In this study, we demonstrate the direct preparation of dihalo-γ-lactams featuring two distinct halogens from dichloroamides using a novel Atom Exchange Radical Cyclization (AERC) procedure. This method integrates the established Atom Transfer Radical Cyclization with halogen exchange in solution. The technique operates under mild conditions and requires little amounts of metallic copper, serving as both a supplemental activator and reducing agent.

The aim of this study was to investigate the physicochemical characterization and biological activities of chitosan (CH) based composite films with the incorporation of chestnut flower essential oil (CFEO). The composite films were prepared by casting method and characterized in terms of structural, morphological and mechanical properties via FT-IR, XRD, UV, SEM and TGA. The results proved the significantly increased water vapor permeability (WVP), heat resistance, antibacterial and antioxidant capabilities of CH-CFEO films. The incorporation of CH and CFEO enhanced the UV blocking, which made the film shield almost all UV light. Films with the tensile strength of 6.37 ± 0.41 MPa and elongation at break of 22.57 ± 0.35% were got with 6 mg mL-1 CFEO. Subsequently, the fruit preservation experiments also confirmed that the composite films could effectively extend the shelf life of bananas through their excellent water vapor and oxygen barrier. These desirable performances enable our newly developed composite films to be a remarkable packaging material to solve the fresh fruit preservation dilemma.

The mechanism underlying microbiologically induced carbonate precipitation have not been thoroughly characterized, although numerous scholars and experts have specifically investigated questions regarding minerals induced by bacteria. The study of the precipitation of carbonate minerals induced by halophilic bacteria has aroused wide concern. The present study aimed to investigate the characterization and process of biomineralization in high salt systems by a halophilic bacterium, Chromohalobacter israelensis strain LD532 (GenBank: KX766026), which was isolated from the Yinjiashan Saltern in China. Carbonate minerals induced by LD532 were investigated in several sets of comparative experiments that employed magnesium sulfate and magnesium chloride as Mg resources. Magnesium calcite and aragonite were induced by LD532 bacteria, whereas these minerals did not appear in the control group. The mineral phases, micromorphologies, and crystal structures were analysed using X-ray powder diffraction, scanning electron microscopy, and energy dispersive X-ray detection. The carbonic anhydrase and urease secreted by strain LD532 through metabolism increased the pH value of the liquid medium and promoted the process of carbonate precipitation. Further study using high resolution transmission electron microscopy, energy dispersive X-ray detection and analysis of ultrathin slices showed that the nucleation sites of carbonate minerals were located on extracellular polymeric substances and the membranes of intracellular vesicles of LD532 bacteria, which provided favourable conditions for the growth of carbonate mineral crystals. The morphologies and compositions of minerals formed in solutions of MgSO₄ and MgCl₂ display significant differences, indicating that different sources of Mg²⁺ may also affect the physiological and biochemical activities of microorganisms and thus mineral deposition. This study will be of some interest for the interpretation of carbonate biomineralization in natural salt environments and has some value as a reference in understanding sedimentary carbonates in ancient marine environments, such as tidal flats.

Background: Nephrolithiasis, or kidney stone disease, presents a significant global health burden, with incidence rates and treatment practices varying widely globally. This study aims to discuss the epidemiology, risk factors, treatment modalities, and challenges for nephrolithiasis in the lower half of the World Bank Rank; low and lower-middle-income countries. Methods: A comprehensive literature review was conducted using PubMed for each country on the list, focusing on studies published from January 2000 onwards and reporting data on prevalence, risk factors, treatment practices, and economic implications. Results: Nephrolithiasis represents a significant burden for healthcare systems, with noteworthy geographical variability in prevalence possibly dependent on socioeconomic status and gender. Risk factors include dietary habits, climate, pollution, and infectious diseases. Treatment practices in some regions still rely on open surgery due to limited access to advanced endourological techniques, while other regions demonstrate high proactivity in research. The burden is exacerbated by inadequate healthcare infrastructure and training. Conclusions: Addressing nephrolithiasis in challenging economic circumstances requires targeted interventions, including improved access to modern treatment methods, enhanced training for healthcare professionals, and better socioeconomic and environmental conditions. Future research should focus on region-specific strategies and the development of sustainable healthcare solutions.

This study aimed to analyze the population dynamics of the mite Varroa destructor in honey bee (Apis mellifera) colonies in a temperate semi-arid climate in Mexico. Ten colonies homogeneous in population, food stores, and levels of mite infestation, were used. The mite infestation rate in brood and adult bees, total number of mites, daily mite fall, brood and adult bee population, and food stores, were determined periodically for 10 months. There was a significant effect (P <0.05) of sampling period on the population of V. destructor in adult bees, brood, total mite population, and daily fallen mites. The total mite population increased 26% on average per colony. The increase in brood amount reduced the mite infestation rate in adult bees, and the opposite occurred when the brood decreased. Monitoring V. destructor populations by recording fallen mites is more reliable than determining mite infestation rates in bees, as mite fall has a dynamic pattern similar to that of the total mite population. The best period to apply an acaricide treatment in the region of study is between November and December because most mites were in the phoretic phase, since there was less brood in the colonies compared to other times.

Probiotics are living microbes that provide benefits to the host. The increasing data on health promotion following probiotics administration triggered growing interest among researchers and pharmaceutical companies looking for novel therapeutic or preventive tools. Infections of the lower genital tract in females are caused by a wide range of pathogens, they are widespread, and represent one of the main areas for the use of probiotics and postbiotics. Vulvovaginal candidiasis (VVC) affects 75% of women in their reproductive age at least once during their lifetime. Of these women 5-8% develop the recurrent form (RVVC). The disease onset is triggered by the overgrowth of Candida species on the vaginal mucosa. Here, we evaluated the beneficial properties of the Bacillus coagulans spore-producing LMG S-24828 against C. albicans and C. parapsilosis. Our results show that both alive B. coagulans and its Cell-Free-Supernatant (CFS) exerted antifungal activity against both fungi. Moreover, alive B. coagulans reduced hyphal formation, inhibited C. albicans adhesion to vaginal epithelial cells and showed co-aggregation capacity. Overall, B. coagulans LMG S-24828 exerted a protective effect on vaginal epithelial cells infected with C. albicans. These data suggest that B. coagulans LMG S-24828 may provide benefits in the context of Candida vaginal infections.

Models of subsurface structures are important for successful deposit exploration but are challenged by the need to integrate data from different geophysical methods. In the present study, we evaluated a method of joint inversion in which audio-magnetotelluric (AMT) and dual frequency induced polarization (DFIP) data sets are inverted simultaneously to produce a consistent 2D resistivity model to show a clear image of subsurface structures. To achieve the objectives, we conducted AMT and DFIP surveys first on the same survey line within the Dongjun lead-zinc deposit in inner Mongolia by developing 31 AMT survey sites with an interstation separation of 40 m on a 1440 m survey track and operated in fifty-three frequencies in the range 1–10,400 Hz to record the resistivity distribution of subsurface to depths exceeding 800 m. The same survey setup up was applied to the DFIP method by utilizing the SQ-3C model with a pole-dipole array configuration and conducted measurements at frequencies of 4 Hz and 4/13 Hz. We first separately inverted AMT and DFIP measurements. The two-dimensional (2D) model obtained from AMT data revealed distinct low resistivity anomalies in the middle of the 2D inversion model. In contrast, the DFIP inversion model showed a high resistive body in the same region. In response to the discrepancies observed in the separate 2D inversion models, we implemented a joint inversion for both the AMT and DFIP datasets. The joint inversion resistivity model shows surficial conducting bodies and a high conductive body along the profile with relatively high Percent Frequency Effect (PEF) indicating high chargeability. The final joint inversion resistivity model clearly images the large silica alteration zone and the Pb-Zn mineralization. This study demonstrates the feasibility of a joint inversion methodology and highlights the value of integrating geophysical methods through joint inversion for enhanced characterization and exploration of lead-zinc ores.

Background: Routine childhood vaccination, e.g., for diphtheria-tetanus-pertussis (DTP), might provide an additional protection towards SARS-CoV-2 infection. This concept of heterologous immunity was explored in healthy children receiving both DTP and inactivated SARS-CoV-2 vaccines. Methods: A cross-sectional study was performed on 154 healthy children aged 6–8 years old in Jakarta, Indonesia. Their vaccination status of DTP (including diphtheria-tetanus booster vaccine at 5 years old) and CoronaVac (from 6 years old) were recorded. Peripheral blood samples were collected from all participants, in which anti-diphtheria toxoid IgG, anti-SARS-CoV-2 S-RBD antibodies and T cell-derived IFN-g were measured. Results: Study participants with complete DTP vaccination had significantly higher titer of anti-diphtheria toxoid IgG than the ones without (median=0.9349 versus 0.2113 IU/mL; p<0.0001). Upon stratification based on DTP and CoronaVac vaccination statuses, participants with complete DTP and CoronaVac vaccinations had the highest titer of anti-SARS-CoV-2 S-RBD antibodies (median=1,196 U/mL) and the highest concentration of SARS-CoV-2-specific T cell-derived IFN-g (median=560.9 mIU/mL) among all groups. Conclusion: Healthy children aged 6-8 years old with complete DTP and CoronaVac vaccinations exhibited higher SARS-CoV-2-specific adaptive immune responses, particularly on their T-cell response. This suggests an additional benefit of routine childhood vaccination to generate protection against novel pathogens, presumably via heterologous immunity.

Precision metagenomic approaches using Oxford Nanopore Technology (ONT) sequencing has been shown to allow recovery of complete genomes of Escherichia coli O157:H7 from overnight enrichments of agricultural waters. This study tests the applicability of a similar approach for Cronobacter genome recovery from powdered infant formula (PIF) overnight enrichments, where Cronobacter typically dominates the overall microbiome (&gt;90%). In this study, we aimed to test whether using ONT sequencing of overnight PIF enrichments could recover a completely closed Cronobacter genome for further genomic characterization. Ten PIF samples, each inoculated with different Cronobacter strains, covering Cronobacter sakazakii, C. muytjensii, C. dublinensis, C. turicensis, and C. universalis, were processed according to the Bacteriological Analytical Manual (BAM) protocol. qPCR was used for initial screening (detection and quantification) of the overnight enrichments and confirmed that the spiked PIF samples after the overnight enrichment have high levels of Cronobacter (107 to 109 CFU/mL). DNA from overnight PIF enrichments was extracted from the enrichment broth and sequenced using ONT. Results showed that ONT sequencing could accurately identify, characterize, and close the genomes of Cronobacter strains from overnight PIF enrichments in 3 days, much faster than the nearly two weeks required by the current BAM method. Complete genome recovery and species differentiation were achieved. This suggests that combining qPCR with ONT sequencing provides a rapid, cost-effective alternative for detecting and characterizing Cronobacter in PIF, enabling timely corrective actions during outbreaks.

The morphological aspects of urban growth on wetlands in Africa are under-researched. Using the Densu Delta Ramsar site in Accra, Ghana, as a case study, this paper analyses the morphological patterns and drivers of urban growth and its impact on wetlands. Data were obtained through remote-sensing, ground truthing and limited key informant interviews. The analysis combined land use/land cover, building coverage and multiple regression techniques, with the aid of GIS and STATA software. The findings reveal that urban growth at the Ramsar site follows discernible spatial patterns consistent with the spreading pancake, village magnet and ribbon development models. However, the primary force behind these patterns is growing demand for land to meet housing needs, aided by the failure of state institutions to perform their land use control and wetland protection functions. To achieve sustainable urban development, there is an urgent need to ensure effective wetland management by enforcing existing land use, development control and wetland protection measures. This calls for the strengthening, resourcing and closer collaboration between the various state agencies responsible for urban planning and wetland management. There is also the need to engage and sensitise political leaders to increase their commitment to implementing wetland protection and pro-environmental policies.

In this paper, a new axial-type magnetic gear with auxiliary flux-enhancing structure (AFS-AMG) is proposed. Compared to conventional AFS-AMG, it has the higher torque density and higher permanent magnet (PM) utilization factor. Firstly, the design rules and operating principles of proposed AFS-AMG are elaborated. Then, the mapping relation between the radial-type magnetic gears (RMGs) and AMGs are elucidated. Compared to its counterpart in RMGs, AFS-AMGs achieve small size. Then, the geometrical parameters of AFS-AMGs are optimized to obtain the better electromagnetic performances, where the torque density per volume and per PM volume is adopted as the evaluation standard. Finally, three different AMG topologies are constructed in finite element analysis (FEA) software for comparison. It is proven that the AFS-AMG has the largest torque density per volume and per PM volume.

This study addresses the implementation of the International Financial Reporting Standard 9 (IFRS 9) in the European Union as of January 1, 2018, replacing the International Accounting Standard 39 (IAS 39) to introduce a new model for recognizing Loan Loss Provisions (LLP) based on Expected Credit Loss (ECL). This model responds to criticisms of the former Incurred Credit Loss (ICL) system for its inability to reflect credit losses in a timely manner, potentially exacerbating the effects of financial crises (Bushman &amp; Williams, 2015; Gebhardt &amp; Novotny-Farkas, 2011). The study focuses on the effects of adopting the ECL model on the level of Loan Loss Allowances (LLA) in loans, own equity, and the Common Equity Tier 1 (CET1) ratio across 13 Portuguese commercial banks. A mean comparison test is used to evaluate scenarios before and after the application of the ECL model, highlighting the importance of regulator actions and the adequacy of loss recognition policies, including the effects of Regulation (EU) 2017/2395 of December 12. The results obtained demonstrate significant negative impacts on the net values of loans, own equity, and the CET1 ratio upon adopting the IFRS 9 ECL model, due to the widespread increase in LLAs.

To ensure consumers can purchase high-quality rice, accurate identification of rice varieties is particularly important. Methods: This article conducts research based on machine learning algorithms from the perspectives of image, spectrum, and spectrogram fusion. Six types of hyperspectral image data of rice were preprocessed using convolutional smoothing (SG) and multiple scatter correction (MSC). Texture information of the images was extracted using gray-level co-occurrence matrix. Spectra, texture, and spectrogram data were fused into a new matrix. Spectral, texture, and spectrogram fusion data were used as inputs for the model, and support vector machines (SVM), logistic regression (LR), and K-nearest neighbors (KNN) classification models were constructed and compared. Results: From the classification results, the spectrogram fusion classification performance was better than classification models using only spectra or texture. Conclusion: The research results showed that the accuracy of SVM and LR classification models exceeded 90%, and the LR model performed the best, effectively classifying rice varieties.

