Structural conservation of HBV-like capsid proteins over hundreds of millions of years despite the shift from non-enveloped to enveloped life-style.

The discovery of nackednaviruses provided new insight into the evolutionary history of the hepatitis B virus (HBV): The common ancestor of HBV and nackednaviruses was non-enveloped and while HBV acquired an envelope during evolution, nackednaviruses remained non-enveloped. We report the capsid structure of the African cichlid nackednavirus (ACNDV), determined by cryo-EM at 3.7 Å resolution. This enables direct comparison with the known capsid structures of HBV and duck HBV, prototypic representatives of the mammalian and avian lineages of the enveloped Hepadnaviridae, respectively. The sequence identity with HBV is 24% and both the ACNDV capsid protein fold and the capsid architecture are very similar to those of the Hepadnaviridae and HBV in particular. Acquisition of the hepadnaviral envelope was thus not accompanied by a major change in capsid structure. Dynamic residues at the spike tip are tentatively assigned by solid-state NMR, while the C-terminal domain is invisible due to dynamics. Solid-state NMR characterization of the capsid structure reveals few conformational differences between the quasi-equivalent subunits of the ACNDV capsid and an overall higher capsid structural disorder compared to HBV. Despite these differences, the capsids of ACNDV and HBV are structurally highly similar despite the 400 million years since their separation.

Pruritus in cutaneous graft-versus-host disease: a systematic review.

Pruritus is a common symptom of cutaneous graft-versus-host disease (GVHD) following haematopoietic stem cell transplantation (HSCT). However, little is known about its prevalence, pathophysiology, perceptual characteristics, impact on quality of life and response to antipruritic therapies. The aim of this review was to determine the current knowledge on pruritus in cutaneous GVHD. The review was conducted according to the Preferred Reporting Items for Systematic Review and Meta-Analyses statement. Of the 338 studies screened, 13 were included. The prevalence of pruritus in cutaneous GVHD was reported in three studies, ranging from 37.0% to 63.8%. Only four trials used pruritus assessment tools. There was little or no information on the intensity of pruritus, its qualitative perception, the location of pruritus, and the impact of pruritus on quality of life. Antipruritic treatments for GVHD-associated pruritus were mentioned in five studies (38.5%), including topical ointments (steroids, tacrolimus, calcipotriene), broadband UVB, systemic antihistamines and oral ursodeoxycholic acid. In conclusion, although pruritus in cutaneous GVHD appears to be common, very little is known about the pathophysiology, impact on quality of life and effective treatment options. Basic research and controlled clinical trials are warranted to improve knowledge and management of this important issue.

Accurate prediction of 11B NMR chemical shift of BODIPYs via machine learning.

In this article, we present the results of developing a model based on an RFR machine learning method using the ISIDA fragment descriptors for predicting the 11B NMR chemical shift of BODIPYs. The model is freely available at https://ochem.eu/article/146458. The model demonstrates the high quality of predicting the 11B NMR chemical shift (RMSE, 5CV (FINALE training set) = 0.40 ppm, RMSE (TEST set) = 0.14 ppm). In addition, we compared the "cost" and the user-friendliness for calculations using the quantum-chemical model with the DFT/GIAO approach. The 11B NMR chemical shift prediction accuracy (RMSE) of the model considered is more than three times higher and tremendously faster than the DFT/GIAO calculations. As a result, we provide a convenient tool and database that we collected for all researchers, that allows them to predict the 11B NMR chemical shift of boron-containing dyes. We believe that the new model will make it easier for researchers to correctly interpret the 11B NMR chemical shifts experimentally determined and to select more optimal conditions to perform an NMR experiment.

Nondestructive label-free detection of peritumoral white matter damage using cross-polarization optical coherence tomography.

