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In our original white paper published in the The Journal of Physiology in 2016, we set out our knowledge of the structural and functional organization of cardiac autonomic control, how it remodels during disease, and approaches to exploit such knowledge for autonomic regulation therapy. The aim of this update is to build on this original blueprint, highlighting the significant progress which has been made in the field since and major challenges and opportunities that exist with regard to translation. Imbalances in autonomic responses, while beneficial in the short term, ultimately contribute to the evolution of cardiac pathology. As our understanding emerges of where and how to target in terms of actuators (including the heart and intracardiac nervous system (ICNS), stellate ganglia, dorsal root ganglia (DRG), vagus nerve, brainstem, and even higher centres), there is also a need to develop sensor technology to respond to appropriate biomarkers (electrophysiological, mechanical, and molecular) such that closed-loop autonomic regulation therapies can evolve. The goal is to work with endogenous control systems, rather than in opposition to them, to improve outcomes., (© 2024 The Author(s). The Journal of Physiology published by John Wiley & Sons Ltd on behalf of The Physiological Society.)

It is known that physical activity is beneficial for the prevention of osteoarthritis (OA), but specific discussions on which types and levels of physical activity are more effective in reducing the incidence of OA are restricted. This study is aimed at exploring the correlation concerning the types of physical activity, levels of physical activity, and the incidence of OA by assessing the participation in five typical forms of physical activity (vigorous work activity, vigorous recreational activity, moderate work activity, moderate recreational activity, and walking or bicycling). Cross-sectional study was conducted. Self-reported data on specific types of physical activity were obtained from individuals in the National Health and Nutrition Examination Survey (NHANES) from 2007 to 2020 with the use of the Physical Activity Questionnaire (PAQ). The incidence of OA was assessed through the "Health Conditions" questionnaire section of NHANES. Weighted logistic regression analysis was employed to study the correlation between physical activity types and levels, and the incidence of OA. Different kinds of physical activity and physical activity levels have varying impacts on the incidence of OA. Among the types of physical activity, vigorous recreational activity and moderate recreational activity are found to have a preventive effect on OA. In terms of physical activity levels, low physical activity levels of moderate work activity are associated with an increased risk of OA, while moderate physical activity levels are confirmed to have a protective effect against OA in the age groups of 20-44 and 45-64. However, gender-stratified analyses reveal that both low and moderate physical activity levels provide protection against OA in males, with moderate physical activity levels showing a more significant protective effect., (© 2024. The Author(s).)

The nucleus of the solitary tract (NTS) receives direct viscerosensory vagal afferent input that drives autonomic reflexes, neuroendocrine function and modulates behaviour. A subpopulation of NTS neurons project to the nucleus accumbens (NAc); however, the function of this NTS-NAc pathway remains unknown. A combination of neuroanatomical tracing, slice electrophysiology and fibre photometry was used in mice and/or rats to determine how NTS-NAc neurons fit within the viscerosensory network. NTS-NAc projection neurons are predominantly located in the medial and caudal portions of the NTS with 54 ± 7% (mice) and 65 ± 3% (rat) being TH-positive, representing the A2 NTS cell group. In horizontal brainstem slices, solitary tract (ST) stimulation evoked excitatory post-synaptic currents (EPSCs) in NTS-NAc projection neurons. The majority (75%) received low-jitter, zero-failure EPSCs characteristic of monosynaptic ST afferent input that identifies them as second order to primary sensory neurons. We then examined whether NTS-NAc neurons respond to cholecystokinin (CCK, 20 μg/kg ip) in vivo in both mice and rats. Surprisingly, there was no difference in the number of activated NTS-NAc cells between CCK and saline-treated mice. In rats, just 6% of NTS-NAc cells were recruited by CCK. As NTS TH neurons are the primary source for NAc noradrenaline, we measured noradrenaline release in the NAc and showed that NAc noradrenaline levels declined in response to cue-induced reward retrieval but not foot shock. Combined, these findings suggest that high-fidelity afferent information from viscerosensory afferents reaches the NAc. These signals are likely unrelated to CCK-sensitive vagal afferents but could interact with other sensory and higher order inputs to modulate learned appetitive behaviours., (© 2024 The Author(s). Journal of Neurochemistry published by John Wiley & Sons Ltd on behalf of International Society for Neurochemistry.)

Simple Summary: Echocardiography and radiography are the two diagnostic imaging methods recommended for the staging of mitral valve disease (MVD) in dogs. In the absence of echocardiography, the vertebral heart size and the vertebral left atrial size (VLAS) can be used for staging. Other methods to assess the left atrial size (LAS) on dogs' radiographs are the modified-vertebral left atrial size (M-VLAS) and the radiographic left atrial dimension (RLAD). They have the transformation of LAS into vertebral units in common. The thoracic inlet (TI) was proposed as a reference point to assess the cardiac silhouette of dogs with MVD. We hypothesized that the TI can be a reference point clinically useful to assess the LAS on dogs' right thoracic X-rays and differentiate different MVD stages. The LAS was measured in a general population of healthy dogs using the TI as a reference with the TILAS method. A group of control dogs from that population was matched to dogs in different MVD stages for LAS comparison using different methods: TILAS, VLAS, M-VLAS, and RLAD. The TILAS was significantly different between control dogs and MVD dogs, increasing with the disease stage, as did VLAS, M-VLAS, and RLAD. The TILAS accuracy to distinguished dogs with cardiac enlargement was like VLAS and RLAD. The left atrial size increases (LAS) in patients with mitral valve disease (MVD) as the disease progresses. The vertebral left atrial size (VLAS), the modified-vertebral left atrial size (M-VLAS), and the radiographic left atrial dimension (RLAD) are methods reported to assess LAS on dogs' radiographs. All these methods transform the LAS into vertebral units. The thoracic inlet (TI) has been used as a reliable reference point to measure the cardiac silhouette of dogs with MVD in different stages. The objective of this study was to assess the clinical utility of measuring a dog LAS on right thoracic X-rays using the TI as a reference and determine whether it could differentiate dogs in different MVD stages. LAS was divided by the TI to obtain the thoracic inlet left atrial score (TILAS). This was a retrospective observational study including 135 apparently healthy dogs performed to assess their LAS with four different methods: VLAS, M-VLAS, RLAD, and TILAS. Thirty-six dogs from the general population were selected and compared to 100 dogs in different MVD stages. The TILAS was significantly different between the control dogs and MVD dogs, increasing with the disease stage: control dogs 0.51 ± 0.08, B1 0.57 ± 0.14, B2 0.75 ± 0.13, and C 0.84 ± 0.18. VLAS, M-VLAS, and RLAD also increased as the disease progressed, as shown in previous studies. The TILAS accuracy to distinguish MVD dogs with cardiac enlargement was comparable to VLAS, M-VLAS, and RLAD (AUC 0.91 vs. 0.93, 0.90, and 0.94 respectively). A TILAS > 0.8 can identify dogs with cardiac enlargement secondary to MVD. [ABSTRACT FROM AUTHOR]

