ncRNA signatures reported for all B-ALL subtypes, focusing on technological developments in transcriptome profiling and recently discovered examples of ncRNAs with biologic and therapeutic relevance in B-ALL.

This paper investigates the photocatalytic characteristics of Ag Nanowire (AgNW)/TiO2 and AgNW/TiO2/Graphene oxide (GO) nanocomposites. Samples were synthesized by the direct coating of TiO2 particles on the surface of silver nanowires. As-prepared AgNW/TiO2 and AgNW/TiO2/GO nanocomposites were characterized by electron microscopy, X-ray diffraction, UV/visible absorption spectroscopy, and infrared spectroscopy. Transmission electron microscope (TEM) images confirmed the successful deposition of TiO2 nanoparticles on the surface of AgNWs. The photocatalytic activity of synthesized nanocomposites was evaluated using Rhodamine B (RhB) in an aqueous solution as the model organic dye. Results showed that synthesized AgNW/TiO2/GO nanocomposite has superior photocatalytic activities when it comes to the decomposition of RhB.

The objective of this research is to measure the perception that teachers had about their own performance when they were forced to carry out an Emergency Remote Teaching due to the COVID-19 pandemic. A questionnaire was provided to teachers of every educational stage in the Basque Country (Pre-school, Primary and Secondary Education, Professional Training and Higher Education) obtaining a total of 4,586 responses. The statistical analysis of the data shows that the greatest difficulties reported by educators are shortcomings in their training in digital skills, which has made them perceive more workload during the lockdown and negative emotions. Another finding is the existing digital divide between teachers based on their gender, age and type of school. A further worrying result is the lower technological competence in lower educational levels, which are the most vulnerable in remote teaching. These results invite us to reflect on the measures to be taken to improve equity, social justice and resilience of the educational system, which align with some of the Sustainable Development Goals.

The aim of the present work was to evaluate the effects of Thalassia testudinum hydroethanolic extract, its polyphenolic fraction, and thalassiolin B on the activity of phase I metabolizing enzymes as well as their antimutagenic effects. Spectrofluorometric techniques were used to evaluate the effect of tested products on rat and human CYP1A and CYP2B activity. The antimutagenic effect of tested products was evaluated in benzo[a]pyrene (BP)-induced mutagenicity assay by Ames test. Finally, the antimutagenic effect of Thalassia testudinum (100 mg/kg) was assessed in a BP-induced mutagenesis in mice. The tested products significantly (p<0.05) inhibit rat CYP1A1 activity, acting as mixed-type inhibitors of rat CYP1A1 (Ki = 54.16±9.09 μg/mL, 5.96±1.55 μg/mL and 3.05±0.89 μg/mL, respectively). Inhibition of human CYP1A1 was also observed (Ki = 197.1±63.40 μg/mL and 203.10±17.29 μg/mL for the polyphenolic fraction and for thalassiolin B, respectively). In addition, the evaluated products significantly inhibit (p<0.05) benzo[a]pyrene (BP)-induced mutagenicity in vitro. Furthermore, oral doses of Thalassia testudinum (100 mg/kg) significantly reduced (p<0.05) the BP-induced micronuclei and oxidative damage, together with an increase of glutathione, in mice. In summary, Thalassia testudinum metabolites exhibit antigenotoxic activity mediated, at least, by the inhibition of CYP1A1-mediated BP biotransformation. Thus, the metabolites of T. testudinum may represent a potential source of chemopreventive compounds for adjuvant therapy of cancer.

Herewith we report a facile synthesis of zinc oxide doped with (5, 10, 15, and 20 wt%) titanium oxide nanocomposites in gelatin under ultra-sonication. The X-ray diffraction (XRD) data revealed ZnO the formation in addition to a rutile phase TiO2. The ZnO phase size decreased, and the rutile TiO2 phase increased with a TiO2 loading increment. The scanning electron microscopy (SEM) displayed a combination of spherical and hexagonal particles with a 60 – 80 nm size distribution. The prepared nanostructures photocatalytic activity was assisted using Rhodamine B dye, where they showed enhanced photodegradation competence under visible light irradiation. The kinetics of photodegradation followed the first-order kinetics with the 20 % wt sample having the maximum activity. The mechanistic investigation revealed the dominance of h+ and •O2- species during the dye photodegradation. The results indicate the potential application of such gelatin stabilized nanostructures for dye illumination from aqueous solutions under sunlight.

Introduction: Dental health care workers, particularly dental medicine students (DMS), are at an increased risk of hepatitis B virus (HBV) and hepatitis C virus (HCV) infection. The aim of our study was to assess the level of knowledge on HBV and HCV, estimate needlestick injury (NSI) prevalence and reporting practice in DMS at the University of Zagreb and analyze how enrolment in obligatory and supplemental courses affects knowledge and needlestick injury reporting practice. Materials and methods: The knowledge was assessed by our questionnaires based on Centers for Disease Control general handouts. Additional information was collected to examine the prevalence and reporting practice of NSI. Data was analyzed by descriptive statistical analysis, independent-samples t-tests, proportion analyses and combined factor analyses of categorical and quantitative variables in SPSS and R. Results: In total, 206 students participated. The overall level of HBV and HCV-related knowledge was poor with average scores being 61.90% and 51.35% respectively. Moreover, students enrolled in the first year demonstrated significantly lower levels of knowledge in comparison with their older peers. Of all participants 18.2% sustained a needlestick injury, and majority of them (78.95%) never reported the injury. Conclusion: In conclusion, DMS have low levels of knowledge on important occupational pathogens and poor NSI reporting practice. Moreover, formal education in the current form failed to significantly improve competence of students and theoretical knowledge translates poorly into more conscientious injury reporting practice. We should look for a better way to increase student awareness and level of knowledge on this topic.

Sulphuric acid is a widely used raw material in the chemical industry. Its corrosive effect on materials varies considerably, depending on impurities, temperature and water content. Accordingly, good corrosion resistance under all conditions is very difficult to achieve. This is especially an issue for micro process apparatus with very thin walls. Furthermore, such devices are often joint by diffusion bonding what may alter materials properties due to high temperatures and long dwell times. In fact, for each new material, the diffusion bonding parameters must be optimized and the impact on mechanical as well as corrosion properties must be investigated. In this paper, two high molybdenum alloys, namely Hastelloy B3 and BC-1, were evaluated. Diffusion bonding tests were performed using ten layers of sheet material in between round stock. Corrosion tests were performed in 70 % sulphuric acid at 100°C for 1000 h. Tensile tests on both alloys were carried out for different material conditions, to determine the change in mechanical strength and elongation at fracture values. In general, independent of the condition of the materials, the fracture behavior of both alloys was found to be ductile and the specimens show the typical dimple structure, in the case of diffusion bonded samples, interrupted by weak spots or rather non-bonded areas. These areas are obviously causing the onset of material failure and thus, a degradation of mechanical properties. Tensile samples, that were aged in 70% sulphuric acid at 100°C for 1000 hours showed local corrosion attacks at the grain boundaries at the circumferential surfaces and especially at the joining planes – for Hastelloy B3 much more pronounced than for Hastelloy BC-1. Accordingly, a further decrease of both, the stress- and elongation at fracture values is observed. However, the typical material parameters like 0.2 % yield strength used for dimensioning components are found to be sufficient high, even when operating the materials under such harsh conditions. When concluding the results, at least Hastelloy BC-1 reveals both sufficient good mechanical properties and an excellent corrosion resistance, regardless of the heat treatment, and could be considered for manufacturing micro-process engineering apparatuses operated in a sulphuric acid environment. This is a significant advance compared to the results obtained within a AiF project, previously carried out on four different materials to investigate the corrosion resistance in sulphuric acid.