Introduction: To improve the quality of brain tumor resections, it is important to differentiate zones with myelinated fibers destruction from tumor tissue and normal white matter. Optical coherence tomography (OCT) is a promising tool for brain tissue visualization and in the present study, we demonstrate the ability of cross-polarization (CP) OCT to detect damaged white matter and differentiate it from normal and tumor tissues. Materials and methods: The study was performed on 215 samples of brain tissue obtained from 57 patients with brain tumors. The analysis of the obtained OCT data included three stages: 1) visual analysis of structural OCT images; 2) quantitative assessment based on attenuation coefficients estimation in co- and cross-polarizations; 3) building of color-coded maps with subsequent visual analysis. The defining characteristics of structural CP OCT images and color-coded maps were determined for each studied tissue type, and then two classification tests were passed by 8 blinded respondents after a training. Results: Visual assessment of structural CP OCT images allows detecting white matter areas with damaged myelinated fibers and differentiate them from normal white matter and tumor tissue. Attenuation coefficients also allow distinguishing all studied brain tissue types, while it was found that damage to myelinated fibers leads to a statistically significant decrease in the values of attenuation coefficients compared to normal white matter. Nevertheless, the use of color-coded optical maps looks more promising as it combines the objectivity of optical coefficient and clarity of the visual assessment, which leads to the increase of the diagnostic accuracy of the method compared to visual analysis of structural OCT images. Conclusions: Alteration of myelinated fibers causes changes in the scattering properties of the white matter, which gets reflected in the nature of the received CP OCT signal. Visual assessment of structural CP OCT images and color-coded maps allows differentiating studied tissue types from each other, while usage of color-coded maps demonstrates higher diagnostic accuracy values in comparison with structural images (F-score = 0.85-0.86 and 0.81, respectively). Thus, the results of the study confirm the potential of using OCT as a neuronavigation tool during resections of brain tumors.

Association of Rural Residence and Receipt of Guideline-Concordant Care for Locoregional Colon Cancer.

BACKGROUND: Incidence and mortality rates of colon cancer (CC) are higher in rural populations. This study aimed to determine whether rural residence is associated with differences in guideline-concordant care for patients with locoregional CC. METHODS: Patients with stages I-III CC from 2006 to 2016 were identified in the National Cancer Database. Guideline-concordant care (GCC) was defined as resection with negative margins, adequate nodal harvest, and receipt of adjuvant chemotherapy for patients with high-risk stage II or III disease. Multivariable logistic regression (MVR) was performed to evaluate the association between rural residence and the odds of receiving GCC. Effect modification was evaluated using a two-way interaction for rurality by insurance status. RESULTS: Of 320,719 identified patients, 6191 (2%) were rural. The rural patients had lower income and lower educational status than the urban patients and were more often Medicare-insured (p < 0.001). The rural patients traveled farther (44.5 vs. 7.5 miles; p < 0.001), although time to surgery was similar (8 vs. 9 days). The two cohorts had similar resection rates (98.8% vs. 98.0%), margin positivity (5.4% vs. 4.8%), adequate lymphadenectomy (80.9% vs. 83.0%), adjuvant chemotherapy (stage III: 69.2% vs. 68.7%), and receipt of GCC (66.5% vs. 68.3%). In the MVR, the odds of receiving GCC did not differ between the rural and urban patients (odds ratio, 0.99; 95% confidence interval, 0.94-1.05%). Insurance status did not differentially influence the receipt of GCC by the rural versus the urban patients (interaction: p = 0.83). CONCLUSIONS: Rural and urban patients with locoregional CC are equally likely to receive GCC, suggesting that differences in cancer care delivery may not explain rural-urban disparities.

Hydroxyurea treatment for sickle cell anemia during pregnancy and lactation: Current evidence and knowledge gaps.

Sickle cell anemia (SCA) is a life-threatening genetic condition contributing to high-risk pregnancies affecting both the mother and fetus. With improved management of children with SCA, this life-threatening hematological disorder has evolved into a chronic disease of adults, and consequently parenthood has now become a possible and important life goal for many patients. Providing continuous management with healthy red blood cell function and avoiding SCA-associated complications, such as pain crises, acute chest syndrome, and stroke, are crucial for a healthy pregnancy. Despite its excellent safety profile in non-pregnant adults and children, and based on theoretical concerns derived from data using animal models and supraphysiological dosing, hydroxyurea is currently contraindicated for pregnant and lactating women with SCA. Clinical experience of hydroxyurea use during pregnancy is increasingly reported, however, and has shown inconsistent results of fetal or infant adverse effects. How the hydroxyurea exposure level may correlate with pregnancy outcomes is still unclear. Accordingly, efforts should be made to systemically evaluate exposure and safety of hydroxyurea treatment during pregnancy and lactation. Novel approaches such as physiologically based pharmacokinetic (PBPK) modeling, coupled with the ex vivo human placental cotyledon perfusion assay, provide opportunities to understand hydroxyurea exposure not only in pregnant women but also in the developing fetus. Combined with animal data, research using these approaches might be able to define safe and effective hydroxyurea dosing regimens for pregnant and lactating women with SCA, when the benefits of continuing hydroxyurea treatment likely outweigh the risks of non-treatment, by avoiding substantial morbidity and even mortality for both mothers and infants.

