We investigate entropy generation in unsteady three-dimensional axisymmetric MHD nanofluid flow over a non-linearly stretching sheet. The flow is subject to thermal radiation and a chemical reaction. The conservation equations were solved using the spectral quasi-linearization method. The novelty of the work is in the study of entropy generation in three-dimensional axisymmetric MHD nanofluid and the choice of the spectral quasilinearization method as the solution method. The effects of Brownian motion and thermophoresis are also taken into account when the nanofluid particle volume fraction on the boundary in passively controlled. The results show that as the Hartman number increases, both the Nusselt number and the Sherwood number decrease whereas the skin friction increases. It is further shown that an increase in the thermal radiation parameter corresponds to a decrease in the Nusselt number. Moreover, entropy generation increases with the physical parameters.

Parkinson’s disease (PD) is characterized by motor deficits and a wide variety of non-motor symptoms. The age of onset, rate of disease progression and the precise profile of motor and non-motor symptoms display considerable individual variation. Neuropathologically, the loss of substantia nigra dopaminergic neurons is a key feature of PD. The vast majority of PD patients exhibit alpha-synuclein aggregates in several brain regions, but there is also great variability in the neuropathology between individuals. While the dopamine replacement therapies can reduce motor symptoms, current therapies do not modify the disease progression. Numerous clinical trials using a wide variety of approaches have failed to achieve disease modification. It has been suggested that the heterogeneity of PD is a major contributing factor to the failure of disease modification trials, and that it is unlikely that a single treatment will be effective in all patients. Precision medicine, using drugs designed to target the pathophysiology in a manner that is specific to each individual with PD, has been suggested as a way forward. PD patients can be stratified according to whether they carry one of the risk variants associated with elevated PD risk. In this review we assess current clinical trials targeting two enzymes, leucine-rich repeat kinase 2 (LRRK2) and glucocerebrosidase (GBA), which are encoded by two most common PD risk genes. Because the details of the pathogenic processes coupled to the different LRRK2and GBA risk variants are not fully understood, we ask if these precision medicine-based intervention strategies will prove “precise“ or “personalized“ enough to modify the disease process in PD patients. We also consider at what phases of the disease that such strategies might be effective, in light of the genes being primarily associated with the risk of developing disease in the first place, and less clearly linked to the rate of disease progression. Finally, we critically evaluate the notion that therapies targeting LRRK2 and GBA might be relevant to a wider segment of PD patients, beyond those that actually carry risk variants of these genes.

Objectives As the epidemiological transition continues in sub-Saharan Africa, we will see in future more conditions that require invasive treatment (surgery, cancer and anaesthesia, ie..). Olders patients are vulnerable to complications such as functional decline, increased length of stay and mortality as a result of this type of treatment. Comprehensive geriatric assessment (CGA) is a multidisciplinary diagnostic process aimed at identifying older people at risk of negative outcome. It is delivered by a multidisciplinary team and its benefits in reducing functional disability, incidence of mortality and other adverse health outcomes are well established. It is important to know whether this approach integrates care management strategies for older people in a context where health services for older people are scarce and staff have little training in geriatrics. The objective of this work was to review the literature on the use of CGA on invasive care (cancer, surgery, etc.) among older people in SSA. Methods A MEDLINE/PubMed database search was conducted to identify articles reporting CGA and conditions requiring invasive treatment in older patients in SSA. Results/Conclusion Taken together, the studies examined in this review show that little work has been done on the impact of CGA in older people invasive care in SSA. This review can help to assess the role of CGA in the care trajectories of older people in terms of prognosis, and thus encourage more in-depth research on this topic.

Precision agriculture and open-source data repositories provide a plethora of field-specific ecological data about agroecosystems, but few mechanisms have been developed to turn that information into management recommendations for crop production. The On-Farm Precision Experiments (OFPE) framework is an agroecological model-based methodology to improve crop manager’s abilities to make field-scale agronomic input decisions. This work evaluates the use of field-specific experiments that employ open-source data and the data emanating from precision agriculture technologies to gain local knowledge of the spatial and temporal variability in agroeconomic performance at the sub-field scale. Quantification of the temporal variability in crop response to inputs (e.g., crop seeding rates, crop rotations, fertilizers, other soil amendments, pesticides, etc.) allows for estimation of the probability that a future management scenario will outcompete another, in terms of crop yield, crop quality, farmer net return, or environmental quality. The challenge is to integrate OFPE into applied management with minimal disruption of stakeholder practices while drawing on historic knowledge about the field and economic constraints. OFPE is the basis of a decision support system that includes a six-step cyclical process that harnesses precision agriculture technology to apply experiments and gather field-specific data, incorporates modern data management and analytical approaches, and generates management recommendations as probabilities of outcomes. The OFPE framework allows field managers to assess the tradeoffs in agronomic input management between the maximization of crop production, quality and profits from production while considering environmental effects.

The aim of this study was to adapt a treadmill-developed method for determination of inner-cycle parameters in cross-country roller ski skating for a field application. The method is based on detecting initial and final ground-contact of poles and skis during cyclic movements. Eleven athletes skied four laps of 2.5 km at low and high endurance-intensity, using two types of skis with different rolling coefficients. Participants were equipped with inertial measurement units (IMUs) attached to their wrists and skis, while insoles with pressure sensors and poles with force measurements were used as reference systems. The method based on IMUs was able to detect more than 97% of the temporal events compared to the reference system. The inner-cycle temporal parameters had a precision ranging from 49 to 59 ms, corresponding to 3.9% to 13.7% of the corresponding inner-cycle duration. Overall, this study showed good reliability of using IMUs on athlete’s wrists and skis to determine temporal events, inner-cycle parameters and the performed sub-techniques in cross-country roller ski skating in field-conditions.

Repeat-Induced Point mutations (RIP) serves as a genome defence mechanism that impedes the deleterious consequences of repeated motifs such as transposable elements in fungi. Genomic regions with RIP are biased for adenosine and thymine transitions and the cumulative influence of RIP is thought to have a considerable impact on genome composition. We investigated the impact of RIP on localized genomic regions and whole-genome sequences for representatives of the pine pathogen, Fusarium circinatum. We set out to determine the intraspecific variation in acquired RIP and the role of RIP in the development of diverse F. circinatum sub-genomic compartments. The results of the study show that the AT-enriched sub-genomic compartment accounts for ca. 97% of the calculated RIP and was further prominent in both core and accessory genomic regions. However, more extensive RIP was observed in the accessory sub-compartment and more variable regions of the genome. Regions with RIP indicated increased intrinsic curvature of the DNA which may influence DNA-protein interactions and may promote constitutive heterochromatin formation. The results show that RIP is an important source of functional novelty and genome variation. RIP contributes to the evolution of the genetic landscape and differentiation of diverse sub-genomic compartments of this important fungal pathogen.

The most massive and fast-eroding thaw slump of the Northern Hemisphere located in the Yana uplands of northern Yakutia was investigated to assess in detail the cryogenic inventory and carbon pools of two distinctive Ice Complex stratigraphic units and the uppermost cover deposits. Differentiating into modern and Holocene near-surface layers (active layer and shielding layer), highest total carbon contents were found in the active layer (18.7 kg m-2), while the shielding layer yielded much lower carbon content of 1.8 kg m-2. The late Pleistocene upper Ice Complex contained 10.4 kg m-2 total carbon, and the mid-Pleistocene lower Ice Complex 17.7 kg m-2. The proportion of organic carbon from total carbon content is well above 70% in all studied units with 94 % in the active layer, 73% in the shielding layer, 83% in the upper Ice Complex and 79% in the lower Ice Complex. Inorganic carbon is low in the overall structure of the deposits.

Trace metals can enter some natural regions with low human disturbance from atmospheric circulation, but little information is available regarding how the canopy can retained trace metals. Therefore, a representative sub-alpine spruce plantation was selected to investigate the net throughfall fluxes of eight trace metals (Fe, Mn, Cu, Zn, Al, Pb, Cd and Cr) of closed canopy and gap-edge canopy from August 2015 to July 2016. Over a one-year observational period, the annual fluxes of Al, Zn, Fe, Mn, Cu, Cd, Cr and Pb were 7.29 kg·ha^-1, 2.30 kg·ha^-1, 7.02 kg·ha^-1, 0.16 kg·ha^-1, 0.19 kg·ha^-1, 0.06 kg·ha^-1, 0.56 kg·ha^-1 and 0.24 kg·ha^-1, respectively, in the deposited precipitation. The annual net throughfall fluxes of these trace metals were 1.73 kg·ha^-1, 0.9 kg·ha^-1, 1.68kg·ha^-1, -0.032 kg·ha^-1, 0.04 kg·ha^-1, 0.018 kg·ha^-1, 0.093 kg·ha^-1 and 0.087kg·ha^-1, respectively, in the gap-edge canopy and -1.6 kg·ha^-1, 1.13 kg·ha^-1, 1.65 kg·ha^-1, -0.10 kg·ha^-1, 0.05 kg·ha^-1, 0.03 kg·ha^-1, 0.26 kg·ha^-1 and 0.15 kg·ha^-1, respectively, in the closed canopy. The closed canopy displayed a greater filter effect on the trace metals from precipitation than did the gap-edge canopy in the sub-alpine forest. In the rainy season, the net filtering ratio of trace metals ranged from -66%-89% in the closed canopy and from -52% to 25% in the gap-edge canopy. However, the net filtering ratio of all trace metals was greater than 50% in the closed canopy in the snowy season. Therefore, the results suggested that the most trace metals moving through the forest canopy are taken up rather than by rainfall leaching; moreover, the closed canopy can efficiently take up trace metals in the snowy season.

Background: The leaf of Telfairia occidentalis Hook f. (Cucurbitaceae) is consumed in different parts of Nigeria because of the numerous nutritional and medicinal attributes ascribed to it. The sub-chronic toxicity of the hydroethanolic leaf extract of Telfairia occidentalis (TO) was investigated in this study. Methods: Rats in different groups were separately administered 80, 400 and 2000 mg/kg TO p.o. for 60 days. Animals were sacrificed and blood samples collected for haematological and biochemical analysis. Vital organs were harvested and evaluated for in vivo antioxidants and histopathological changes. Results: Results showed no significant changes in the weight of vital organs except in respect of the testes of the group treated with 2000 mg/kg extract which showed a significant (p<0.05) reduction in weight compared to the control group. There was a significant (p<0.01) increase in sperm motility and count of the group administered 80 mg/kg extract and a significant (p<0.001) reduction was observed at 2000 mg/kg. There were significant increases in the level of Hb and PCV at 80 and 2000 mg/kg of the extract. In respect of liver function parameters, a significant decrease in AST and ALT levels at doses of 400 and 2000 mg/kg relative to control was observed. A significant reduction (p<0.05) in the level of total cholesterol (400 mg/kg) and increase (p<0.05) in level of HDL (80-2000 mg/kg) compared to control was observed. There was also significant (p<0.05) increase in the level of MDA and significant (p<0.05) decrease in SOD level in the testes at 2000 mg/kg. Histopathological assessment of the testes revealed abnormality at this dose. These effects were reversed after 30 days of cessation of administration of TO. Conclusions: The findings showed that the hydroethanolic leaf extract of Telfairia occidentalis is relatively non-toxic on acute and sub-chronic exposure, with potential to elicit anti-anaemic effect, reduce the risk of atherosclerosis and cardiovascular disease, and enhance antioxidant status in the brain and liver. Although possibly beneficial at low dose, the extract could be harmful to the testes on prolonged oral exposure at high dose.