The design complexity of the new generation of civil aero-engines results in higher demands on engines’ components, higher component temperature, higher heat generation, and, finally, critical thermal management issues. This paper will propose a methodological approach to create physics-based models for heat loads developed by sources as well as a systematic sensitivity analysis to identify the effects of design parameters on the thermal behaviour of civil aero-engines. The ranges and levels of heat loads generated by heat sources (e.g., accessory gearbox, bearing, pumps, etc.) and heat absorption capacity of heat sinks (e.g., engine fuel, oil, and air) are discussed systematically. The practical research challenges for thermal management system design and development for the new and next generation of turbofan engines will then be addressed through a sensitivity analysis of the heat load values as well as the heat sinks flow rates. The potential solutions for thermal performance enhancements of propulsion systems will be proposed and discussed accordingly.

Familial Alzheimer’s disease (FAD) can be caused by mutations in PSEN1 that encodes presenilin-1, a component of the gamma-secretase complex that cleaves amyloid precursor protein. Alterations in calcium (Ca2+) homeostasis and glutamate signaling are implicated in the pathogenesis of FAD, however it has been difficult to assess in humans whether or not these phenotypes are the result of amyloid or tau pathology. This study aimed to assess early calcium and glutamate phenotypes of FAD by measuring the Ca2+ response of induced pluripotent stem cell (iPSC)-derived neurons bearing PSEN1 mutations to glutamate and the ionotropic glutamate receptor agonists NMDA, AMPA and kainate compared to isogenic control and healthy lines. The data shows that in early neurons, even in the absence of amyloid and tau phenotypes, FAD neurons exhibit increased Ca2+ responses to glutamate and AMPA, but not NMDA or kainate. Together this suggests that PSEN1 mutations alter Ca2+ and glutamate signaling as an early phenotype of FAD.

Occupational accidents, despite continuous safety updates, are still a scourge in the occupational and forensic spheres, constituting, among other things, the subject of a large share of litigation. Demographic data can help to understand the areas where the application of health surveillance is lacking. This meta-analysis sets out to analyze data from studies on accidents at work, focusing on the correlation between the areas in which accidents occur and whether or not personal safety equipment is used, about the different regulations in force. For the selection of the data, a systematic review was carried out according to the PRISMA guidelines, with the primary objective of identifying the trend of occupational accidents in specific geographical areas, which differ in terms of the attention paid to preventive aspects. The data we highlighted showed, regarding the type of accident, substantial differences between low-income countries and industrialized countries (stratified according to the Human Development Index) and, an overall indifference as to whether or not individual safety devices were used, revealing that, despite the continuous normative evolution in the field of safety at work, even today, the investigative data on the actual application of the regulations, during accidents at work, is underestimated and little researched.

Abstract: High step-up voltage gain nonisolated DC-DC converter have attracted much attention in photovoltaic, fuel cells and other renewable energy system applications. In this paper, by combining input current ripple-free boost cell with coupled-inductor voltage-doubler cell, an input current ripple-free high voltage gain nonisolated converter is proposed. In addition, passive lossless clamp circuit is adopted to recycle the leakage inductor energy and to reduce the voltage spike across the power switch. By utilizing voltage-doubler cell consisting of diode and capacitor, the voltage stress of switch is further reduced and the resonance between the leakage inductor and the stray capacitor of the output diode is eliminated. A low switch-on-resistance low-voltage-rated MOSFET can therefore be employed to reduce the conduction loss and cost. The reverse recovery loss of output diode is reduced, and the efficiency of converter can be improved. Furthermore, the proposed converter can achieve nearly zero input current-ripple and make the design of electromagnetic interference (EMI) filter easy. Steady state analysis and operation mode of the converter is performed. Finally, experimental results are presented to verify the analysis results of the proposed converter.

Tissue-like phantoms are widely used as a model for mimicking the optical properties of live tissue. This paper presents the results of a diffusion reflection method as well as fluorescence lifetime imaging microscopy measurements of fluorescein-conjugated gold nanorods in solution as well as inserted in solid tissue-imitating phantoms. A lack of consistency between the fluorescence lifetime results of the solutions and the phantoms raises a question about the ability of tissue-like phantoms to maintain the optical properties of inserted contrast agents.

In this research, catalytic steam reforming acetic acid derived from the aqueous portion of bio-oil for hydrogen production was investigated by using different Ni/ATC (Attapulgite Clay) catalysts prepared by precipitation, impregnation and mechanical blending methods. The fresh and reduced catalysts were characterized by XRD, N₂ adsorption-desorption, TEM and H₂-TPR. The comprehensive results demonstrated that the interaction between active metallic Ni and ATC carrier was significantly improved in Ni/ATC catalyst prepared by precipitation method, and in which the mean Ni particle size was the smallest (~13 nm) resulted in the highest metal dispersion (7.5%). The catalytic performance of the three catalysts was evaluated through the process of steam reforming of acetic acid in a fixed-bed reactor under atmospheric pressure at two different temperatures, such as 550 ℃ and 650 ℃. Results showed that the Ni/ATC (PM-N/ATC) prepared by precipitation method, achieved the highest H₂ yield of ~82% and little lower acetic acid conversion efficiency of ~85% than that (~95%) of Ni/ATC (IM-NATC) prepared by impregnation method. In addition, the deactivation catalysts after reaction for 4 h were analyzed by XRD, TGA-DTG and TEM, which demonstrated that the catalyst deactivation was not caused by the amount of carbon deposition, but owed to the significant agglomeration and sintering of Ni particles in the carrier.

With advancements in digital technologies such as 5G communications, big data, and cloud computing, the components of network operation systems have become increasingly complex, significantly complicating system monitoring and maintenance. Correspondingly, automated log anomaly detection has become a crucial means to ensure stable network operation and protect them from malicious attacks or failures. Conventional machine learning and deep learning methods assume consistent distributions between the training and testing data, adhering to a closed-set recognition paradigm. Nevertheless, in realistic scenarios, systems may encounter new anomalies that were not present in the training data, especially in log anomaly detection. Inspired by evidential learning, we propose a novel anomaly detector called LogEDL, which supervises training of the model through an evidential loss function. Unlike traditional loss functions, the evidential loss function not only focuses on correct classification, but also quantifies the uncertainty of predictions. This enhances the robustness and accuracy of the model in handling anomaly detection tasks, while achieving functionality similar to open-set recognition. To evaluate the proposed LogEDL method, we conduct extensive experiments on three datasets, i.e., HDFS, BGL, and Thunderbird, to detect anomalous log sequences. Experimental results demonstrate that our proposed LogEDL achieves state-of-the-art performance in anomaly detection.

To enhance the applicability of dual-phase high-entropy alloys (HEAs) like Fe32Cr33Ni29Al3Ti3, fabricated via selective laser melting (SLM), a focus on improving their mechanical properties is essential. As part of this effort, heat treatment was explored. This study compares the microstructure and mechanical properties of the as-printed sample with those cooled in water after undergoing heat treatment at temperatures ranging from 1000 to 1200 ℃ for 1 hour. Both pre- and post-treatment samples reveal a dual-phase microstructure comprising FCC and BCC phases. Although heat treatment led to a reduction in tensile and yield strength, it significantly increased ductility compared to the as-printed sample. This strength-ductility trade-off is related to changes in grain sizes with ultrafine grains enhancing strength and micron grains optimizing ductility, also the influence of the content of FCC/BCC phases and dislocation density. In particular, the sample heat-treated at 1000 °C for 1 hour and then water-cooled exhibited a better combination of strength and ductility, a yield strength of 790 MPa, and an elongation of 13%. This research offers innovative perspectives on crafting dual-phase HEA of Fe32Cr33Ni29Al3Ti3, allowing for tailorable microstructure and mechanical properties through a synergistic approach involving SLM and heat treatment.

Background: Diabetes mellitus (DM) and osteoporosis are two of the most widespread metabolic disease in the world. The aim of this study is to investigate the prevalence of DM among patients affected by osteoporosis and fragility fractures, and to search differences in clinical features. Methods: 713 patients belonging to CTO Bone Unit because of osteoporosis and fragility fractures were divided into two groups, according to the diagnosis of DM. The clinical and bone characteristics of patients were compared. Results: Prevalence of DM was 10.8%. When compared to patients without DM, the median age at the time of first fracture was similar (72 years ± 14 IQR vs 71 years ± 12 IQR); prevalence of combination of vertebral and hip fractures was higher (p=0.039), as well as prevalence of males, although not significantly (p=0.051). Bone mineral density (BMD) at all sites was higher in DM group; Trabecular Bone Score (TBS), instead, was significantly lower (p&lt;0.001). Conclusions: Patients with fragility fractures and DM more frequently show combination of major fractures with higher BMD levels. In these patients, TBS could be a better indicator of bone health than BMD and therefore should be used as a diagnostic tool in clinical practice.

Pteridine reductase 1 is a trypanosomatid multifunctional enzyme that provides a mechanism for escape of Dihydrofolate reductase (DHFR) inhibition. This is because PTR1 can reduce pterins and folates. Trypanosomes require folates and pterins for survival and are unable to synthesize them de novo. Currently there are no anti-folate based Human African Trypanosomiasis (HAT) chemotherapeutics in use. Thus, successful dual inhibition of TbDHFR and TbPTR1 has implications in the exploitation of anti-folates. We carried out molecular docking of a ligand library of 5742 compounds against TbPTR1 and identified 18 compounds showing promising binding modes. The protein-ligand complexes were subjected to Molecular dynamics to characterize their molecular interactions and energetics followed by in vitro testing. In this study, we identified five potential TbPTR1 inhibitors that showed low micromolar Trypanosome growth inhibition in in vitro experiments with no significant human cell cytotoxicity. Compounds RUBi004, RUBi007, RUBi014, and RUBi018 displayed moderate to strong antagonism when used in combination with the known TbDHFR inhibitor, WR99210. This gave an indication that the compounds might inhibit both TbPTR1 and TbDHFR. RUBi016 showed an additive effect in the isobologram assay. Our results provide a basis for scaffold optimization for further studies in the development of HAT antifolates.

Keywords: spinal muscular atrophy (SMA); survival of motor neuron 1 (SMN1); SMN2; SMN protein; antisense oligonucleotide (ASO); nusinersen; gene therapy; onasemnogene; risdiplam; small molecule, combination therapy

Neuroblastoma (NB) is a solid tumor occurring in infancy and childhood, whose high-risk form has currently a survival rate &lt; 50 %, despite aggressive treatments. Additionally, drugs-induced secondary tumorigenesis and the emergency of drug resistance worsen the already worrying scenario, calling for an urgent development of new extra-genomic treatments. Quaternary phosphonium salts (QPSs) possess both antimicrobial and anticancer effects. Triphenyl phosphonium salts (TPPs) are mitochondria-targeting compounds, exerting anticancer effects, impairing mitochondria functions and damaging DNA, at the same time. TPP-based bola-amphiphiles, previously proven to self-assemble nanoparticles (NPs) in water and successfully assayed as possible antibacterials, were never tested as suitable antitumor agents. Here, aiming at the development of new antitumor devices to counteract resistant forms of NB, the anticancer effects of a TPP-based amphiphile molecule have been investigated for the first time. To this end, we considered the water-soluble sterically hindered quaternary phosphonium salt (BPPB) encompassing two triphenyl phosphonium groups linked by a C12 alkyl chain, thus embodying both the characteristics of mitochondria-targeting compounds and those of bola-amphiphiles. The anticancer effects of BPPB were assessed against HTLA-230 human stage-IV NB cells and their counterpart resistant to etoposide (ETO), doxorubicin (DOX) and to many other therapeutics (HTLA-ER). Determined IC50 values were very low on both cell populations, already after 24 hours of treatment, when cells viability did not significantly differ from that observed for the longest exposure timing. Moreover, to investigate a putative future inclusion of BPPB in a chemotherapeutic cocktail for NB, its cytotoxic effects were assessed against mammalian cell lines. These included monkey kidney cells (Cos-7), human hepatic cells (HepG2), a lung-derived fibroblast cell line (MRC-5) and red blood cells. From appreciable to very high selectivity indices have been determined after 24 hours treatments, an exposure time after which both NB cell populations tested appeared already fully exterminated.

The main challenges in oil platforms are how to define optimal setpoints and decision-making for controlling variables due to many existing dynamical production uncertainties while conceding safe operation and minimizing discharge to sea and atmosphere without killing plantwide inventory. A novel scheduling model to optimize the whole essential units of an oil platform production gathering topside and subsea variables is disclosed. A proper topside and subsea scheduling model enables and creates harmony between optimal production, supply chain, costs, and market dynamics, satisfying demands, environmental and operations constraints leading to stability. The interest of the present research lies in determining the optimal topside and subsea operational settings and decision-making, establishing maximum E&P performance and production control setpoints while predicting and manipulating reservoir lifespan and its revitalization. This objective is attained through a novel multiperiod large-scale model for the planning and operational production scheduling and model predictive control (MPC) in oil platforms complying with sustainability, profitability, platform design capacities, and offloading of oil and gas to supply chains or to pipeline exportation. The present model details heat and mass transfer, PVT, flow profiles along a planning horizon and can be used to any oil platform since comprises all the essential unit operations for oil, gas, CO₂, H₂S and water. The model maximizes the total oil production over any planning horizon. The model is versatile, and decision-making can be either linear or nonlinear but rather a MILP or LP as best choice on optimizing large-scale systems. If the model is applied with auto rescheduling on site within variable hours or minutes, it becomes a real-time optimization schedule approach. Due to its high-velocity performance and robustness, a novel multi-objective function strategy, acting as an LP generic plantwide MPC with industrial scope to maximize production while controlling the process is presented, and as an example is here used to control slug flow to avoid equipment trips and inventory instability, at the same time production is maximized. The output from the decision-making was compared to actual plant data, and the results proved compliance to the design capacity with process safety and sustainability. Comparing to official Brazil's government data for oil, the case study showed superiority to the same size platforms, like FPSOs P-75 and MV32, e.g., more than 101.5% more capacity to produce oil in beginning of campaign after first oil, and 10.5% during campaign. The present work indicates that: 1) the production of millions of barrels is being delayed or left aside; 2) not scheduling production harms the environment and diminish process safety; 3) not scheduling production can create stochastic supply chain deliveries instead of organizing it by deterministic offloading days; 4) scheduling is essential to manipulate, revitalize and monitor reservoir's pressure and content under uncertainty; 5) the oil platform can be automatic optimized by a plantwide MPC reducing human activity/dependency; 6) scheduling gives more transparency to stakeholders and contractors by forecasting business data and capability, and can design, develop or enable new businesses.