The appearance of several variants of concern (VOCs) of SARS-CoV-2 affects the efficacy of currently available vaccines and causes continuous spread and reinfection between humans. These variants possess different spike (S) protein mutations, which could affect viral pathogenicity, transmission, and immune escape. Herein, we develop a synthetic codon-optimized DNA vaccine (VIU-1007) expressing full-length S protein. The developed vaccine is stabilized by two K986P and V987P proline substitutions and resistant to cleavage by proteases such as furin by deletion of arginine residues (R682, R683, and R685) in multibasic furin cleavage site (RRAR). Additionally, it carries K417N, E484K, N501Y, and D614G substitutions in the receptor binding domain (RBD) derived from the beta VOC. Following the validation and characterization of the in vitro S protein expression, the humoral and cellular immunogenicity of VIU-1007 was assessed in immunized Balb/c mice. While both regimens elicited a Th-1-biased immune response based on S1-specific binding IgG isotypes, three vaccine doses significantly enhanced IgG levels. Furthermore, CD4+ and CD8+ memory T cell responses in spleens and draining inguinal lymph nodes were significantly higher in mice received three doses of VIU-1007 when compared to those received two doses only. Importantly, sera from mice immunized with three doses showed broad neutralization breadth against several SARS-CoV-2 variants, including alpha, beta, gamma, delta, and omicron VOCs. Moreover, the sera showed limited neutralization capacity against SARS-CoV-1, Bat SARS-like coronavirus WIV1, and MERS-CoV. Together, while these data suggest the presence of common neutralizing-rich epitopes between SARS-CoV-2 variants and some other betacoronaviruses, the ongoing evolution of SARS-CoV-2 could result in escape from vaccine-induced immunity, which requires a continuous update of vaccines. [ABSTRACT FROM AUTHOR]

The continuous emergence of SARS-CoV-2 variants has led to a protracted global COVID-19 pandemic with significant impacts on public health and global economy. While there are currently available SARS-CoV-2 vaccines and therapeutics, most of the FDA-approved antiviral agents directly target viral proteins. However, inflammation is the initial immune pathogenesis induced by SARS-CoV-2 infection, there is still a need to find additional agents that can control the virus in the early stages of infection to alleviate disease progression for the next pandemic. Here, we find that both the spike protein and its receptor CD147 are crucial for inducing inflammation by SARS-CoV-2 in THP-1 monocytic cells. Moreover, we find that 3-epi-betulin, isolated from Daphniphyllum glaucescens, reduces the level of proinflammatory cytokines induced by SARS-CoV-2, consequently resulting in a decreased viral RNA accumulation and plaque formation. In addition, 3-epi-betulin displays a broad-spectrum inhibition of entry of SARS-CoV-2 pseudoviruses, including Alpha (B.1.1.7), Eplison (B.1.429), Gamma (P1), Delta (B.1.617.2) and Omicron (BA.1). Moreover, 3-epi-betulin potently inhibits SARS-CoV-2 infection with an EC50 of <20 μM in Calu-3 lung epithelial cells. Bioinformatic analysis reveals the chemical interaction between the 3-epi-betulin and the spike protein, along with the critical amino acid residues in the spike protein that contribute to the inhibitory activity of 3-epi-betulin against virus entry. Taken together, our results suggest that 3-epi-betulin exhibits dual effect: it reduces SARS-CoV-2-induced inflammation and inhibits virus entry, positioning it as a potential antiviral agent against SARS-CoV-2. [ABSTRACT FROM AUTHOR]

This paper shows the research conducted to respond to a continuous requirement of justice regarding the application of scientifically supported forensic tools. Considering ontological engineering as the appropriate framework to respond to this requirement, the article presents OntoFoCE (Spanish abbreviation for Ontology for Electronic Mail Forensics), a specific ontology for the forensic analysis of emails. The purpose of this ontology is to help the computer expert in the validation of an email presented as judicial evidence. OntoFoCE is the fundamental component of the ObE Forensics (Ontology-based Email Forensics) tool. Although there are numerous forensic tools to analyze emails, the originality of the one proposed here lies in the implementation of semantic technologies to represent the traceability of the email transmission process. From that point on, it is possible to provide answers to the items of digital evidence subject to the expert examination. These answers make it possible to support these evidence items in the forensic analysis of an email and to guarantee the gathering of scientifically and technically accepted results that are valid for justice. Thus, the research question that is tried to be answered is: Is it possible to apply ontological engineering as a scientific support to design and develop a forensic tool that allows automatic answers to the evidence items subject to the expert examination in the forensic analysis of emails? [ABSTRACT FROM AUTHOR]

Although chimeric antigen receptor (CAR) T cells have demonstrated significant promise in suppressing hematopoietic cancers, their applications in treating solid tumors have been limited by onset of CAR T cell exhaustion that accompanies continuous CAR T cell exposure to tumor antigen. To address this limitation, we have exploited the abilities of recently designed universal CARs to bind fluorescein and internalize a fluorescein-TLR7 agonist conjugate by CAR-mediated endocytosis. We demonstrate here that anti-fluorescein CAR-mediated uptake of a fluorescein-TLR7-3 conjugate can reactivate exhausted CAR T cells, leading to dramatic reduction in T cell exhaustion markers (PD-1 + Tim-3 + ) and shrinkage of otherwise resistant tumors without inducing systemic activation of the immune system. We conclude that CAR T cell exhaustion can be reversed by administration of a CAR-targeted TLR7 agonist, thereby enabling the CAR T cells to successfully treat solid tumors without incurring the systemic toxicity that commonly accompanies administration of nontargeted TLR7 agonists., (© 2022 Wiley-VCH GmbH.)

Photosynthetic pigment–protein complexes control local chlorophyll (Chl) transition frequencies through a variety of electrostatic and steric forces. Site-directed mutations can modify this local spectroscopic tuning, providing critical insight into native photosynthetic functions and offering the tantalizing prospect of creating rationally designed Chl proteins with customized optical properties. Unfortunately, at present, no proven methods exist for reliably predicting mutation-induced frequency shifts in advance, limiting the method's utility for quantitative applications. Here, we address this challenge by constructing a series of point mutants in the water-soluble chlorophyll protein of Lepidium virginicum and using them to test the reliability of a simple computational protocol for mutation-induced site energy shifts. The protocol uses molecular dynamics to prepare mutant protein structures and the charge density coupling model of Adolphs et al. [Photosynth. Res. 95, 197–209 (2008)] for site energy prediction; a graphical interface that implements the protocol automatically is published online at http://nanohub.org/tools/pigmenthunter. With the exception of a single outlier (presumably due to unexpected structural changes), we find that the calculated frequency shifts match the experiment remarkably well, with an average error of 1.6 nm over a 9 nm spread in wavelengths. We anticipate that the accuracy of the method can be improved in the future with more advanced sampling of mutant protein structures. [ABSTRACT FROM AUTHOR]