Binge drinking is a pattern of alcohol abuse. Its prevalence and associated risk factors are not well documented. Heavy drinking, on the other hand, has a well-studied association with bereavement . This report uses a cross-sectional, population-based survey to estimate prevalence of bingeing and its association with new bereavement. Bingeing is defined as 4 or more drinks (women) or 5 or more drinks (men) in a 2-to-4-hour setting. For the first time, the Georgia Behavioral Risk Factor Surveillance Survey (BRFSS) included a bereavement item, ‘Have you experienced the death of a family member or close friend in the years 2018 or 2019?’. Methods: Georgia BRFSS is a complex sampling survey administered annually. It is designed to represent the 8.1 million persons in the U.S. state of Georgia aged 18 years and older. Alcohol consumption patterns are routinely measured in the common core. In the 2019 field survey, the state added a new item probing for bereavement in the prior 24 months predating the pandemic of COVID-19. Imputation and weighting techniques were applied to yield population prevalence rates of new bereavement, bingeing, and their co-occurrence with other high-risk health states. Models, adjusted for age, gender, and race were used to estimate the risk for other unhealthy behaviors posed by the co-occurrence of bereavement and bingeing. Results: In Georgia, bereavement is common (45.8 %), and alcohol consumption is common (48.8 %). Bereavement and alcohol use co-occurred among 1,796,817 persons (45 % of all drinkers). The subset of co-occurring bereavement and binging totaled 608,282 persons. Within this group, the highest rates of bereavement were associated with death of a friend / neighbor (30.7%) or 3 plus deaths (31.8%). Conclusions: While bingeing is a known risk to public health, its co-occurrence with recent bereavement is a new observation. Public health surveillance systems need to monitor this co-occurrence to protect both individual and societal health. In a time of global bereavement, documenting its influence on binge drinking can support the work towards Sustainable Goal #3 – Good health and Well-Being. Keywords: BRFSS, Binge Drinking, Population Survey, Bereavement, SDG#3. Mental Health

LPA3 receptors were expressed in TREx HEK 293 cells, and their signaling and phosphorylation were studied. The agonist, lysophosphatidic acid (LPA), increased intracellular calcium and ERK phosphorylation through pertussis toxin-insensitive processes. Phorbol myristate acetate, but not LPA, desensitizes LPA3-mediated calcium signaling. The agonists and the phorbol ester-induced LPA3 internalization. Pitstop 2 (clathrin heavy chain inhibitor) markedly reduced LPA-induced receptor internalization; in contrast, phorbol ester-induced internalization was only delayed. LPA induced rapid β-arrestin-LPA3 receptor association. The agonist and the phorbol ester induced marked LPA3 receptor phosphorylation, and phosphorylation sites were detected using mass spectrometry. Phosphorylated residues were detected in the intracellular loop 3 (S221, T224, S225, and S229) and in the carboxyl terminus (S321, S325, S331, T333, S335, Y337, and S343). Interestingly, phosphorylation sites are within sequences predicted to constitute β-arrestin binding sites. These data provide insight into LPA3 receptor signaling and regulation.

Systemic lupus erythematosus (SLE) is a prevalent autoimmune condition, yet its alignment with a specific host immunological pathway remains unclear. The THαβ host immunological pathway, recognized for its defense against viruses and prions, has recently emerged as a response to DNA, RNA, and protein pathogens. SLE patients often produce anti-double strand DNA antibodies and anti-nuclear antibodies, suggesting a potential association with the THαβ host immune reaction. Throughout the course of SLE, elevated levels of type 1 interferons, type 3 interferons, interleukin-10, IgG1, and IgA1 are commonly observed. These cytokines and antibody isotypes are indicative of the THαβ host immunological pathway. Similarly, Myasthenia gravis, Grave’s disease, Graft versus host disease, autoimmune hemolytic anemia, immune thrombocytopenia, dermatomyositis, and Sjogren’s syndrome are also linked to THαβ-related type 2 hypersensitivities. Considering the potential association of these diseases with dysregulated THαβ immune responses, therapeutic strategies such as anti-interleukin-10 or anti-interferons α/β could be explored to manage these disorders effectively.

Green and sustainable electrocatalytic conversion of nitrogen-containing compounds to ammonia are currently in high demand in order to replace the eco-unfriendly Haber-Bosch process. Model catalysts for the nitrate reduction reaction were obtained by electrodeposition of metal Co, Fe and bimetallic Fe/Co nanoparticles from aqueous solutions onto a graphite substrate. The samples were characterized by the following methods: SEM, XRD, XPS, UV-vis spectroscopy, cyclic (and linear) voltammetry, chronoamperometry and electrochemical impedance spectroscopy. Besides, the determination of electrochemically active surface was also performed for all electrocatalysts. The best electrocatalyst was a sample containing Fe-nanoparticles on the layer of Co-nanoparticles, which showed the Faradaic efficiency 58.2% (E=-0.785 V vs. RHE) at the ammonia yield rate of 14.6 μmol h-1 cm-2. An opinion was expressed on elucidation of the mechanism of coordinated electrocatalytic action of a bimetallic electrocatalyst. This work can serve primarily as a starting point for future investigations on electrocatalytic conversion reactions to ammonia using model catalysts of the proposed type.

Abstract: The YF3: (Eu3+, Nd3+) nanoparticles (orthorhombic phase, D ~ 130 nm)) were synthesized via the co-precipitation method with subsequent hydrothermal treatment and annealing. The Eu3+ τdecay linearly descends with the increase of temperature in the 80 - 320 K range. The τdecay (T) slope values of the annealed YF3: Eu3+ (2.5 and 5.0 mol. %) nanoparticles were the highest (110·10-4 and 67·10-4, μs/K in the whole 80 – 320 K range, respectively. Thus, these samples were chosen for further doping with Nd3+. The maximum Sa and Sr values based on the LIR (IEu/INd) function were 0.67 K-1 (at 80 K) and 0.86 %·K-1 (at 154 K), respectively. As it was mentioned above, the sin-gle-doped YF3: Eu3+ (2.5. %) nanoparticles showed the linearly decreasing τdecay (T) function (5D0 – 7F1 emission). The main idea of Nd3+ co-doping was to increase this slope value (as well as the sensitivity) by increasing the rate of τdecay (T) descent via the addition of one more tempera-ture-dependent channel of 5D0 excited state depopulation. Indeed, we managed to increase the slope (Sa) up to 180·10-4 K-1 at 80 K. This result is one of the highest compared to the world analogs.

Exposure to vaccine lipid nanoparticles, mRNA, adenoviral DNA, and or Spike protein from one of the approved Covid-19 vaccines, or through secondary exposure, as through blood transfusion, is a potential source of harm. Blood reactions are an acknowledged side-effect of Covid-19 vaccination, not limited to hemolysis, paroxysmal nocturnal hemoglobinuria, chronic cold agglutinin disease, immune thrombocytopenia, haemophagocytosis, hemophagocytic lymphohistiocytosis, and many other blood related conditions. The observation of adverse events has motivated investigation into the cardiovascular mechanisms of harm by Covid-19 vaccines, and the biodistribution of vaccine contents. Biodistribution may not be limited to the body of the vaccine recipient, as a growing body of evidence demonstrates the possibility of secondary exposure to vaccine particles. These can be via bodily fluids and include the following routes of exposure: blood transfusion, organ transplantation, breastfeeding, and possibly other means. As covid-19 vaccines are associated with an increased risk of stroke, the persistence of vaccine artifacts in the blood presents a possible threat to a recipient of a blood donation from a vaccinated donor who suffered from vaccine induced thrombosis or thrombocytopenia. (VITT) We assess the feasibility and significance of these risks through an overview of the case report literature of blood disorders in vaccinated individuals, pharmacovigilance reports from the US Vaccine Adverse Events Reporting System (VAERS) and a meta-analysis of the available literature on organ transplants from vaccinated organ donors. Our analysis establishes biological mechanistic plausibility, a coherent safety signal in pharmacovigilance databases for secondary vaccine contents exposure (for the cases of blood transfusion and breastfeeding) and also an elevated level of adverse events in organ transplants from VITT-deceased donors, echoing increases in organ transplantation related complications seen in national statistics for some countries. Secondary exposure to vaccine artifacts is a potential explanation for some of the cases put forth, and requires a deeper investigation.

Mesoporous silica nanoparticles (MSNs) can be used as carrier materials for the controlled release of pesticides while reducing their negative environmental impact. In this study, we screened an active ingredient, p-cymene (PC), with an excellent inhibitory effect on rice bacterial blight. Subsequently, the PC was successfully loaded onto MSNs via physisorption(PC@MSNs). PC@MSNs, characterized by a regular spherical shape, smooth surface, and an MSN average size of 262.9 nm, achieved an 8.6 % drug loading capacity. The release kinetics of the PC from the PC@MSNs demonstrated a sustained release (288 h) pattern influenced by drug diffusion. The efficacy of the PC@MSNs against Xanthomonas oryzae pv. Oryzae paralleled those of PC. Acute toxicity assays re-vealed that the PC@MSNs were less toxic to aquatic life (LC50=257.867 mg/L) and that the formu-lation showed no adverse effects on rice seedling growth. In summary, these results suggest that PC@MSNs can broaden PC's application scope in managing rice diseases.

Staphylococcus aureus is a causative agent of nosocomial infections and its antibiotic-resistant strains are concerning. Solutions are being explored to improve the treatment of these infections, including repositioning drugs such as statins and using nanoparticles with antimicrobial properties. This study aimed to evaluate the antimicrobial effects of simvastatin (SIM) and biologically synthesized silver nanoparticles (bio-AgNPs) in isolate form and in combination by assays of minimum inhibitory concentration (MIC), an in vitro biofilm model, and the association of antimicrobials against clinical strains of S. aureus. Bio-AgNPs showed a 53.8 ± 1.23-nm mean diameter and standard deviation, a 0.23 polydispersity index, and a −25.66 ± 2.19-mV mean potential and standard deviation. Transmission electron microscopy confirmed the formation of nanoparticles and the presence of Ag0 and AgCl. S. aureus strains were sensitive to bio-AgNPs and SIM, showing 31.88-187.5 and 74.66-149.32 μM concentrations, respectively. Our association assay showed 2.0 fractional inhibitory concentration indices (i.e., indifferent for clinical strains) and 0.32 values for the standard ATCC 29213 strain (synergy). Our biofilm inhibition assays with isolated SIM and bio-AgNPs showed decreased biofilm formation from 4× to ⅛ MICs, showing no synergism in association. These findings evince that simvastatin and bio-AgNPs at subinhibitory concentrations can serve as antimicrobial agents against S. aureus biofilm.

(1) Background: The synthesis of core-shell magnetic mesoporous nanoparticles (MMSN) from phase transfer process is usually performed at 100-250 mg scale. At the gram scale, nanoparticles without core or with multicore systems are observed. (2) Methods: Iron oxide core nanoparticles (IO) were synthesized through thermal decomposition procedure of -FeO in oleic acid. Phase transfer from chloroform to water was then performed in order to wrap IO with mesoporous silica shell through the sol-gel procedure. MMSN were then functionalized with DTPA, and used for the separation of metal ions. Their toxicity was evaluated (3) Results: The phase transfer pro-cedure was crucial to obtained MMSN at large scale. Three synthesis parameters were rigorously controlled: temperature, time and glassware. Homogeneous dispersion of MMSN at the gram scale was successfully obtained. After functionalization with DTPA, the MMSN-DTPA were shown to have a strong affinity for Ni ions. Furthermore toxicity was evaluated in cells, zebrafish and through seahorse metabolic assays, and the nanoparticles were found nontoxic. (4) Conclusions: We developed a method of preparation of MMSN at the gram scale. After function-alization with DTPA, the nanoparticles were efficient in metal ion removal and separation, fur-thermore, no toxicity was noticed up to 125 µg.mL-1 in zebrafish.

Many of the current strategies for removing pollutants from water are based on nanomaterials and 18nanotechnology. Lower values of Biological Oxygen Demand (BOD5) and Chemical Oxygen De- 19 mand (COD) in water results in reduction in the amount of oxidizable pollutants. We present a study 20 on the reduction of COD and BOD5in water from Wadi El Bey River (Tunisia), using magnetite na- 21 noparticles (MNPs) and magnetic fields. The COD and BOD5 removal reached values higher than 22 50% after 60 min, with optimum efficiency at pH values of ≈8 and for MNPs concentrations of 1 g/L. 23 The use of a permanent magnetic field (0.33 T) showed an increase of COD and BOD5 removal from 2461% to 76% and from 63% to 78%, respectively. This enhancement is discussed in terms of the MNPs 25coagulation induced by the magnetic field and the adsorption of ionic species onto the MNPs sur- 26face due to Fe3O4 affinity.

A series of LaF₃:Ce³⁺ phosphors for the application in photodynamic therapy is synthesized using a one-stage solvothermal synthesis. The conditions providing the maximum intensity of UV- and X-ray-excited luminescence, lowest size and highest colloidal stability of the phosphor nanoparticles are found to respectively include cerium content 5% mol., use of ethanol as the reaction medium for the solvothermal synthesis and addition of polyvinylpyrrolidone as a stabilizer in an optimized amount.

Notwithstanding the advances achieved in the last decades in the field of synthetic bone substitutes, the development of biodegradable 3D scaffolds with ideal mechanical and biological properties remains an unattained challenge. In this work, a novel approach is explored to produce synthetic bone grafts mimicking the complex bone structure using additive manufacturing. For the first time, scaffolds were produced, using an extrusion technique, composed of a thermoplastic polymer, polycaprolactone (PCL), hydroxyapatite nanoparticles (HANp), and polyethylene glycol diacrylate (PEGDA). These scaffolds were further compared with two groups of scaffolds: one composed of PCL and another of PCL and HANp. After production, optimisation and characterisation of these scaffolds, an in vitro evaluation was performed using human dental pulp stem/stromal cells (hDPSCs). Through the findings it was possible to conclude that PEGDA scaffolds were successfully produced presenting networks of interconnected channels, presenting hydrophilic properties (15.15 4.06°), adequate mechanical performance (10.41MPa 0.934), and allowing a cell viability significantly superior to the other groups analysed. To conclude, findings in this study demonstrated that PCL, HANp and PEGDA scaffolds may have promising effects on bone regeneration and might open new insights for 3D tissue substitutes.