PIP4K2B is mechanoresponsive and controls heterochromatin-driven nuclear softening through UHRF1.

Phosphatidylinositol-5-phosphate (PtdIns5P)-4-kinases (PIP4Ks) are stress-regulated phosphoinositide kinases able to phosphorylate PtdIns5P to PtdIns(4,5)P2. In cancer patients their expression is typically associated with bad prognosis. Among the three PIP4K isoforms expressed in mammalian cells, PIP4K2B is the one with more prominent nuclear localisation. Here, we unveil the role of PIP4K2B as a mechanoresponsive enzyme. PIP4K2B protein level strongly decreases in cells growing on soft substrates. Its direct silencing or pharmacological inhibition, mimicking cell response to softness, triggers a concomitant reduction of the epigenetic regulator UHRF1 and induces changes in nuclear polarity, nuclear envelope tension and chromatin compaction. This substantial rewiring of the nucleus mechanical state drives YAP cytoplasmic retention and impairment of its activity as transcriptional regulator, finally leading to defects in cell spreading and motility. Since YAP signalling is essential for initiation and growth of human malignancies, our data suggest that potential therapeutic approaches targeting PIP4K2B could be beneficial in the control of the altered mechanical properties of cancer cells.

Molecular Orientation of Carboxylate Anions at the Water-Air Interface Studied with Heterodyne-Detected Vibrational Sum-Frequency Generation.

The carboxylate anion group plays an important role in many (bio)chemical systems and polymeric materials. In this work, we study the orientation of carboxylate anions with various aliphatic and aromatic substituents at the water-air interface by probing the carboxylate stretch vibrations with heterodyne-detected vibrational sum-frequency generation spectroscopy in different polarization configurations. We find that carboxylate groups with small aliphatic substituents show a large tilt angle with respect to the surface normal and that this angle decreases with increasing size of the substituent. We further use the information about the orientation of the carboxylate group to determine the hyperpolarizability components of this group.

Middle meningeal artery embolization as a perioperative adjunct to surgical evacuation of nonacute subdural hematomas: An multicenter analysis of safety and efficacy.

BACKGROUND: By 2030, nonacute subdural hematomas (NASHs) will likely be the most common cranial neurosurgery pathology. Treatment with surgical evacuation may be necessary, but the recurrence rate after surgery is as high as 30%. Minimally invasive middle meningeal artery embolization (MMAE) during the perioperative period has been posited as an adjunctive treatment to decrease the potential for recurrence after surgical evacuation. We evaluated the safety and efficacy of concurrent MMAE in a multi-institutional cohort. METHODS: Data from 145 patients (median age 73 years) with NASH who underwent surgical evacuation and MMAE in the perioperative period were retrospectively collected from 15 institutions. The primary outcome was the rate of recurrence requiring repeat surgical intervention. We collected clinical, treatment, and radiographic data at initial presentation, after evacuation, and at 90-day follow-up. Outcomes data were also collected. RESULTS: Preoperatively, the median hematoma width was 18 mm, and subdural membranes were present on imaging in 87.3% of patients. At 90-day follow-up, median NASH width was 6 mm, and 51.4% of patients had at least a 50% decrease of NASH size on imaging. Eight percent of treated NASHs had recurrence that required additional surgical intervention. Of patients with a modified Rankin Scale score at last follow-up, 87.2% had the same or improved mRS score. The total all-cause mortality was 6.0%. CONCLUSION: This study provides evidence from a multi-institutional cohort that performing MMAE in the perioperative period as an adjunct to surgical evacuation is a safe and effective means to reduce recurrence in patients with NASHs.