In the present paper, Co-B/SiC composite coatings were obtained via electrodeposition from colloidal suspensions with different concentrations of SiC particles and subsequent heat treatments at 350 °C. The composition, morphology and structure of the Co-B/SiC composite coatings were analyzed using glow discharge spectrometry (GDS), scanning electron microscopy (SEM) coupled with energy-dispersive spectroscopy (EDS) and X-ray diffraction (XRD). Hardness and tribological properties were also studied. The results showed that an increase in the SiC concentration in the colloidal suspensions resulted in both an increase in the SiC content and a decrease in the B content in the obtained Co-B/SiC coatings. The Co-B/SiC coatings were adherent, glossy and soft and exhibited a homogeneous composition in all thicknesses. By contrast, an increase in the SiC particle content of the Co-B/SiC composite coating from 0 to 2.56 at.% SiC reduced the hardness of the film from 680 to 360 HV and decreased the wear volume values from 1180 to 23 mm³ N^-1 m^-1, respectively (that is, the wear resistance increased). Moreover, when the Co-B/SiC coatings with SiC content ranging from 0 to 2.56 at.% SiC were subjected to a heat treatment process, the obtained coating hardness values were in the range of 1200 to 1500 HV and the wear volume values were in the range of 382 to 19 mm³ N^-1 m^-1.

Endo-reticular stress induces the unfolded protein response including a highly conserved set of genes crucial for cell survival against a variety of onslaughts. Among the activated stress response genes is Ire1, which undergoes auto-phosphorylation and acquires a regulated Ire1-dependent mRNA decay activity. Ire1P non-canonically splices the mRNA for Xbp1 in the cytoplasm. This spliced Xbp1 serves as mRNA encoding a transcription factor for unfolded protein response genes. Meanwhile the mRNA decay function of Ire1P degrades other cellular mRNAs and can cause changes to the translation machinery by altering regulators in a cell specific manner. Naïve splenic B cells differentiate into Antibody Secreting Cells and activate Ire1 phosphorylation early on after LPS stimulation, within 18 hrs. When Ire1 is activated in B cells, in addition to Xbp1 splicing, there are large-scale changes in mRNA; inhibition of the mRNA degradation function of Ire1 both reduces the number and changes the type of genes involved in altered splicing patterns, including factors for snRNA transcription. Some of the splicing changes seen at 18 hrs after LPS persist into the late stages of antibody secretion, up to 72 hrs, while others are supplanted by new splicing changes introduced by the induction of ELL2, a transcription elongation factor. ELL2 changes mRNA processing patterns and is necessary for Immunoglobulin secretion. RNA splicing patterns in antibody secreting cells are thus shaped by endo-reticular stress, ELL2 induction, and are associated with changes in the levels of snRNAs.

B chromosomes (Bs) were discovered a century ago, and since then most studies have focused on describing their distribution and abundance using traditional cytogenetics. Only recently have attempts been made to understand their structure and evolution at the level of DNA sequence. Many questions regarding the origin, structure, function and evolution of B chromosomes remain unanswered. Here we identify B chromosome sequences from several species of cichlid fish from Lake Malawi by examining the ratios of DNA sequence coverage in individuals with and without B chromosomes. We examine the efficiency of this method, and compare results using both Illumina and PacBio sequence data. The B chromosome sequences detected in 13 individuals from 7 species were compared to assess the rates of sequence replacement. B-specific sequence common to at least 12 of the 13 datasets are identified as the “Core” B chromosome. The location of B sequence homologs throughout the genome provides further support for theories of B chromosome evolution. Finally, we identified candidate genes located on the B chromosome which may regulate the segregation and maintenance of the B chromosome.

B chromosomes are supernumerary chromosomes which are found in addition to the normal standard chromosomes (A chromosomes). B chromosomes are well known to accumulate several types of repeats. Although the evolution of B chromosomes has been subject of numerous studies, the mechanisms of accumulation and evolution of repetitive sequences is not fully understood. Recently, new genomic approaches have shed light on the origin and accumulation of different classes of repetitive sequences in the process of B chromosome formation and evolution. Here we discuss the impact of repetitive sequences accumulation on the evolution of plant B chromosomes.

We describe the genomes of two Echovirus isolates from Nigeria as reference enterovirus species B genomes for the region. These Echovirus 7 and 19 genomes have 7,411nt and 7,426nt, and were recovered from sewage contaminated water (in 2010) and an acute flaccid paralysis case (in 2014), respectively.

The tetracyclic pyrido[4,3-b]carbazole olivacine and four of its oxygenated derivatives have been synthesized by a late-stage palladium-catalyzed Heck-type cyclization of the pyrrole ring as key step. In a test for inhibition of the growth of Mycobacterium tuberculosis 9-methoxyolivacine showed the most significant inhibiting activity against Mycobacterium tuberculosis with an MIC₉₀ value of 1.5 μM.

An analysis of the performance of Automatic Dependent Surveillance-Broadcast (ADS-B) data received from the Grand Forks, North Dakota International Airport was carried out in this study. The purpose was to understand the vulnerabilities of Universal Access Transceiver (UAT) ADS-B system and recognize the effects on present and future Air Traffic Control (ATC) operation. The Federal Aviation Administration (FAA) mandated all the General Aviation aircraft to be equipped with ADS-B. The aircraft flying within United States and below the transition altitude (18,000 feet) are more likely to install an UAT ADS-B. At present unmanned aircraft systems (UAS) and autonomous air traffic control (ATC) towers are being integrated into the aviation industry and UAT ADS-B is a basic sensor for both class 1 and class 2 Detect and Avoid (DAA) systems. As a fundamental component of future surveillance system, the anomalies and vulnerabilities of ADS-B system need to be identified to enable a fully utilized airspace with enhanced situational awareness. The data received was archived in GDL-90 format, which was parsed into readable data. The anomaly detection of ADS-B messages was based on the FAA ADS-B performance assessment report. The data investigation revealed ADS-B message suffered from different anomalies including drop out; missing payload; data jump; low confident data and altitude discrepancy. Among those studied, the most severe was drop out and 32.49% of messages suffered from this anomaly. Dropout is an incident where ADS-B failed to update within a specified rate. Considering the potential danger being imposed, an in-depth analysis was carried out to characterize message dropout. Three flight parameters were selected to investigate their effect on drop out. Statistical analysis was carried out and Friedman Statistical Test identified that altitude affected drop out more than any other flight parameters.