Wounds are structural and functional disruptions of the skin that occur because of an accident. Chronic wounds are caused by a breakdown in the finely coordinated cascade of events that occurs during wound healing. Wound healing is a long process that split into at least three continuous and overlapping processes: an inflammatory response, a proliferative phase that leads to tissue repair, and third one is tissue remodeling. Therefore, wound healing studies are extensively studied to develop techniques that can achieve maximum recovery with minimum scar. Several growth hormones and cytokines secreted at the wound site tightly regulate wound healing processes. The traditional approach for wound management has been represented by topical treatments. Metal nanoparticles (e.g., silver, gold, zinc) are increasingly being employed in dermatology due to their favorable effects on wound healing, as well as in treating and preventing bacterial infections. The development of wound dressings materials has now been used to overcome the issues of external environments. The impregnated nanomaterials have provided moist environment that removes the exudates and avoid maceration. This review highlights the mechanism and focus on the current advancement of various nanoparticles impregnation material for wound healing process that can protect wound from infection and maintain the optimum exchange of gases.

The supramolecular aggregation processes occurring on metallic (aluminum and gold) surfaces in aqueous solutions of bovine serum albumin (BSA) during drying were studied using advanced scanning electron microscopy (SEM). The possible mechanism for the formation of amazing intricate fractal structures on metallic surfaces was proposed based on the analysis of SEM images, size distribution diagrams and EDX-scanning elements distribution maps.

Among the different ways to reduce the secondary effects of antineoplastic drugs in cancer treatment, the use of nanoparticles has demonstrated good results due to the protection of the drug and the possibility of releasing compounds to a specific therapeutic target. The α-isoform of folate receptor (FR) is overexpressed on a significant number of human cancers; therefore, folate-targeted crosslinked nanoparticles based on BSA and alginate mixtures and loaded with paclitaxel (PTX) have been prepared to maximizing the proven antineoplastic activity of the drug against solid tumors. Nanometric-range sized particles (169 ± 28nm - 296 ± 57nm), with negative Z-potential values (between -0.12 ± 0.04 and -94.1± 0.4), were synthesized. The loaded PTX (2.63±0.19 - 3.56 ±0.13 µg PTX/mg Np) was sustainably released along 23 and 27h. Three cell lines (MCF-7, MDA-MB-231 and HeLa) were selected to test the efficacy of the folate-targeted PTX-loaded BSA/ALG nanocarriers. The presence of FR on cell membrane led to a significant larger uptake of BSA/ALG-Fol nanoparticles regarding to the equivalent nanoparticles without folic acid on its surface. The cell viability results demonstrated a cytocompatibility of unloaded nanoparticle-Fol and a gradual decrease in cell viability after treatment with PTX-loaded nanoparticles-Fol due to the sustainable PTX release.

Heterogeneous distribution of delivery or treatment modalities within the tumor mass is a crucial limiting factor for a vast range of theranostic applications. Understanding the interactions between a nanomaterial and the tumor microenvironment will help to overcome challenges associated with tumor heterogeneity as well as the clinical translation of nanotheranostic materials. This study aims to evaluate the influence of protein surface adsorption on gold nanoparticle (GNP) biodistribution using high resolution Computed Tomography (CT) preclinical imaging in C57BL/6 mice harboring Lewis Lung Carcinoma (LLC) tumors. LLC provides a valuable model for study due to its highly heterogenous nature which makes drug delivery to the tumor challenging. By controlling the adsorption of proteins on the GNP surface, we hypothesize that we can influence the intratumoral distribution pattern and particle retention. We performed an in vitro study to evaluate the uptake of GNPs by LLC cells and an in vivo study to assess and quantify the GNP biodistribution by injecting concentrated GNPs citrate stabilized or passivated with Bovine Serum Albumin (BSA) intratumorally into LLC solid tumors. Quantitative CT and Inductively Coupled Plasma Optical Emission Spectrometry (ICP-OES) results both confirm the presence of particles in the tumor 9 days post-injection (n=8 mice/group). Significant difference is highlighted between citrate-GNP and BSA-GNP groups (**p < 0.005, Tukey’s multiple comparisons test), confirming the protein corona of GNPs modifies intratumoral distribution and retention of the particles. In conclusion, our investigations show that the surface passivation of GNPs influences the mechanism of cellular uptake and intratumoral distribution in vivo highlighting the spatial heterogeneity of the solid tumor.

In the present study, we have followed the hydrothermal path for the synthesis of gold nanoparticles (Au NPs) from the biomaterial Elaeocarpus ganitrus seeds extract, which is a rapid, eco-friendly, non-chemical way. The prepared NPs were thoroughly analyzed by PXRD & HR-TEM studies and also tested for photocatalytic dye degradation and anticancer studies. Besides, antioxidant, antibacterial and anticancer properties of Au NPs were studied. In vitro studies revealed the dose-dependent cytotoxic effect of Au NPs. The prepared nanoparticles showed good cytotoxic impact against Prostate cancer (PC-3) cells line. The results of the present study could contribute to synthesize new and cost-effective drugs from Elaeocarpus ganitrus seeds extract by using bio approach.

Owing to fascinating applications of ZnO in modern devices, it is interesting to explore its more features for future devices. Hence, herein, we have synthesized the high quality ZnO spherical nanoparticles (SNPs) through a facile green synthesis route and robust structural and biomedical studies are carried out. Hexagonal phase with 93.2% crystallinity was confirmed through XRD analysis. ZnO nanoparticles were tested for their bioactivities both in vivo (acute cytotoxicity test) and in vitro (Anti-cancer activities on liver (HepG2) and cervical (Hela) cancer cell lines, stimulatory/inhibitory effects on normal rat splenic cells and hemolytic effects on red blood cells). Results showed that ZnO SNPs has no cytotoxic effects on vital organ like liver and has no hemolytic action on red blood cells. ZnO SNPs showed inhibitory consequence on normal rat splenic cells growth at all tested concentrations. ZnO nanoparticles showed an inhibitory effect on HepG2 cell line. While showed stimulatory effect on Hela cell line. Current study presents the synthesized ZnO SNPs as highly applicable in bio-optoelectronics.

The release profiles of methotrexate, an anticancer drug, from the monoolein liquid crystalline cubic phases were studied. The cubic phases were used either in the form of a lipidic film deposited onto a glassy carbon electrode surface or in the dispersed form of magnetocubosomes, which are considered a prospective hybrid drug delivery system. Commonly, cubosomes or liposomes are employed, but not in the case of toxic methotrexate, known to block receptors responsible for folate transport into the cells. The release profiles of the drug from the lipidic films were monitored electrochemically and described using the Higuchi model. They were also modified via changes in temperature; the release was faster, although deviating from the model when the temperature was increased. Magnetocubosomes - cubic phase nanoparticles containing hydrophobic magnetic nanoparticles placed in an alternating magnetic field of low frequency and amplitude, stimulated drug release from the suspension, which was monitored spectroscopically. These new biocompatible hybrid materials are very promising, allowing to control the release of the drug at the appropriate sites, but do require further investigations into their in vitro cytotoxicity and in vivo biodistribution.

In this work, silver nanoparticles (AgNPs) were synthesized rapidly and eco-friendlily using the extract of Mulberry leaves and aqueous solution of silver nitrate without any toxic chemical [1,2]. The Mulberry leaves extract acts as both reducing agent and stabilizing agent. The UV-Vis spectrum shows peak at 430 nm. The TEM image of synthesized AgNPs sample shows spherical shaped particles whose size range from 15 to 20 nm. TEM image of nano silver solution sample synthesized by microwave assisted method shows nearly spherical particles with an average particle size of 10 nm. The absorption UV-vis spectrum of silver nanoparticles synthesized by microwave assisted method (AgNPsmw) shows a sharp absorption band around 415 nm. After two month storage of AgNPsmw, the absorption spectrum of AgNPsmw was taken again. The UV-Vis spectrum shows negligible peak changes of silver nanoparticles have occurred after two months of storage. The synthesized AgNPs material could be used as an antimicrobial, used in the field of textile and in wastewater treatment.

Nanoparticles (NPs) are widely used in diverse disciplines, including biology, medicine science. The central question that need to be answered is whether NPs have toxic effects on biological cells and molecules or are they safe. The safety of NPs including targeted drug delivery is critical and so is their toxicity in the environment. In recent years, in vitro and in vivo research on animals has generated abundant information about the toxicity of NPs. However, due to varying laboratory conditions, the comparison of the results from ensuing studies is somewhat unreliable. It should be noted that, depending on the type of production, NPs can enter the body through inhalation, skin and via digestive routes. Due to the diversity of NPs and their properties, there is paucity of accurate information on their toxicological effects; particle size, shape, surface area and the chemical levels are considered as key factors in creating health and toxicological effects. Consequently, there is a need for reliable information about their effects on various organs so as to deal with NPs effectively and their impact on health and the environment. This review covers the existing knowledge base on the subject that hopefully prepares us better to address these challenges.

The wide range of applications of nanoparticles (NPs) has increased the probability of environmental and occupational exposure. In a previous comparative study on cell line A549, we observed that oxidative stress caused by Co₃O₄ NPs affects the energetic homeostasis and the detoxification capacity, preventing autophagy induced by TiO₂ NPs. In this study, we have investigated the effects of NPs on the cell cycle.Cytofluorimetric analysis showed a slow-down of the cell cycle progression for both NPs, with increases in the percentage of resting cells in the G0/G1. These observations were confirmed by a reduced expression of all cyclins, especially of CCNE1 and CDK2, involved in the late stages of the G1 phase, coupled with a significant increase in the expression of p21 only for Co₃O₄ NP exposure. On the contrary, the effects of TiO₂ NPs were modest. Cell cycle related miRNA-34a, miRNA-126 and miRNA-1290 resulted increased at different early time-points (4-8h) but were down-expressed at 24h-48h only after TiO₂ NP exposure. Our results show that NPs have an antiproliferative effect and deregulate cell cycle on A549 cells. These effects should not be underestimated because regulation of cycle progression is crucial for cell survival and repair of genetic damage.

The possibility of releasing gold nanoparticles (GNP) into the environment has been rapidly increasing with the wide spread and flourishing application of gold nanoparticles (GNPs) in a wide range of areas. Consequently, environmental effects of GNP, especially toxicities to living organisms have drawn great attention. However, their toxicological characteristics still remain unclear. Fungi, as the decomposers of the ecosystem, interact directly with the environment and critically control the overall health of the biosphere. Thus, their sensitivity to GNP toxicity is particularly important. The aim of this study was to evaluate the role of shape and size of GNPs on their toxicities to fungi, which could help reveal the ecotoxicity of GNPs. Aspergillus niger, Mucor hiemalis and Penicillium chrysogenum were chosen for toxicity assessment, and spherical and star/flower-shaped GNPs sized from 0.7 nm to large aggregates of 400 nm have been synthesised. After exposure to GNPs and their corresponding reaction agents and incubation for 48 hours, the survival rates of each kind of fungus was calculated and compared. The results indicated that fungal species was the major determinant of the variation of survival rates, whereby A. niger was most sensitive and M. himalis was least sensitive to GNP exposure. Additionally, larger and non-spherical GNPs had relatively stronger toxicities.

A new approach is presented for dynamic modeling of chemical and isotopic evolution of C1-3 during the hydrocarbon generation process. Based on systematic data obtained from published papers for pyrolysis of various hydrocarbon sources(type I kerogen/source rock, type II kerogen/source rock, type III kerogen/source rock, crude oil, asphalt, etc), the empirical evolution framework of chemical and isotopic composition of C1-3 during the hydrocarbon generation process was built. Although the empirical framework was built only by fitting large amount of pyrolysis data, the chemical and isotopic composition of C1-3 derived from the pyrolysis experiments all follow the evolution laws, convincing us that it is applicable to the thermal evolution process of various hydrocarbon sources. Based on the simplified formula of the isotopic composition of mixed natural gas at different maturities (δ13Cmixed) δ13Cmixed=(X〖*n〗_iA 〖*δ〗^13 C_iA+Y〖*n〗_iB 〖*δ〗^13 C_iB)/(X〖*n〗_iA+Y〖*n〗_iB ), it can be derived that the cumulative isotopic composition of alkane generated in certain maturity interval can be expressed by the integral of the product of instantaneous isotopic composition and instantaneous yield at certain maturity point, and then divided by the cumulative yield of alkane generated in corresponding maturity interval. Thus, the cumulative isotopic composition(A(X)), cumulative yield(B(X)), instantaneous isotope(C(X)),and instantaneous yield(D(x)) in the dynamic model comply with the following formula during the maturity interval of (X0-X) A(X)=(∫_(X_0)^X▒〖C(X)*D(X)dx〗)/(B(X)), where A(X) and B(X) can be obtained by fitting of pyrolysis data, and D(x) can also be obtained from the derivation of B(X). The dynamic model was applied on the pyrolysis data of Pingliang Shale to illustrate the quantitative evolution of cumulative yield ,instantaneous yield, cumulative isotope and instantaneous isotope of C1-3 with increasing maturity.The dynamic model can quantify the yield of methane, ethane and propane as well as δ13C1, δ13C2 and δ13C3 respectively during the hydrocarbon generation process, which is of great significance to evaluate the natural gas resources of hydrocarbon source rock with different maturity and to identify the origin and evolutionary process of hydrocarbons by chemical and isotopic data. Moreover, this model provides an approach to study the dynamic evolution of isotope series of C1-3 (including reversed isotopic series), which is hopeful to reveal the mechanism responsible for isotopic reversal when combined with post-generation studies.