High-resolution (2 km) high-frequency (hourly) SST data from 2015-2021 provided by the Advanced Himawari Imager (AHI) onboard the Japanese Himawari-8 geostationary satellite were used to study spatial and temporal variability of the China Coastal Front (CCF) in the South China Sea. The hourly SST data were processed with the Belkin and O’Reilly (2009) algorithm to generate long-term mean monthly maps of SST gradient magnitude (GM) and frontal frequency (FM). The horizontal structure of CCF was investigated from cross-frontal distributions of SST along 11 fixed lines that allowed to determine inshore and offshore boundaries of the CCF and calculate the CCF strength defined as the total cross-frontal step dSST = Offshore SST – Inshore SST. Combined with the results of Part1 of this study (Belkin, Lou, Yin, 2023), where the CCF was documented in the East China Sea, the new results reported in this paper allowed the CCF to be reliably traced from the East China Sea via Taiwan Strait into the northern South China Sea and farther west up to the east coast of Hainan Island.

The COVID 19 pandemic saw the emergence of various Variants of Concern (VOCs) that took the world by storm, often replacing the ones that preceded them. The characteristic mutant constellations of these VOCs increased viral transmissibility and infectivity. Their origin and evolution remain puzzling. With the help of data mining efforts and the GISAID database, a chronology of 22 haplotypes described viral evolution up until July 23, 2023. Since the 3-dimensional atomic structures of proteins corresponding to the identified haplotypes are not available, ab initio methods were here utilized. Regions of intrinsic disorder proved to be important for viral evolution, as evidenced by the targeted change to the nucleocapsid (N) protein at the sequence, structure, and biochemical levels. The linker region of the N-protein, which binds to the RNA genome and self-oligomerizes for efficient genome packaging, was greatly impacted by mutations throughout the pandemic, followed by changes in structure and intrinsic disorder. Remarkably, VOC constellations acted cooperatively to balance the more extreme effects of individual haplotypes. Our strategy of mapping the dynamic evolutionary landscape of genetically linked mutations to the N-protein structure demonstrates the utility of ab initio modeling and deep learning tools for therapeutic intervention.

Abstract Sodium glucose cotransporter type 2 inhibitors are a new class of drugs acting on cardiovascular system, renal and metabolism in a multiple way. Indeed, even their principal action is on the transporter of sodium and glucose in the convoluted distal tubule, they have multiple actions as antifibrotic and endothelial protective action. Their principal mechanism consist in the loss of sodium and glucose. Therefore, they have effect on blood pressure and glucose metabolism. In a first period their use has been in the diabetic general population, later on some studies documented their activity in non-diabetic general population, in heart failure in chronic kidney disease. Only in recent years several small studies documented their efficacy in diabetic and non-diabetic kidney transplant patients, larger studies are few and very recent and open new ways for these drugs

Network centrality analyses have proven successful in identifying important nodes in diverse host-pathogen interactomes. The current study presents a comprehensive investigation of the human interactome and SARS-CoV-2 host targets. We first constructed a comprehensive human interactome by compiling experimentally validated protein-protein interactions (PPIs) from eight distinct sources. Additionally, we compiled a comprehensive list of 1,449 SARS-CoV-2 host proteins and analyzed their interactions within the human interactome, which identified enriched biological processes and pathways. Seven diverse topological features were employed to reveal the enrichment of SARS-CoV-2 targets in the human interactome, with Load centrality emerging as the most effective metric. Furthermore, a novel approach called CentralityCosDist was employed to predict SARS-CoV-2 targets, which proved effective in expanding the pool of predicted targets. Pathway enrichment analyses further elucidated the functional roles and potential mechanisms associated with predicted targets. Overall, this study provides valuable insights into the complex interplay between SARS-CoV-2 and the host cellular machinery, contributing to a deeper understanding of viral infection and immune response modulation.

Keywords: COVID-19, SARS-CoV-2, Antibody, ELISA, Spike, S1, S2, RBD, epitopes, Neutralization

Abstract: The worldwide spread of SARS-CoV-2 has led to a significant economic and social burden on a global scale. Even though the pandemic has concluded, there remains apprehension regarding the emergence of highly transmissible variants capable of evading immunity induced by either vaccination or prior infection. The success of viral penetration is the specific amino acid residues of the Receptor Binding Motif (RBM) involved in viral attachment. This region interacts with the cellular receptor ACE2, triggering a neutralizing antibody (nAb) response. In this study, we have evaluated the immunogenicity of serum from individuals who received either a single dose or a combination of different vaccines against the original SARS-CoV-2 strain and mutated linear RBM. Despite a modest antibody response to the wild-type SARS-CoV-2 RBM, the Omicron variants exhibit four mutations in the RBM (S477N, T478K, E484A, F486V) that result in even lower antibody titers. The primary immune responses observed were directed towards IgA and IgG. While nAbs typically target the RBD, our investigation has unveiled a reduced seroreactivity within the RBD's crucial subregion, the RBM. This deficiency may have implications for the generation of protective nAbs. Evaluation of S1WT and S2WT RBM peptides binding to nAbs using microscale thermophoresis revealed a higher affinity (35 nM) for the S2WT sequence (GSTPCNGVEGFNCYF), which includes the FNCY patch. Our findings suggest that the linear RBM of SARS-CoV-2 is not an immunodominant region in vaccinated individuals. Comprehending the intricate dynamics of the humoral response, its interplay with viral evolution, and host genetics is crucial for formulating effective vaccination strategies, not only targeting SARS-CoV-2 but also anticipating potential future coronaviruses.

The emergence of SARS-CoV-2 subvariant BA.2.86, also known as Pirola, has raised concerns about its transmissibility, virulence, and immune escape. The aim of this letter is to address the current evidence on the origin, spread, and characteristics of Pirola, and discuss its implications for public health and vaccine development. The need for enhanced surveillance, genomic sequencing, and epidemiological studies to monitor the evolution and impact of Pirola and other SARS-CoV-2 variants are highlighted in this letter along with the importance of global cooperation and coordination to prevent and control future outbreaks of this novel coronavirus strain.

Background: To describe epidemiological characteristics and perform a SARS-CoV-2 genomic surveillance in the southeastern region of São Paulo state. Methods: During the first months of 2022, we compared weekly SARS-CoV-2 infection prevalence considering age, Ct value and variants lineages. Results: An increase in the number of SARS-CoV-2 positive cases until the fourth epidemiological week were observed. From the 4th epidemiological week onwards, the number of tests for SARS-CoV-2 diagnosis began to decrease, but the number of positive samples for SARS-CoV-2 remained high, reaching its most expressive level with a rate of 60% of infected individual cases. In this period, we observed a growing increase in SARS-CoV-2 infection within the age group 0-10 throughout the epidemiological weeks, from 2.8% in the 1st epidemiological week to 9.2% in the 8th epidemiological week. We further observed significantly higher Ct values within younger patients samples compared to other older age groups. According to lineage assignment, SARS-CoV-2 (BA.1) was the most prevalent (74.5%) in the younger group, followed by BA.1.1 (23%), BA.2 (1.7%) and Delta (1%). Phylogenetic analysis showed that BA.2 sequences clustered together, indicating sustained transmission of this Omicron VOC sublineage by that time. Our results suggest the initial dissemination steps of the Omicron’s sublinage BA.2 into the younger group, due specific genomic features of the detected sequences. Conclusion: These data provide interesting results related to the spread, emerging and evolution of the Omicron variant in the Southeast Brazilian population.

Aberrant estrogen receptor (ER) signaling is a major driver of breast tumor growth and progression. Sigma 2 receptor has long been implicated in breast carcinogenesis based on pharmacological studies, but its molecular identity had been elusive until TMEM97 was identified as the receptor. Herein we report that TMEM97/sigma 2 receptor is highly expressed in ER positive breast tumors and its expression is strongly correlated with ER and progesterone receptor (PR) but not with HER2 status. High expression levels of TMEM97 are associated with reduced overall survival of patients. Breast cancer cells with increased expression of TMEM97 had growth advantage over the control cells under both nutrition limiting and sufficient conditions, while knockdown of TMEM97 expression reduced tumor cell proliferations. When compared to their vector control cells, MCF7 and T47D cells with increased TMEM97 expression presented increased resistance to tamoxifen treatment and also grew better under estrogen depleted conditions. TMEM97/sigma 2 receptor enhanced ERα transcriptional activities and increased the level of transactivated ERα, especially the nuclear soluble and chromatin bounded ERα. Increased TMEM97 also stimulated mTOR/S6K1 signaling pathways in MCF7 and T47D cells. The increased level of active, phosphorylated ERα, and the enhanced resistance to tamoxifen treatment with increased TMEM97 could be blocked by an mTOR inhibitor. Knockdown of TMEM97 expression reduced ERα and mTOR/S6K1 signaling activities, rendering the cells with increased sensitivity to tamoxifen. The observations suggest that TMEM97/sigma 2 receptor is a novel regulator of ERα activities in breast tumor cell growth.

Hexakis(2-alkoxy-1,5-phenyleneimine) macrocycles were synthesized using a simple one−pot procedure through by precipitation−driven cyclization. The acetal−protected AB−type monomers, 2-alkoxy-5-aminobenzaldehyde diethyl acetals, underwent polycondensation in water or acid−containing tetrahydrofuran. The precipitation−driven cyclization based on imine dynamic covalent chemistry and π−stacked columnar aggregation played a decisive role in the one−pot synthesis. The progress of the reaction was analyzed by MALDI−TOF mass spectrometry. The macrocycles with alkoxy chains were soluble in specific organic solvents such as chloroform, allowing their structures to be analyzed by NMR. The shape−anisotropic, nearly planar, and persistent macrocycles aggregated into columnar assemblies in polymerization solvents, driven by aromatic π−stacking. The octyloxylated macrocycle OcO−Cm6 exhibited an enantiotropic columnar liquid crystal−like mesophase between 165°C and 197°C. In the SEM image of (S)-(−)-3,7-dimethyloctyloxylated macrocycle (−)BCO-Cm6, columnar substances with a diameter of 100−200 nm were observed. The polymerization solution for 2-(2-methoxyethoxy)ethoxy)ethoxylated macrocycle (TEGO−Cm6) gelled and showed thixotropic properties by forming a hydrogen bond network.

To study the fermentation process of biocatalyzing decanoic acid to synthesize trans-2-decenoic acid, this study was based on the engineering E.coli constructed in the laboratory in the early stage and studied the effect of seed liquid culture time, culture temperature, inoculum amount, induction temperature, dissolution effects of substrate solvent, metal ions, and substrate loading on the yield of trans-2-decenoic acid. Based on single-factor experimental optimization, the Box–Behnken design was used to conduct response surface testing using the substrate feeding concentration, inducer concentration, and MnCl2 concentration as response variables and trans-2-decenoic acid production as the response value. The optimal fermentation process was determined through experiments: seed culture time 20 h, culture temperature 37°C, inoculation amount 1%, induction temperature 30°C, substrate flow amount 0.15 g/L, inducer concentration 5.60 g/L, MnCl2 concentration was 0.10 mM. Under these conditions, the average production of trans-2-decenoic acid was 1.982 ± 0.110 g/L. Compared with the basic LB medium, the production of trans-2-decenoic acid increased by 1.042 g/L; compared with the previous period, the yield of trans-2-decenoic acid studied increased by 1.501 ± 0.110 g/L, which provides a reliable basis for further research on the fermentation process of biocatalytic decanoic acid synthesis of trans-2-decenoic acid.

Pregnant women have been considered a high-risk group for SARS-CoV-2 infection; the impact of the disease on the health of a mother and her child is still being studied. The emotional impact of the pandemic on pregnant women has been extensively studied. Emotional distress is proposed as a perspective to explain the emotional manifestations of women during this stage as something common rather than pathological. The objective of this study was to know the emotional experience of women who tested positive for SARS-CoV-2 towards the end of their pregnancy, during the first and second waves of COVID in Mexico. A qualitative study was carried out: 18 pregnant women with COVID were interviewed. A thematic analysis of the data was performed, resulting in three main themes and 14 subthemes. The COVID-infected mothers-to-be experienced mild to moderate emotional distress. It was more intense for those with comorbidities. This distress was aggravated during obstetrical complications and comorbidities, as well as during COVID and postpartum. The emotional distress was appeased by both the perception of medical care and social support. The emotional distress of pregnant women with COVID requires emotional accompaniment to reduce its impact.

Omicron variants 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. Omicron is 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, who vanished after 1921 and has been turned to be 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. Dynamic changes in the viral virulence should be monitored constantly.

A green, fast and selective approach for the synthesis of mono-substituted closo-decaborate derivatives [2-B10H9COR]n– has been established via a nucleophilic addition reaction between the carbonyl derivative of closo-decaborate [2-B10H9CO]– and the corresponding Grignard reagent RMgX, where R is the ethyl, iso-propyl, pentyl, allyl, vinyl, and propynyl groups. This approach is accomplished under mild conditions with 70–80% yields. The significance of these derivative is their ability to constitute building blocks for polymeric integration via the allyl, vinyl and propynyl substituents. All products were characterized by 11B, 1H, and 13C NMR, elemental analysis and mass spectrometry.

The COVID-19 pandemic has had a major impact on health systems around the globe and Romania is no exception. The impact on healthcare expense for pregnant women has been considerable, especially in COVID-only tertiary centers, where specialized care is being provided .The aim of this study is to analyze the impact of SARS-CoV-2 infection on healthcare costs, in particular by managing cases in COVID-only maternity. Material and Methods: The objective of the study was to analyze if the model adopted by the health system consisting in complete separation of delivering obstetrical care for covid and non-covid patients was efficient. We conducted an observational study in which we compared a group of pregnant women infected with SARS-CoV-2 (study group) with a control group in which we included uninfected pregnant women. The patients were recruited from Bucur Maternity Hospital, declared a COVID-only center in march 2020. We compared the two groups in terms of expenses over the entire period of hospitalization, i.e. expense on hospitalization, medicines, medical supplies, and medical investigations.