This work analyzes the severity and risk associated with Automatic Dependent Surveillance-Broadcast (ADS-B) message drop out in Detect and Avoid (DAA) function of Unmanned Aircraft System (UAS). Performance assessment of the Universal Access Transceiver (UAT) ADS-B message implies that in some cases ADS-B fails to update within a specified update interval, which is referred to as drop out in this work. ADS-B is a fundamental surveillance sensor for both class 1 and class 2 DAA systems. Message loss or drop out has been found as one of the common limitations of the ADS-B system. The key feature of this study is incorporating the update rate of real ADS-B data transmitted from the manned aircraft. The data were received from the Grand Forks International Airport, North Dakota. Monte Carlo method has been adopted to resolve encounter scenarios in the presence of drop out. The change in the alert triggered by the UAS DAA in the presence of ADS-B drop out has been investigated. Furthermore, the risk matrices are created to quantify the associated risk with drop out affected alerts. Simulation results depict that both the duration of drop out and DAA look-ahead time affect the alert-triggering function of UAS. With a small look- ahead window and longer duration of drop out, the number of warning alerts increases. Also, alerts are affected more during an overtaking encounter than that of a head-to-head encounter. A system-level analysis is also carried out to recognize the potential reasons behind the ADS-B drop out.

Acidic ostreolysin A/pleurotolysin B (OlyA/PlyB, formerly known as ostreolysin (Oly), and basic 20 kDa equinatoxins (EqTs) are cytolytic proteins isolated from the edible mushroom Pleurotus ostreatus and the sea anemone Actinia equina, respectively. Both toxins, although from different sources, share many similar biological activities: (i) colloid-osmotic shock by forming pores in cellular and artificial membranes enriched in cholesterol and sphingomyelin; (ii) increased vascular endothelial wall permeability in vivo and perivascular oedema; (iii) dose-dependent contraction of coronary vessels; (iv) haemolysis with pronounced hyperkalaemia in vivo; (v) bradycardia, myocardial ischemia and ventricular extrasystoles accompanied by progressive fall of arterial blood pressure and respiratory arrest in rodents. Both types of toxins are haemolytic within nanomolar range concentrations, and it seems that hyperkalaemia plays an important role in toxin cardiotoxicity. However, it was observed that the haemolytically more active EqT III is less toxic than EqT I, the most toxic and least haemolytic EqT. In mice, EqT II is more than 30 times more toxic than OlyA/PlyB when applied intravenously. These observations imply that haemolysis with hyperkalaemia is not the sole cause of the lethal activity of both toxins. Additional mechanisms responsible for lethal action of the two toxins are direct effects on heart, coronary vasoconstriction and related myocardial hypoxia. In this review, we appraise the pathophysiological mechanisms related to the chemical structure of OlyA/PlyB and EqTs, as well as their toxicity.

The objective of the this study was to reduce the benzo[a]pyrene-induced hepatotoxicity method in herbal medicine products and to give proof that neferine, daidzein, genistein possess antihepa-totoxic effects. B[a]P which classified as a group 1 carcinogen and metabolized to B[a]P-7,8-dihydrodiol-9,10-epoxide (BPDE) causes mutagenic DNA addition products. The reduc-tion of BPDE-DNA adduct formation by B[a]P-7,8-dihydrodiol-9,10-epoxide (BPDE) was derived by benzo[a]pyrene (B[a]P). In HepG2 cells, B[a]P exhibited toxicity and substance treatment of the cells with B[a]P with neferine in lotus and daidzein, genistein in soybean reduced the BPDE-DNA ad-ducts level. The level of B[a]P-metabolites in the substance treatment of the cells was presented that BPDE levels were reduced by neferine in lotus and daidzein, genisten in soybean. These results suggest that neferine in lotus and daidzein, genistein in soybean prevent B[a]P-induced hepato-toxicity for BPDE-DNA adduct formation.

Taiwan's bed and breakfast (B&B) development has been more than 25 years ago, from the first generation of retirement to the B&B industry, serving tourists from all over the world accom-modation, providing breakfast and accommodation mode to the present, after the change of employees from the second generation, more and more attention is paid to the cultivation and cultivation of business ability. With the advent of the era of AI technology networking, the ca-pabilities required for B&B operation are more focused on all aspects of service, and the good marketing ability of B&B can promote a green chimney-free tourism economy, which is also a favorite industry of various governments and the public. This study explores the basic vocational competency indicators required for running a B&B, with (1)EQ emotion management skills, (2)Financial management ability, (3)(SK) technical skills, and (4)Marketing and promotion management capabilities. Through the study method, the K-S Z test was determined by the con-sensus conclusion of expert reliability and validity p value

Garlic (Allium sativum L.) is a species of the onion family, Alliaceae that has been widely used as a food and a folk medicine. The objective of this study was to determine the effects of AGE (Aged garlic extract) on proinflammatory genes relevant to COVID-19. To this aim, we treated bronchial epithelial IB3-1 cells with SARS-CoV-2 Spike protein (S-protein) or with the COVID-19 BNT162b2 vaccine in the absence or in the presence of AGE. The results obtained demonstrated that AGE is a potent inhibitor of the S-protein in-duced expression of the IL-1beta, IL-6 and IL-8 genes. Bio-plex analysis demonstrate that AGE reduced release of IL-6 and IL-8, that were highly induced by S-protein. No inhibition of cells growth, toxicity and proapoptotic effects were found in AGE-treated cells. The effects of one of the major AGE constituents (S-allyl cysteine, SAC) were studied on the same experimental model systems. SAC was able to inhibit the S-protein induced expression of IL-1beta, IL-6 and IL-8 genes and extracellular release of IL-6 and IL-8, con-firming that S-allyl cysteine is one of the constituents of AGE that are responsible for inhibiting S-protein induced pro-inflammatory genes. Docking experiments suggest that a possible mechanism of action of SAC is an interference with the activity of Toll-like receptors (TLRs), particularly TLR4, thereby inhibiting NF-B and NF-B regulated genes, such as IL-1beta, IL-6 and IL-8 genes. These results suggest that both AGE and SAC deserve further experimental efforts to verify their effects on pro-inflammatory genes in SARS-CoV-2 infected cells.