Anemia in children aged 6-59 months was significantly associated with maternal anemia status in rural Zimbabwe.

Globally, anemia is a public health problem affecting mostly women of reproductive age (WRA, n = 452) and children aged 6-59 months (n = 452) from low- and lower-middle-income countries. This cross-sectional study assessed the prevalence and determinants of anemia in WRA and children aged 6-59 months in rural Zimbabwe. The venous blood sample was measured for hemoglobin utilizing a HemoCue machine. Anthropometric indices were assessed and classified based on World Health Organization standards. Socioeconomic characteristics were assessed. The median (±inter quartile range (IQR)) age of WRA was 29 ± 12 years and that for children was 29 ± 14 months. The prevalence of anemia was 29.6% and 17.9% in children and WRA, respectively, while the median (±IQR) hemoglobin levels were 13.4 ± 1.8 and 11.7 ± 1.5 g/dl among women and children, respectively. Multiple logistic regression analysis was used to assess determinants of anemia. Anemia in children was significantly associated with maternal anemia (odds ratio (OR) = 2.02; 95% CI 1.21-3.37; p = .007) and being a boy (OR = 0.63; 95% CI 0.41-0.95; p = .029), while anemia in WRA was significantly associated with the use of unimproved dug wells as a source of drinking water (OR = 0.36; 95% CI 0.20-0.66; p = .001) and lack of agricultural land ownership (OR = 0.51; 95% CI 0.31-0.85; p = .009). Anemia is a public health problem in the study setting. The positive association between maternal and child anemia reflects the possibility of cross-generational anemia. Therefore, interventions that focus on improving preconceptual and maternal nutritional status may help to reduce anemia in low-income settings.

Inhomogeneous Superconductivity Onset in FeSe Studied by Transport Properties.

Heterogeneous superconductivity onset is a common phenomenon in high-Tc superconductors of both the cuprate and iron-based families. It is manifested by a fairly wide transition from the metallic to zero-resistance states. Usually, in these strongly anisotropic materials, superconductivity (SC) first appears as isolated domains. This leads to anisotropic excess conductivity above Tc, and the transport measurements provide valuable information about the SC domain structure deep within the sample. In bulk samples, this anisotropic SC onset gives an approximate average shape of SC grains, while in thin samples, it also indicates the average size of SC grains. In this work, both interlayer and intralayer resistivity were measured as a function of temperature in FeSe samples of various thicknesses. To measure the interlayer resistivity, FeSe mesa structures oriented across the layers were fabricated using FIB. As the sample thickness decreases, a significant increase in superconducting transition temperature Tc is observed: Tc raises from 8 K in bulk material to 12 K in microbridges of thickness ∼40 nm. We applied analytical and numerical calculations to analyze these and earlier data and find the aspect ratio and size of the SC domains in FeSe consistent with our resistivity and diamagnetic response measurements. We propose a simple and fairly accurate method for estimating the aspect ratio of SC domains from Tc anisotropy in samples of various small thicknesses. The relationship between nematic and superconducting domains in FeSe is discussed. We also generalize the analytical formulas for conductivity in heterogeneous anisotropic superconductors to the case of elongated SC domains of two perpendicular orientations with equal volume fractions, corresponding to the nematic domain structure in various Fe-based superconductors.

COVID-19 Biogenesis and Intracellular Transport.

SARS-CoV-2 is responsible for the COVID-19 pandemic. The structure of SARS-CoV-2 and most of its proteins of have been deciphered. SARS-CoV-2 enters cells through the endocytic pathway and perforates the endosomes' membranes, and its (+) RNA appears in the cytosol. Then, SARS-CoV-2 starts to use the protein machines of host cells and their membranes for its biogenesis. SARS-CoV-2 generates a replication organelle in the reticulo-vesicular network of the zippered endoplasmic reticulum and double membrane vesicles. Then, viral proteins start to oligomerize and are subjected to budding within the ER exit sites, and its virions are passed through the Golgi complex, where the proteins are subjected to glycosylation and appear in post-Golgi carriers. After their fusion with the plasma membrane, glycosylated virions are secreted into the lumen of airways or (seemingly rarely) into the space between epithelial cells. This review focuses on the biology of SARS-CoV-2's interactions with cells and its transport within cells. Our analysis revealed a significant number of unclear points related to intracellular transport in SARS-CoV-2-infected cells.