Background: This study investigated the biological effects on circulating monocytes after challenge with SARS-CoV-2 recombinant spike protein. Methods: Whole blood collected form seven ostensibly healthy healthcare workers was incubated for 15 min with 2 and 20 ng/mL recombinant spike protein of Ancestral, Alpha, Delta and Omicron variants. Samples were analyzed with Sysmex XN and DI-60 analyzers. Results: Cellular complexity (i.e., presence of granules, vacuoles and other cytoplasmic inclusions) increased in all samples challenged with the recombinant spike protein of Ancestral, Alpha and Delta variants, but not in those containing Omicron. The cellular content of nucleic acids was constantly decreased in most samples, achieving statistical significance in those containing 20 ng/mL of Alpha and Delta recombinant spike proteins. The heterogeneity of monocyte volumes significantly increased in all samples, achieving statistical significance in those containing 20 ng/mL of recombinant spike protein of Ancestral, Alpha and Delta variants. The monocyte morphological abnormalities after spike protein challenge included dysmorphia, granulation, intense vacuolization, platelet phagocytosis, development of aberrant nuclei and cytoplasmic extrusions. Conclusions: The SARS-CoV-2 spike protein triggers important monocyte morphological abnormalities, more evident in cells challenged with spike protein of the more clinically severe Alpha and Delta variants.

We explored the outcomes of germline BRCA1/2 pathogenic/likely pathogenic variants (PVs/LPVs) in the endocrine-sensitive disease treated with first line standard of care cyclin-dependent kinase 4/6 (CDK4/6) inhibitors. Three studies retrospectively showed a reduction in overall survival (OS) and progression free survival (PFS) in gBRCA1/2m patients compared to both germinal BRCA1/2 wild type (gBRCA1/2wt) and to the untested population. Regarding the efficacy of PI3K inhibitors, there are no subgroup or biomarker analyses in which germinal BRCA status was explored. However, the biological interactions between the PIK3CA/AKT/mTOR pathway and BRCA1/2 at a molecular level could help us to understand the activity of these drugs when used to treat BC in BRCA1/2 PVs/LPVs carriers. The efficacy of trastuzumab deruxtecan (T-DXd), an antibody-drug conjugate (ADC) targeting HER2 for HER2-low and HER2-positive (HER2+) BC, has been increasingly described. Unfortunately, data on T-DXd in HER2+ or HER2-low metastatic BC harboring germinal BRCA1/2 PVs/LPVs is lacking. Including germinal BRCA1/2 status in the subgroup analysis of the registration trials of this ADC would be of great interest, especially in the phase III trial DESTINY-breast04. This trial enrolled patients with HER2-negative (HER2-) and both HR+ and HR- metastatic disease, which can now be categorized as HER2-low. The HER2-low subgroup includes tumors that were previously classified as triple negative, so it is highly likely that some women were germline BRCA1/2 PVs/LPVs carriers and this data was not reported. Germline BRCA1/2 status will be available for a higher number of individuals with BC in the near future and data on the prognostic and predictive role of these PVs/LPVs is needed in order to choose the best treatment options.

COVID-19 is one of the deadliest respiratory diseases, and its emergence caught the pharmaceutical industry off guard. While vaccines have been rapidly developed, treatment options for infected people remain scarce, and COVID-19 poses a substantial global threat. This study presents a novel workflow to predict robust druggable targets against emerging RNA viruses using metabolic networks and information of the viral structure and its genome sequence. For this purpose, we implemented pymCADRE and PREDICATE to create tissue-specific metabolic models, construct viral biomass functions and predict host-based antiviral targets from more than one genome. We observed that pymCADRE reduces the computational time of flux variability analysis for internal optimizations. We applied these tools to create a new metabolic network of primary bronchial epithelial cells infected with SARS-CoV-2 and identified enzymatic reactions with inhibitory effects. The most promising reported targets were from the purine metabolism, while targeting the pyrimidine and carbohydrate metabolisms seemed to be promising approaches to enhance viral inhibition. Finally, we computationally tested the robustness of our targets in all known variants of concern, verifying our targets’ inhibitory effects. Since laboratory tests are time-consuming and involve complex readouts to track processes, our workflow focuses on metabolic fluxes within infected cells and is applicable for rapid hypothesis-driven identification of potentially exploitable antivirals concerning various viruses and host cell types.

We aimed to study the knowledge of diabetes among high-risk individuals for diabetes in the Indian state of Kerala. The baseline data collected from 1007 participants of the Kerala Diabetes Prevention Program were analyzed. Diabetes knowledge was assessed using a scale adapted from a large nationwide study conducted in India. The composite score of the scale ranges from 0 to 8. The mean age of participants was 46.0 (SD: 7.5) years, and 47.2% were female. The mean diabetes knowledge score was 6.9 (SD: 2.1), with 59.5% having the maximum possible score of 8. Of 1007 participants, 968 (96.1%) had heard the term diabetes, and of them, 84.7% know what diabetes is, 87.2% think more and more people are getting diabetes nowadays, 79.6% know that diabetes can cause complications in organs, and 75.9% know that diabetes can be prevented. While the level of diabetes knowledge was high among our participants, a quarter of them (24.1%) were not aware that diabetes can be prevented. Thus, there is a need for health promotion programs to increase the knowledge of diabetes prevention among high-risk individuals in Kerala.

Background: The duration of the vaccine's protective efficacy against SARS-CoV-2 is unknown. Evaluation of the clinical performance of available tests is required. Objectives: To evaluate the clinical performance of three immunoassays for the detection of IgG antibodies generated by mRNA vaccines against SARS-CoV-2. Methods: Two automated immunoassays (Euroimmun Anti-SARS-CoV-2 ELISA IgG and Abbott SARS-CoV-2 CLIA IgG) and one lateral flow immunoassay (LFIA Test Livzon IgG) were tested. 300 samples distributed in 3 groups were analyzed: 100 subjects over 18 years old and under 45 years old, 100 subjects between 45-65 years old and another 100 over 65 years old. collected before vaccination, at 21 days, 1, 2, 3 and 6 months post-vaccination. Sensitivity, specificity, positive predictive value, negative predictive value, positive likelihood ratio, negative likelihood ratio, and agreement (I. Kappa) were calculated for each serological test. Results: Maximum sensitivity for IgG was 98.7%, 98.1%, and 97.8% for the ELISA Euroimmun, CLIA Abbott, and Livzon LFIA assays and maximum specificity for IgG was 99.4%, 99.9%. % and 98.4% ELISA, CLIA and LFIA respectively at 3 months after vaccination with a decrease in antibody levels from the sixth month. The best agreement was observed between ELISA and CLIA 100%; (k = 1.00). The agreement between ELIA, CLIA and LIFIA was 99% (k = 0964) at the second and third month after vaccination. Seroconversion was faster and longer lasting in the younger age groups. Conclusion: Our study showed an equivalent and homogeneous clinical performance for IgG of three immunoassays after vaccination and that the LIFIA assay is the most cost-effective, reliable and accurate for routine use in population studies of seroconversion and seroprevalence.

Wheat and barley are among the primary food resources of the world population; therefore, their growth and observation are essential in farms to enhance food security worldwide. On top of that, careful observation of the product is essential to find solutions for the issues faced during their production and to reduce the impacts of weather changes. With the advancement of Remote Sensing technology, the observation and estimation process has increased. In this study, numbers of spectral vegetation indices was used along with canopy biophysical properties ( LAI ) and biochemical properties (chlorophyll), there calculated from (Landsat 8 and Sentinel-2) satellite data. The wheat and barley samples were collected before were be ready for harvest, and a relation with the vegetarian indices was established using the Multi-Linear Regression module, in which the equations used in predicting the harvest were developed and used to create a graph for expected harvest. The result indicated that there is a strong relationship between the vegetation indices of Sentinel-2 and Landsat images and the actual grain yield with R² of 0.77 and 0.71, respectively. The results show that the strongest correlation is observed between the LAI data obtained from Sentinel data and cereal yield data, with an R² 0.68, and the highest correlation for the indices of Landsat images is observed in the NDWI with R² 0.59 and the lowest degree of error was in the root mean square error (RMSE) for the Sentinel-2 and Landsat 8 with 0.57 and 1.54. In addition, this study also showed that the least relationship for grain yield prediction was observed between the NDRI for Sentinel-2 (R² 0.1) and SAVI for Landsat image (R² 0.47).

The repurposing of licenced drugs for use against COVID-19 is one of the most rapid ways to develop new and alternative therapeutic options to manage the ongoing pandemic. Given the approximately 8,000 licenced compounds available from Compounds Australia that can be screened, this paper demonstrates the utility of commercially-available ex vivo/3D airway and alveolar tissue models. These models are a closer representation of in vivo studies compared to in vitro models, but retain the benefits of rapid in vitro screening for drug efficacy. We demonstrate that several existing drugs appear to show anti-SARS-CoV-2 activity against both Delta and Omicron Variants of Concern in the airway model. In particular, fluvoxamine, as well as aprepitant, everolimus, and sirolimus have virus reduction efficacy comparable to the current standard of care (remdesivir, molnupiravir, nirmatrelvir). Whilst these results are encouraging, further testing and efficacy studies are required before clinical use can be considered.

During the SARS-CoV-2 vaccination campaign, people with CF (pwCF) were considered a clinically vulnerable population. However, data on immunogenicity of anti-SARS-CoV-2 vaccines in pwCF are lacking. We conducted a prospective study enrolling all patients aged >12 and followed-up in our CF centre, who received two doses of the BNT162b2 vaccine in March-­­­October 2021. They underwent a blood sample for quantification of antibodies to the SARS-CoV-2 spike protein receptor binding domain immediately before receiving the first dose and after 3 and 6 months from the second dose. We enrolled 143 patients (median age: 21 years, range: 13-38); of whom 16 had a previous infection. Median antibody titer (interquartile range) after 3 months from vaccination was 1288 U/mL (730-2115) and decreased to 918 U/mL (534-1488) after 6 months (P<0.0001). Median values were higher among previously infected patients as compared to those naïve to SARS-CoV-2 (9107 vs 1229 U/mL at 3 months and 4810 vs 829 U/mL at 6 months, P<0.0001) with no significant differences in the rate of decline over time (P=0.135). All pwCF mounted an antibody response after two-doses of BNT162b2 vaccine that waned at 6 months from vaccination. Age ≥30 years and use of inhaled corticosteroids were associated with a lower humoral response.

Gal-3BP is a multifunctional glycoprotein involved in cell-cell and cell-matrix interactions known to be upregulated in cancer and various viral infections, including HIV-1, HCV and SARS-CoV-2, with a key role in regulating the antiviral immune response. Studies have identified a direct correlation between circulating levels of Gal-3BP and the severity of disease and/or disease progression for some viral infections, including SARS-CoV-2, suggesting a role of Gal-3BP in these processes. Due to Gal-3BP’s complex biology, the molecular mechanisms underlying its role in viral diseases have been only partially clarified. Gal-3BP induces the expression of IFN and pro-inflammatory cytokines, including interleukin-6, mainly interacting with galectin-3, targeting TRAF-6 and TRAF-3 complex, thus having a putative role in the modulation of TGF-β signaling. In addition, an antiviral activity of Gal-3BP has been ascribed to a direct interaction of the protein with virus components. In this review, we explored the role of Gal-3BP in viral infections and the relationship between Gal-3BP upregulation and disease severity and progression, mainly focusing on SARS-CoV-2. Augmented knowledge of Gal-3BP role in virus infections can be useful to evaluate its possible use as a prognostic biomarker and as a putative target to block or attenuate severe disease.

Since the detection of the first COVID-19 patient, 2 years have passed, during which more than 287,862,000 people fell ill globally, of which about 1.9% died. Implementation of SARS-CoV-2 control programs required efforts from almost all countries. An important direction in the fight against COVID-19 was the formation of herd immunity, the main tool for managing the pandemic. Study goal: to assess the seroprevalence of antibodies (Abs) to SARS-CoV-2 nucleocapsid (Nc) and receptor binding domain (RBD) in the St. Petersburg population during the COVID-19 pandemic. Materials and methods. A longitudinal cohort randomized monitoring study of Ab seroprevalence (SARS-CoV-2 Nc, RBD) was organized and conducted according to a unified methodology developed by Rospotrebnadzor with the participation of the St. Petersburg Pasteur Institute. For this purpose, a cohort of 1000 volunteers was formed who participated in all five stages of seromonitoring. The cohort was divided into 7 age groups: 1-17; 18-29; 30-39; 40-49; 50-59; 60-69; 70; and older (70+) years. Seropositivity levels (Nc, RBD) were assessed by quantitative and qualitative enzyme immunoassays. During the 2nd year of monitoring, some volunteers were vaccinated with the GamCOVIDVac (84%) or EpiVacCorona (11.6%) vaccines approved in Russia. Statistical processing was carried out using the Excel 2010 software package. Confidence intervals for shares and percentages (95% CI) were calculated using the method of A. Wald and J. Wolfowitz with adjustment (A. Agresti, B.A. Coull). The statistical significance of differences was calculated by z-test, using the appropriate online calculator (p<0.05), unless indicated. Results. There was a trend towards: an increase in Nc seropositivity in stages 1-3 of seromonitoring, with a decrease in stages 4-5 among children and adults. The share of RBD seropositive steadily increased during all 5 stages of seromonitoring. The most frequently found were low anti-RBD Abs levels (22.6-220 BAU/ml). High Ab levels were recorded statistically significantly less frequently. Asymptomatic forms were observed in 84-88% of SARS-CoV-2 seropositive volunteers. By the 5th stage of monitoring, this indicator significantly decreased to 69.8% (95% CI: 66.1-73.4). The monitoring revealed a statistically significant increase in anti-RBD Abs, alongside a statistically significant decrease in the proportion of Nc seropositive. This dynamic was especially characteristic of persons vaccinated with GamCOVIDVac. Conclusion. Prior to the use of specific vaccines, a seroprevalence of anti-Nc Abs was noted. After the introduction of the GamCOVIDVac vaccine in adults, a decrease in the level of anti-Nc Abs was noted due to an increase in the proportion of RBD seropositive persons.