Hepatitis B virus (HBV) can cause chronic infections, significantly increasing the risk of death from cirrhosis and hepatocellular carcinoma (HCC). A key player in chronic HBV infection is covalently closed circular DNA (cccDNA), a stable episomal form of viral DNA that acts as a persistent reservoir in infected hepatocytes and drives continuous viral replication. Despite the development of several animal models, few adequately replicate cccDNA formation and maintenance, limiting our understanding of its dynamics and the evaluation of potential therapeutic interventions targeting cccDNA. In this study, we aimed to develop a mouse model to investigate cccDNA formation and maintenance. We infected C57BL/6 mice with recombinant adeno-associated virus (rAAV) carrying a 1.3-overlength HBV genome (genotype C) and collected liver tissue at various time points to assess cccDNA levels and viral replication. Our results demonstrated the successful establishment of a chronic hepatitis B mouse model using rAAV-HBV1.3, which supported persistent HBV infection with sustained cccDNA expression in hepatocytes. Serum levels of HBsAg and HBeAg were elevated for up to 12 weeks, while alanine transaminase (ALT) levels remained within the normal range, indicating limited liver damage during this period. We confirmed HBV DNA expression in hepatocytes, and importantly, cccDNA was detected using qPCR after Plasmid-Safe ATP-Dependent DNase treatment, which selectively removes non-cccDNA forms. This established model provides a valuable platform for studying the long-term maintenance of cccDNA in chronic HBV infection and offers an important tool for testing novel therapeutic strategies aimed at targeting cccDNA.

Objectives: This study aimed to evaluate the risk of hepatitis B virus reactivation (HBVr) in COVID-19 patients receiving immunosuppressive treatment, which has been insufficiently studied to date. Secondarily, we aimed to evaluate the seroprevalence of HBV infection in COVID-19 patients. Methods: We performed an HBV screening in all Romanian adults hospitalized in 4 COVID-19 wards between October 2021 and September 2022. We enrolled patients with positive hepatitis B core antibody (anti-HBc) without protective hepatitis B surface antibody (anti-HBs), HBV treatment or immunosuppressive conditions, whom we followed virologically at 3 months. Results: We identified 333/835 (39.9%) anti-HBc-positive patients. Follow-up was performed in 13 patients with positive hepatitis B surface antigen (HbsAg) and 19 HBsAg-negative/anti-HBc-positive patients. Among those who received immunosuppressants, 4/23 (17.4%) patients experienced HBVr: 1 out of 8 (12.5%) HBsAg-positive patients (with 1.99 log increase in HBV DNA level) and 3 out of 15 (20%) HBsAg-negative/anti-HBc-positive patients (with de novo detectable HBV DNA level). Conclusions: Administration of COVID-19 immunosuppressants may result in a significant risk of HBVr in co-infected patients. We recommend performing an HBV triple screen panel (HBsAg, anti-HBs, anti-HBc) in all COVID-19 patients receiving immunosuppressive treatment. HBV prophylaxis may be indicated in certain patients. Larger studies are needed in order to establish an appropriate and cost-effective management in these patients.

Certain species of Mucorales have been identified as causative agents of mucormycosis, a rare yet often lethal fungal infection. Notably, these fungi exhibit intrinsic resistance to common azole drugs, which target lipids. Given the pivotal role of lipids in drug resistance and their contribution to the innate resistance to azoles, this study provides a comprehensive overview of key lipid classes, including sphingolipids (SLs), glycerophospholipids(GPLs), and sterols, in Rhizopus delemar 99-880, a well-characterized reference strain among Mucorales. Through high-throughput analysis involving the identification and quantification of intermediates, we have elucidated the biosynthetic pathways of SLs, PGLs, and sterols. Notably, the acidic SLs were not found probably because the acidic branch of the SL biosynthesis pathway terminates at α-hydroxy phytoceramides as evident by their high abundance. Intermediates in the neutral SL pathway incorporated higher levels of 16:0 fatty acid compared to other pathogenic fungi. A strikingly high phosphatidylethanolamine (PE)/phosphatidylcholine (PC) ratio was observed among GPLs. Ergosterol remains the major sterol, similar to other fungi, and our analysis confirms the existence of alternate ergosterol biosynthesis pathways. The total lipidomic profile of R. delemar 99-880 offers insights into its lipid metabolism and potential implications for studying pathogenesis and drug resistance mechanisms.

Infection with the Chikungunya virus (CHIKV) manifests as a febrile illness known as chikungunya fever (CHIKF). CHIKF is characterized by sudden-onset high fever, rash, polyarthritis, and polyarthralgia. Alt-hough the infection typically resolves within two weeks, many patients experience recurrent joint pain and inflammation that can outlast the other symptoms for many months. CHIKF has been previously linked to rheumatoid arthritis (RA) due to similar inflammatory processes. This study aimed to identify molecular markers in the blood of CHIKV-infected individuals associated with joint pain and chronicity of CHIKF. Sequencing of B and T cell receptors (BCR and TCR) revealed that CHIKV infection reduces CDR3 diver-sity. Lower BCR diversity was linked to increased expression of genes involved in osteoclast differentiation and activation through RANK/RANKL signaling. If osteoclast involvement in CHIKF pathogenesis is con-firmed, existing therapeutic approaches could be used as alternative treatments for CHIKF patients.

Background: Hepatitis B virus (HBV), a lethal form of viral hapatitis, is an extra burden on the socioeconomic status of a country. Objectives: The population-based studies to quantify the incidence of hepatitis B. Data sources: in the North Waziristan, formally known as EX-FATA (Federal Administrated Tribal Area), Pakistan, are still rare. Study eligibility criteria: 943 individuals were selected on the basis of signs and symptoms to determine the epidemiology of HBV in the study population. Tests: Hepatitis B virus (HBV). Methods of data synthesis: Among these, 626 were male and 317 were female. All the HBV suspected individual were screened through ICT (Indirect Coombs Test) , ELISA (enzyme-linked immunosorbent assay) and RT-PCR (Re-verse transcription polymerase chain reaction). Results: The results obtained from the screening tests for HBV revealed that RT-PCR based results are more reliable and it indicated that HBV infection is more common in male 41 (6.54%) than female 15 (4.73%). The age range selected for the study was 1-75 years. Age wise analysis indicated that HBV is more prevalent among individuals of age group between 16 to 45 years. This age range also showed higher number of patients having either mild, moderate or elevated viral loads. The HBV genotype D was the most common, present in 62.5% patients. However, 16.07 % patients were having genotype U, 12.5 % genotype C, 8.92 % genotype A, and 7.14% had genotype B. Discussion: The questionnaire based investigation revealed that HBV was most prevalent among married individuals (64.6%), whereas least prevalent among individuals having HBV positive family member (1.4 %). The other risk factors contributed were history of dental procedures (57.8%), ear, nose, piercing, or tattooing and uses of un-disposable syringes (56.5%), transfusion of blood or plasma (42.9%), surgery (41.8%), frequent visits to barber shops (39.45%), and addiction of injectable drugs (38.1%). The current study is providing a clear picture of the alarming situation HBV transmission and emphasis on the need for more effective planing, strategies and policies for the control and prevention of HBV.