Spatio-Temporal Dynamics of Diffusion-Associated Deformations of Biological Tissues and Polyacrylamide Gels Observed with Optical Coherence Elastography.

In this work, we use the method of optical coherence elastography (OCE) to enable quantitative, spatially resolved visualization of diffusion-associated deformations in the areas of maximum concentration gradients during diffusion of hyperosmotic substances in cartilaginous tissue and polyacrylamide gels. At high concentration gradients, alternating sign, near-surface deformations in porous moisture-saturated materials are observed in the first minutes of diffusion. For cartilage, the kinetics of osmotic deformations visualized by OCE, as well as the optical transmittance variations caused by the diffusion, were comparatively analyzed for several substances that are often used as optical clearing agents, i.e., glycerol, polypropylene, PEG-400 and iohexol, for which the effective diffusion coefficients were found to be 7.4 ± 1.8, 5.0 ± 0.8, 4.4 ± 0.8 and 4.6 ± 0.9 × 10-6 cm2/s, respectively. For the osmotically induced shrinkage amplitude, the influence of the organic alcohol concentration appears to be more significant than the influence of its molecular weight. The rate and amplitude of osmotically induced shrinkage and dilatation in polyacrylamide gels is found to clearly depend on the degree of their crosslinking. The obtained results show that observation of osmotic strains with the developed OCE technique can be applied for structural characterization of a wide range of porous materials, including biopolymers. In addition, it may be promising for revealing alterations in the diffusivity/permeability of biological tissues that are potentially associated with various diseases.

Synthesis and Functional Characterization of CoxFe3-xO4-BaTiO3 Magnetoelectric Nanocomposites for Biomedical Applications.

Nowadays, magnetoelectric nanomaterials are on their way to finding wide applications in biomedicine for various cancer and neurological disease treatment, which is mainly restricted by their relatively high toxicity and complex synthesis. This study for the first time reports novel magnetoelectric nanocomposites of CoxFe3-xO4-BaTiO3 series with tuned magnetic phase structures, which were synthesized via a two-step chemical approach in polyol media. The magnetic CoxFe3-xO4 phases with x = 0.0, 0.5, and 1.0 were obtained by thermal decomposition in triethylene glycol media. The magnetoelectric nanocomposites were synthesized by the decomposition of barium titanate precursors in the presence of a magnetic phase under solvothermal conditions and subsequent annealing at 700 °C. X-ray diffraction revealed the presence of both spinel and perovskite phases after annealing with average crystallite sizes in the range of 9.0-14.5 nm. Transmission electron microscopy data showed two-phase composite nanostructures consisting of ferrites and barium titanate. The presence of interfacial connections between magnetic and ferroelectric phases was confirmed by high-resolution transmission electron microscopy. Magnetization data showed expected ferrimagnetic behavior and σs decrease after the nanocomposite formation. Magnetoelectric coefficient measurements after the annealing showed non-linear change with a maximum of 89 mV/cm*Oe with x = 0.5, 74 mV/cm*Oe with x = 0, and a minimum of 50 mV/cm*Oe with x = 0.0 core composition, that corresponds with the coercive force of the nanocomposites: 240 Oe, 89 Oe and 36 Oe, respectively. The obtained nanocomposites show low toxicity in the whole studied concentration range of 25-400 µg/mL on CT-26 cancer cells. The synthesized nanocomposites show low cytotoxicity and high magnetoelectric effects, therefore they can find wide applications in biomedicine.

Unexpected Effects of Sulfate and Sodium Chloride Application on Yield Qualitative Characteristics and Symmetry Indicators of Hard and Soft Wheat Kernels.