Rapid antigen detection tests (RAD) are commonly used for the diagnosis of SARS-CoV-2 infections. However, with the continuous emergence of new variants of concern (VOC) presenting various mutations potentially affecting the nucleocapsid protein, the analytical performances of these assays should be frequently reevaluated. One-hundred and twenty samples were selected and tested with both RT-qPCR and five commercial RAD commonly sold in Belgian pharmacies. Of these, direct whole genome sequencing identified the strains present in 116 samples, of which 70 were Delta and 46 were Omicron. Sensitivity across a wide range of Ct values (13.5 to 35.7; median = 21.3) were comparable and ranged from 70.0% to 77.1% for Delta strains and from 69.6% to 78.3% for Omicron strains. When taking swabs with a low viral load (Ct &gt; 25), poor performances were observed for the Delta strains (20.0 to 40.0%) and, even more so, for Omicron strains (0.0 to 23.1%). Two devices failed to detect all samples (n = 13) containing Omicron strains with a low viral load. The poor performance observed with low viral loads is an important limitation of RAD, which is not sufficiently highlighted in the instruction for use of these devices.

Introduction. COVID-19 is a pathology caused by the SARS-CoV2 virus. The World Health Organization has reported more than 94 million cases and two million deaths worldwide. Objective: To describe the seroprevalence, spatial distribution, and clinical and sociodemographic variables of SARS-CoV2 in a community of the Colombian Amazon region. Methods. In December 2020, a cross-sectional observational study was carried out in a population located in the Colombian Amazon in the municipality of Mitú. Sociodemographic and clinical data were taken. Besides, 590 blood samples were taken, and an antibody detection was carried out with an ELISA and a recombinant protein N antigen of SARS-CoV2. Results. A seroprevalence of 57.6% was observed. The highest proportion of the infection is located in inter-municipal transport zones. The bivariate analysis did not show differences in the SARS-CoV2 infection rate concerning the variables sex, age-range, and the presence of comorbidities (P> 0.05). The bivariate and multivariate analysis showed that being symptomatic and presenting neurological manifestations of the upper respiratory tract are clinical variables associated with SARS-CoV2 infection (P <0.05). One of the causes of this virus's high spread in this community could be that 53.3% of the people were asymptomatic. Conclusions. Our data showed a high burden and transmission of SARS-CoV-2 in this indigenous community. This could be linked to cultural behaviors and the high infection rate in asymptomatic patients.

The SARS-CoV-2 pandemic has resulted in the generation of evolutionary-related variants. The S-protein of the B.1.1.7 variant (deletion N-terminal domain (NTD) His69Val70Tyr144) may contribute to altered infectivity. These mutations may have been presaged by animal mutations in minks housed in mink farms that according to the present analysis by modelling of protein ligand docking altered a high affinity binding site in the S-protein NTD. These mutants likely occurred only sporadically in humans. Tissue-adaptations and the size of the mink relative to the infected human population size back then may have comparatively increased the relative mutation rate. Simple, multi-threaded automated docking that is widely available, assigns increased binding of the blood type II A antigen to the SARS-Cov-2 S-protein NTD of B.1.1.7 with an overall increased docking interaction of blood group A harbouring glycolipids relative to group B or H (H, p=0.04). The top scoring glycan is identified as a DSGG (also classified as sialosyl-MSGG or disialosyl-Gb5) that may compete with heparin, which is similar to heparan sulfate linked to proteinaceous receptors on the tissue surface. Other glycolipids are found to interact with lower affinity, except long ligands that have suitable ligand binding poses to match the curved binding pocket.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the etiological agent of COVID-19 , is considered a pathogen with animal origin, mainly transmitted human to human. It has been experimentally and naturally demonstrated that several animals can be infected by SARS-CoV-2. There are strong evidences that minks are highly susceptible to SARS-CoV-2 infection, since several cases of human to mink infection have been reported, and it has been suggested mink to human infection exists, which so far it is the most reliable example of a zoonotic event of COVID-19 . However, all these cases reported are form mink farms, with the exception of one case in the USA in which the virus was detected in a mink located in the wild, but it was demonstrated that the animal was infected on a fur farm. In the present work, we have detected SARS-CoV-2 RNA in two wild American minks (Neovison vison) in Valencian Community (Eastern Spain) during invasive species trapping campaigns. The animals were trapped from areas known for harbouring self-sustained populations, far away from the nearest fur farm. SARS-CoV-2 RNA was detected in mesenteric lymph nodes samples by RT-PCR. A partial region of the Spike protein gene was amplified and sequence obtaining a 397 nt size sequence. Phylogenetic analysis shown that both sequences were identical to the consensus variant SARS CoV-2 sequence (from Wuhan). This research describes the first infection report of a true wild American mink not related to infected fur farms or direct contact with humans, which is believed to be the first example of wild animals in which SARS-CoV-2 has been detected.

Background: The aim of this study was to investigate the persistence of SARS-CoV-2 in post-mortem swabs of subjects who died from SARS-CoV-2 infection. Methods: The presence of the virus was evaluated post-mortem from airways of 27 SARS-CoV-2 positive patients at three different time points (T1 2 hours; T2 12 hours – T3 24 hours) by real-time PCR. Detection of antibodies to SARS-CoV-2 was performed by Maglumi 2019-nCoV IgM/IgG chemiluminescence assay. Results: SARS-CoV-2 viral RNA was still detectable in 70,3% of cases within 2 hours after death and in 66,6% of cases up to 24 hours after death. Our data showed an increase of the viral load in 78,6% of positive individuals 24 hours post-mortem (T3) in comparison to that evaluated 2 hours after death (T1). Noteworthy, we detected a positive T3 post-mortem swab (24 hours after death) from 4 subjects who were negative at T1 (2 hours after death). Conclusion: The results of our study may have an important value in the management of deceased subjects not only with a suspected or confirmed diagnosis of SARS-CoV-2, but also for unspecified causes and in the absence of clinical documentation or medical assistance.

The center vortex model of quantum-chromodynamics can explain confinement and chiral symmetry breaking. We present a possible resolution for problems of the vortex detection in smooth configurations and discuss improvements for the detection of center vortices.

Coronavirus disease 2019 (COVID-19) was initially characterized as a respiratory illness. Neurological manifestations were reported mostly in severely affected patients. Routes for brain infection and the presence of virus particles in situ have not been well described, raising controversy about how the virus causes neurological symptoms. Here, we report the autopsy findings of a 1-year old infant with COVID-19. In addition to pneumonitis and multiple organ damage related to thrombosis, SARS-CoV-2 infected the choroid plexus, ventricles, and cerebral cortex. This is the first evidence of SARS-CoV-2 detection in an infant post-mortem brain.

The interest in renewable energy to replace fossil fuel is increasing as the problem caused by climate change become more severe. Small hydropower (SHP) is evaluated as a resource with high development value because of its high energy density compared to other renewable energy sources. SHP may be an attractive and sustainable power generation environmental perspective because of its potential to be found in small rivers and streams. The power generation potential could be estimated based on the discharge in the river basin. Since the river discharge depends on the climate conditions, the hydropower generation potential changes sensitively according to climate variability. Therefore, it is necessary to analyze the SHP potential in consideration of future climate change. In this study, the future prospect of SHP potential is simulated for the period of 2021 to 2100 considering the climate change in three hydropower plants of Deoksong, Hanseok, and Socheon stations, Korea. As the results, SHP potential for the near future (2021 to 2040) shows a tendency to be increased and the highest increase is 23.4% at the Deoksong SPH plant. Through the result of future prospect, we have shown that hydroelectric power generation capacity or SHP potential will be increased in the future. Therefore, we believe that it is necessary to revitalize the development of SHP in order to expand the use of renewable energy. Also, a methodology presented in this study could be used for the future prospect of the small hydropower potential.

To date, uncertainty remains about how long the protective immune responses against SARS-CoV-2 persists and reports of suspected reinfection began to be described in recovered patients months after the first episode. Viral evolution may favor reinfections, and the recently described spike mutations, particularly in the receptor binding domain (RBD) in SARS-CoV-2 lineages circulating in the UK, South Africa, and most recently in Brazil, have raised concern on their potential impact in infectivity, immune escape and reinfection. We report a case of reinfection from distinct SARS-CoV-2 lineages presenting the E484K mutation in Brazil, a variant associated with escape from neutralizing antibodies.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for the disease COVID-19 that has decimated the health and economy of our planet. The virus causes the disease not only in people but also in companion and wild animals. People with diabetes are at risk of the disease. As yet we do not know why the virus is highly successful in causing the pandemic within 3 months of its first report. The structural proteins of SARS include, membrane glycoprotein (M), envelope protein (E), nucleocapsid protein (N) and the spike protein (S). The structure and function of the most abundant structural protein of SARS-CoV-2, the membrane (M) glycoprotein is not fully understood. Using in silico analyses we determined the structure and potential function of the M protein. The M protein of SARS-CoV-2 is 98.6% similar to the M protein of bat SARS-CoV, maintains 98.2% homology with pangolin SARS-CoV, and has 90% homology with M protein of SARS-CoV; whereas, the similarity was only 38% with the M protein of MERS-CoV. In silico analyses showed that the M protein of SARS-CoV-2 has a triple helix bundle, form a single 3-transmembrane domain (TM), and are homologous to the prokaryotic sugar transport protein semiSWEET. SemiSWEETs are related to the PQ-loop family that function as cargo receptors in vesicle transport, mediates movement of basic amino acids across lysosomal membranes, and is also involved in phospholipase flippase function. The advantage and role of the M protein having a sugar transport-like structure is not clearly understood. The M protein of SARS-CoV-2 interacts with S, E and N protein. The S protein of the virus is glycosylated. It could be hypothesized that the sugar transporter-like structure of the M protein influences glycosylation of the S protein. Endocytosis is critical for the internalization and maturation of RNA viruses, including SARS-CoV-2. Sucrose is involved in endosome and lysosome maturation and may also induce autophagy, pathways that help in the entry of the virus. Overall, it could be hypothesized that the semiSWEET sugar transporter-like structure of the M protein may be involved in multiple functions that may aid in the rapid proliferation, replication and immune evasion of the SARS-CoV-2 virus. Biological experiments would validate the presence and function of the semiSWEET sugar transporter.

As the number of infections and deaths caused by the recent COVID-19 pandemic is increasing dramatically day-by-day, scientists are rushing towards developing possible counter-measures to fight the deadly virus, SARS-CoV-2. Although many efforts have already been put forward for designing and developing potential vaccines, however, most of them are proved to possess negative consequences. Therefore, in this study, the methods of immunoinformatics were exploited to design novel epitope-based subunit vaccine against the SARS-CoV-2, targeting four essential proteins of the virus i.e., spike glycoprotein, nucleocapsid phosphoprotein, membrane glycoprotein, and envelope protein. The highly antigenic, non-allergenic, non-toxic, non-human homolog and 100% conserved (across other isolates from different regions of the world) epitopes were used for constructing the vaccine. In total, fourteen CTL epitopes and eighteen HTL epitopes were used to construct the vaccine. Thereafter, several in silico validations i.e., the molecular docking, molecular dynamics simulation (including the RMSF and RMSD studies), and immune simulation studies were also performed which predicted that the designed vaccine should be quite safe, effective, and stable within the biological environment. Finally, in silico cloning and codon adaptation studies were also conducted to design an effective mass production strategy of the vaccine. However, more in vivo and in vitro studies are required on the predicted vaccine to finally validate its safety and efficacy.

There is a rising global concern for the ongoing outbreak of SARS-CoV-2 due to its high transmission rate and unavailability of treatment. Through the binding of its spike glycoprotein with angiotensin type 2 (ACE2), SARS-CoV-2 can efficiently get in the cells of patients and start its pandemic cycle. Herein, the biological diversity of SARS-CoV-2 infection was assessed in Babylon province of Iraq by investigating the possible genetic variations of the spike glycoprotein. A specific coding region of 795 bp within the viral spike (S) gene was amplified from 19 patients who suffered from obvious symptoms of SARS-CoV-2 infection. Sequencing results identified fifteen novel nucleic acid variations with a variety of distributions within the investigated samples. The electropherograms of all the identified variations showed obvious co-infections with at least two different viral strains per sample. Within these co-infections, the majority of samples exhibited three nonsense single nucleotide polymorphism (SNP)s, p.301Cdel, p.380Ydel, and p.436del, which yielded three truncated SARS-CoV-2 spike glycoproteins of 301, 380, and 436 amino acids length, respectively. The network and phylogenetic analyses indicated that for all viral infections were derived from multi-ancestral origins. Results inferred from the specific clade-based tree entailed that some viral strains were derived from European G-clade sequences. In conclusion, our data demonstrated the absence of any single strain infection among all investigated viral samples in the studied area, which may entail a higher risk of SARS-CoV-2 in this country. Through the identified high frequency of truncated spike proteins, we suggest that defective SARS-CoV-2 may depend on helper strains having intact spikes in its infection. Alternatively, another putative ACE2-independent route of viral infection way also suggested. To the best of our knowledge, this is the first report to describe the co-infection of multiple strains of SARS-CoV-2 in patients with COVID-19.

The pandemic respiratory disease COVID-19, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), emerged in Wuhan in December 2019 and then spread throughout the world; Italy was the most affected European country. Despite the close pet-human contact, little is known about the predisposition of pets to SARS-CoV-2. Among these, felines are the most susceptible. In this study, a domestic cat with clear symptoms of pneumonia, confirmed by Rx imaging, was found to be infected by SARS-CoV-2 using quantitative RT–qPCR from a nasal swab. This is the first Italian study reporting on the request of the scientific community to focus attention on the possible role of pets as a SARS-CoV-2 reservoir. An important question remains unanswered: did the cat die from SARS-CoV-2 infection?

High levels of air pollution can contribute to high rate of the COVID-19 outbreaks. Air pollutants induce oxidative stress, inflammatory process, immune imbalance and coagulation at systemic level, making the organism susceptible to complications caused by various pathogens, including viruses, resulting in a possible important damage co-factor. Sperm cells are highly sensitive to the pro-oxidant effects of environmental pollutants, and may represent an important alarm bell indicating that the burden of environmental pressure in a certain area is causing damage to humans. A comparison of the maps of COVID-19 case fatality rates, male infertility rates and air pollution may suggest a way to understand the dynamics of the virus impact. Semen quality may be considered as an early and sensitive environmental marker, and also a potential susceptibility indicator to viral insults (including SARS-CoV-2 ) in heavily polluted areas. Therefore, assessing the burden of environmental exposure of a given population and its potential susceptibility to insults through early biological stress indicators may be helpful for predicting the risk of the adverse effects by the SARS-CoV-2 epidemic .