Molecular electronic or vibrational states can be superimposed temporarily in an extremely short laser pulse, and the superposition-state transients formed therein receive much attention, owing to the extensive interest in molecular fundamentals and the potential applications in quantum information processing. Using the crossed-beam ion velocity map imaging technique, we disentangle two distinctly different pathways leading to the forward-scattered N2+ yields in the large impact-parameter charge transfer from low-energy Ar+ to N2. Besides the ground-state (X2Σg+) N2+ produced in the energy-resonant charge transfer, a few slower N2+ ions are proposed to be in the superpositions of the X2Σg+-A2Πu and A2Πu-B2Σu+ states on the basis of the accidental degeneracy or energetic closeness of the vibrational states around the X2Σg+-A2Πu and A2Πu-B2Σu+ crossings in the non-Franck–Condon region. This finding potentially shows a brand-new way to prepare the superposition-state molecular ion. [ABSTRACT FROM AUTHOR]

Azoaromatics are an important class of functional organic molecules. Herein, we formulated a sustainable metal-free photocatalytic oxidative coupling of arylamines to azoaromatics at the charged aqueous interfaces (CAIs) of micelles with excellent yields (up to 100%) and selectivity (100%) under ambient air atmosphere. The micellar surface acts as an efficient scaffold to host both Eosin Y (EY) as the photocatalyst (PC) and arylamines as substrates for a non-diffusive photoinduced electron transfer (PET) with a time constant of 0.3 ps. The present approach shows fast kinetics (4 h) and a broad substrate scope with only 0.6 mol% of PC. Our present approach outperforms all the previously reported catalytic methodologies. This remarkable boosting of the catalytic efficacy arises mainly due to the non-diffusive PET and modulation of redox potentials at the CAI. Being the most sustainable and first report on the aqueous phase synthesis of azo compounds, this work opens newer opportunities in the synthesis of azoaromatics. [ABSTRACT FROM AUTHOR]

Background: Omicron's high transmissibility and variability present new difficulties for COVID-19 vaccination prevention and therapy. In this article, we analyzed the sensitivity of vaccine-induced antibodies as well as the effect of booster vaccinations against Omicron sublineages. Methods: We looked for Randomized Controlled Trials and cohort studies that reported the COVID-19 vaccines against Omicron sublineages up to 28 July 2022 through PubMed, the Cochrane Library, EMBASE, and Web of Science. Quantitative synthesis was carried out using Stata 16.0 and RevMa5.3, then the serum NT50 and antibody sensitivity to neutralize Omicron sublineages were assessed before and after booster vaccination. This study was registered with PROSPERO number CRD42022350477. Results: This meta-analysis included 2138 patients from 20 studies, and the booster vaccination against Omicron sublineages showed a significant difference compared to 2 dosage: BA.1/BA.1.1 (SMD = 0.80, 95% CI: 0.75–0.85, P = 0.00), BA.2/BA.2.12.1 (SMD = 0.77, 95% CI: 0.69–0.85, P = 0.00), BA.3 (SMD = 0.91, 95% CI: 0.83–1.0, P = 0.00), and BA.4/5 (SMD = 0.77, 95% CI: 0.60–0.94, P = 0.00). The sensitivity of vaccines-induced antibodies decreased by at least 5-folds after booster vaccination, particularly in the case of BA.4/5 which had the most notable decline in vaccine effectiveness. Conclusion: After the booster vaccination, the NT50 and the neutralization ability of vaccine-induced antibodies increased, but the susceptibility of antibodies decreased compared with the control virus, which may be a clue for future Omicron sublineages prevention. [ABSTRACT FROM AUTHOR]

Background: Given the increasing integration of digital health technologies in team-based primary care, this review aimed at understanding the impact of eHealth on patient-provider and provider-provider relationships. Methods: A review of reviews was conducted on three databases to identify papers published in English from 2008 onwards. The impact of different types of eHealth on relationships and trust and the factors influencing the impact were thematically analyzed. Results: A total of 79 reviews were included. Patient-provider relationships were discussed more frequently as compared to provider-provider relationships. Communication systems like telemedicine were the most discussed type of technology. eHealth was found to have both positive and negative impacts on relationships and/or trust. This impact was influenced by a range of patient-related, provider-related, technology-related, and organizational factors, such as patient sociodemographics, provider communication skills, technology design, and organizational technology implementation, respectively. Conclusions: Recommendations are provided for effective and equitable technology selection, application, and training to optimize the impact of eHealth on relationships and trust. The review findings can inform providers' and policymakers' decision-making around the use of eHealth in primary care delivery to facilitate relationship-building. [ABSTRACT FROM AUTHOR]

In this modern world, artificial intelligence has revolutionized human life in multiple ways. Like other fields, education industry is also transforming with the influence of AI with its smart learning platform and automation of tasks. The introduction of fusion of machine learning tools (FMLT) in the field of education helps to predict learning outcomes and identify challenges in learning. The objective of this paper is to study the fusion of application of machine learning tools in education. This paper highlights the role of data driven FMLT in teaching and learning and also analyzes students and teachers' experiences as well as challenges faced during the implementation of FMLT system. This article discusses various machine learning tools that can be fused into academics. The experiment is conducted on students at graduate level and the results reveal an increase of 88% in terms of learning efficiency for the proposed FMLT system compared to traditional methods, which reflects high positive impact of the contributions of FMLT in academics. Results of the findings also reveal that FMLT applications facilitate thinking, creativity, class engagement and quality teaching inside and outside classrooms. The feedback findings express mixed attitudes concerning the use of machine learning tools in classrooms. [ABSTRACT FROM AUTHOR]

This work deals with the optimization of an extracellular phospholipase C production by Bacillus cereus (PLCBc) using Response Surface Methodology (RMS) and Box-Behnken design. In fact, after optimization, a maximum phospholipase activity (51 U/ml) was obtained after 6 h of cultivation on tryptone (10 g/L), yeast extract (10 g/L), NaCl (8.125 g/L), pH 7.5 with initial OD (0.15). The PLCBc activity, esteemed by the model (51 U) was very approximate to activity gutted experimentally (50 U). The PLCBc can be considered as thermoactive phospholipase since it showed a maximal activity of 50 U/mL at 60 °C using egg yolk or egg phosphatidylcholine (PC) as substrate. In addition, the enzyme was active at pH 7 and is stable after incubation at 55 °C for 30 min. The application of B. cereus phospholipase C in soybean oil degumming was investigated. Our results showed that when using enzymatic degumming, the residual phosphorus decrease more than with water degumming, indeed, it passes from 718 ppm in soybean crude oil to 100 ppm and 52 ppm by degumming using water and enzymatic process, respectively. The diacylgycerol (DAG) yield showed an increase of 1.2% with enzymatic degumming compared to soybean crude oil. This makes our enzyme a potential candidate for food industrial applications such as enzymatic degumming of vegetable oils. [ABSTRACT FROM AUTHOR]

Exploiting the terahertz (THz) part of the electromagnetic spectrum is attracting attention in various scientific and applied disciplines worldwide. THz technology has also revealed its potential as an effective tool for gas analysis in astronomy, biomedicine and chemical analysis. Recently, it has also become important in environmental applications for monitoring hazardous and toxic gases in the atmosphere. This paper gives an overview of THz gas detection analytical methods for environmental and biomedical applications, starting with a brief introduction to THz technology and an explanation of the interaction of THz radiation with gaseous species and the atmosphere. The review focuses on several gaseous species and groups of air pollutants that have been or can be analysed by THz spectrometry. The review concludes that different but complementary THz detection methods allow unique detection, identification and quantification of gaseous and particulate air pollutants with high selectivity, specificity and sensitivity. THz detection methods also allow further technological improvements and open new application possibilities. [ABSTRACT FROM AUTHOR]