Breast cancer (BCa) is the most frequently diagnosed malignant tumor in women and is also one of the leading causes of cancer-related death. Most breast tumors are hormone-dependent and estrogen signaling plays a critical role in promoting the survival and malignant behaviors of these cells. Estrogen signaling involves ligand-activated cytoplasmic estrogen receptors that translocate to the nucleus with various co-regulators such as steroid receptor co-activator (SRC) family members, and bind to the promoters of target genes and regulate their expression. SRC-3 is a member of this family that interacts with, and enhances the transcriptional activity of the ligand activated estrogen receptor. Although SRC-3 has important roles in normal homeostasis and developmental processes, it has been shown to be amplified and overexpressed in breast cancer and to promote malignancy. The malignancy-promoting potential of SRC-3 is diverse and involves both promoting malignant behavior of tumor cells and creating a tumor microenvironment that has an immunosuppressive phenotype. SRC-3 also inhibits the recruitment of tumor-infiltrating lymphocytes with effector function and promotes stemness. Furthermore, SRC-3 is also involved in the development of resistance to hormone therapy and immunotherapy during breast cancer treatment. The versatility of SRC-3 in promoting breast cancer malignancy in this way makes it a good target, and methodical targeting of SRC-3 probably will be important for the success of breast cancer treatment.

Carthamin potassium salt isolated from Carthamus tinctorius L. was purified by an improved traditional Japanese method, without using column chromatography. The 1H and 13C nuclear magnetic resonance (NMR) signals of the pure product were fully assigned using one- and two-dimensional NMR spectroscopy, while the high purity of the potassium salt and deprotonation at the 3’ position of carthamin were confirmed by atomic adsorption spectroscopy and nano-electrospray ionization mass spectrometry.

A series of penta-1,4-dien-3-one containing a H-phosphonate scaffold were designed and synthesized. The structures of all title compounds were determined by 1H-NMR, 13C-NMR, 31P-NMR, and HRMS. Bioassay results showed that several of the title compounds exhibited remarkable antibacterial and antiviral activities. Among these, compounds 3c and 3o exhibited substantial antibacterial activities against Xanthomonas oryzae pv. Oryzae (Xoo) and Xanthomonas axonopodis pv. citri (Xac). In addition, compounds 3c, 3f, and 3r showed remarkable curative activities against tobacco mosaic virus (TMV), with 50% effective concentration (EC50) values of 290.0, 234.0, and 373.6 μg/mL, respectively. These were superior to that of ningnanmycin (386.2 μg/mL). Compound 3r exhibited comparative protective activity against TMV, with an EC50 value of 291.1 μg/mL, which was better than that of ningnanmycin (297.1 μg/mL). Notably, the solubility of all title compounds improved relative to the lead compound curcumin. These results suggest that penta-1,4-dien-3-one containing a H-phosphonate scaffold may be considered as an activator for antibacterial and antiviral agents.

In this paper we investigate in different scenarios the feasibility of using massive multiple-input multiple-output (mMIMO) with Reconfigurable Intelligent Surfaces (RISs) to boost the throughput and coverage performances with high energy efficiency, considering sub-6 GHz, mmWave and THz bands. With that objective, a centralized radio access network (C-RAN) suitable for beyond fifth generation (B5G) systems is considered, where we integrate the base stations (BSs) with multiple RISs and devices or user equipment. RISs with a large number of quasi-passive reflecting elements constitute a low-cost approach capable of shaping the radio wave propagation and improve wireless connectivity. We consider a scenario where multiple RISs are combined with mMIMO in the uplink in order to provide connectivity to Smart City (thousands of active low power devices) wirelessly, in the 3.6GHz and 28GHz bands. We also address a scenario where RISs are adopted with mMIMO in the downlink so as to offer connectivity to a Stadium with Pitch, (thousands of active user equipment) in the 28GHz band. Finally, we have also studied the connectivity at 100GHz of a Factory where several RIS panels replacing most of the BSs equipped with mMIMO assure improved throughput and coverage. We concluded that RISs are capable of improving the performance in any of these analyzed scenarios at the different frequency bands, justifying that they are a key enabling technology for 6G.

Cardiovascular diseases (CVDs) and type 2 diabetes mellitus (T2DM) are two of the four major chronic non-communicable diseases (NCDs), representing the leading cause of death worldwide. Several studies demonstrate that endothelial dysfunction (ED) plays a central role in the pathogenesis of these chronic diseases. Although it is well known that systemic chronic inflammation and oxidative stress are primarily involved in the development of ED, recent studies have shown that perivascular adipose tissue (PVAT) is implicated in its pathogenesis, also contributing to the progression of atherosclerosis and to insulin resistance (IR). In this review we describe the relationship between PVAT and ED, and we also analyse the role of PVAT in the pathogenesis of CVDs and T2DM, further assessing its potential therapeutic target with the aim of restoring normal ED and reducing global cardiovascular risk.

Objectives To develop and validate a prediction model for 28-day in-hospital mortality among adult patients critically ill with COVID-19 in the UK. Design Observational cohort study. Setting 287 adult critical care units in England, Wales and Northern Ireland, of which 260 admitted at least one eligible patient. Participants 10,933 patients with confirmed COVID-19 of whom 10,401 were eligible (excluding 532 patients with a duration of critical care less than 24 hours and 1 patient with unknown 28-day outcome): 8,666 development (March-April 2020) and 1,735 temporal validation (May-August 2020). Main outcome measures 28-day in-hospital mortality from start of critical care. Results Two models were developed using 14 patient level predictors selected from 30 candidate predictors, with and without adjustment for calendar time. In the temporal validation data, the model discrimination was maintained (c index 0.78) but calibration was poor, particularly for the model not adjusted for calendar time (ratio of observed to predicted mortality 0.74 versus 0.88 for the model adjusted for calendar time). Conclusions We developed and validated a prediction model for 28-day in-hospital mortality for patients critically ill with COVID-19. Although absolute predictions were inaccurate due to changing outcomes, the models will support risk-adjustment in analyses and monitoring changes in risk-adjusted outcome over time.

Silybum marianum is a therapeutic plant belonging to the family Asteraceae. It contains silymarin, as its principal component, and has been reported to demonstrate hepatoprotective activity. The study was aimed to investigate the phytochemical constituents, synthesis of nanoparticles, antioxidant activity and antimicrobial effects of the leaf extract. Extracts were synthesized from AgNO3 and characterized via FT-IR, U.V and XRD. The antioxidant activity was determined using DPPH, H2O2 and β-carotene assays. Similarly, all extracts expressed significant DPPH inhibition (IC50) of 5.1, 5.0, 4.7, 2.3, 4.3 and 1.1 (ug/mL), H2O2 of 1.3, 2.2, 4.7, 5.6, 4.0 and 1.0 (ug/mL) from the methanol/water extract, nanoparticles, n-Hexane, ETOAC, n-Butanol and Ascorbic acid (standard) respectively. The extract exerted scavenging activity on β-carotene with a significant IC50 inhibition of 1.5, 0.8, 5.2, 0.8, 2.7, 4.8 at 0 hour and 1.5, 0.8, 5.2, 0.8, 2.7 and 4.8 (ug/mL) after 2 hours water bath incubation at 50°C in the order of the extracts above. Additionally, nanoparticles and plant extracts significantly (p<0.0001) inhibited the growth of bacteria with mean zone of inhibition ranging 7-13 mm and 4-11 mm. This study demonstrated that extracts from different solvents of S. marianum possess significant antioxidant activity, as well as antimicrobial effects which are all concentration dependent. Thus, the result suggests that methanolic/water leaf extract of S. marianum could serve as a potential source of antioxidants and can be explored as a therapeutic agent in free radical induced diseases.

Silver in different forms is used for medical purposes from ancient times. It is not yet well known, which form of silver is more biocompatible and less toxic. Here we considered silver nanoparticles and silver citrate. Also, the relationships of neurotoxicity of silver compaunds with ageing factor is not yet described. To assess the role of nanoform in neurotoxicity of silver and role of ageing a long-term experiment was conducted. We had four control groups of intact mice and four experimental groups which were exposed to silver nanoparticles and silver citrate for two months. Four groups of mice were introduced into the experiment since the age of five months to assess ageing factors. It was shown that the nanoform does play a certain role in neurotoxicity of silver. Silver citrate seems to be a more preferable silver compound. Ageing can be regarded as a positive factor that neutralizes toxic action of silver compounds. It may be due to the development of physiological/cognitive functions with the age as well as adaptation to unnatural content in the individual cages that is definitely stressful for mice.

Understanding the phenomena underlying the non-selective susceptibility to ischemia of py-ramidal neurons in the CA3 area of the hippocampus is important from the point of view of elu-cidating the mechanisms of memory loss and the development of post-ischemic dementia. We used an ischemic model of Alzheimer's disease to study changes in amyloid protein precursor gene expression, its cleavage enzymes and tau protein in the CA3 area of the hippocampus af-ter a 10-minute brain ischemia with 12, 18, and 24-month survival. Quantitative reverse tran-scriptase PCR assay showed that the expression of all the genes that contribute to amyloid pro-duction was dysregulated within 2 years in the CA3 area of the hippocampus after ischemia. The expression of the amyloid protein precursor gene was above the control values at all times of the study. The expression of the α-secretase gene also exceeded the control values throughout the study. In contrast, the expression of the β-secretase gene reaching its maximum increase 12 months after ischemia, was below control values after 18 months and again above control values after 24 months of survival. Presenilin 1 and 2 gene expression was significantly elevated throughout the follow-up period, with peak expression of both genes occurring 12 months after ischemia. This suggests that the genes studied are involved in the non-amyloidogenic processing of amyloid protein precursor. Also, tau protein gene expression was significantly elevated throughout the observation period, and peak gene expression was present 12 months after is-chemia. Data indicate that an episode of brain ischemia with long-term survival causes damage and death of pyramidal neurons in the CA3 area of the hippocampus in a manner dependent on modified tau protein. Thus defining a new and important mechanism of pyramidal neuronal death in the CA3 area after ischemia. In addition tau protein gene modification after brain is-chemia is useful in identifying ischemic mechanisms occurring in Alzheimer's disease.

The coronavirus 2019 (COVID-19) pandemic was caused by a positive sense single-stranded RNA (ssRNA) severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, other human coronaviruses (hCoVs) exist, of which Middle East Respiratory Syndrome (MERS) and SARS-CoV (SARS) showed higher mortality rates without causing a pandemic. As of December 2022, SARS-CoV-2 has resulted in over 6.6 million deaths worldwide through an array of acute to chronic pathologies. Historical pandemics include smallpox and influenza with efficacious therapeutics utilized to reduce overall disease burden. Therefore, immune system process analysis is required to compare innate and adaptive immune system interactions. Lymphatic system organs include bone marrow and thymus using a network of nodes throughout which white blood cells traverse glycolipid membranes utilizing cytokines and chemokine gradients that affect cell development, differentiation, proliferation, and migration processes as well as genetic factors affecting cell receptor expression. Innate processes involve antigen-presenting cells and B lymphocyte cellular responses to pathogens relevant to other viral and bacterial infections but also in oncogenic diseases. Such processes utilize cluster of differentiation (CD) marker expression, major histocompatibility complexes (MHC), pleiotropic interleukins (IL) and chemokines. The adaptive immune system consists of Natural Killer (NK) and T cells. Other viruses are also contributory to cancer including human papillomavirus (cervical carcinoma ), Epstein-Barr virus (EBV) ( lymphoma), hepatitis B and C (hepatocellular carcinoma) and human T cell leukemia virus-1 (adult T-cell leukemia). Bacterial infections also increase the risk of developing cancer( e.g. H. pylori). Therefore, as the above factors can cause both morbidity and mortality along-side being transmitted within clinical and community settings, it is appropriate to now examine advances in single cell sequencing, FACS analysis and many other laboratory techniques that allow insights into discoveries of newer cell types. These developments offer improved clarity and understanding that over-lap with known autoimmune conditions that could be affected by innate B cell or T cell responses to SARS-CoV-2 infection. Thus, this review quantifies and outlines the nature of specific receptors and proteins relevant to clinical laboratories and medical research by documenting both innate and adaptive immune system cells within current coronavirus immunology case study data and other pathologies to date.