SARS-CoV-2 has been the talk of the town ever since the beginning of 2020. The pandemic has brought the complete world on a halt. Every country is trying all possible steps to combat the disease ranging from shutting the complete economy of the country to repurposing of drugs and vaccine development. The rapid data analysis and widespread tools, software and databases have made bioinformatics capable of giving new insights to the researchers to deal with the current scenario more efficiently. Vaccinomics, the new emerging field of bioinformatics uses concepts of immunogenetics and immunogenomics with in silico tools to give promising results for wet lab experiments. This approach is highly validated for the designing and development of potent vaccines. The present in-silico study was attempted to identify peptide fragments from spike surface glycoprotein that can be efficiently used for the designing and development of epitope-based vaccine designing approach. Both B-cell and T-cell epitopes are predicted using integrated computational tools. VaxiJen server was used for prediction of protective antigenicity of the protein. NetCTL was studied for analyzing most potent T cell epitopes and its subsequent MHC-I interaction through tools provided by IEDB. 3D structure prediction of peptides and MHC-I alleles (HLA-C*03:03) was further done to carry out docking studies using AutoDock4.0. Various tools from IEDB were used to predict B-cell epitopes on the basis of different essential parameters like surface accessibility, beta turns and many more. Based on results interpretation, the peptide sequence from 1138-1145 amino acid and sequence WTAGAAAYY and YDPLQPEL were obtained as a potential B-cell epitope and T-cell epitope respectively. This in-silico study will help us to identify novel epitope-based peptide vaccine target in spike protein of SARS-CoV-2. Further, in-vitro and in-vivo study needed to validate the findings.

Although phylogenetic analysis shows coronaviruses (CoV) share similar genome sequences, CoVs encode different number of proteins (5 to 14), which has implication on viral pathogenicity and infection. Here, we aimed to identify (in-silico) the similarities between different members of coronavirus family. The analysis included 50 coronavirus proteomes, including SARS-CoV-2 (COVID-19), to find the variation of the number of protein functional motifs and domain in each coronavirus. For this role, we used the experimentally validated domain (motif) that known to be crucial for viral infection. Although human CoVs are classified within one genus, we found variations among them. SARS-CoV-1, SARS-CoV-2 and MERS-CoV encode different type of domains, which has implications on the molecular interactions triggered by each virus within human cells. Secondly, we used functional motifs to reconstruct the potential molecular pathways or interactions triggered by SARS-CoV-2 proteins within human cell.

In the surgical treatment of lung cancer, systemic mediastinal lymph node dissection, as one important routine procedure, has been accepted by most peers in the world. However, due to the special location of some mediastinal lymph nodes, the difficulty of dissection, and the negative preoperative CT results, the specific scope of lymph node dissection is still controversial. Especially the second group, which is located at the top of thorax, is likely to be overlooked for the above reasons. Here, we report a case of lung adenocarcinoma in which the preoperative CT showed no abnormal lymph nodes in the second group and also no enlarged lymph nodes of the second group were found during the surgery, yet lymphadenectomy was still performed according the routine with the lymph node of station 2 being sampled. In the postoperative pathological report, cancer cells were found in the second group, instead of lung adenocarcinoma, these cells come from thyroid and were proved to be papillary thyroid carcinoma, which is unusual because no obvious indication of thyroid carcinoma was found in preoperative color doppler ultrasound of superficial lymph nodes.

Severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2/2019-nCoV) infection is an emerging pandemic. The virus binds to angiotensin converting enzyme 2 (ACE2) and TMPRSS2 which are abundantly expressed on various human cells including lung epithelial cells and intestinal cells and the virus can infect these cells. Currently no specific treatments or vaccines are available for this disease. A per oral live attenuated vaccine can be beneficial in SARS-Cov-2 infection because the attenuated virus initially infects the gut, stimulates the mucosa associated immune system sparing the respiratory system during the initial immune response. The live virus can also spread in the community boosting herd immunity.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is characterized by a high mortality of elderly men with age-related comorbidities. In most of these patients, uncontrolled local and systemic hyperinflammation induces severe and often lethal outcomes. The aging process is characterized by the gradual development of a chronic subclinical systemic inflammation (inflamm-aging) and by acquired immune system impairment (immune senescence). Here, we advance the hypothesis that some key features of aging contribute to the disproportionate SARS-CoV-2 mortality suffered by elderly men. At least four well-recognized aging-related characteristics that are strongly expressed in older men go some way towards explaining why these patients account for the vast majority of fatalities: i. the presence of subclinical systemic inflammation without overt disease, ii. a blunted acquired immune system and type I interferon response due to the chronic inflammation; iii. the downregulation of ACE2 (SARS-CoV-2 receptor), which triggers inflammation, particularly in patients with age-related comorbid diseases such as type II diabetes; and iv. accelerated biological aging, as measured by epigenetic and senescence markers (e.g. telomere shortening) associated to the chronic inflammatory state. Though typical of the aged, especially of elderly men, it is conceivable that these features are also shared by some subsets of the younger population. The high mortality rate of SARS-CoV-2 infection suggests that clarification of the mechanisms of inflamm-aging and immune senescence can help combat not only age-related disorders but also SARS-CoV-2 infection.

To date, viral RNA detection is almost the only way to confirm SARS-CoV-2infectionin practice.However, variousreasons can cause low sensitivity for RNA detection, and thisposes aserious challenge to disease control. We tested the performance of detecting total antibody(Ab) and IgM levels in serum by the methods of chemiluminescence, enzyme-linked immunosorbent assay (ELISA), and colloidal golddetection. The datashowed that the sensitivity and specificity for detecting total Ab and IgM levels were high by all three methods, and the sensitivity was higher for detecting total Ab than for detecting IgM. Evidence from studieshas shown thatviral RNA testingcombinedwith serological testing could increase the diagnostic sensitivity while maintaining a high specificity. Specific serology testsfor SARS-CoV-2 havegreat value for clinical practice and public health.

There is an urgent need to identify effective therapies for COVID-19 given that a broadly available and effective vaccine is likely at least one year away. Here, we identify compounds that transcriptionally inhibit host proteins required for SARS-CoV-2 entry and should be evaluated for efficacy in SARS-CoV-2 viral infection assays. Recognizing the need for immediately available treatment options, we focused particular attention on FDA-approved drugs that could be immediately repurposed to treat COVID-19 patients. By mining publicly available gene expression data, we identify several compounds that down-regulate TMPRSS2, a protein required for SARS-CoV-2 entry that has emerged as a promising therapeutic target. Among these, we find twenty independent studies that implicate estrogen-related and androgen-related compounds as transcriptional modulators of TMPRSS2 expression, suggesting that these drugs and others acting on the pathway may be promising therapeutic candidates for COVID-19 for further testing. It is also noteworthy that TMPRSS2 has highly variable and skewed expression in humans, spanning two orders of magnitude with a small minority of individuals having extremely high expression. Combined with literature showing that TMPRSS2 loss-of-function in mouse is protective against SARS while anti-estrogen treatment predicted to increase TMPRSS2 expression exacerbates SARS, this observation raises the hypothesis that TMPRSS2 expression may positively correlate with severity in COVID-19.

The novel coronavirus (SARS-CoV-2) is a human pathogen recently emerged in China, causing a global pandemic of severe respiratory illness (COVID19). SARS-CoV-2 makes entry into human cells through its spike (S) protein that binds to cell surface receptors. Widespread of SARS-CoV-2 has been attributed to high affinity of S protein to its receptor. A homology model of the receptor binding domain of SARS-CoV-2 S protein (RBD) was built. RBD- receptor docking and published molecular dynamics data were used to map the key RBD-receptor interaction hotspot (RBDhp) on the RBD. Primary virtual screening was carried out against RBDhp using more than 3300 compounds approved by U.S Food and Drug Administration (FDA) and other authorities for human use. Compounds that bind to hpRBD with a binding energy ≤ - 6.5 kcal/mol were subjected to secondary screening using a recently published cryo EM (2.9 Å) structure of RBD. A cardiac glycoside (dgitoxin), two anthracyclines (zorubicin and aclarubicin), a tetracycline derivative (rolitetracycline), a cephalosporin (cefoperazone) and a food dye (E-155) were predicted to be most potent inhibitors of RBD – receptor interaction. An anti-asthmatic drug (zafirlukast) and several other drugs (itrazol, fazadinium, troglitazone, gliquidone, Idarubicin, Oxacillin) were found to be high affinity binders that may have a potential to inhibit RBD – receptor interaction.

An outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) occurred in China towards the end of 2019, and has spread rapidly ever since. Previous studies showed that some virus could affect the reproductive system and cause long-term complications. Recent studies exploring the source of SARS-CoV-2 using genomic sequencing have revealed that SARS-CoV-2 enters the host cells via the angiotensin-converting enzyme II (ACE2), the receptor that recognizes SARS-CoV. To investigate the expression of ACE2 and to explore the potential risk of infection in the reproductive system, we performed a thorough bioinformatic analysis on data from public databases involving RNA expression, protein expression, and single-cell RNA expression studies. The analyzed data showed high levels of ACE2 mRNA and protein expression in the testis and spermatids and equal levels of ACE2 expression in the uterus and lung. Comprehensive single-cell analysis identified ACE2 expression in the lung, testis, spermatids, and uterus. In conclusion, this study revealed the potential risk associated with the SARS-CoV-2 infection in the reproductive system and predicted that long-term complications might have a significant impact on the prevention and management of COVID-19, the disease caused upon infection with SARS-CoV-2.

In Portugal, cork oak (Quercus suber L.) stands cover 737 Mha, being the most predominant species of the montado agroforestry system, contributing for the economic, social and environmental development of the country. Cork oak decline is a known problem since the late years of the 19th century that has recently worsen. The causes of oak decline seem to be a result of slow and cumulative processes, although the role of each environmental factor is not yet established. The availability of Sentinel-2 high spatial and temporal resolution dense time series enables gradual processes monitoring. These processes can be monitored using spectral vegetation indices (VI) once their temporal dynamics are expected to be related with green biomass and photosynthetic efficiency. The Normalized Difference Vegetation Index (NDVI) is sensitive to structural canopy changes, however it tends to saturate at moderate-to-dense canopies. Modified VI have been proposed to incorporate the reflectance in the red-edge spectral region, which is highly sensitive to chlorophyll content while largely unaffected by structural properties. In this research, in-situ data on the location and vitality status of cork oak trees are used to assess the correlation between chlorophyll indices (CI) and NDVI time series trends and cork oak vitality at the tree level. Preliminary results seem to be promising since differences between healthy and unhealthy (diseased/dead) trees were observed.

The snow melt from the High Atlas is a critical water resource in Morocco. In spite of its importance, monitoring the spatio-temporal evolution of key snow cover properties like the snow water equivalent remains challenging due to the lack of in situ measurements at high elevation. Since 2015, the Sentinel-2 mission provides high spatial resolution images with a 5 day revisit time, which offers new opportunities to characterize snow cover distribution in mountain regions. Here we present a new data assimilation scheme to estimate the state of the snowpack without in situ data. The model was forced using MERRA-2 data and a particle filter was developed to dynamically reduce the biases in temperature and precipitation using Sentinel-2 observations of the snow cover area. The assimilation scheme was implemented using SnowModel, a distributed energy-balance snowpack model and tested in a pilot catchment in the High Atlas. The study period covers 2015-2016 snow season which corresponds to the first operational year of Sentinel-2A, therefore the full revisit capacity was not yet achieved. Yet, we show that the data assimilation led to a better agreement with independent observations of the snow height at an automatic weather station and the snow cover extent from MODIS. The performance of the data assimilation scheme should benefit from the continuous improvements in MERRA-2 reanalyses and the full revisit capacity of Sentinel-2.

Quantum Computation, in the gate array version, uses logical gates adopting convenient forms for computational algorithms based on those of classical computation. There, two-level quantum systems are the basic elements connecting the binary nature of classical computation with the settlement of quantum processing. Despite, their design depends on specific quantum systems and physical interactions involved, exacerbating the dynamics analysis. Predictable and controllable manipulation should be addressed to control the quantum states, but resources are restricted to limitations imposed by the physical settlement. This work presents a formalism to decompose the quantum information dynamics in SU(2^2d) for 2d-partite two-level systems into 2^2d-1 SU(2) quantum subsystems. Decomposition lets to set control procedures, to generate large entangled states and to design specialized dedicated quantum gates. There, easy and traditional operations proposed by quantum computation are recovered for more complex and large systems. Alternating the parameters of local and non-local interactions, the procedure states a universal exchange semantics on the generalized Bell states basis. It could be understood as a momentary splitting of the 2d information channels into 2^2d-1 pairs of 2 level quantum information subsystems and a settlement of the quantum information manipulation free of the imposed restrictions by the underlying physical system.

Dengue virus (DENV), the causative agent of dengue fever (DF), is one of the most important mosquito-borne viruses that can infect humans. Although much effort has been made on prevention and control of dengue, there are currently no anti-viral drugs or worldwide approved vaccines yet. In this study, we immunized six-week-old Balb/c mice with DNA vaccine candidates E and NS1-2a of DENV serotype 2 or the combination of them (E+NS1-2a) via an electroporation (EP)-assisted intramuscular gene delivery system and evaluated the immune response and protection. The highest specific antibody titres and cytokine levels secreted by splenocytes as well as the highest survival rate were observed in the E+NS1-2a group, followed by E group and NS1-2a group. Our data suggested that the combination of E and NS1-2a delivered by EP may be a superior preventive strategy against DENV.

Diabetes mellitus (DM) has been defined as a group of metabolic diseases characterized by hyperglycemia resulting from defects in insulin secretion, insulin action, or both. This study includes (84) subjects, their age ranged from (40 to 54) years. (20) subjects were healthy chosen as control group and (64) patients with type 2 diabetes mellitus were divided into three groups according to their type of anti diabetic therapy: (23) newly diagnosed group without therapy (Group1), (20) with metformin therapy (Group2) and (21) with metformin plus glibenclamide therapies (Group3). In the study lipid profile level were quantitatively determine by enzymatic methods, in addition to that fasting plasma glucose (FPG), Glycated hemoglobin (HbA1c%) and body mass index (BMI) were identified in the patients. There is significant increase in the level of lipid profile in patients group. Metformin alone produce a non-significant favorable effect on all lipids profile parameters while metformin plus glibenclamide showed a significant reduction in TC and LDL-C.