Although the anti-COVID-19 vaccination has proved to be an effective preventive tool, "breakthrough infections" have been documented in patients with complete primary vaccination courses. Most of the SARS-CoV-2 neutralizing antibodies produced after SARS-CoV-2 infection target the spike protein receptor-binding domain which has an important role in facilitating viral entry and the infection of the host cells. SARS-CoV-2 has demonstrated the ability to evolve by accumulating mutations in the spike protein to escape the humoral response of a host. The aim of this study was to compare the titers of neutralizing antibodies (NtAbs) against the variants of SARS-CoV-2 by analyzing the sera of recovered and vaccinated healthcare workers (HCWs). A total of 293 HCWs were enrolled and divided into three cohorts as follows: 91 who had recovered from SARS-CoV-2 infection (nVP); 102 that were vaccinated and became positive after the primary cycle (VP); and 100 that were vaccinated with complete primary cycles and concluded the follow-up period without becoming positive (VN). Higher neutralization titers were observed in the vaccinated subjects' arms compared to the nVP subjects' arms. Differences in neutralization titers between arms for single variants were statistically highly significant (p < 0.001), except for the differences between titers against the Alpha variant in the nVP and in VP groups, which were also statistically significant (p < 0.05). Within the nVP group, the number of subjects with an absence of neutralizing antibodies was high. The presence of higher titers in patients with a complete primary cycle compared to patients who had recovered from infection suggested the better efficacy of artificial immunization compared to natural immunization, and this further encourages the promotion of vaccination even in subjects with previous infections. [ABSTRACT FROM AUTHOR]

Omicron variants of SARS-CoV-2 virus have higher infectivity, more immune escape but lower risk of severe clinical outcomes than the ancestral variants. However, people are still wondering whether SARS-CoV-2 may become lethal again or whether some highly-pathogenic strain may emerge in the future. Compared with ancestral variants, Omicron has more selective proliferation in the upper respiratory tract (URT). The temperature of human URT is 33–34°C, and the virus strains other than Omicron cannot replicate effectively at this temperature. While Omicron adapted to the low temperature environment, so its distribution mainly depends on the expression levels of ACE2 in cells. Similar distribution switch from lungs to URT has been observed for the 1918 H1N1 influenza virus, which vanished after 1921 and has been turned to become the seasonal human influenza A viruses. However, some relatively high-pathogenic SARS-CoV-2 strains and influenza virus strains may still emerge in the future. Future evolutionary directions of SARS-CoV-2 and influenza viruses are discussed. [ABSTRACT FROM AUTHOR]

In this study, the vibrational and optical responses of 0–10% excess Cu incorporated ZnO nanoparticles (NPs) prepared by the low temperature (∼400 °C) wet chemical route were investigated experimentally and were found to be predominantly linked to the formation of both intrinsic and Cu induced crystallographic defects instead of substitutional Cu itself for the first time. For low temperature chemical synthesis, the effective band gap (Eg) of pristine ZnO NPs was found to be as low as 2.84 eV, which was followed by a further reduction by as high as ∼24.4% with gradual Cu inclusion. Excess Cu incorporation was found to drastically restrict the particle growth phenomenon by ∼61% and alter the shape morphology from anisotropic to irregular isotropic. Although all NPs showed a single phase structure with hexagonal P63mc symmetry, the X-ray peak profile analysis along with the characteristic E2(High) Raman peak and electron–phonon coupling strength obtained from the 2nd order Raman mode suggested the presence of appreciable crystallographic disorders pertaining to point defects like Cu induced Zn and O interstitials and vacancies. Optical analysis revealed a gradual increase in Urbach tailing (Eu) from 0.35 to 0.96 eV directly associated with both intrinsic and Cu induced disorders arising from successive Cu incorporation at low processing temperature. A correlation between Eg and Eu predicted a direct-type band-to-band transition energy of ∼3.2 eV for the pristine ZnO crystal, suggesting both intrinsic and excess Cu induced extrinsic disorders to be the primary source of optical modulation of the NPs for the low temperature processing condition. [ABSTRACT FROM AUTHOR]

Insectivorous Old World horseshoe bats (Rhinolophus spp.) are the likely source of the ancestral SARS-CoV-2 prior to its spillover into humans and causing the COVID-19 pandemic. Natural coronavirus infections of bats appear to be principally confined to the intestines, suggesting fecal-oral transmission; however, little is known about the biology of SARS-related coronaviruses in bats. Previous experimental challenges of Egyptian fruit bats (Rousettus aegyptiacus) resulted in limited infection restricted to the respiratory tract, whereas insectivorous North American big brown bats (Eptesicus fuscus) showed no evidence of infection. In the present study, we challenged Jamaican fruit bats (Artibeus jamaicensis) with SARS-CoV-2 to determine their susceptibility. Infection was confined to the intestine for only a few days with prominent viral nucleocapsid antigen in epithelial cells, and mononuclear cells of the lamina propria and Peyer's patches, but with no evidence of infection of other tissues; none of the bats showed visible signs of disease or seroconverted. Expression levels of ACE2 were low in the lungs, which may account for the lack of pulmonary infection. Bats were then intranasally inoculated with a replication-defective adenovirus encoding human ACE2 and 5 days later challenged with SARS-CoV-2. Viral antigen was prominent in lungs for up to 14 days, with loss of pulmonary cellularity during this time; however, the bats did not exhibit weight loss or visible signs of disease. From day 7, bats had low to moderate IgG antibody titers to spike protein by ELISA, and one bat on day 10 had low-titer neutralizing antibodies. CD4+ helper T cells became activated upon ex vivo recall stimulation with SARS-CoV-2 nucleocapsid peptide library and exhibited elevated mRNA expression of the regulatory T cell cytokines interleukin-10 and transforming growth factor-β, which may have limited inflammatory pathology. Collectively, these data show that Jamaican fruit bats are poorly susceptible to SARS-CoV-2 but that expression of human ACE2 in their lungs leads to robust infection and an adaptive immune response with low-titer antibodies and a regulatory T cell-like response that may explain the lack of prominent inflammation in the lungs. This model will allow for insight of how SARS-CoV-2 infects bats and how bat innate and adaptive immune responses engage the virus without overt clinical disease. Author summary: Bats are reservoir hosts of many viruses that infect humans, yet little is known about how they host these viruses, principally because of a lack of relevant and susceptible bat experimental infection models. Although SARS-CoV-2 originated in bats, no robust infection models of bats have been established. We determined that Jamaican fruit bats are poorly susceptible to SARS-CoV-2; however, their lungs can be transduced with human ACE2, which renders them susceptible to the virus. Despite robust infection of the lungs and diminishment of pulmonary cellularity, the bats showed no overt signs of disease and cleared the infection after two weeks. Despite clearance of infection, only low-titer antibody responses occurred and only a single bat produced neutralizing antibody, consistent with other experimental infection studies of bats. Assessment of the CD4+ helper T cell response showed that activated cells expressed the regulatory T cell cytokines IL-10 and TGFβ that may have tempered pulmonary inflammation. [ABSTRACT FROM AUTHOR]