Novel antibacterial silver nanomaterials have become promising substitutes for traditional antibiotics, because pathogens do not develop resistance to them. However, it is necessary to produce silver nanoparticles with appropriate size and better performance through a green and simple synthesis process. In the present study, Fructus mori-composite silver nanoparticles (M-AgNPs) were greenly synthesized using medicinal plant mulberry fruits (Fructus mori), with silver nitrate (AgNO3) as a precursor. UV-Vis spectroscopy and X-ray diffraction (XRD) indicated the formation of silver nanoparticles with face centered cubic structure. Fourier transform infrared (FTIR) spectroscopy confirmed the reducing and capping effects of mulberry fruits' active components (polyphenols, flavonoids, etc.) on M-AgNPs. The reaction parameters including temperature, time, pH, and concentration of AgNO3 were gradually optimized. The particle size and morphology of M-AgNPs were measured by dynamic light scattering (DLS) and transmission electron microscopy (TEM) techniques. The minimum particle size of M-AgNPs was about 30 nm, and they were approximately spherical and equably distributed. The excellent stability of M-AgNPs ensured that no agglomeration occurred for up to 60 days. The antioxidant activity of M-AgNPs was evaluated by 1,1-diphenyl-2-trinitrophenylhydrazine (DPPH) assay, and the DPPH radical clearance rate of M-AgNPs was up to about 79%. Greenly synthesized M-AgNPs exhibited better antibacterial activity than chemically synthesized commercial silver nanoparticles (C-AgNPs), due to the active molecules attached to their surfaces. The inhibition zone diameters of M-AgNPs against P.aeruginosa, E.coli and S.aureus were 13.9±0.4、12.2±0.3、12.8±0.7 mm, respectively. Such greenly synthesized AgNPs from medicinal plants have good prospects in the field of biomedicine.

Keywords: bariatric surgery, sleeve gastrectomy, Roux-en-y gastric bypass, obesity, microbiota, gut-brain axis, beck scale, depression, diet, probiotics

To improve the understanding of soil–pile interaction of laterally loaded piles, the quasi-static test of pile group foundation in silty clay with 5 foundation piles arranged in cross shape is carried out. The direct measurement-based p–y curves at different depths showed nonlinear behavior, in which the initial stiffness and ultimate soil reaction increased as the depth increased. The loading displacement amplitude corresponding to the failure of each foundation pile in the high axial compression reinforced concrete pile group foundation is given as follows: the front-end nappe foundation pile (#3 pile) is 6mm, the middle pile is 16mm, the front-end nappe foundation pile is 20mm, and the loading displacement amplitude of side pile is 24mm. In silty clay, due to the existence of pile group effect, the edge effect has little effect on the horizontal foundation bed coefficient of foundation pile in pile group, while the influence of masking effect on the horizontal foundation bed coefficient of each foundation pile in pile group is not related to the position of pile, but only to the existence of masking effect, and the influence of different columns of masking effect on the horizontal foundation bed coefficient is the same.

In the context of evaluating physical function in individuals with stroke, the 3-meter backward walk test (3MBWT) emerges as a potential tool of interest. The purpose of this study was to assess the test-retest reliability and construct validity of the 3MBWT and its correlation with falling incidents. Conducted in a neurological rehabilitation center, 35 ambulatory individuals with stroke were enrolled within a month post-stroke onset. These participants, with a Functional Ambulation Category score of ≥4, underwent the 3MBWT, Functional Gait Assessment (FGA), 10-Meter Walk Test (10MWT), and 6-Minute Walk Test (6MWT) three times by different physiotherapists. Results indicated the 3MBWT displayed high reliability (r=0.97-0.98) and showed significant construct validity with other established walking tests like the 6MWT (r=-0.78) and 10MWT (r=0.71), with a moderate correlation to the FGA (r=-0.54). No marked differences in test outcomes were observed between participants based on their fall history. Conclusively, the 3MBWT proves to be highly reliable and validates well with existing walking function assessments for stroke patients, suggesting its potential as a time-efficient alternative.

Detailed kinetics for a 3-wavelength photopolymerization confinement (PC) system is presented for both numerical solutions and analytic formulas. The dynamic profiles are simulated for oxygen, free radical, and conversion for various situations of: blue-light only, 2-light (red and UV), and 3-light (red, blue, UV). An effective PC requires two conditions: (i) a strong N-inhibition for uncured regime with a low conversion (triggered by the UV-light); and (ii) a weak S-inhibition (oxygen-induced) for high conversion under the blue-light or blue and red-light initiation. Good PC candidates are governed by collective factors of: (i) the double ratio of light-intensity and initiator-concentration, (ii) monomers rate-constant; and (iii) effective absorption constants at specific wavelength and initiators. A new reverse feature for the role of N-inhibition on the blue-conversion is found. Higher oxygen concentration leads to a lower conversion, which could be enhanced by reducing the S-inhibition via a red or blue-light pre-irradiation, having a pre-irradiation time TP=200 s for red-light only, and reduced to 150 s, when both red and blue-light. System under UV-only leads a conversion lower than that of blue-only. However, conversion could be improved by the dual-light (blue and UV), and further enhanced by the pre-irradiation of red-light. The two competing factors, N-inhibition and S-inhibition, could be independently and selectively tailored to achieve: (a) high conversion of blue-light (without UV-light), enhanced by red-light pre-irradiation for minimal S-inhibition; and (b) efficient PC initiated by UV-light produced N-inhibition for reduced confinement thickness and for high print speed.

Infection of liver flukes (Opisthorchis viverrini) is partly due to their suitability for habitats in sub-basin areas, which causes the intermediate host to remain in the watershed system in all seasons. Spatial monitoring of fluke infection at the small basin analysis scale is important because this can enable analysis at the level of the spatial factors involved and influencing infections. The spatial mathematical model was weighted by the nine spatial factors by dividing the analysis into two levels. 1) sub-basin boundary level analyzed with ordinary least square (OLS) model used to analyze spatial factors of liver fluke aimed at analyzing spatial factors related to human liver fluke infection according to sub-basin boundaries, and 2) infection risk positional analysis level with machine learning-based forest classification and regression (FCR) and displaying predictive results of infection risk locations along stream lines. The analysis results show 4 prototype models that import different independent variable factors. The results show that Model-1 and Model-2 give the most AUC = 0.964 and the variables that influence infection risk the most were distance to stream lines, and distance to water bodies, NDMI and NDVI factors rarely affect accuracy. This FCR machine learning application approach can be applied to the analysis of infection risk areas at the sub-basin level, but independent variables must be screened with a preliminary mathematical model weighted to the spatial units in order to obtain the most accurate predictions.

Indigenous trees have great economic potential and ecological benefits for enhancing environmental prosperity, mostly in forestry and the forest products sector in the developing countries of Sub-Sahara Africa. The baobab (Adansonia Digitata L.) is known as the African green jewel in both fruit production and medicinal benefits also remarkable for so many forest products exported across the world. Research conducted in the different Sub-Saharan African sub-regions has shown this iconic tree with a majestic outlook has a priority tree species for local and foreign use and conservation. However, data on the benefits and conservation of baobab trees in Africa, especially the Sub-Saharan countries is limited. This study aimed to assess the predominant geo-graphical distribution of the tree, the indigenous (cultural, socio-economic, ecological, and medical/health) benefits, and the conservation strategies of the baobab resources in Sub-Saharan Africa. The baobab tree's succulent roots, bulbs, branches, fruit, pods, foliage, and petals are all nourishing. Baobab parts have been used for diverse reasons in Africa, some countries of Asia, and Europe for the past two centuries due to their medicinal well-being properties. In addition, the medicinal applications of the plant parts are discussed. Many authors have highlighted the baobab tree as one of the most important trees to be saved and localized in Africa because of its high indigenous usage and commercial worth. Anthropogenic global warming may induce a drop in baobab species, which could inflict negative impacts on African economies. As a result, it's critical to research the species' likely future distribution and develop conservation policies. Literature was consulted for records and availability of this tree in the Western, Central, Eastern, and Southern African species records and it was also analyzed what percentage of the current environment would be appropriate in the future. Recent studies suggested that farmers and the locals be provided free seeds and seedlings to encourage biological rejuvenation to maximize the plant's potential, people should be informed about the additional uses of baobab that have been discovered. Individuals must also be educated on simple sustainable agroforestry activities that can be performed in plant and forest management.

Objectives: Low and Middle Income Countries (LMICs) are experiencing a fast-paced epidemiological rise in clusters of non-communicable diseases (NCDs) such as diabetes and cardiovascular disease, forming an imminent rise in multimorbidity (MMD). However, preventing MMD has received little attention in LMICs, especially in Sub-Saharan African Countries. Design: Narrative review which scoped the most recent evidence in LMICs about MMD determinants and appropriated them for potential MMD prevention strategies. Methods: MMD in LMICs is affected by several determinants including increased age, female gender, environment, lower socio-economic status, obesity, and lifestyle behavious, especially poor nutrition and physical inactivity. Results: MMD public health interventions in LMICs, especially Sub-Saharan are currently impeded by local and regional economic disparity, underdeveloped healthcare systems, and concurrent prevalence of communicable diseases. However, lifestyle interventions that are targeted towards preventing highly prevalent MMD clusters, especially hypertension, diabetes and cardiovascular disease, can provide an early prevention of MMD, especially within Sub-Saharan African countries with emerging economies and socio-economic disparity. Conclusion: Future public health initiatives should consider targeted lifestyle interventions and appropriate policies and guidelines in preventing MMD in LMICs.

Background: The epidemiological situation generated by COVID-19 has cast into sharp relief the delicate balance between public health priorities and the economy, with businesses obliged to toe a line between employee health and continued production. In an effort to detect as many cases as possible, isolate contacts, cut transmission chains and limit the spread of the virus in the workplace, mass testing strategies have been implemented in both public health and industrial contexts to minimize the risk of disruption in activity. Objective: To evaluate the economic impact of mass workplace testing strategy as carried out by a large automotive company in Catalonia in terms of health and healthcare resource savings. Methodology: Analysis of health costs and impacts based on the estimation of mortality and morbidity avoided because of screening and the resulting savings in healthcare costs. Results: The economic impact of the mass workplace testing strategies (using both PCR and RAT tests) was approximately €10.44 per test performed or €5,575.49 per positive detected. 38% of this figure corresponds to savings derived from better use of health resources (hospital beds, ICU beds and follow-up of infected cases), while the remaining 62% corresponds to improved health rates due to avoided morbidity and mortality. In scenarios with higher positivity rates and a greater impact of the infection on health and the use of health resources, these results could be up to ten times higher (€130.24 per test performed or €69,565.59 per positive detected). Conclusion: In the context of COVID-19, preventive actions carried out by the private sector to safeguard industrial production also have concomitant public benefits in the form of savings in healthcare costs. Thus, governmental bodies need to recognize the value of implementing such strategies in private settings and facilitate them through, for example, subsidies.

(R)-1-(4-Amino-3,5-dichlorophenyl)-2-bromoethan-1-ol has been synthesised in 93% enantiomeric excess (ee) by asymmetric reduction of the corresponding ketone catalysed by a ketoreductase and NADPH as the co-factor in DMSO. (S)-N-(2,6-Dichloro-4-(1-hydroxyethyl)phenyl)acetamide has been synthesised in >98% ee by the same system. Both synthons are potential precursors for clenbuterol enantiomers. Clenbuterol is a β₂-agonist used in veterinary treatment of asthma in several countries. The drug is listed on the World Anti-doping Agency’s Prohibited list due to its effect on increased protein synthesis in the body. However, racemic clenbuterol has recently been shown to reduce the risk of Parkinson’s disease. In order to reveal which one (or both) of the enantiomers that cause this effect, the pure enantiomers need to be studied separately. Our biocatalytic approach in order to obtain enantiopure clenbuterol should be applicable to industrial scale.

Seafood products are the main dietary source of n-3 polyunsaturated fatty acids (n-3 PUFA), which are essential for human health. However, due to the widespread use of processed fish products, the presence of these n-3 PUFAs may be subject to changes related to different processing methods. The aim of this study was to determine the fatty acid composition, with a focus on n-3 polyunsaturated fatty acids (n-3 PUFAs), in different processed fish and shellfish food of EU and non-EU origin purchased in supermarkets and ethnic food shops in Messina (Italy), using gas chromatography with flame-ionization detector (GC-FID). From the fatty acid profile, the atherogenic index (AI), thrombogenicity index (TI) and flesh-lipid quality index (FLQ) were determined: 0.13-1.04 (AI), 0.31-9.84 (TI) and 0.41-29.90 (FLQ). The percentages of saturated (SFA), monounsaturated (MUFA) and polyunsaturated (PUFA) fatty acids had the following ranges: 13.55-50.48%, 18.91-65.58%, 13.84-52.73%, respectively. All samples showed a good presence of PUFAs and, in particular, eicosapentaenoic (EPA, 20:5n-3) and docosahexaenoic acid (DHA, 22:6n-3) were the main n-3 polyunsaturated fatty acids (n-3 PUFA).