Mediterranean diet has been widely suggested to exert significant beneficial effects on endothelial oxida-tive status and cardiometabolic health. Greek Orthodox monasteries, due to their specific nutritionaland sartorial habits, comprise a population which strictly adheres to nutritional patterns with restricted eating and a plant-based subset of the Mediter-ranean diet, often accompanied by profound hypovitaminosis D. Time –restricted eating is also adopted from a large part of general lay Greek population for health promoting reasons, without restrictions on an-imal product consumption, as imposed by Orthodox religious fasting. However, comparative effects of these nutritional patterns on oxidative stress markers remain scarce. The present study attempted to evaluate the effects of Christian Orthodox fasting (COF) in a group of vitamin D –deficient and overweight Orthodox nuns from Central and Northern Greece, compared to the implementation of TRE, 16:8 dietary regimen in a cohort of adult women from the general population from the same region, with regard to markers of endothelial oxidative status. A group of 50 women from two Orthodox monasteries in Northern Greece and one group of 50 healthy lay women were included. During enrollment a detailed recording of dietary habits was performed, along with a scientific registry of demographic and anthropometric characteristics (via bioimped-ance).Orthodox nuns followed a typical Orthodox fasting regimen[daily feeding window (8 am–4 pm)] whereas lay women followed a TRE 16:8 regimen with the same feeding time-window with recommenda-tion to follow a low-fat diet, without characteristics of the Mediterranean diet. We included a complete biochemical analysis, as well as calciotropic profiles [Calcium-Ca, Albumin, Parathyroid hormone-PTH, 25-hydroxyvitamin D- 25(OH)D] as well as and markers of TAC (trichloroacetic acid), (glutathione) GSH and thiobarbituric acid reactive substances (TBARS) concentrations, as markers of oxidative status. All groups were comparable at baseline for calcium, PTH and 25(OH)D concentrations, with no significant differences between groups. Orthodox nuns manifested a lower median GSH compared to con-trols (6.0 vs. 7.2, p 0.04) and a higher median TAC (0.92 vs. 0.77, p <0.001). TBARS comparisons showed no significant difference between the two groups. No significant associations of oxidative status with 25(OH)D, PTH and markers of glucose homeostasis were evident. Results of this small pilot study indicate that both dietary regimens have advantages over oxidative markers compared to each other, with increased TAC in the groups of Orthodox Nuns after a 16th week period of COF compared to a 16:8 TRE and increased GSH concentrations in the lay women group. Future randomized trials are required to investigate superiority or non-inferiority between these dietary patterns, in the daily clinical setting.

The SARS-CoV-2-induced acute COVID-19 pandemic disorder seems to have begun all of the sudden in 2020, with very little data available regarding prior times in which people experienced mysterious flu-like illness symptoms characteristic of the pandemic disease. The scientific community seems to be divided into a few parts with regards to the belief of the kind of viral origins. A significant number of scientists believe that the virus solely has natural origins and that it underwent a thorough process of zoonosis, independent of laboratory research-based research that would only catalyse zoonosis due to helping the virus gain additional function of transmission and virulence. Many other scientists believe that the virus has wide origins characteristic of “gain-of-function” laboratory research, whilst many other scientists believe that most of the viral genome has natural origins, with the zoonotic process having been artificially catalysed only in its latter part of transmission to humans. Considerable extent of scientific evidence suggests that the virus underwent a restricted, but considerable extent of “gain-of-function” research, prior to having been accidentally leaked into the nearby environment, whilst its process of zoonotic spillover into humans was influenced by such events, given for example the multidimensional pathogenetic process displayed by the virus and its main antigen of action, the spike glycoprotein, causing all kinds of immune pathophysiology - including transient immunosuppression. Investigations into the origins of the novel coronavirus have been lasting for years, seemingly with no concrete end in sight, and the available molecular testing methods to detect SARS-CoV-2 infection displaying less than perfect results have not significantly helped the process. Evidence even started pointing toward the existence of artificial, laboratory research-based viral origins, exposing a probable accidentally-induced artificial process of “accelerated viral evolution”, which could be particularly dangerous because of the nature of the SARS-CoV-2 pathogenic agent. Likewise, it is possible that the prevention of distribution of scientific data regarding scenarios as such in fact constitutes censorship, rather than regulation of data that may be considered not to be significantly evidence based. Simultaneously, it is important not to regard all hypotheses and preliminary reports of scientific research as evidence-based, but to ensure that due diligence is performed in all cases. The integrity of scientific research and ultimately of the innovation process of medical solutions depends on the integrity of democracy and the rule of law, as well as on regulating partnerships with scientific companies from world nations where autocracy rules their society.

This study focuses on the design, development, and evaluation of an educational mobile robot, named Robot-T2, to be used in educational activities within a technical school. The primary objective was to create a versatile platform that allows students to explore programming, engineering, and science concepts in a practical and collaborative manner. The methodology included an iterative design and testing approach, incorporating feedback from students and teachers to continuously improve the robot's functionality. The tests covered autonomous navigation, line following, and object manipulation, using the OnBotJava programming software and the Control Hub as the main interface. The results demonstrated that Robot-T2 is highly efficient and adaptable in various educational contexts, showing remarkable precision in navigation and object manipulation. The design iterations significantly improved the robot's performance, enriching the educational experience and promoting active learning. In conclusion, educational robotics, represented by Robot-T2, has great potential to enhance the teaching and learning process in technical schools, fostering teamwork, problem-solving, and the integration of technology in the classroom. This project is expected to inspire future developments in educational robotics.

This study was conducted to determine the role of pre-operative 2 weeks use of Finasteride in reducing intra-operative blood loss in patients undergoing monopolar TURP. Number of enrolled patients were 120, on the basis of inclusion criteria. Patients who were candidates of monopolar TURP were given 5mg Finasteride for 2 weeks before the surgery. On the 13th day of medicine, they got admitted in ward and prepared for surgery. During surgery intra-operative irrigation fluid was measured and gathered, then tested for Hemoglobin and the blood loss was calculated with equation formula. Blood loss evaluation was done on the basis of irrigation fluid, hemoglobin in irrigation fluid, preoperative hemoglobin and resected tissue weight. Significant reduction in blood loss was observed in interventional group as compared to the control group. Mean blood loss was 296ml in Group-A and 370ml in Group-B while blood loss per gram was 11.7ml/g in Group-A and 14.7 ml/g in Group-B. Mean operative time was measured 42 minutes in Group-A and 49 minutes in Group-B. This research proclaims a clear-cut supremacy of pre-operative use of Finasteride for two weeks. It significantly reduces intraoperative blood loss and blood loss per gram in patients undergoing monopolar TURP.

Late type II endoleak (T2EL) arising from internal iliac artery (IIA) network may occur after endovascular aortic repair (EVAR) of aortoiliac aneurysm and may require embolization if sac enlargement is demonstrated. When direct antegrade access to ipsilateral IIA is not achievable due to previous vessel coverage and/or embolization, access to the nidus can be challenging. We report a case of T2EL originating from IIA network causing iliac sac enlargement in a patient previously treated by EVAR for artoiliac aneurysm with IIA embolization and coverage, in which embolization of the nidus was performed through a percutaneous sheathless access to ip-silateral superior gluteal artery (SGA). A literature review dealing with all cases of percutaneous direct SGA access for retrograde embolization of T2EL arising from IIA after previous EVAR is also reported. The research was conducted on Pubmed database using keywords “superior glu-teal artery access,” “transgluteal embolization” and “retrograde embolization for type II endo-leak”. Related articles and references were screened for suitable articles.

Sodium glucose cotransporter 2 inhibitors (SGLT2i) are currently available for the management of type 2 diabetes mellitus. SGLT2i act by inhibiting renal SGLT2, thereby increasing glucosuria and lowering serum glucose. Recent trials are emerging supporting a role for SGLT2i irrespective of the diabetic status pointing towards that SGLT2i have other mechanisms of actions beyond blood sugar control. In this review, we will shed light on the role of this group of medications that act as SGLT2i in non-diabetics focusing on pre-clinical and clinical data highlighting the mechanism of renoprotection and effects of SGLT2i in the non-diabetic kidneys.

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

SARS-CoV-2, influenza A/B virus (IAV/IBV) and respiratory syncytial virus (RSV) are among the common viruses causing acute respiratory infections. Clinical diagnosis to differentiate these viruses is challenging due to similar clinical presentations, thus laboratory-based real-time RT PCR is the gold standard for diagnosis. The study aimed to evaluate the diagnostic performance of STANDARD M10 Flu/RSV/SARS-CoV-2 (SD Biosensor Inc, Seoul, Korea). This retrospective study was conducted with archived respiratory samples positive and negative for SARS-CoV-2, IAV, IBV or RSV. The evaluation study involved a total of 322 respiratory samples comprising 215 positive samples (49 SARS-CoV-2, 48 IAV, 53 IBV, 65 RSV) and 107 negative samples. All samples were tested with both STANDARD M10 and either Xpert Xpress SARS-CoV-2 or Xpert Xpress Flu/RSV (Cepheid, USA). The sensitivity, specificity, positive predictive value and negative predictive value rates of STANDARD M10 were very similar to Xpert Xpress SARS-CoV-2 or Xpert Xpress Flu/RSV ranges for each virus (98-100%). The overall agreement was 99.4% with 99.1% agreement for positive samples and 100% agreement for negative samples. In conclusion, the STANDARD M10 point-of-care test is suitable for rapid simultaneous detection of SARS-CoV-2, IAV, IBV and RSV.

Staphylococcus aureus is a common pathogen in human. Methicillin resistant Staphylococcus aureus (MRSA) infection poses a big and perplexing difficulty in terms of therapy. The acquisition of the non-native gene PBP2a, which has a decreased tolerance for β-lactam antibiotics, frequently confers resistance. PBP2a has a less attraction for methicillin and it helps bacteria to continue peptidoglycan biosynthesis, and it is cell wall’s core component in bacteria. So, even in the presence of methicillin or any other antibiotic, bacteria develop resistance. Due to resistance-causing genes, S. aureus becomes MRSA. The main premise of the resistance mechanism is well understood. The current demand for novel antibiotics is legitimate in the face of therapeutic concerns posed by resistant micro-organisms. The emphasis of this review is on PBP2a scaffolds and the different screening approaches used to find PBP2a inhibitors. Penicillin, Cephalosporins, Pyrazole-Benzimidazole based derivatives, Oxadiazole containing derivatives, non-β-lactam allosteric inhibitors, 4-(3H)-Quinazolinones, Pyrrolylated chalcone, Bis-2-Oxoazetidinyl macrocycle (β-lactam antibiotics with 1, 3-Bridges), Macrocycle-embedded β-lactams as novel inhibitors, Pyridine-Coupled Pyrimidinones, novel Naphthalimide corbelled aminothiazoximes, non-covalent inhibitors, Investigational-β-lactam antibiotics Carbapenem, novel Benzoxazole derivatives, Pyrazolylpyridine analogues, and other miscellaneous classes of scaffolds for PBP2a are also represented as well as with their biological activity is discussed. The penicillin-binding protein is also discussed, which is the crucial target for the cell wall of MRSA. Various aspects of PBP2a, the cell wall of bacteria, peptidoglycans, different crystal structures of PBP2a, synthetic routes for PBP2a inhibitors, and future perspectives of MRSA inhibitors are also enumerated.

Green products have excellent potential for discovering and producing new medicinal products. In recent years, there is a growing interest towards the green synthesis of metal nanoparticles, particularly from plants sources. This eco-friendly approach was used in the recent research to biosynthesize zinc oxide nanoparticles (ZnO NPs) from Cissus antractica plant. The present study aims to examine the cell cytotoxicity, cell death, and pathways of apoptosis in lung cancer cells (A549) and inflammation properties treated with biosynthesized ZnO NPs. Additionally, synthe-sized ZnO nanoparticles were characterized using UV–vis spectroscopy, X-ray diffraction (XRD), Transmission electron microscopy (TEM), Fourier-transform infrared spectroscopy (FT-IR), and Energy-dispersive X-ray spectroscopy (EDS). The XRD and TEM analyses exhibited 31 nm as the size of synthesized nanoparticles, the pure crystal form of ZnO NPs, and the shape of the NPs as nearly spherical and hexagonal quartzite. The MTT assay used for cytotoxicity evaluation de-picted the significant toxic effect of CA-ZnONPs against the A549 lung cancer cells at concentra-tions up to 20 µg/mL than non-cancerous cells. Furthermore, we observed an elevated ROS level in cancer cells. These NPs also demonstrated dose-dependent ability to suppress colony for-mation and cell migration, which increases their potential as a lung cancer treatment. Further-more, The NPs formulation's ability to induce apoptosis in cancer cells was further supported by Hoechst and propidium iodide dye. Further, CA ZnO NPs increased the gene expression of BAX, Cyto-c, Caspase 3 and 9, but decreased the expression of Bcl-2, indicating that the nanoformulation triggered mitochondrial-mediated apoptosis. Besides, this study showed that NPs suppressed in-flammatory responses by subsequently decreasing reactive oxygen species (ROS) generation, downregulating the expression of the pro-inflammatory cytokines TNF-α, iNOS, COX-2, IL-6, IL-8, and NO. Moreover, the study's findings imply that Cissus antractica are a potential source with biosynthesize nanoparticles that can might be further investigated for the progress of an-ti-inflammatory and anti-cancer drugs with further study.

Abstract Despite the lightning-fast advances in the management of SARS-CoV after 2 years of pandemic, COVID-19 continues to pose a challenge for fragile patients, who could benefit from early administration of monoclonal antibodies (mAbs) to reduce the risk of severe disease progression. We conducted a prospective study to evaluate effectiveness of mAbs against SARS-CoV-2 among patients at risk for severe disease progression, namely elderly and those with comorbidities, before the omicron variant surge. Patients were treated with either casirivimab/imdevimab, sotrovimab, and bamlanivimab/etesevimab. The rates and risk factos for clinical worsening, hospitalization, ICU admission and death (unfavourable outcomes) were evaluated. A stratified analysis according to the presence of SARS-CoV-2 IgG was also performed. Among 185 included patients, we showed low rates of unfavorable outcomes (9.2%), which were more frequent in patients with chronic kidney disease (aOR: 10.44, 95CI: 1.73-63.03; p<0.05) and basal D-dimer serum concentrations >600 ng/ml (aOR 21.74, 95CI: 1.18-397.70; p<0.05). Patients with negative SARS-CoV-2 serology at baseline showed higher C-reactive protein values compared with patients with positive serology (p <0.05) and showed a trend toward a higher admission rate to SICU and ICU compared with patients with positive serology. Our results thus showed, in a real-life setting, the efficacy of mAbs against SARS-CoV-2 before Omicron surge when the available mabs become not effective.