Objective. This study aims to evaluate the outcomes of single intramedullary K-wire fixation in nonthumb, metacarpal shaft fractures with immediate postoperative hand mobilization without any immobilization. Method. This is a retrospective case series conducted from January 2019 to December 2022. We included patients with closed, simple transverse, or short oblique metacarpal shaft fracture treated with single, 1.4 mm, intramedullary K-wire fixation. Gentle postoperative range of motion exercise was encouraged in every patient without any hand, finger, or wrist motion restriction material. Clinical outcomes were evaluated with total active flexion; grip strength; disability of arm, shoulder, and hand (DASH) score; and the American Society for Surgery of the Hand Total Active Flexion (ASSH TAF) score. Results. This study included 34 patients, 25 males and 9 females with a mean age of 33.14 years (ranging 18–59). A total of 43 metacarpal shafts were treated. The mean DASH score at two and 6 weeks postoperative was 41.5 (ranging 19.16–60.34) and 9.58 (ranging 0.83–23.27). The mean final DASH score at last follow-up was 3.48 (ranging 0–8.33). Mean TAF at 2 weeks postoperative, 6 weeks postoperative, and at final follow-up was 203.8 (ranging 185–240), 238.2 (ranging 220–270), and 259.25 (ranging 240–270) degrees, respectively. The mean grip strength of the injured hand was 66.14 and 86.1% of the uninjured hand at 6 weeks and 3 months postoperative. There was no nonunion, malrotation, or infection. In conclusion, single intramedullary K-wire fixation gives excellent outcomes in the treatment of single or multiple, simple, metacarpal shaft fractures without the need of postoperative immobilization. [ABSTRACT FROM AUTHOR]

Simple Summary: The progression of PDAC is also regulated at the transcription/transduction stage. RNA metabolism is manipulated by different RNA-binding proteins (RBPs), and insulin-like growth factor 2 mRNA-binding proteins (IMPs), such as IMP1, have been associated with a poor prognosis in PDAC patients; however, little is known about its contribution to PDAC carcinogenesis. Public data suggest that PDAC patients with higher IMP1 expression showed poor overall survival. IMP1 silencing leads to reduced cell growth in PDAC cells and three-dimensional spheroids. Abrogation of IMP1 in PDAC cells showed lower levels of CDC25A, increased phosphorylation of the cyclin-dependent kinase (CDK)2, and accumulation of cells in the G1 phase. Immunoprecipitation revealed that IMP1 binds CDC25A mRNA, thereby controlling cell cycle progression. Ultimately, we proved that suppression of IMP1 blocked in vivo growth of Panc-1 transferred into immunodeficient mice. Our results indicate that IMP1 drives the PDCA cell cycle and represents a novel strategy for overcoming PDCA cell proliferation. A number of data indicate that the sources of different kinds of PDAC may be discovered at the transcription/transduction stage. RNA metabolism is manipulated at various steps by different RNA-binding proteins (RBPs), and the deregulation or irregular activity of RBPs is known to contribute to tumor promotion and progression. The insulin-like growth factor 2 mRNA-binding protein family (IMPs), and IMP1 in particular, has been linked with a poor prognosis in PDAC patients; however, little is known about its contribution in PDAC carcinogenesis. In this study, we investigated the function of IMP1 in PDAC. To evaluate IMP1 expression and correlation with PDAC prognosis, we utilized several public databases. Using a specific siRNA IMP1, we analyzed cell death and cell cycle progression in PDAC cell lines and 3D spheroids. The role of IMP1 was also evaluated in vivo in a Panc-1-derived tumor xenograft murine model. Public data suggest that PDAC patients with higher expression of IMP1 showed poor overall and progression-free survival. IMP1 silencing leads to reduced cell growth in PDAC cells and three-dimensional spheroids. Abrogation of IMP1 in PDAC cells showed lower levels of CDC25A, increased phosphorylation of the cyclin-dependent kinase (CDK)2, and accumulation of PDAC cells in the G1 phase. Immunoprecipitation experiments revealed that IMP1 binds CDC25A mRNA, thus controlling cell-cycle progression. Ultimately, we proved that suppression of IMP1 blocked in vivo growth of Panc-1 transferred into immunodeficient mice. Our results indicate that IMP1 drives the PDCA cell cycle and represents a novel strategy for overcoming PDCA cell proliferation. [ABSTRACT FROM AUTHOR]

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has greatly affected all aspect of life. Although several vaccines and pharmaceuticals have been developed against SARS-CoV-2, the emergence of mutated variants has raised several concerns. The angiotensin-converting enzyme (ACE2) receptor cell entry mechanism of this virus has not changed despite the vast mutation in emerging variants. Inhibiting the spike protein by which the virus identifies the host ACE2 receptor is a promising therapeutic countermeasure to keep pace with rapidly emerging variants. Here, we synthesized two ACE2-derived peptides, P1 and P25, to target and potentially inhibit SARS-CoV-2 cell entry. These peptides were evaluated in vitro using pseudoviruses that contained the SARS-CoV-2 original spike protein, the Delta-mutated spike protein, or the Omicron spike protein. An in silico investigation was also done for these peptides to evaluate the interaction of the synthesized peptides and the SARS-CoV-2 variants. The P25 peptide showed a promising inhibition potency against the tested pseudoviruses and an even higher inhibition against the Omicron variant. The IC50 of the Omicron variant was 60.8 μM, while the IC50s of the SARS-CoV-2 original strain and the Delta variant were 455.2 μM and 546.4 μM, respectively. The in silico experiments also showed that the amino acid composition design and structure of P25 boosted the interaction with the spike protein. These findings suggest that ACE2-derived peptides, such as P25, have the potential to inhibit SARS-CoV-2 cell entry in vitro. However, further in vivo studies are needed to confirm their therapeutic efficacy against emerging variants. [ABSTRACT FROM AUTHOR]

Amongst the potential contribution of protein or peptide-display systems to study epitopes with relevant immunological features, the RAD display system stands out as a highly stable scaffold protein that allows the presentation of constrained target peptides. Here, we employed the RAD display system to present peptides derived from the SARS-CoV-2 Spike (S) protein as a tool to detect specific serum antibodies and to generate polyclonal antibodies capable of inhibiting SARS-CoV-2 infectivity in vitro. 44 linear S-derived peptides were genetically fused with the RAD scaffold (RAD-SCoV-epitopes) and screened for antigenicity with sera collected from COVID-19-infected patients. In a second step, selected RAD-SCoV-epitopes were used to immunize mice and generate antibodies. Phenotypic screening showed that some of these antibodies were able to recognize replicating viral particles in VERO CCL-81 and most notably seven of the RAD-SCoV-epitopes were able to induce antibodies that inhibited viral infection. Our findings highlight the RAD display system as an useful platform for the immunological characterization of peptides and a potentially valuable strategy for the design of antigens for peptide-based vaccines, for epitope-specific antibody mapping, and for the development of antibodies for diagnostic and therapeutic purposes. [ABSTRACT FROM AUTHOR]