Cerebral blood flow (CBF) decreases across the lifespan, and chronic conditions such as dementia and stroke accelerate this decline. Impaired CBF results in reduced delivery of oxygen and nutrients, which can damage the brain over time. Thus, there is a need to identify lifestyle interventions including diet and exercise to maintain CBF with aging and in the presence of chronic disease. In the present study, we used transcranial Doppler ultrasound to record middle cerebral artery velocity (MCAv), a surrogate measure of CBF, during moderate-intensity exercise in sedentary, cognitively-normal older adults (N = 90). A multiple linear regression model (F(4, 85) = 3.21, p = 0.02) showed self-reported omega-3 supplement use significantly moderated the association between age and mean exercising MCAv in these individuals (p = 0.01). Older age was associated with lower exercising MCAv in the group not taking omega-3 supplements, while exercising MCAv showed no decline with increasing age in the group who reported omega-3 supplement use. These findings suggest omega-3 supplementation may have an important role in the preservation of CBF with aging.

The neurologic effects of long-COVID are a therapeutic challenge. This article discusses the immunologic manifestations of long-COVID and proposes a non-androgenic, synthetic analog of dehydroepiandrosterone (DHEA), bromo-epi-androsterone (BEA), as a candidate for clinical trials for this exigent collection of neurologic conditions. Moreover, because there is an association between long-COVID and Alzheimer’s disease, the evaluation of BEA in long-COVID may serve as a proxy for its effect on neuroinflammatory biomarkers of Alzheimer’s disease that are shared with long-COVID.

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.

Viruses continue to provide vital insights into the field of control of gene expression. Viral transactivators, in concert with other viral and cellular proteins, regulate expression of self, other viruses, and host genes with profound effects on infected cells, underlying inflammation, control of immune responses, and pathogenesis. The multifunctional Tat proteins of lentiviruses (HIV-1, HIV-2, and SIV) transactivate gene expression by recruiting host proteins and binding to trans-acting responsive regions (TARs) in viral and host RNAs. SARS-CoV-2 nucleocapsid participates in early viral transcription, recruits similar cellular proteins, and shares intracellular, surface, and extracellular distribution with Tat. SARS-CoV-2 nucleocapsid interacting with the Replication-Transcription complex might, therefore, transactivate viral and cellular RNAs in transcription and reactivation of self and other viruses, acute and chronic pathogenesis, immune evasion, and viral evolution, constituting a potential pan-coronaviral therapeutic target. Here, we show by using primary and secondary structural comparisons that the leaders of SARS-CoV-2 and other coronaviruses contain TAR-like sequences in stem-loops 2 and 3, the coronaviral nucleocapsid C-terminal domains (N-CTDs) harbor a region of similarity to TAR-binding regions of lentiviral Tat proteins, and the coronaviral nonstructural protein 12 has a cysteine-rich metal binding, dimerization domain similar to that in lentiviral Tat proteins.

Background: Infections of Coronavirus Disease-2019 (COVID-19) can cause long-term effects known as long COVID. This pilot study aimed to evaluate the feasibility of a clinical study as well as the efficacy and safety of traditional East Asian herbal medicines in alleviating fatigue and cognitive dysfunction “brain fog” in patients with long COVID. Methods: This prospective pilot study investigated the use of three types of herbal medicines, Bojungikki-tang (BIT), Kyungok-go (KOG), and Cheonwangbosim-dan (CBD), for a 12-week period as potential treatments for fatigue and cognitive dysfunction in patients with long COVID. Forty-five patients with long COVID were recruited, and one of three drugs was given based on the patient’s symptoms and pattern identification. The effect of herbal medications on fatigue and cognitive function outcomes was assessed over a 36-week period, with patient adherence closely monitored. Results: After 12 weeks of herbal drug administration, fatigue symptoms improved significantly across all groups, with treatment success rates of 80%, 53.33%, and 46.67% in the BIT, KOG, and CBD groups, respectively. However, “brain fog” symptoms showed less improvement, with treatment success rates of 40%, 46.67%, and 13.33% in the BIT, KOG, and CBD groups, respectively. All adverse events reported were mild and unrelated to the medication. The study design was found to be feasible with high medication adherence. Conclusions: This study demonstrated the feasibility of conducting a clinical trial with three herbal medicines to treat long COVID symptoms like fatigue and “brain fog.”

A change in biological properties of the SARS-CoV-2 virus can enhance its transmissibility and virulence, complicate the disease course, and reduce the effectiveness of anti-viral therapy and vaccination. We have studied 16 genetic lineages of the Omicron variant. The viral reproduction course was analyzed based on plaque morphology in the agar layer and the maximum titer in Vero E6 cells. BALB/c mice and Syrian hamsters were used as animal models. Viral load and infectious SARS-CoV-2 titer were determined in the nasal tissue and lungs. The severity of infectious process was assessed using histological methods. An increased plug size was observed in CH.1.1 and BQ.1.2.1 strains after six passages. This was due to substitutions D614G, H655Y, and N764K in the coronavirus S protein. The same changes in gene variants Gamma and BA.1 were caused by the substitution R682W, which is not present in lineages CH.1.1 and BQ.1.2.1. A similar substitution, namely R682P, was observed in the BA.5.1 strain. We characterized BA.1 (as a reference), BA.5.2, and XBB.3 strains in vivo as representatives of the main circulating genetic lineages. For the BA.1 strain, ID50 was 1.3 and 14 TCD50 in Syrian hamsters and BALB/c mice, respectively. An insignificant increase in the BA.5.2 virulence compared to that of BA.1 was noted (ID50 was 07. and 10 TCD50, respectively). The XBB.3 pathogenicity in laboratory animals is similar to that of BA.1 (ID50 was 1.8 and 15 TCD50, respectively). Experiments showed a consistent decrease in the virulence of Omicron strains compared to previously circulating SARS-CoV-2 variants. A co-evolutionary change in amino acid sequences, affecting the conformation of the coronavirus S protein and its surface epitopes in representatives of different genetic lineages, was noted. The emergence of potential proteolysis sites and alterations of the furin cleavage site have been observed in numerous Omicron coronavirus variants.

Global economic and social burden was caused by the SARS-CoV-2 spread worldwide. Despite the end of the pandemic, there is a concern about virulent evolving variants of the virus which can bypass the humoral immune response induced by vaccination or infection. Crucial to the viral entrance, amino acid residues in the RBM region, which interacts with cellular receptor ACE2, can elicit neutralizing antibody response. Herein we determine the immunogenicity of one-dose or heterologous dose vaccinated serum against wild-type and mutated RBM region. Despite low antibody response to wild-type SARS-CoV-2 RBM, omicron variants possess four mutations in RBM (S477N, T478K, E484A, F486V) that induce even less antibody titers. The most predominant responses were against IgA and IgG. While neutralizing antibodies (nAbs) predominantly target the RBD, our investigation revealed a diminished seroreactivity within the RBD's crucial region, the receptor-binding motif (RBM), potentially impacting the production of protective nAbs. S1WT and S2WT RBM peptides binding to nAbs were evaluated through microscale thermophoresis, and higher affinity (35 nM) was obtained for sequence S2WT (GSTPCNGVEGFNCYF), containing the FNCY patch. Our data indicates that SARS-CoV-2 RBM is not an immunodominant region in vaccinated individuals. Understanding the intricate dynamics of the humoral response and its interplay with viral evolution and host genetics is essential for the formulation of effective vaccination strategies, not only against SARS-CoV-2 but also for future emerging coronaviruses.

Pre-exposure prophylaxis for COVID-19 with Tixagevimab/Cilgavimab in immunocompromised patients has reduced the risk of breakthrough infection, disease, hospitalization, and COVID-19 related mortality. However, the advent of the Kraken variant (XBB.1.5) has limited the use of this monoclonal antibody, based on poor efficacy in in vitro studies The objective of the study was to evaluate the risk of breakthrough infection, symptomatic disease, hospitalization, intensive care admission and COVID-19 related death in kidney transplanted recipients receiving pre-exposure prophylaxis with Tixagevimab/Cilgavimab for COVID-19 in the era of the Kraken variant (XBB.1.5). In a prospective, observational study, we enrolled kidney transplant patients undergoing pre-exposure prophylaxis for COVID-19 with Tixagevimab/Cilgavimab at the Division of Infectious Diseases of Federico II University of Naples between February 2023 and August 2023. Each patient subsequently underwent a six-month follow-up with symptom monitoring and surveillance nasopharyngeal swab for SARS-CoV-2 RNA detection every 30 days, regardless of symptoms. Thirty-four kidney transplant patients were enrolled and in the follow-up period, only one tested positive for the nasopharyngeal swab for SARS-CoV-2 research with asymptomatic infection and virological recovery on the eighth day from the diagnosis of infection. Therefore, no patient developed disease and no patient needed hospitalization and no death occurred. No adverse drug reaction to Tixagevimab/Cilgavimab occurred. Our data, although derived from a limited and uncontrolled sample, show the potential of Tixagevimab/Cilgavimab as a valid and viable therapeutic strategy in pre-exposure prophylaxis for immunocompromised patients. These findings highlight the importance of conducting clinical studies on this topic.

To map Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV 2) spreading and evaluate immune responses variations against this virus, it was essential to locally set up efficient serological tests. The SARS-CoV2 immunogenic proteins were very expensive and not affordable mainly for Low and Middle Income Countries (LMICs). For this purpose, the commonly used antigen, Re-ceptor-Binding Domain (RBD) of Spike S1 protein (S1RBD), was produced using the the Baculovirus Expression Vector System (BEVS) . During the current study, the expression of S1RBD was monitored using western blot under different culture conditions. Different parameters were studied: Multiplicity Of Infection (MOI), cell density at infection and harvest time. Hence, optimal conditions for efficient S1RBD production were identified: MOI 3; cell density at infection 2-3x 106 cells/mL and time post-infection (tpi or harvest time) of 72h and 72-96 h successively for expression in shake-flasks and 7L-bioreactor. A high production yield of S1RBD varying between 4mg and 70 mg per liter of crude cell culture supernatant was achieved, respectively, in shake-flasks and in 7L-bioreactor. Moreover, the produced S1RBD showed an excellent antigenicity potential against COVID-19 patient sera evaluated by western blot. Thus, additional serological assays, such as ELISA, were developed using the purified S1RDB (published by other research groups).

Long coronavirus disease 2019 (COVID-19) may occur after experiencing acute COVID-19 infec-tion with many effects on patients´ kidneys. This study aimed to evaluate the clinical and labora-tory aspects of kidney function in individuals with long COVID in the Amazon region of Brazil. This cross-sectional study selected participants from a ‘long COVID’ clinical care program. Clini-cal data and baseline demographics were obtained, and blood samples were collected to quantify kidney-related markers. Patients were evaluated after COVID-19 infection at several time points as follows: 0–3 months, 3–6 months, 6–12 months, and 12 months. Altogether, 246 patients were selected for this study, and only 79 were hospitalised (9 in the intensive care unit because of COVID-19. Of the patients, 38 were diagnosed with hypertension after COVID-19, 52 cases had to have their medications adjusted, and 83 patients presented with kidney function decline. The older age group and individuals with glycaemic alterations presented with a higher risk of devel-oping kidney dysfunction. Therefore, health professionals should monitor long-term kidney mark-ers in long COVID.

Background and aim: To explore the discriminant accuracy of Cytokeratin 18 (CK18, including M65 and M30 forms) for an elevated fatty liver index (FLI) as a validated proxy of Non-Alcoholic Fatty Liver Disease (NAFLD), and cardiovascular disease (CVD) risk in the general population. Methods: Both serum CK18 forms were measured using a commercial immunoassay in randomly selected samples from 312 participants of the PREVEND general population cohort. FLI ≥60 was used to indicate NAFLD. Framingham Risk Score (FRS) and the SCORE2 were used to estimate the 10-year risk of CVD. Receiver Operating Characteristic (ROC) curve, linear/logistic regression models and Spearman's correlations were used. Results: Intricate associations were found between CK18, FLI and CVD risk scores. While M30 was the only independent predictor of FLI≥60, M65 discriminated best NAFLD individuals at very-high 10-years CVD risk according to SCORE2 (AUC:0.71; p=0.001). Values above the predefined manufacturer cut-off (400 U/l), were associated with an independent 5-fold increased risk (adjusted odds ratio: 5.44, p=0.01), with negative predictive value of 93%. Conclusions: Confirming that NAFLD is associated with an increased CVD risk, our results point to CK18 M65 as a candidate biomarker to identify NAFLD individuals at low CVD risk in European general population.