This study aimed to evaluate the influence of olive cake on the diet of autochthonous Bísaro pigs in processed products. To this purpose, loins and “cachaços” were used and subjected to a manufacturing flowchart to obtain a dry-cured product. Both products were subjected to the same formulation, ingredients, and curing steps. Regarding the physicochemical composition, there were significant differences between the two products for the parameters of aw (p&lt;0.001), moisture (p&lt;0.001), total fat (p&lt;0.001), protein (p&lt;0.001), and haem pigments (p&lt;0.001). As for the diet, it only significantly influences the NaCl content (p&lt;0.05). Neither the product nor the diet had any influence (p&gt;0.05) on the fraction of saturated fatty acid (SFA), monounsaturated fatty acid (MUFA), and polyunsaturated fatty acids (PUFA). However, there is a significant difference when it comes to omega 3 (p&lt;0.05). These fatty acids increased with the addition of olive cake, and the diet with olive cake centrifuged by 25% had the highest value for both products. The increase in this omega 3 resulted in a decrease in the PUFA n-6/n-3 ratio (p&lt;0.01) in the diets with olive cake, compared to the control diets.

Viral hepatitis is currently acknowledged as a significant public health issue that necessitates a prompt and immediate response. Hepatitis is a significant worldwide health problem that causes the death of approximately 1.5 million individuals annually. The objective of this study was to ascertain the occurrence rate of hepatitis A, E, B, and C infections in the Hajjah governorate of Yemen from 2020 to 2023.A retrospective study was conducted in the Hajjah Governorate of Yemen for four years, 2020– 2023. About 41162 cases were collected from the clinical records of epidemiological surveillance in the Public Health Office of the Hajjah Governorate. All cases were diagnosed in different laboratories based on direct observation of viral hepatitis in the blood sample. The required data were obtained by using the designed questionnaire. The findings of the present investigation were summarized as follows: The current findings indicate that the prevalence rate of Hepatitis A and E was 761 (1.85%), while the prevalence rate of Hepatitis B and C was 971 (2.36%) among the participants of the study. The current findings indicate that the incidence of Hepatitis A and E was greater in 2022 (2.3%), while Hepatitis B and C had a higher rate in 2020 (2.9%). The study revealed a higher prevalence of hepatitis A and E among individuals originating from Al Miftah district 116, with a rate of 7.5%. Furthermore, the prevalence of hepatitis B and C in Hajjah city was significantly higher, reaching 579 cases (22.9%). The month with the highest incidence of hepatitis A and E viruses was September, with a rate of 85 cases (2.6%), while the lowest incidence was observed in April, with a rate of 1.3%. The prevalence of hepatitis B and C viruses was highest in October 1997, with a rate of 2.8%, followed by November 1997 with the same rate. The lowest observed incidence of 1.6% was recorded in April. In Autumn, a significant prevalence of hepatitis A and B viruses, as well as hepatitis B and C viruses, was identified at rates of 2.2% and 2.6%, respectively.The study findings indicate that the occurrence of HAV, HEV, HBV, and HCV in the study area is consistent with global trends. Although the study found a low prevalence of hepatitis viruses, these types of viruses will continue to pose a significant risk to public health. Based on this study, it is imperative for authorities to actively enhance public awareness in order to enable prompt planning and essential arrangements for an effective response to outbreaks or epidemics. This will ultimately lead to a reduction in illness, death, and economic burden.

Microglia-related retinal inflammation is associated with a variety of retinal diseases. Lycium barbarum Glycopeptide (LBGP) is the main active component of Lycium barbarum polysaccharide (LBP) isolated from Lycium barbarum, which possesses antioxidation, neuroprotection, and immunoregulation. However, whether LBGP has beneficial effects on LPS/IFN-γ (L/I) induced retinal microglial activation and its underlying mechanism remains to be elucidated. In this study, we observed the anti-inflammatory properties of LBGP in microglia activated by LPS and IFN-γ (L/I), examining both primary retinal microglia and BV2 microglial cells. Cells were pretreated with LBGP for 2h before stimulated with LPS/IFN-γ (L/I) for 24h. The dosages of LBGP for cells were evaluated by using the CCK-8 assay. The morphological changes were observed using an optical microscope. The changes in expression of cytokines and inflammatory mediators were measured with Griess assay, ELISA, qPCR, and immunofluorescence. Western blotting was used to assess MAPK, NF-κB signal transducer. LBGP pre-treatment significantly reversed L/I-induced microglia morphological alterations in area, perimeter, Feret's diameter, and roundness. LBGP significantly alleviated the L/I-induced microglial activation in primary and BV2 microglial cells. LBGP switched the M1 pro-inflammatory phenotype to the M2 anti-inflammatory phenotype by downregulating the expression of M1 markers (iNOS, IL-1β, IL-6, COX2, CD16, and CD86) and upregulating the expression of M2 markers (arginase 1 and CD206). Furthermore, LBGP attenuated the activation of NF-κB and MAPK pathways in L/I-activated BV2 cells. In summary, it is suggested that LBGP pretreatment significantly alleviated L/I-induced retinal inflammation by regulating microglial(M1/M2) polarization via NF-κB and MAPK signaling pathways.

(1) Background: We aimed to determine the prevalence of hepatitis B virus (HBV) resistance-associated mutations (RAMs) in people with HBV and human immunodeficiency virus (HBV/HIV) in Botswana. (2) Methods: We sequenced HBV from participants with HBV/HIV from the Botswana Combination Prevention Project study (2013-2018) using the Oxford Nanopore GridION platform. Consensus sequences were analyzed for genotypic and mutational profiles. (3) Results: Overall, 98 HBV sequences had evaluable reverse transcriptase region coverage. The median participant age was 43 years (IQR: 37, 49) and 66/98 (67.4%) were female. Most participants, 85/97 (87.6%) had suppressed HIV viral load (VL). HBV RAMs were identified in 61/98 (62.2%) participants. Most RAMs were in positions 204 (60.3%), 180 (50.5%) and 173 (33.3%), mostly associated with lamivudine resistance. The triple mutations, rtM204V/L180M/V173L and was the most predominant (17/61 [27.9%]). Most participants (96.7%) with RAMs were on antiretroviral therapy for a median duration of 7.5 years (IQR: 4.8, 10.5). Approximately 27.9% (17/61) of participants with RAMs had undetectable HBV VL, 50.8% (31/61) had VL &lt;2000IU/mL and 13/61 (21.3%) had VL ≥2000 IU/mL. (4) Conclusions: The high prevalence of lamivudine RAMs discourages the use of ART regimens with 3TC as the only HBV-active drug in people with HIV/HBV.