Coronavirus disease 2019 (COVID-19) is an infectious disease affecting multiple systems and organs, including the reproductive system. SARS-CoV-2, the virus that causes COVID-19, can damage reproductive organs through direct (angiotensin converting enzyme-2, ACE-2) and indirect mechanisms. The immune system plays an essential role in the homeostasis and function of the male and female reproductive systems. Therefore, an altered immune response related to infectious and inflammatory diseases can affect reproductive function and fertility in both males and females. This narrative review discussed the dysregulation of innate and adaptive systems induced by SARS-CoV-2 infection. We reviewed the evidence showing that this altered immune response in COVID-19 patients is the major indirect mechanism leading to adverse reproduction outcomes in these patients. We summarized studies reporting the long-term effect of SARS-CoV-2 infection on women's reproductive function and proposed the chronic inflammation and chronic autoimmunity characterizing long COVID as potential underlying mechanisms. Further studies are needed to clarify the role of autoimmunity and chronic inflammation (long COVID) in altered female reproduction function in COVID-19. [ABSTRACT FROM AUTHOR]

Myxomatous mitral valve disease (MMVD) is one of the most common heart diseases in Cavalier King Charles spaniel (CKCS) dogs. The American College of Veterinary Internal Medicine (ACVIM) uses clinical, echocardiographic, and radiographic criteria to diagnose the disease, but measurement of vertebral left atrial size (VLAS) provides a simpler assessment. The aim of this study was to determine VLAS values in MMVD cases of CKCS and to investigate their clinical significance at different MMVD stages. Eighteen CKCS dogs of both sexes, different ages and weights, and different MMVD stages (6 at B1 stage, 6 at B2 stage, and 6 at C stage) were included in the study, as well as 6 healthy CKCS as control group A. We performed clinical, radiological, and echocardiographic examinations. VHS and VLAS values were significantly higher in the MMVD group than in the control group (p<0.001). VLAS showed high diagnostic accuracy in the detection of LA enlargement (area under the curve [AUC]: 0.98, cutoff ≥ 2.25, sensitivity: 88%, specificity: 100%, p<0.001). We also found high positive correlations between the VLAS and other values (LA /Ao, LVIDDn, and VHS) (r=0.88, r=0.88, and r=0.86, respectively) (p<0.001). It has been concluded that a VLAS value ≥2.25 can provide a meaningful diagnosis of left atrial enlargement in dogs with MMVD CKCS. [ABSTRACT FROM AUTHOR]

Eukaryotic cell‐free protein synthesis (CFPS) can accelerate expression and high‐throughput analysis of complex proteins with functionally relevant post‐translational modifications (PTMs). However, low yields and difficulties scaling such systems have prevented their widespread adoption in protein research and manufacturing. Here, we provide detailed demonstrations for the capabilities of a CFPS system derived from Nicotiana tabacum BY‐2 cell culture (BY‐2 lysate; BYL). BYL is able to express diverse, functional proteins at high yields in 48 h, complete with native disulfide bonds and N‐glycosylation. An optimized version of the technology is commercialized as ALiCE® and advances in scaling of BYL production methodologies now allow scaling of eukaryotic CFPS reactions. We show linear, lossless scale‐up of batch mode protein expression from 100 µL microtiter plates to 10 and 100 mL volumes in Erlenmeyer flasks, culminating in preliminary data from a litre‐scale reaction in a rocking‐type bioreactor. Together, scaling across a 20,000x range is achieved without impacting product yields. Production of multimeric virus‐like particles from the BYL cytosolic fraction were then shown, followed by functional expression of multiple classes of complex, difficult‐to‐express proteins using the native microsomes of the BYL CFPS. Specifically: a dimeric enzyme; a monoclonal antibody; the SARS‐CoV‐2 receptor‐binding domain; a human growth factor; and a G protein‐coupled receptor membrane protein. Functional binding and activity are demonstrated, together with in‐depth PTM characterization of purified proteins through disulfide bond and N‐glycan analysis. Taken together, BYL is a promising end‐to‐end R&D to manufacturing platform with the potential to significantly reduce the time‐to‐market for high value proteins and biologics. [ABSTRACT FROM AUTHOR]

Dialysis patients are more likely to die or become hospitalized from coronavirus disease 2019 (COVID-19). Currently, only a few studies have evaluated the efficacy of a fourth booster vaccination in hemodialysis (HD) patients and there is not enough evidence to recommend for or against a fourth booster vaccination. This study compared the humoral response and disease severity of patients on HD who received either three or four doses of COVID-19 vaccine. A total of 88 patients were enrolled. Humoral response to vaccination was measured by quantifying immunoglobulin G levels against the receptor binding domain of SARS-CoV-2 (anti-RBD IgG) at five different times and plaque reduction neutralization tests (PRNT) at two different times after vaccination over a period of 18 months. Antibody levels were measured at approximately two-month intervals after the first and second dose, then four months after the third dose, and then one to six months after the fourth dose of vaccine. PRNT was performed two months after the second and four months after the third dose of vaccine. We classified patients into four groups according to the number of vaccine doses and presence of COVID-19 infection. Severe infection was defined as hospital admission for greater than or equal to two weeks or death. There was no difference in antibody levels between naïve and infected patients except after a fourth vaccination, which was effective for increasing antibodies in infection-naïve patients. Age, sex, body mass index (BMI), dialysis vintage, and presence of diabetes mellitus (DM) did not show a significant correlation with antibody levels. Four patients who experienced severe COVID-19 disease tended to have lower antibody levels prior to infection. A fourth dose of SARS-CoV-2 vaccine significantly elevated antibodies in infection-naïve HD patients and may be beneficial for HD patients who have not been previously infected with SARS-CoV-2 for protection against severe infection. [ABSTRACT FROM AUTHOR]

While mRNA SARS-CoV-2 vaccination elicits strong humoral responses in the general population, humoral responses in people living with HIV (PLWH) remain to be clarified. Here, we conducted a longitudinal study of vaccine immunogenicity elicited after two and three doses of mRNA SARS-CoV-2 vaccine in PLWH stratified by their CD4 count. We measured the capacity of the antibodies elicited by vaccination to bind the Spike glycoprotein of different variants of concern (VOCs). We also evaluated the Fc-mediated effector functions of these antibodies by measuring their ability to eliminate CEM.NKr cells stably expressing SARS-CoV-2 Spikes. Finally, we measured the relative capacity of the antibodies to neutralize authentic SARS-CoV-2 virus after the third dose of mRNA vaccine. We found that after two doses of SARS-CoV-2 mRNA vaccine, PLWH with a CD4 count < 250/mm3 had lower levels of anti-RBD IgG antibodies compared to PLWH with a CD4 count > 250/mm3 (p < 0.05). A third dose increased these levels and importantly, no major differences were observed in their capacity to mediate Fc-effector functions and neutralize authentic SARS-CoV-2. Overall, our work demonstrates the importance of mRNA vaccine boosting in immuno-compromised individuals presenting low levels of CD4. [ABSTRACT FROM AUTHOR]