Introduction: Studies conducted in real-life scenarios on vaccine protection against COVID-19 constitute an important global priority, but one that is currently mostly neglected in low- and middle-income countries such as Angola. Here, we analyze for the first-time vaccine protection against COVID-19 in a real-life scenario after 6 months of implementing a multi-vaccination plan in Angola, providing estimation of odds ratios in vaccinated individuals and vaccine efficacy against infection by SARS-CoV-2 in a period that coincided with the identification of the Omicron variant in the country. Methods: We used a negative test case-control design to assess the effectiveness of vaccination against confirmed SARS-CoV-2 infection. A total of 4.232 vaccinated and unvaccinated individuals with the result of a rapid antigen diagnostic test against SARS-CoV-2 performed from December 27 to 28, 2021 were included in the study. Data were extracted from the Digital Vaccination Record Platform (Rediv) of the Ministry of Health of Angola. All ethical procedures related to the authorization necessary to carry out the study were followed. Statistical analyzes were performed using version 7.5.2.0 of CDC's Epi Info. Frequency distributions and measures of central tendency were used to characterize the study universe. The general and sex-adjusted and age-adjusted odds ratios, were evaluated by comparing the chances of vaccination between cases and controls, and their associated 95% CI, which were calculated using the Mantel-Haenszel stratification method. The risk classification of Axel Kroeger, Piscoya and Alarcon was used to interpret the odds ratio. The Breslow-Day statistic was used to assess the homogeneity of the odds ratios. Vaccine efficacy was calculated using the odds ratio applying the accepted statistical vaccine efficacy formula:(1 − odds ratio) × 100. For all estimates, a P value < 0.05 was considered statistically significant. Results: The population consisted of 63.63% male and 36.37% female. The mean age was 36 years with a standard deviation of 13. 83. Regarding vaccination status, 83.27% of individuals were vaccinated and 16.73% were unvaccinated, with 21.81% positive and 78.19% negative for SARS -CoV-2. The odds of SARS-CoV-2 infection were 0.85 (95% CI 0.70 – 1.03) times lower in vaccinated compared to unvaccinated individuals, with P=0.09. The overall vaccine efficacy (VE) was 15% (95% CI -3 – 30). Conclusion: There was no statistically significant decrease in the chances of SARS-CoV-2 infection in vaccinated versus unvaccinated individuals. However, the overall vaccine efficacy was 15%.

Immune escape is observed with SARS-CoV-2 Omicron (Pango lineage B.1.1.529), the predominant circulating strain worldwide. Booster dose was shown to restore immunity against Omicron infection, however, real world data comparing mRNA (BNT162b2; Comirnaty) and inactivated vaccine (CoronaVac; Sinovac) homologous and heterologous boosting is lacking. A retrospective study was performed to compare the rate and outcome of COVID-19 in healthcare workers (HCWs) with various vaccination regime during a territory-wide Omicron outbreak in Hong Kong. During the study period 1 Feb – 31 Mar 2022, 3167 HCWs were recruited, 871 HCWs reported 746 and 183 episodes of significant household and non-household close contact. 737 HCWs acquired COVID-19 which were all clinically mild. Time dependent Cox regression showed that, comparing with 2-dose vaccination, 3-dose vaccination reduced infection risk by 31.7% and 89.3% in household contact and non-household close contact respectively. Using 2-dose BNT162b2 as reference, 2-dose CoronaVac recipient had significantly higher risk of being infected (HR 1.69 P<0.0001). Three-dose BNT162b2 (HR 0.4778 P<0.0001) and 2-dose CoronaVac + BNT162b2 booster (HR 0.4862 P=0.0157) were associated with lower risk of infection. Three-dose CoronaVac and 2-dose BNT162b2 + CoronaVac booster were not significantly different from 2-dose BNT162b2. The mean time to achieve negative RT-PCR or E gene cycle threshold 31 or above was not affected by age, number of vaccine dose taken, vaccine type and timing of the last dose. In summary, we have demonstrated lower risk of breakthrough SARS-CoV-2 infection in HCWs given BNT162b2 as booster after 2 doses of BNT162b2 or CoronaVac.

Introduction: The presence of multiple comorbidities increases the risk of all-cause mortality, but the effects of the comorbidity sequence before the baseline date on mortality remained unexplored. This study investigated the relationship between coronary heart disease (CHD), atrial fibrillation (AF) and heart failure (HF) sequence on all-cause mortality risk in type 2 diabetes mellitus. Methods: This study included patients with type 2 diabetes mellitus prescribed antidiabetic/cardiovascular medications in public hospitals of Hong Kong between January 1st, 2009 and December 31st, 2009 with follow-up until death or December 31st, 2019. Cox regression was used to identify comorbidity sequences predicting all-cause mortality in patients with different medication subgroups. Results: A total of 249291 patients (age: 66.0±12.4 years, 47.4% male) were included. At baseline, 7564, 10900 and 25589 patients had AF, HF and CHD, respectively. Over follow-up (3524±1218 days), 85870 patients died (mortality rate: 35.7 per 1000 person-years). Sulphonylurea users with CHD developed later, but insulin users with CHD developing earlier, in the disease course had lower mortality risks. Amongst insulin users with two of the three comorbidities, CHD with preceding AF (hazard ratio [HR]: 3.06, 95% CI: [2.60-3.61], p<0.001) or HF (HR: 3.84 [3.47- 4.24], p<0.001) had a higher mortality. In users of lipid-lowering agents with all three comorbidities, those with preceding AF had higher risk of mortality (AF-CHD-HF: HR: 3.22, [2.24-4.61], p<0.001; AF-HF-CHD: HR: 3.71, [2.66-5.16], p<0.001). Conclusion: The sequence of comorbidity development affects the risk of all-cause mortality to varying degrees in diabetic patients on different antidiabetic/cardiovascular medications.

Little is understood about the impact of nebulisation on the viability of SARS-CoV-2. In this study, a range of nebulisers with differing methods of aerosol generation were evaluated to determine SARS-CoV-2 viability following aerosolisation. The aerosol particle size distribution was assessed using an aerosol particle sizer (APS) and SARS-CoV-2 viability was determined after collection into liquid media using All-Glass Impingers (AGI). Viable particles of SARS-CoV-2 were further characterised using the Collison 6-jet nebuliser in conjunction with novel sample techniques in an Andersen size-fractioning sampler to predict lung deposition profiles. Results demonstrate that all the tested nebulisers can generate stable, polydisperse aerosols (Geometric standard deviation (GSD) circa 1.8) in the respirable range (1.2 to 2.2µm). Viable fractions (PFU/particle, the virus viability as a function of total particles produced) were circa 5x10^-3 and were not significantly affected by relative humidity. The novel Andersen sample collection methods successfully captured viable virus particles across all sizes; with most particle sizes below 3.3µm. MMADs (Mass Median Aerodynamic Diameters) were calculated from linear regression of log10-log10 transformed cumulative PFU data, and calculated MMADs accorded well with APS measurements and did not differ across collection method types. This data will be vital in informing animal aerosol challenge models, and infection prevention and control policies.

Wastewater surveillance for SARS-CoV-2 has garnered extensive public attention during the COVID-19 pandemic as a proposed complement to existing disease surveillance systems. Over the past year, methods for detection and quantification of SARS-CoV-2 viral RNA in untreated sewage have advanced, and concentrations in wastewater have been shown to correlate with trends in reported cases. Despite the promise of wastewater surveillance, for these measurements to translate into useful public health tools, it is necessary to bridge the communication and knowledge gaps between researchers and public health responders. Here we describe the key uses, barriers, and applicability of SARS-CoV-2 wastewater surveillance for supporting public health decisions and actions, including establishing ethical consideration for monitoring. Overall, while wastewater surveillance to assess community infections is not a new idea, by addressing these barriers, the COVID-19 pandemic may be the initiating event that turns this emerging public health tool into a sustainable nationwide surveillance system.

Background: Overcrowded housing, as well as inadequate sanitary conditions, contribute to making homeless people particularly vulnerable to the SARS-CoV-2 infection. We aimed to assess the seroprevalence of the SARS-CoV-2 infection among people experiencing homelessness on a large city-wide scale in France, taking into account different community settings. Methods: A consortium of outreach teams in 48 different locations including streets, slums, squats, emergency or transitional shelters and drop-in centres participated in the inclusion process. All participants consented to receive a validated rapid assay for immunoglobulins M (IgM) and G (IgG) antibodies and to answer a questionnaire on medical health conditions, comorbidities, historic of symptoms compatible with COVID-19, with a retrospective calendar of types of accommodation since COVID-19 crisis. Results: From June 01 to August 05, 2020, 1,156 homeless participants were enrolled in the study and tested. Seroprevalence of SARS-CoV-2 IgG/IgM antibodies was 5.6% (95%CI 2.3–7.0), with a range of 2.2% in people living on the streets to 8.1% in people living in emergency shelters (P=0.009). Around one third of the seropositive participants reported symptoms with COVID-19. Compared to the general population in Marseille (3.6%), the homeless population living in the same urban area experienced an significant increased risk of SARS-CoV-2 infection (|z|=3.65 > 1.96). Conclusion: These results highlight the need for organizing regular screening to prevent clusters forming in homeless accommodations and for providing basic resources for health maintenance.

Favipiravir is a broad-spectrum inhibitor of viral RNA-dependent RNA polymerase (RdRp) currently being used to manage COVID-19 in several countries. By acting as a substrate for RdRp, favipiravir gets incorporated into the nascent viral RNA and prevents strand extension. A high mutation rate of SARS-CoV-2 RdRp may facilitate antigenic drift as an answer to the host immune response, thereby generating resistance of virus to favipiravir. Therefore, it is extremely crucial to predict potential mutational sites in the RdRp and the emergence of structural modifications contributing to drug resistance. Here, we used high-throughput interface-based protein design to generate >100,000 designs and identify mutation hotspot residues in the favipiravir-binding site of RdRp. Several mutants had lower binding affinities to favipiravir, out of which hotspot residues with a high propensity to undergo positive selection were identified. The results showed that the designs retained an average of 97 to 98% sequence identity, suggesting that SARS-CoV-2 can develop favipiravir resistance with just a few mutations. Notably, we observed that out of 134 mutations predicted designs, 63 specific mutations were already present in the CoV-GLUE database, thus attaining ~47% correlation match with the clinical sequencing data. The findings improve our understanding of the potential signatures of adaptation in SARS-CoV-2 against favipiravir and management of COVID-19. Furthermore, they can help develop exhaustive strategies for robust antiviral design and discovery.

Risk factors for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection are not well-defined in resident physicians and fellows (trainees). We aimed to identify sociodemographic, occupational and community factors associated with SARS-CoV-2 infection among trainees during the first wave of the coronavirus disease 2019 (COVID-19) pandemic in New York City (NYC). In this retrospective cohort study, we administered an electronic survey between June 26 and August 31, 2020 to trainees at the Mount Sinai Health System in NYC to assess risk factors for SARS-CoV-2 infection between February 1 and June 30, 2020. We used Bayesian generalized linear mixed effect regression and structural equation models to examine associations. SAR-CoV-2 infection was determined by self-reported IgG antibody and reverse transcriptase-polymerase chain reaction results and confirmed with laboratory results. Among 2354 trainees invited to participate, 328 (14%) completed the survey and reported test results. The cumulative incidence of SARS-CoV-2 infection was 20.1%. Assignment to medical-surgical units (odds ratio [OR], 2.51; 95% CI, 1.18-5.34), and training in emergency medicine, critical care and anesthesiology (OR, 2.93; 95% CI, 1.24-6.92) were independently associated with infection. Deployment to care for unfamiliar patient populations was protective against infection (OR, 0.16; 95% CI, 0.03-0.73). Community factors were not significantly associated with infection after adjustment for occupational factors. Our findings may inform tailored infection prevention strategies for trainees responding to the COVID-19 pandemic.

Poly(2-methoxyethyl acrylate) (PMEA) and poly(ethylene oxide) (PEO) have protein-antifouling properties and blood compatibility. ABA triblock copolymers (PMEAn-PEO11340-PMEAn (MEOMn)) were prepared using single-electron transfer-living radical polymerization (SET-LRP) using a bi-functional PEO macroinitiator. Two types of MEOMn composed of PMEA blocks with a degree of polymerization (DP = n) of 85 and 777 were prepared using the same PEO macroinitiator. MEOMn formed flower micelles with a hydrophobic PMEA (A) core and hydrophilic PEO (B) loop shells in diluted water with a similar appearance to petals. The hydrodynamic radii of MEOM85 and MEOM777 were 151 and 108 nm, respectively. The PMEA block with a large DP formed a tightly packed core. The aggregation number (Nagg) of the PMEA block in a single flower micelle for MEOM85 and MEOM777 was 156 and 164, respectively, which were estimated using a light scat-tering technique. The critical micelle concentrations (CMCs) for MEOM85 and MEOM777 were 0.01 and 0.002 g/L, respectively, as determined by the light scattering intensity and fluorescence probe techniques. The size, Nagg, and CMC for MEOM85 and MEOM777 were almost the same inde-pendent of hydrophobic DP of the PMEA block.

The bacterial genus and species of Bacillus thuringiensis var israelensis (Bti), is entomotoxic, used in the biological control of mosquito vectors of human diseases, such as malaria and dengue. Following the studies carried out in Mexico and Guatemala with ovillantas, in which the presence of larvae of both species of Anopheles albimanus W and Aedes aegypti L were observed, and with the intention of continuing to develop an ecologically friendly mosquito control, Bti was added to the ovillantas, to improve and already efficient method on the elimination of both types of mosquitoes. The objectives of this work were: to analyze the effectiveness of two commercial formulations of Bti, serovar H-14 (Bactimos) wettable powder, 3,500 ITU, from Biochem prods., and Vectobac, 2,000 ITU wettable powder, (Abbot Lab.) on second and third instars larvae of A. albimanus and Ae. aegypti (Diptera Culicidae). The two formulations were effective against A. albimanus W(higher concentrations), while Ae. aegypti L was very susceptible to Bti, therefore it is proposed for the best control of these genus and vector species of malaria and dengue at adequate concentrations.