Diffuse large B-cell lymphoma (DLBCL) requires a complete staging at diagnosis that may have prognostic and therapeutic implications. The role of bone marrow (BM) biopsy (BMB) is contro-versial in the era of nuclear-imaging techniques. We performed a comparative review of 25 studies focused on BM evaluation at DLBCL diagnosis, including at least two of the following techniques: BMB, flow cytometry, and positron emission tomography (PET-FDG). The report about BM involvement (BMi), diagnostic accuracy and prognostic significance was collected and compared among techniques. A concordance analysis between BMB, FCM and PET was also per-formed, and we deeply evaluated the implications of the different types of BMi: concordant by LBCL or discordant by low-grade B-cell lymphoma for both BMB and FCM, and focal or diffuse uptake pattern for PET. As main conclusion, BMB, FCM and PET are complementary tools which provide different and clinically relevant information in the assessment of BMi in newly DLBCL.

Primary bone lymphoma of the scapula is a rare tumor that usually causes local pain. Presented patient suffered for two years from paresthesia, tingling, numbness, and edema of the little and ring finger. The 45-year-old man underwent several radiological and neurological assessments of the palm, elbow and neck prior to radiographs revealing the tumor of the left shoulder. Once diffuse large B cell lymphoma was confirmed, immunochemotherapy with rituximab, cyclophosphamide, doxorubicin, vincristine, and methylprednisolone (R-CHOP) started. The treatment was accompanied by antiviral treatment with lamivudine due to positive hepatitis B virus serology and with bisphosphonate treatment for the prevention of bone resorption. Once immunochemotherapy was finished, the treatment was supplemented by radiotherapy of the shoulder. After more than three years of accomplishing remission, the patient had an ischemic stroke manifesting with right-sided hemiparesis. Following the physical therapy, the patient is currently in the process of evaluation for thrombophilia, as well as further cardiac assessment due to the positive transcranial Doppler bubble test setting high suspicion for the presence of patent foramen ovale.

Mucormycosis is an opportunistic fungal infection that is increasingly affecting patients with Coronavirus Disease (COVID-19). This connection is particularly pronounced in specific populations, including individuals with diabetes or those who have recently undergone corticosteroid therapy. Additionally, Cytomegalovirus (CMV) infection is a frequent complication among COVID-19 patients who have previously received corticosteroid or other immune-modulatory treatments. In this case report, we present the clinical details of a 56-year-old male who developed post-COVID pneumonia complicated by both cutaneous mucormycosis and CMV infection.

Influenza is an acute respiratory illness caused by influenza virus infection, which is managed using vaccines and antiviral drugs. Recently, the antiviral effects of plants and foods have gained attention. This review summarizes the therapeutic properties of Euglena against influenza from a functional food viewpoint. While it has been reported that Euglena contributes to suppressing blood sugar levels and ameliorates symptoms caused by stress by acting on the autonomic nervous system, the immunostimulatory and antiviral activities of Euglena have also been reported. In this review, I focused on the immunostimulation of antiviral activity via the intestinal environment and the suppression of viral replication in infected cells. The functions of specific components of Euglena, which also serve as a source of a wide range of nutrients such as vitamins, minerals, amino acids, unsaturated fatty acids, and β-1,3-glucan (paramylon), are also reviewed. Euglena has animal and plant properties and natural compounds with a wide range of functions, providing crucial information for improved antiviral strategies.

The emergence of multidrug-resistant pathogens such as Listeria monocytogenes and Shiga toxin-producing Escherichia coli (STEC) poses public health challenges, and this has led to a continuous search for effective novel antimicrobial agents. This study aimed to isolate marine actinomycetes from South Africa, evaluate their in vitro antimicrobial activity against Listeria and STEC, and characterize their mechanisms of action. Marine actinoymcetes were isolated and identified by 16S rRNA sequencing. Gas chromatography-mass spectrometry (GC-MS) was used to identify the chemical constituents of bioactive actinomycetes secondary metabolites. Antibacterial activity of the secondary metabolites was assessed by the broth microdilution method and their mode of actions were predicted using computational docking. While five strains showed antibacterial activity during primary screening, only Nocardiopsis dassonvillei strain SOD(B)ST2SA2 exhibited activity during secondary screening for antibacterial activity. GC-MS identified five major bioactive compounds: 1-octadecene, diethyl phthalate, pentadecanoic acid, 6-octadecenoic acid, and tri-fluoroacetoxy hexadecane. SOD(B)ST2SA2`s extract demonstrated the minimum inhibitory con-centration and minimum bactericidal concentration ranging from 0.78–25 mg/ml and 3.13 to > 25 mg/ml, respectively. Diethyl phthalate displayed the lowest bacterial protein binding energies (kcal/mol): −7.2, dihydrofolate reductase; −6.0, DNA gyrase B, and −5.8, D-alanine:D-alanine lig-ase. Thus, marine N. dassonvillei SOD(B)ST2SA2 is a potentially good source of antibacterial compounds that can be used to control STEC and Listeria monocytogenes.

Respiratory infections constitute a major reason for infants and children seeking medical advice and visiting health facilities, thus remaining a significant public threat with high morbidity and mortality. The predominant viruses causing viral respiratory infections are influenza A and B viruses (Flu-A, Flu-B), Respiratory Syncytial Virus (RSV), Adenovirus and Coronaviruses. We aimed to record the incidence of RSV, SARS-CoV-2, Influenza A/B and Adenovirus cases with rapid antigen tests and validate the results with RT-PCR assay of upper respiratory specimens with a wide range of viral loads and (co)-infection patterns in children. Clinical samples were collected from early symptomatic children (presenting with fever and/or cough and/or headache within 5–7 days). The surveillance program was conducted in five private pediatrician dispensaries and one Pediatric care unit, from 10 January 2023 to 30 March 2023 in central Greece. The total sample of specimens collected was 784 young children and infants, of which 383 (48.8%) ware female and 401 were male (51.2%). The mean age of participants was 7.3 + 5.5 years. The sensitivity of FLU A &amp; B test was 91.15% (95% CI: 84.33% -95.67%), and the specificity was 98.96% (95% CI: 97.86% - 99.58%). The sensitivity and specificity of the adenovirus and RSV test was {92.45% (95% CI: 81.79% - 97.91%), 99.32% (95% CI: 98.41% -99.78%)} and {92.59% (95% CI: 75.71% -99.09%), 99.47% (95% CI: 98.65% - 99.86%)} respectively. Lastly, the sensitivity of the SARS-CoV-2 test was 100.00% (95% CI: 79.41%-100.00%) and the specificity was 99.74% (95% CI: 99.06% - 99.97%). We recorded proportion of incidence for the Influenza-A and B, (14.3%), - (3.44%) correspondingly, followed by the adenovirus with a proportion (6.9%) and the RSV with (3.7%) incidence proportion and finally, the SARS-CoV-2 (2.3%). The combination of a new multiple rapid test with multiple antigens, will be probably a useful tool with financial impact for health systems targeting the early detection and right treatment of respiratory infections in the emergency departments in primary health care facilities.