The high demand for SARS-CoV-2 tests but limited supply to South African laboratories early in the COVID19 pandemic, resulted in a heterogenous diagnostic footprint of open and closed molecular testing platforms. Novel approaches were required to monitor test quality especially during the introduction of newly circulating variants. The National Health Laboratory Service centrally collected cycle threshold (Ct) values from 1,497,669 test results reported from six commonly used PCR assays in 36 months, and visually monitored changes in their median Ct within a 28-day centered moving average for each assays’ gene targets. This continuous quality monitoring rapidly identified delayed hybridization of RdRp in the Allplex™ SARS-CoV-2 assay due to the Delta (B.1.617.2) variant; S-gene target failure in the TaqPath™ COVID-19 assay due to B.1.1.7 (Alpha) and the B.1.1.529 (Omicron); and recently E-gene delayed hybridization in the Xpert® Xpress SARS-CoV-2 due to XBB.1.5. This near “real-time” monitoring helped inform the need for sequencing and the importance of multiplex molecular nucleic acid amplification technology designs used in diagnostics for patient care. This continuous quality monitoring approach at the granularity of Ct values should be included in ongoing surveillance and with application to other disease use cases that rely on molecular diagnostics.

Background. Chest CT is widely regarded as a dependable imaging technique for detecting pneumonia in COVID-19 patients, but there is growing interest in microwave radiometry (MWR) of the lungs as a possible substitute for diagnosing lung involvement. Aim. The aim of the study is to examine the utility of the MWR approach as a screening tool for diagnosing pneumonia with complications in patients with COVID-19. Methods. Our study involved two groups of participants. The control group consisted of 50 individuals (24 male and 26 female) between the ages of 20 to 70 years who underwent clinical evaluations and had no known medical conditions. The main group included 142 participants (67 men and 75 women) between the ages of 20 to 87 years who were diagnosed with COVID-19 complicated by pneumonia and were admitted to the emergency department between June 2020 to June 2021. Skin and lung temperatures were measured at 14 points, including 2 additional reference points, using a previously established method. Lung temperature data were obtained with the MWR2020 (RTM-01-RES) (MMWR LTD, Edinburgh, UK), a CE Class I device. All participants underwent clinical evaluations, laboratory tests, chest CT scans, MWR of the lungs, and reverse transcriptase polymerase chain reaction (RT-PCR) testing for SARS-CoV-2. Results. The MWR exhibits a high predictive capacity as demonstrated by its sensitivity of 98.6% and specificity of 84.0%. Conclusions. MWR of the lungs can be a valuable substitute for chest CT in diagnosing pneumonia in patients with COVID-19, especially in situations where chest CT is unavailable or impractical.

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.

During COVID-19 pandemic, drug repurposing represented an effective strategy to obtain quick answers to medical emergencies. Basing on previous data on Methotrexate (MTX), we evaluated the anti-viral activity of several DHFR inhibitors in two cell lines. We observed that this class of compounds showed a significant influence on the virus-induced cytopathic effect (CPE) partly associated to the intrinsic antimetabolic activity of these drugs, but also to a specific antiviral function. To elucidate the molecular mechanisms, we took advantage of our EXSCALATE platform for in-silico molecular modelling and further validated the influence of these inhibitors on nsp13 and viral entry. Interestingly, Pralatrexate and Trimetrexate showed superior effects in counteracting the viral infection compared to other DHFR inhibitors. Our results indicate that their higher activity is due to their polypharmacological and pleiotropic profile. These compounds can thus potentially give a clinical advantage in the management of SARS-CoV-2 infection in patients already treated with this class of drugs.

Arf-like protein 2 (ARL2) is a ubiquitously expressed small GTPase with multiple functions. In cell culture, ARL2 participates with tubulin cofactor D (TBCD) in the neogenesis of tubulin αβ-heterodimers, the building blocks of microtubules. To evaluate this function in retina, we conditionally deleted ARL2 in mouse retina at two distinct stages, either during embryonic development (retArl2-/-) or after ciliogenesis specifically in rods (rodArl2-/-). retArl2-/- retina sections displayed distorted nuclear layers and a disrupted microtubule cytoskeleton (MTC) as early as postnatal day 6 (P6). Rod and cone outer segments (OS) did not form. By contrast, rod ARL2 knockouts were stable at postnatal day 35 and revealed normal ERG responses. Cytoplasmic dynein is reduced in retArl2-/- inner segments (IS), suggesting that dynein may be unstable in the absence of a normal MTC. We investigated microtubular stability in the absence of either ARL2 (retARL2-/-) or DYNC1H1 (retDync1h1-/-), the dynein heavy chain, and found that both the retArl2-/- and retDync1h1-/- retinas exhibited reduced microtubules and nuclear layer distortion. The results suggest that ARL2 and dynein depend on each other to generate a functional MTC during early photoreceptor development.

Glaucoma is a leading cause of blindness. Surgical and pharmacological treatment of glaucoma aims to lower the intraocular pressure (IOP) and preserve visual function. The severe acute res-piratory syndrome coronavirus 2 pandemic has placed a strain on the healthcare system. We aimed to compare the quantity, type of anti-glaucoma surgeries, and the disease stage before and during the coronavirus disease pandemic. We analyzed 362 eyes of 306 patients and 172 eyes of 149 patients from the pre-pandemic and pandemic groups, respectively. The number of an-ti-glaucoma surgeries was halved during the pandemic compared to a similar pre-pandemic pe-riod, with a significant difference in the procedural structures between the two groups (p<0.001). The most common procedures in the pre-pandemic group were Ex-Press implantation (33.7%) and trabeculectomy (31.5%). Within the pandemic group, half of the eyes underwent tra-beculectomy (50.0%), followed by Preserflo microshunt (11.6%). A significant difference in the average IOPs was revealed among patients who qualified for surgery 22.21 ± 7.83 mmHg in the pre-pandemic group and 25.16 ± 9.48 mmHg in the pandemic group; p<0.001). There was no significant difference in the best corrected visual acuity between the groups (p=0.263). Glaucoma treatment remained relatively accessible during the pandemic.

The aim of this study was to investigate the role of DNA methylation in the regulation of in vitro and in vivo cartilage formation. Based on the data of an RNA chip-assay performed on chondrifying BMP2-overexpressing C3H10T1/2 cells, the relative expression of Tet1 (tet methylcytosine dioxygenase 1), Dnmt3a (DNA methyltransferase 3) and Ogt (O-linked N-acetylglucosamine transferase) genes was examined with RT-qPCR in mouse cell-line based and primary micromass cultures. RNA probes for in situ hybridization were used on frozen sections of 15-day-old mouse embryos. DNA methylation was inhibited with 5-azacytidine during culturing. We found very strong but gradually decreasing expression of Tet1 throughout the entire course of in vitro cartilage differentiation along with strong signals in the cartilaginous embryonic skeleton. Dnmt3a and Ogt expressions did not show significant changes with RT-qPCR and gave weak in situ hybridization signals. Inhibition of DNA methylation applied during early stages of differentiation reduced cartilage-specific gene expression and cartilage formation. In contrast, it had stimulatory effect when added to differentiated chondrocytes. Our results indicate that the DNA demethylation-inducing Tet1 is a significant epigenetic factor of chondrogenesis, and inhibition of DNA methylation exerts distinct effects in different phases of in vitro cartilage formation.

Gut microbiota and its metabolites like short chain fatty acids (SCFAs) are linked with pathology of Alzheimer’s disease (AD)- a debilitating public health problem in older adults. However, strategies to beneficially modulate gut microbiota and its sensing signaling pathways remain largely unknown. Here, we screened, validated and established the agonists of free fatty acid receptor 2 (FFAR2) signaling, which senses beneficial signals from SCFAs produced by microbiota in the gut. We demonstrated that inhibition of FFAR2 signaling increases amyloid-beta (Aβ) stimulated neuronal toxicity. Thus, we screened FFAR2 agonists, using in-silico library of more than 144,000 natural compounds, and 15 compounds were selected based on binding with FFAR2 agonist sites. Further, cell culture toxicity and FFAR2 stimulatory experiments demonstrated that Fenchol (a natural compound commonly present in basil) was potent FFAR2 agonist in neuronal cells. Interestingly, we also demonstrated that Fenchol protects Aβ-stimulated neurodegeneration in FFAR2 dependent manner. In addition, Fenchol reduced AD like phenotypes such as Aβ-accumulation and, learning and memory behaviors in Caenorhabditis (C.) elegans. Fenchol increased Aβ-clearance by increasing proteasome/lysosome activity and reduced senescence in neuronal cells. These results demonstrated that the inhibition of FFAR2 signaling promotes Aβ-induced neurodegeneration, while activating it by Fenchol as a natural agonist reverse it by promoting Aβ-clearance and reducing cellular senescence; thus stimulation of FFAR2 signaling can be a therapeutic approach to prevent/ treat AD.

Decisions affecting the COVID-19 pandemic, by the individual and those with highest authority, are being made on the basis of unreliable data. Data about cases and deaths are collected daily but represent only a sample of reality. Statistics convert sample data into more reliable estimates. However, statistics have no magical powers; reliability requires dependable data. It is futile to rail against this darkness; COVID-19 is not a scientific experiment. However, we must do better both with data collection and data analysis. In this review, I focus on one element of the data, the asymptomatic case of COVID-19. Without reliable information about this number, decision makers are significantly blinded. By its nature, the asymptomatic case is hidden but contaminating to understanding COVID-19. The true case rate and death rate per case are unknowable without knowing the fraction of cases that are asymptomatic. The best estimate of asymptomatic cases is in the CDC document: COVID-19 Pandemic Planning Scenarios. For four different scenarios the estimates range from 10% to 70%, with the best estimate of 40% for asymptomatic cases. However, even the definition of the asymptomatic case is problematic. In simplest terms, two elements are required: an infection and no symptoms. How is “no symptoms” to be usefully defined? It appears to be analogous to pontificating about black swans from studying only white swans. It implies infection, but how is infection defined? Is it presence of the virus, replication of the virus, or presence of antibodies? Is asymptomatic disease an oxymoron? Without extensive, purposeful screening for specifically defined, essential symptoms and appropriate virus and antibody testing over time, the class of asymptomatic cases remains unknown. Current estimates range from <20% to ˃80%. If low, it can be ignored; if high, it dramatically and proportionately lowers the case rate and the death rate per case. Consequentially, the asymptomatic rate dramatically affects our societal and political responses. In this focused review, we assess the limitations of the published estimates, bring attention to the importance of obtaining accurate data, and exhort that high priority be given in the scientific community to understanding the issue, asymptomatic COVID-19 cases.

At a time when the world faces an emotional breakdown, crushing our dreams if not taking our lives, we realize that together we must fight the war against the COVID-19 outbreak even if almost the majority of the scientific community finds itself confined to home. Every day, like everyone else, we, scientists, listen to the latest news with its promises and announcements. Across the world, a surge of clinical trials trying to cure or slow down the coronavirus pandemic has been launched to bring hope instead of fear and despair. One first proposed clinical trial has drawn worldwide hype to the benefit of chloroquine (CQ), a well-known and broadly used anti-malarial drug, in the treatment of patients infected by the recently emerged deadly coronavirus (SARS-CoV-2). We should consider this information in the light of the long-standing anti-inflammatory and anti-viral properties of CQ-related drugs. Yet, none of the articles promoting the use of CQ in the current pandemic evoked a possible molecular or cellular mechanism of action that could account for any efficacy. Here, given the interaction of viruses with macroautophagy (hereafter referred to as autophagy), a CQ-sensitive anti-viral safeguard pathway, we would like to discuss the pros, but also the cons concerning the current therapeutic options targeting this process.

Infection by the Severe Acute Respiratory Syndrome-Coronavirus-2 (SARS-CoV-2) results in the novel coronavirus disease COVID-19, which has posed a serious threat globally. Infection of SARS-CoV-2 during pregnancy is associated with complications like preterm labor and premature rupture of membranes; a proportion of neonates born to the infected mothers are also positive for the virus. During pregnancy, the placental barrier protects the fetus from pathogens and ensures healthy development. However, whether or not SARS-CoV-2 can infect the placenta is unknown. Herein, utilizing single-cell RNA-seq data, we report that the SARS-CoV-2 binding receptor ACE2 and the S protein priming protease TMPRSS2 are co-expressed by a subset of syncytiotrophoblasts (STB) in the first trimester and extra villous trophoblasts (EVT) in the second trimester human placenta. The ACE2- and TMPRSS2-positive (ACE2+TMPRSS2+) placental subsets express mRNA for proteins involved in viral budding and replication. These cells also express mRNA for proteins that interact with SARS-CoV-2 structural and non-structural proteins in the host cells. We also discovered unique signatures of genes in ACE2+TMPRSS2+ STBs and EVTs. The ACE2+TMPRSS2+ STBs are highly differentiated cells and express genes involved mitochondrial metabolism and glucose transport. The second trimester ACE2+TMPRSS2+ EVTs are enriched for markers of endovascular trophoblasts. Further, both these subtypes abundantly expressed genes in Toll like receptor pathway, the second trimester EVTs (but not first trimester STBs) are also enriched for component of the JAK-STAT pathway that drive inflammation. To conclude, herein we uncovered the cellular targets for SARS-CoV-2 entry and show that these cells can potentially drive viremia in the developing human placenta. Our results provide a basic framework towards understanding the paraphernalia involved in SARS-CoV-2 infections in pregnancy.