Nowadays, everybody needs to secure his/her activities. Existing levels of cyber-criminals need technology for detecting malicious activity. This work proposes a real-time Hardware IDS implemented on FPGA and an algorithm for classifying features from network traffic through the network interface card (NIC). It minimizes search time for extracting statistical features from connection records stored in connection queues to memory references. Therefore, it can detect most internal and external network attacks. A decision tree classifier is used as an inference engine and gives a high detection rate of 99.93%. [ABSTRACT FROM AUTHOR]

Despite that more than one hundred vaccines against SARS-CoV-2 have been developed and that some of them were evaluated in clinical trials, the latest results revealed that these vaccines still face great challenges. Among the components of the virus, the N-protein constitutes an attractive target for a subunit vaccine because it is the most abundant, highly conserved and immunogenic protein. In the present work, a chimeric protein (N-CD protein) was constructed by the fusion of the N-protein to the extracellular domain of human CD154 as the molecular adjuvant. HEK-293 cells were transduced with lentiviral vector bearing the N-CD gene and polyclonal cell populations were obtained. The N-CD protein was purified from cell culture supernatant and further characterized by several techniques. Immunogenicity studies in mice and non-human primates showed the N-CD protein induced high IgG titers in both models after two doses. Moreover, overall health monitoring of non-human primates demonstrated that animals were healthy during 228 days after first immunization. Data obtained support further investigation in order to develop this chimeric protein as vaccine candidate against COVID-19 and other coronavirus diseases. [ABSTRACT FROM AUTHOR]

Novel photocathode materials like ordered surfaces of single crystal metals, epitaxially grown high quantum efficiency thin films, and topologically non-trivial materials with dirac cones show great promise for generating brighter electron beams for various accelerator and ultrafast electron scattering applications. Despite several materials being identified as brighter photocathodes, none of them have been tested in electron guns to extract electron beams due to technical and logistical challenges. In this paper, we present the design and commissioning of a cryocooled 200 kV DC electron gun that is capable of testing a wide variety of novel photocathode materials over a broad range of temperatures from 298 to 35 K for bright electron beam generation. This gun is designed to enable easy transfer of the photocathode to various standard ultra-high-vacuum surface diagnostics and preparation techniques, allowing a full characterization of the dependence of beam brightness on the photocathode material and surface properties. We demonstrate the development of such a high-voltage, high-gradient gun using materials and equipment that are easily available in any standard university lab, making the development of such 200 kV electron guns more accessible. [ABSTRACT FROM AUTHOR]

Coronavirus disease 2019 (COVID-19) is a worldwide public health and economic threat, and virus variation amplifies the difficulty in epidemic prevention and control. The structure of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been studied extensively and is now well defined. The S protein is the most distinguishing feature in terms of infection and immunity, mediating virus entrance and inducing neutralizing antibodies. The S protein and its essential components are also the most promising target to develop vaccines and antibody-based drugs. Therefore, the key site mutation in the S gene is of high interest. Among them, RBD, NTD, and furin cleavage sites are the most mutable regions with the most mutation sites and the most serious consequences for SARS-CoV-2 biological characteristics, including infectivity, pathogenicity, natural immunity, vaccine efficacy, and antibody therapeutics. We are also aware that this outbreak may not be the last. Therefore, in this narrative review, we summarized viral variation and prevalence condition, discussed specific amino acid replacement and associated immune challenges and attempted to sum up some prevention and control strategies by reviewing the literature on previously published research about SARS-CoV-2 variation to assist in clarifying the mutation pathway and consequences of SARS-CoV-2 for developing countermeasures against such viruses as soon as possible. [ABSTRACT FROM AUTHOR]

Even with its endemic transition, the COVID-19 pandemic remains a public health threat, particularly in the light of emerging variants of concern (VoCs) and the need for pandemic preparedness in the future. In November 2021, the SARS-CoV-2 VoC Omicron emerged and its subvariants BA.1, BA.2 and BA.5 became predominant. Although the protease inhibitor Paxlovid® and the polymerase inhibitors Molnupiravir and Remdesivir were approved as specific antiviral treatment options for COVID-19 patients in the early stages after infection, effective prophylactically acting substances without adverse effects are not available yet. In a recent study, we demonstrated that iota-carrageenan, a sulfated polysaccharide extracted from red seaweed, efficiently inhibits the replication of the SARS-CoV-2 Wuhan Type and the VoCs Alpha, Beta, Gamma and Delta. Now, we extended this study by investigating the antiviral effects of iota-, lambda- and kappa-carrageenans on the VoC Omicron subvariants BA.1, BA.2 and BA.5. Using a VoC Omicron BA.1 spike pseudotyped murine leukemia virus (BA.1 MLVOMVLP) as well as patient-derived SARS-CoV-2 Omicron isolates BA.1, BA.2 and BA.5 (SARS-CoV-2OM BA.1, SARS-CoV-2OM BA.2 and SARS-CoV-2OM BA.5), we demonstrate that iota-carrageenan exhibits similar antiviral activity against all analyzed Omicron subvariants. As with other VoCs shown before, the biologically inert iota-carrageenan was more efficient than kappa- and lambda-carrageenan. Altogether, these results confirm that, independent of the current and potential future variants, the physical barrier provided by iota-carrageenan might be applicable for prophylaxis and early treatment of SARS-CoV-2 infections. [ABSTRACT FROM AUTHOR]

The competing landscape between malware authors and security analysts is an ever-changing battlefield over who can innovate over the other. While security analysts are constantly updating their signatures of known malware, malware variants are changing their signature each time they infect a new host, leading to an endless game of cat and mouse. This survey looks at providing a thorough review of obfuscation and metamorphic techniques commonly used by malware authors. The main topics covered in this work are (1) to provide an overview of string-scanning techniques used by antivirus vendors and to explore the impact malware has had from a security and monetary perspective; (2) to provide an overview of the methods of obfuscation during disassembly, as well as methods of concealment using a combination of encryption and compression; (3) to provide a comprehensive list of the datasets we have available to us in malware research, including tools to obfuscate malware samples, and to finally (4) discuss the various ways Windows APIs are categorized and vectorized to identify malicious binaries, especially in the context of identifying obfuscated malware variants. This survey provides security practitioners a better understanding of the nature and makeup of the obfuscation employed by malware. It also provides a review of what are the main barriers to reverse-engineering malware for the purposes of uncovering their complexity and purpose. [ABSTRACT FROM AUTHOR]

Photodissociation of [Ar–N2]+ induced by a near-IR (800 nm) femtosecond laser pulse is investigated using ion-trap time-of-flight mass spectrometry. The intra-complex charge transfer proceeding in the course of the decomposition of the electronically excited Ar+(2P3/2)⋯N2(X1Σg+), prepared by the photoexcitation of the electronic ground Ar(1S0)⋯N2+(X2Σg+), is probed by the ion yields of Ar+ and N2+. The yield ratio γ of N2+ with respect to the sum of the yields of Ar+ and N2+ is determined to be γ = 0.62, which is much larger than γ ∼ 0.2 determined before when the photodissociation is induced by a nano-second laser pulse in the shorter wavelength region between 270 and 650 nm. This enhancement of γ at 800 nm and the dependence of γ on the excitation wavelength are interpreted by numerical simulations, in which the adiabatic population transfer from Ar+(2P3/2)⋯N2(X1Σg+) to Ar(1S0)⋯N2+(X2Σg+) at the avoided crossings is accompanied by the vibrational excitation in the N2+(X2Σg+) moiety followed by the intra-complex vibrational energy transfer from the N2+(X2Σg+) moiety to the intra-complex vibrational mode leading to the dissociation. [ABSTRACT FROM AUTHOR]