The chitin synthase B gene is a key enzyme in the chitin synthesis of insect peritrophic matrix (PM), affecting insects' feeding behavior. The chitin synthase B gene has been cloned from the transcription library of Heortia vitessoides Moore. RT-qPCR showed that HvChsb was highly expressed in the larval stage of H. vitessoides, especially on the first day of the prepupal stage, and in the midgut of larvae and the abdomen of adults. After starvation treatment, HvChsb was found to be significantly inhibited with time. After 48 h of starvation, the feeding experiment showed that HvChsb increased with the prolongation of the refeeding time. The experimental data showed that feeding affected the expression of HvChsb. HvChsb was effectively silenced by RNA interference, so its function was lost, significantly decreasing the survival rate of H. vitessoides. The survival rate from larval-to-pupal stages was only 43.33%, accompanied by abnormal phenotypes. It can be seen that HvChsb plays a key role in the average growth and development of H. vitessoides.

Treating relapsed and refractory diffuse large B-cell lymphoma is still challenging for clinicians, but the available CAR-T and bispecific antibodies revolutionized therapy. Autologous stem cell transplantation was the most effective treatment modality previously. The authors report data from a single center over ten years. The retrospective study included 116 patients. There were 53 relapsed, 39 primary refractory cases, 19 had CNS involvement, and 5 received primary consolidation transplants. The median duration of follow-up was 46 months. The median event-free survival was 75 months, and the median overall survival was 105 months for all cases. Five-year overall survival was 59%, and event-free survival was 54%. Pretreatment prognostic factors at diagnosis had no effect on the outcome of transplantation. The authors found no difference between survival in relapsed or refractory cases, and the number of salvage lines or the germinal center / activated B-cell type also did not influence the results. Complete metabolic response before transplant confirmed by 18FDG PET/CT strongly affected survival. The pretransplant creatinine and CRP levels significantly influenced the long-term outcome. The number of stem cells infused did not affect survival, but engraftment within nine days did result in better survival. These data support the finding that the response to salvage therapy did select a better prognostic group who may still benefit from autologous transplantation.

Hypoxia represents one of the key factors that stimulate the growth of leukemic cells in their niche. Leukemic cells in hypoxia are forced to reprogram their original transcriptome, miRNome, and metabolome. How the coupling of miRNAs/mRNAs helps to maintain or progress the leukemic status is still not fully described. MicroRNAs (miRNAs) regulate practically all biological processes within cells and play a crucial role in leukemia development/progression. Here we worked with the human cell line MEC-1 (human chronic lymphocytic leukemia (CLL)) where we deleted mature miR-155 by CRISPR/Cas9. MEC-1 cells in hypoxia showed a higher proliferation rate with a relatively low level of apoptosis. Interestingly, miR-155 deficiency decreased the proliferation rate in both, normoxia and hypoxia. Besides common hypoxia-related genes (HIF1α, EGLN1, VHL, HK1, and HK2), we also measured, genes for glucose transporters SLC2A1 (GLUT1) and SLC2A3 (GLUT3). Surprisingly, only SLC2A3 (GLUT3) showed significant overexpression in hypoxia conditions in miR-155 deficient MEC-1cells which points to the possible novel target of miR-155 in CLL. Increased glucose uptake and decreased lactate support our hypothesis that miR-155 deficiency and hypoxia transform cell metabolism. To conclude, miR-155 deficiency and hypoxia-impaired glucose metabolism stimulate GLUT3 in CLL cells.

Duke University was founded in 1930 primarily due to funds generated from James B. Duke’s tobacco business. Duke achieved great financial wealth primarily due to the early application of machine rolled cigarettes, as opposed to hand rolled. This early adoption of technology allowed Duke Tobacco to out-produce other companies still selling hand rolled cigarettes. By making smoking more inexpensive and easier than pipe smoking, the cigarette formed the foundation for nicotine addiction in the 1900s, generating huge profits for the tobacco industry. At the time Duke University was founded, little was known about the connection between nicotine, cigarettes, and respiratory diseases such as emphysema and lung cancer. Through James Duke’s philanthropy, the devastating harm from cigarettes has been mitigated in part through the founding of one of the world’s most prominent medical centers and research universities.

Academic and corporate research has been focusing on analyzing stock performances, financial markets, and investment strategies for decades. According to Lynch and Rothchild (1989), certain investments can be described as plays. In this work, the authors use the term for investments in value stocks, spin-offs, and turnarounds to analyze the long-term stock performance and risk-adjusted excess returns of up to five years for those stocks. Additionally, stocks with a supe-rior return performance are identified within an investment play based on low P/E and P/B mul-tiples. The study finds that value stocks, spin-offs, and turnarounds outperform the S&P 500 on average on a one-, three- and five-year investment horizon. The analysis of the three investment plays confirms earlier studies that investment plays constitute a profitable investment opportunity. Moreover, the research exemplifies that private investors could achieve an excess return (alpha) through a passive buy-and-hold investment strategy. Overall, the analysis provides a deeper in-sight into the long-term performance of value stocks, spin-offs, and turnarounds.

Viruses can induce the fusion of infected and neighboring cells, leading to the formation of syncytia. Cell-cell fusion is mediated by viral fusion proteins on the plasma membrane of infected cells that interact with cellular receptors on neighboring cells. Viruses use this mechanism to spread rapidly to adjacent cells or escape host immunity. For some viruses, syncytium formation is a hallmark of infection and a known pathogenicity factor. For others, the role of syncytium formation in viral dissemination and pathogenicity remains poorly understood. Human cytomegalovirus (HCMV) is an important cause of morbidity and mortality in transplant patients and the leading cause of congenital infections. Clinical HCMV isolates have broad cell tropism but differ in their ability to induce cell-cell fusions, and little is known about the molecular determinants. We developed a system to analyze HCMV glycoprotein B (gB) variants in a defined genetic background. HCMV strains TB40/E and TR were used as vectors to compare the fusogenicity of six gB variants from congenitally infected fetuses with those from three laboratory strains. Five of them conferred the ability to induce fusion of MRC-5 human embryonic lung fibroblasts to one or both backbone strains, as determined by a split GFP-luciferase reporter system. The same gB variants were not sufficient to induce syncytia in infected ARPE-19 epithelial cells, suggesting that additional factors are involved. The system described here allows a systematic comparison of the fusogenicity of viral envelope glycoproteins and may help to clarify whether fusion-promoting variants are associated with increased pathogenicity.

Several biomedical products, like scaffolds, implants, prostheses, and orthoses, require materials having superior physicochemical and biological properties. Polyethylene terephthalate glycol (PETG) is being increasingly used for various biomedical applications. There are a few studies on PETG-based composites, however, natural fibers like silk short fibers reinfored PETG composites have not been attempted. Being a cost-effective widely available material, PETG-Silk combination can be potential biocomposite for several biomedical applications. Here, we report a novel short silk fiber reinforced PETG composite prepared by a wet-mixing route, ensuring homogenous dispersion of the filler. Different ratios (2-10%) of short silk fibers were used to prepare composites with varied compositions. The mechanical, physicochemical, and biological properties of the prepared composites were analyzed. Thermogravimetric analysis showed that such composites are thermally stable up to 390 °C and can be used for thermal extrusion-based manufacturing. The tensile modulus of the samples increased with fiber content; however, the failure strain reduced with fiber content. Furthermore, upon annealing, the tensile modulus increased but, the failure strain of the composites decreased, XRD study revealed that heat treatment has altered the crystalline nature of the composites. Finally, we evaluated the cytocompatibility of the prepared composites to assess their suitability for various biomedical applications.