The heterogeneity of grain quality can lead to limited predictability of qualitative and quantitative characteristics of the wheat yield, especially with an increase in the importance of drought and salinity caused by climate change. This study was undertaken with the aim of creating basic tools for phenotyping and assessing the sensitivity of genotypes to salt effects at the level of some wheat kernel attributes. The study considers 36 variants of the experiment, including four wheat cultivars-Zolotaya, Ulyanovskaya 105, Orenburgskaya 10, Orenburgskaya 23; three treatment variants-control (without salt) and two salts exposure (NaCl at a concentration of 1.1 g L-1 and Na2SO4 at a concentration of 0.4 g L-1); as well as three options for the arrangement of kernels in a simple spikelet-left, middle, and right. It has been established that the salt exposure had a positive effect on the percentage of kernel fulfilling in the cultivars Zolotaya, Ulyanovskaya 105, and Orenburgskaya 23 compared to control. The kernels of the Orenburgskaya 10 variety matured better in the experiment with Na2SO4 exposure, while the control variant and NaCl gave the same effect. When exposed to NaCl, significantly greater values of weight, transverse section area, and transverse section perimeter of the kernel were noted in the cv Zolotaya and Ulyanovskaya 105. Cv Orenburgskaya 10 responded positively to the use of Na2SO4. This salt caused an increase in the area, length, and width of the kernel. The fluctuating asymmetry of the left, middle, and right kernels in the spikelet was calculated. In the cv Orenburgskaya 23 the salts affected only the kernel perimeter among parameters examined. The indicators of the general (fluctuating) asymmetry were lower in the experiments with the use of salts, i.e., kernels were more symmetrical than in the control variant, both for the cultivar as a whole and when compared taking into account the kernel location in spikelet. However, this result was unexpected, since salt stress inhibited a number of morphological parameters: the number and average length of embryonic, adventitious, and nodal roots, flag leaf area, plant height, dry biomass accumulation, and plant productivity indicators. The study showed that low concentrations of salts can positively affect the fulfilling of kernels (the absence of a cavity inside the kernel) and the symmetry of the left and right sides of the kernel.

Thermal and Electrical Properties of Additively Manufactured Polymer-Boron Nitride Composite.

The efficiency of electronic microchip-based devices increases with advancements in technology, while their size decreases. This miniaturization leads to significant overheating of various electronic components, such as power transistors, processors, and power diodes, leading to a reduction in their lifespan and reliability. To address this issue, researchers are exploring the use of materials that offer efficient heat dissipation. One promising material is a polymer-boron nitride composite. This paper focuses on 3D printing using digital light processing of a model of a composite radiator with different boron nitride fillings. The measured absolute values of the thermal conductivity of such a composite in the temperature range of 3-300 K strongly depend on the concentration of boron nitride. Filling the photopolymer with boron nitride leads to a change in the behavior of the volt-current curves, which may be associated with the occurrence of percolation currents during the deposition of boron nitride. The ab initio calculations show the behavior and spatial orientation of BN flakes under the influence of an external electric field at the atomic level. These results demonstrate the potential use of photopolymer-based composite materials filled with boron nitride, which are manufactured using additive techniques, in modern electronics.

A Multimodal Phantom for Visualization and Assessment of Histotripsy Treatments on Ultrasound and X-Ray Imaging.

OBJECTIVE: Histotripsy is an emerging non-invasive, non-ionizing and non-thermal focal tumor therapy. Although histotripsy targeting is currently based on ultrasound (US), other imaging modalities such as cone-beam computed tomography (CBCT) have recently been proposed to enable the treatment of tumors not visible on ultrasound. The objective of this study was to develop and evaluate a multi-modality phantom to facilitate the assessment of histotripsy treatment zones on both US and CBCT imaging. METHODS: Fifteen red blood cell phantoms composed of alternating layers with and without barium were manufactured. Spherical 25-mm histotripsy treatments were performed, and treatment zone size and location were measured on CBCT and ultrasound. Sound speed, impedance and attenuation were measured for each layer type. RESULTS: The average ± standard deviation signed difference between measured treatment diameters was 0.29 ± 1.25 mm. The Euclidean distance between measured treatment centers was 1.68 ± 0.63 mm. The sound speed in the different layers ranged from 1491 to 1514 m/s and was within typically reported soft tissue ranges (1480-1560 m/s). In all phantoms, histotripsy resulted in sharply delineated treatment zones, allowing segmentation in both modalities. CONCLUSION: These phantoms will aid in the development and validation of X-ray-based histotripsy targeting techniques, which promise to expand the scope of treatable lesions beyond only those visible on ultrasound.