Allosteric mechanisms provide finely-tuned control over signalling proteins. Proteins of the same family may share high sequence identity and structural similarity but show distinct traits of allosteric control and evolutionary divergent regulation. Revealing the determinants of such properties may be important to understand the molecular bases of different regulatory pathways. Herein, we investigate whether and how evolutionarily-divergent traits of allosteric regulation in homologous proteins can be decoded in terms of internal dynamics and interaction networks that support functionally oriented conformations. In this framework, we start from the comparative analysis of the dynamics and energetics of the yeast MAP Kinases (MAPKs) Fus3 and Kss1 in their native basins. Importantly, distinctive dynamic and energetic stabilization features emerge, which can be related to the two proteins' differential ability to be phosphorylated and engage with the allosteric activator Ste5. We then expanded our study to other evolutionarily-related MAPKs. We show that the dynamical and energetical traits defining the distinct regulatory profiles of Fus3 and Kss1 can be traced along their evolutionary tree. Overall, our approach is able to reconnect (latent) allostery with the principal elements of protein structural stabilization and dynamics, showing how allosteric regulation was encrypted in MAPKs structure well before Ste5 appearance., (© 2024 Wiley-VCH GmbH.)

The sudden global crisis of COVID-19, driven by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), demands swift containment measures due to its rapid spread and numerous problematic mutations, which complicate the establishment of herd immunity. With escalating fatalities across various nations no foreseeable end in sight, there is a pressing need to create swiftly deployable, rapid, cost-effective detection, and treatment methods. While various steps are taken to mitigate the transmission and severity of the disease, vaccination is proven throughout mankind history as the best method to acquire immunity and circumvent the spread of infectious diseases. Nonetheless, relying solely on vaccination might not be adequate to match the relentless viral mutations observed in emerging variants of SARS-CoV-2, including alterations to their RBD domain, acquisition of escape mutations, and potential resistance to antibody binding. Beyond the immune system activation achieved through vaccination, it is crucial to develop new medications or treatment methods to either impede the infection or enhance existing treatment modalities. This review emphasizes innovative treatment strategies that aim to directly disrupt the virus's ability to replicate and spread, which could play a role in ending the SARS-CoV-2 pandemic., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

"Drawing inspiration from nature" offers a wealth of creative possibilities for designing cutting-edge materials with improved properties and performance. Nature-inspired thylakoid-based nanoarchitectures, seamlessly integrate the inherent structures and functions of natural components with the diverse and controllable characteristics of nanotechnology. These innovative biomaterials have garnered significant attention for their potential in various biomedical applications. Thylakoids possess fundamental traits such as light harvesting, oxygen evolution, and photosynthesis. Through the integration of artificially fabricated nanostructures with distinct physical and chemical properties, novel photosynthetic nanoarchitectures can be catalytically generated, offering versatile functionalities for diverse biomedical applications. In this article, an overview of the properties and extraction methods of thylakoids are provided. Additionally, the recent advancements in the design, preparation, functions, and biomedical applications of a range of thylakoid-based photosynthetic nanoarchitectures are reviewed. Finally, the foreseeable challenges and future prospects in this field is discussed., (© 2023 Wiley‐VCH GmbH.)

Conventional chemotherapy is insufficient for precise cancer treatment due to its lack of selectivity and inevitable side effects. Targeted drugs have emerged as a promising solution for precise cancer treatment. A common strategy is to conjugate therapeutic agents with ligands that can specifically bind to tumor cells, providing targeted therapy. Similar to the more successful antibody drug conjugates (ADCs), small molecule drug conjugates (SMDCs) are another promising class of targeted drugs, consisting of three parts: targeting ligand, cleavable linker and payload. Compared to ADCs, SMDCs have the advantages of smaller size, better permeability, simpler preparation process and non-immunogenicity, making them a promising alternative to ADCs. This review describes the characteristics of the targeting ligand, linker and payload of SMDCs and the criteria for selecting a suitable one. We also discuss recently reported SMDCs and list some successful SMDCs that have entered clinical trials., (© 2024 Wiley-VCH GmbH.)

Squalene-based adjuvant compositions that can provide effective induction of specific humoral immune response have been developed. Recombinant receptor-binding domain (RBD) of surface S-protein of SARS-CoV-2 was used to evaluate the properties of the composition. Immunization of mice with the developed squalene-based compositions in combination with RBD allows obtaining high titers of specific antibodies: from 10 5 to 2×10 6 . The blood sera from immunized mice exhibit neutralizing activity against SARS-CoV-2 Delta variant (B.1.617.2) with a titer up to 1:2000., (© 2024. Springer Science+Business Media, LLC, part of Springer Nature.)

The present study aimed at preparing three biocatalysts via physical adsorption of lipases from Candida rugosa (CRL), Mucor javanicus, and Candida sp. on a hydrophobic and mesoporous support (Diaion HP-20). These biocatalysts were later applied to the synthesis of aromatic esters of apple peel and citrus (hexyl butyrate), apple and rose (geranyl butyrate), and apricot and pineapple (propyl butyrate). Scanning electron microscopy and gel electrophoresis confirmed a selective adsorption of lipases on Diaion, thus endorsing simultaneous immobilization and purification. Gibbs free energy (∆G) evinced the spontaneity of the process (-17.9 kJ/mol ≤ ∆G ≤ -5.1 kJ/mol). Maximum immobilized protein concentration of 30 mg/g support by CRL. This biocatalyst was the most active in olive oil hydrolysis (hydrolytic activity of 126.0 ± 2.0 U/g) and in the synthesis of aromatic esters. Maximum conversion yield of 89.1% was attained after 150 Min for the synthesis of hexyl butyrate, followed by the synthesis of geranyl butyrate (87.3% after 240 Min) and propyl butyrate (80.0% after 150 Min). CRL immobilized on Diaion retained around 93% of its original activity after six consecutive cycles of 150 Min for the synthesis of hexyl butyrate., (© 2020 International Union of Biochemistry and Molecular Biology, Inc.)

The synthesis and characterization of a novel DNA-encoded library of macrocyclic peptide derivatives are described; the macrocycles are based on three sets of proteinogenic and non-proteinogenic amino acid building blocks and featuring the use of copper(I)-catalyzed alkyne-azide cycloaddition (CuAAC) reaction for ring closure. The library (termed YO-DEL) which contains 1 254 838 compounds, was encoded with DNA in single-stranded format and was screened against target proteins of interest using affinity capture procedures and photocrosslinking. YO-DEL selections yielded specific binders against serum albumins, carbonic anhydrases and NKp46, a marker of activated Natural Killer cells., (© 2021 Wiley-VCH GmbH.)