Oral immunization with the choleric toxin (CT) elicits a high level of protection against its enterotoxin activities and can control cholera in endemic settings. However, the complete B-cell epitope map of the CT responsible for protection remains to be clarified. Here, we have mapped the B-cell linear epitopes of the three chains of the CT protein (CTP) prepared by Spot synthesis. The immunoreactivity of sera from mice immunized with an oral, inactivated vaccine (Schankol†™) was measured against membrane-bound peptides for mapping. Results: Eighteen IgG epitopes were identified; eight in the CTA, three in the CTB, and seven in the protein P. Three epitopes, TQTGFVRHDDGYVST (aa 66-77, Vc/TxA-3), KNGAIFQVE VPGSQN (aa 64-78, Vc/TxB-11), and LNDEHK (aa 90-95, Vc/TxP-16), were chosen to synthesize a multiple antigen peptide that was used to coat ELISA plates to screen immunized mouse sera as a test for an in vitro diagnostics for cholera. Conclusion: Vaccination with inactive CT-generated antibodies against multiple linear epitopes and the selected epitopes can be used to construct immunological reagents for rapid serological diagnosis of cholera with high sensitivity and specificity.

B chromosomes (Bs) or supernumerary chromosomes are extra chromosomes in the species karyotype that can vary in their copy number. Bs are widespread. Usually, the Bs of specimens collected from natural populations are involved in studies. We applied another approach analyzing the Bs in animals of laboratory cultures. In this study, three species of the Macrostomum genus that underwent a recent whole-genome duplication (WGD) were involved. In laboratory lines of M. lignano and M. janickei, the frequency of Bs was less than 1%, while in the laboratory culture of M. mirumnovem, it was nearer 30%. Their number in specimens of the culture varied from 1 to 14. Mosaicism on Bs was discovered in parts of these animals. We analyzed the distribution of Bs among the worms of the laboratory cultures during long-term cultivation, the transmission rates of Bs in the progeny obtained from crosses of worms with different numbers of Bs, and from self-fertilized isolated worms. The DNA content of the Bs in M. mirumnovem was analyzed with the chromosomal in situ suppression (CISS) hybridization of microdissected DNA probes derived from A chromosomes (As). Bs mainly consisted of repetitive DNA. The cytogenetic analysis also revealed the divergence and high variation in large metacentric chromosomes (LMs) containing numerous regions enriched for repeats. The possible mechanisms of the appearance and evolution of Bs and LMs in species of the Macrostomum genus were also discussed.

Immune checkpoints are a set of molecules dysregulated in several human and canine cancers and aberrations of the PD-1/PD-L1 axis are often correlated with a worse prognosis. To gain insight into the role of immune checkpoints in canine diffuse large B-cell lymphoma (cDLBCL), we investigated PD-L1, PD-1 and CD8A expression by RNAscope. Results were correlated with several clinico-pathological features, including treatment, Ki67 index and outcome. A total of 33 dogs treated with CHOP (n=12) or CHOP plus APAVAC (n= 21) were included. PD-L1 signal was diffusely distributed among neoplastic cells, whereas PD-1 and CD8A were localized in tumor infiltrating lymphocytes. However, PD-1 mRNA was also retrieved in tumor cells. An association between PD-L1 and PD-1 scores was identified and a higher risk of relapse and lymphoma-related death was found in dogs treated with chemotherapy alone and dogs with higher PD-L1 and PD-1 scores. The correlation between PD-L1 and PD-1 is in line with the mechanism of immune checkpoints in cancers, where neoplastic cells overexpress PD-L1 that, in turn, binds PD-1 receptors in activated TIL. We also found that Ki67 index was significantly increased in dogs with the highest PD-L1 and PD-1 scores, indirectly suggesting a role in promoting tumor proliferation. Finally, even if the biological consequence of PD-1+ tumor cells is unknown, our findings suggest that PD-1 intrinsic expression in cDLBCL might contribute to tumor growth escaping adaptive immunity.

Chimeric Antigen Receptor (CAR) T-cell therapy has demonstrated high rates of response in recurrent B-cell Acute Lymphoblastic Leukemia in children and young adults. Despite this success, a fraction of patients experience relapse after treatment. Relapse is often preceded by recovery of healthy B cells, which suggests loss or dysfunction of CAR T cells in bone marrow. This site is harder to access, and thus is not monitored as frequently as peripheral blood. Understanding the interplay between B cells, leukemic cells and CAR T cells in bone marrow is paramount in ascertaining the causes of lack of response. In this paper, we put forward a mathematical model representing the interaction between constantly renewing B cells, CAR T cells and leukemic cells in the bone marrow. Our model accounts for the maturation dynamics of B cells and incorporates effector and memory CAR T cells. The model provides a plausible description of the dynamics of the various cellular compartments in bone marrow after CAR T infusion. After exploration of the parameter space, we found that the dynamics of CAR T product and disease were independent of the dose injected, initial B-cell load and tumor burden. We also show theoretically the importance of CAR T product attributes in determining therapy outcome, and have studied a variety of possible response scenarios, including second dosage schemes. We conclude by setting out ideas for the refinement of the model.

Growing evidence has revealed the implication of germline variation in cancer predisposition and prognostication. Here, we describe an analysis of putatively disruptive rare variants across the genomes of 726 patients with B-cell lymphoid neoplasms. We discovered a significant enrichment of 26 genes in germline protein truncating variants (PTVs), affecting cell signaling (MET, JAK2, ANGPT2), energy metabolism (ACO1) and nucleic acid metabolism and repair pathways (NT5E, DCK). Interestingly, some of these variants were restricted to either chronic lymphocytic leukemia (CLL) (i.e., ANGPT2 and AKR1C3) or B-cell lymphoma cases (PNMT, TPT1 and IGHMBP2). Additionally, we detected 1,675 likely disrupting variants in genes associated with cancer, of which 44.75% were novel events and 7.88% were PTVs. Among these, the most frequently affected genes were ATM, BIRC6, CLTCL1A and TSC2. Homozygous or compound heterozygous variants were detected in 28 cases; and coexisting somatic events were observed in 17 patients, some of which affected key lymphoma drivers such as ATM, KMT2D and MYC. Finally, we observed that variants in the helicase gene WRN were independently associated with shorter survival in CLL. Our study results support an important role for rare germline variation in the pathogenesis, clinical presentation and disease outcome of B-cell lymphoid neoplasms.