A striking aspect of COVID-19 is the difference in the outcome of the infection between different countries, and different ethnic groups within one country. We surveyed the literature on SARS-CoV-2 complemented with comparative publications on SARS-CoV and other coronaviruses to capture the current understanding of virus – host interactions including virus subtypes, transmission, zoonotic aspects, and potential host determinants.

Introduction: Coronavirus 2019 (COVID-19) is caused by the severe acute respiratory syndrome coronavirus-2. The majority of patients have at most mild symptoms, however, a significant proportion develops respiratory failure. COVID-19 may also progress beyond the lungs. Coagulopathy and thromboembolism are prevalent in severe COVID-19 and relate to decreased survival. Coagulation is an intricate balance between clot promoting and dissolving processes in which vitamin K plays a well-known role. We hypothesized that vitamin K status is reduced in patients with severe COVID-19. Methods: Vitamin K status was assessed by measuring desphospho-uncarboxylated matrix Gla protein (dp-ucMGP; inversely related to vitamin K status) and the rate of elastin degradation by measuring desmosine. We included 123 patients who were admitted with COVID-19 and 184 controls. Results: Dp-ucMGP levels were significantly elevated in COVID-19 patients (1,673Å}1,584 pmol/L) compared to controls (536±291 pmol/L; p<0.0005). Dp-ucMGP levels were significantly higher in COVID-19 patients with unfavorable outcome compared to those with less severe disease. Furthermore, dp-ucMGP and desmosine levels were significantly associated (r=0.65; p<0.0005). Conclusions: Vitamin K status was reduced in patients with COVID-19 and related to poor prognosis. Also, low vitamin K status seems to be associated with accelerated elastin degradation. An intervention trial is now needed to assess whether vitamin K administration improves outcome in patients with COVID-19.

Starting from December 2019, coronavirus disease 2019 (COVID-19) has emerged as a once-in-a-century pandemic with deadly consequences, which urgently calls for new treatments, cures and supporting apparatuses. Remdesivir was reported by World Health Organization (WHO) as the most promising drug currently available for the treatment of COVID-19. Here, we use molecular dynamics simulations and free energy perturbation methods to study the inhibition mechanism of remdesivir to its target SARS-CoV-2 virus RNA-dependent RNA polymerase (RdRp). In the absence of a crystal structure of the SARS-CoV-2 RdRp, we first construct the homology model of this polymerase based on a previously available structure of SARS-CoV NSP12 RdRp (with a sequence identify of 95.8%). We then build the putative binding mode by aligning the remdesivir + RdRp complex to the ATP bound poliovirus RdRp. The putative binding structure is further optimized with molecular dynamics simulations and demonstrated to be stable, indicating a reasonable binding mode for remdesivir. The relative binding free energy of remdesivir is calculated to be -8.28 ± 0.65 kcal/mol, much stronger than the natural substrate ATP (-4.14 ± 0.89 kcal/mol) which is needed for the polymerization. The ~800-fold improvement in the K_d from remdesivir over ATP indicates an effective replacement of APT in blocking of the RdRp binding pocket. Key residues D618, S549 and R555 are found to be the contributors to the binding affinity of remdesivir. These findings demonstrate that remdesivir can potentially act as a SARS-CoV-2 RNA-chain terminator, effectively stopping its RNA reproduction, with key residues also identified for future lead optimization and/or drug resistance studies.

As a result of the cancer immunotherapy revolution hundreds of clinical trials of the newly approved immunotherapies are now under way to improve responses. Not unexpectedly, the 2018 Nobel Prize in Physiology or Medicine was awarded to James P. Allison and Tasuku Honjo for their development of cancer therapy by blockade of co-inhibitory signals. While success stories of terminal cancer patients achieving complete remissions are accumulating, not enough research has been done into the risks of the new therapies. Since the use of immunotherapy is becoming more common, and is expected to develop into first- and second-line treatments, immunotoxicity and autoimmunity are emerging as the nemesis of immunotherapy. Immune-related adverse events (IrAEs) could affect any tissue, their incidence may reach up to 90% of patients and toxicity is dose-dependent. While the combination of two immune checkpoint inhibitors (ICIs) increased efficacy, the incidence of severe adverse events was also increased. Apparently, ICIs cannot be restricted to the targeted anti-tumor T cell population. The long lasting objective of cancer regression can only be achieved by paying a price: tolerance to healthy self tissues is compromised. In the face of an ipilimumab induced pan-lymphocytic activation, a therapeutic paradigm shift is required. The task is not desperately trying to put the genie back in the bottle by immune suppressive treatments, but instead harnessing the autoimmune forces by an off label low-dose combined anti-CTLA-4 and anti-PD1 antibody blockade, which is supplemented with conventional interleukin-2 stimulation and hyperthermia. The proof-of-principle of the low-dose-combination therapy was demonstrated in a heavily pre-treated triple negative breast cancer (TNBC) patient with far advanced pulmonary metastases and severe shortness of breath, who had exhausted all conventional treatment. Her pulmonary metastases went into complete remission with transient WHO I-II diarrhea and skin rash. She lived for 27 months after starting the low-dose-combination therapy. She had recurrence as a sternal mass and pleural metastases up to 3 cm. Since the low-dose-combination protocol consists only of approved drugs and treatments, this exceptional response should instigate further research efforts.

G protein-coupled receptors (GPCRs, also called seven-transmembrane or heptahelical receptors) are a superfamily of cell surface receptor proteins that bind to many extracellular ligands and transmit signals to an intracellular guanine nucleotide-binding protein (G protein). When a ligand binds, the receptor activates the attached G-protein by causing the exchange of Guanosine-5'-triphosphate (GTP) for guanosine diphosphate (GDP). They play a major role in many physiological functions as well as in the pathology of many diseases including cancer progression and metastasis. Only a few GPCR members have been exploited as targets for developing drugs with therapeutic benefit in cancer. Present review deals with the Prostaglandin E receptor EP4, a member of the EP family of GPCR, as a promising newer therapeutic target for treating breast cancer. We show that aberrant over-expression of cyclooxygenase (COX)-2, an inflammation-associated enzyme, occurring in 40-50% of breast cancer patients leads to tumor progression and metastasis due to multiple cellular events resulting from an increased prostaglandin (PG) E2 production in the tumor milieu. They include inactivation of host anti-tumor immune (NK and T) cells, increased immuno-suppressor function of tumor-associated macrophages, promotion of tumor cell migration, invasiveness and tumor-associated angiogenesis (due to upregulation of VEGF-A), lymphangiogenesis (due to upregulation of VEGF-C/D) and a stimulation of stem-like cell (SLC) phenotype in cancer cells. All these events were primarily mediated by activation of the PGE receptor EP4 on tumor or host cells. We show that selective EP4 antagonists (EP4A) could mitigate all these events tested with cells in vitro as well as in vivo in syngeneic COX-2 expressing mammary cancer bearing mice or immune-deficient mice bearing COX-2 over-expressing human breast cancer xenografts. We suggest that EP4A can avoid thrombo-embolic side effects of long term use of COX-2 inhibitors by sparing cardio-protective roles of PGI2 via IP receptor activation or PGE2 via EP3 receptor activation. Furthermore, we identified two COX-2/EP4 induced oncogenic and SLC-stimulating microRNAs - miR526b and miR655, one of which (miR655) appears to be a potential blood biomarker in breast cancer patients, for monitoring SLC-ablative therapies such as with EP4A. We suggest that EP4A will likely produce the highest benefit in aggressive breast cancers such as COX-2 expressing triple-negative breast cancers, when combined with other newer agents such as PD-1 or PD-L1 inhibitors.

According to the risk investigations of being involved in an accident, alcohol-impaired driving is one of the major causes of motor-vehicles accidents. Preventing highly intoxicated persons from driving would potentially save many lives. This paper proposes a lightweight in-vehicle alcohol detection that processes the data generated from 6-alcohol sensors (MQ-3 Alcohol Sensors) using an optimizable shallow neural network (O-SNN). The experimental evaluation results exhibit a high-performance detection system scoring a 99.8% of detection accuracy with a very short inferencing delay of 2.22 µ seconds. Hence, the proposed model can be efficiently deployed and used to discover in-vehicle alcohol with high accuracy and low inference overhead as a part of the driver alcohol detection system for safety (DADSS) system aiming at massive deployment of alcohol sensing systems that could potentially save thousands of lives annually.

Cadmium (Cd) is a heavy metal that suppresses plant growth; however, application of endophytic bacteria can increase resistance of plants against Cd, as well as improve plant growth. Two bacterial endophytic strains were isolated from Solanum nigrum and were identified as Serratia sp. AI001 and Enterobacter sp. AI002 by 16S DNA sequencing. Strains AI001 and AI002, tolerated up to 25 mg/mL Cd in broth culture and showed phosphate solubilization potential in Pikovskaya agar medium. AI001 and AI002 produced indole-3-acetic acid, which was confirmed by gas spectrometry-mass chromatography. Brassica plants stressed with 0, 5, 15, and 25 mg/L Cd showed significant decrease in plant growth, chlorophyll content and biomass, and significant increase in Cd dose-dependent electrolyte leakage. Inoculation of strain AI001 or AI002 significantly enhanced the plant growth attributes of shoot length, root length, chlorophyll content, and biomass as compared to those in uninoculated plants. Reduced glutathione contents in plants stressed with different concentrations of Cd also increased with inoculation of AI001 and AI002. The reason of Cd resistance enhancement in plants by inocula could be due to their greater plant growth promoting activities as well as their antioxidative response.

Accurate calculation of non-covalent interaction energies in nucleotides is crucial for understanding the driving forces governing nucleic acid structures and functions, as well as developing advanced molecular mechanics forcefields or machine learning potentials tailored to nucleic acids. Here, we dissect the nucleotides’ structure into three main constituents: nucleobases (A, G, C, T, and U), sugar moieties (ribose and deoxyribose), and phosphate group. The interactions among these fragments and between fragment and water were analyzed. Different quantum mechanical methods were compared for their accuracy in captuing the interaction energy. The non-covalent interaction energy was decomposed into electrostatics, exchange-repulsion, dispersion, and induction using two ab-initio methods: Symmetry-Adapted Perturbation Theory (SAPT) and Absolutely Localized Molecular Orbitals (ALMO). These caculations provide the benchmark for different QM methods while providing valuable understanding of the roles of various interamolecular forces in hydrogen bonding and aromatic stacking.

Hip joint surgeries, including total hip replacement or resurfacing, have increased tremendously in the last decades. Number of patients of all ages, replace their hip, due to severe injuries or trauma problems, so as to have a better life. According to these factors, new material and processes in implants manufacturing are imported to medicine, through research programs, every year. In the scope of one of these programs, that has to do with ceramic coatings on metallic resurfacing implants, a new 3axis Hip simulator was designed and manufactured in the Laboratory of Manufacturing Technology of the National Technical University of Athens. The scope of this paper is to present the main parts, materials and process used to manufacture the simulator as well as the way the simulator is working and how its movement in 3axis is accomplished. Furthermore, the evaluation of the machine and its use to examine resurfacing implants is presented.

This article presents an experimental approach to fatigue testing of cableway gondolas, carried out in accordance with the EN 13796-3 standard. Due to the limitations of the aforementioned regulations and the lack of clarity in their content, when designing and conducting fatigue tests of gondolas, there is a need to find solutions that meet the normative requirements, while ensuring the cost-effectiveness of the tests. The work presents the method of loading, receiving the degrees of freedom, the methodology of gondola strength verification, and additional suggestions allowing for the satisfactory preparation of a plan of fatigue tests and their implementation. The paper shows problems and ways to solve it, what may occur during cableway gondolas fatigue test design. The research object is a 6-seater gondola designed by TRANSSYSTEM S.A. with its registered office in Wola Dalsza (Poland).

We previously found increases in uncoupling protein (Ucp)-1 transcription in brown adipose tissue (BAT) of mice following a single oral dose of flavan 3-ols (FL), a fraction of catechins and procyanidins. It was confirmed that these changes were totally reduced by co-treatment of adrenaline blockers. According to these previous results, FL possibly activates sympathetic nervous system (SNS). In this study, we confirmed the marked increase in urinary catecholamine (CA) s projecting SNS activity following a single dose of 50 mg/kg FL. In addition, we examined the impact of the repeated administration of 50 mg/kg FL for 14 days on adipose tissues in mice. In BAT, FL tended to increase the level of Ucp-1 along with thermogenic transcriptome factors, such as peroxisome proliferator-activated receptor γ coactivator (PGC)-1α and PR domain-containing (PRDM)1. Transcription of browning markers, such as CD137 and transmembrane protein (TMEM) 26 in addition to PGC-1α were increased in epididymal adipose (eWAT) by FL. A multilocular morphology with cell size reduction was shown in the inguinal adipose (iWAT), together with increasing the level of Ucp-1 following administration of FL. These results suggest that FL produces browning in adipose through activation of the SNS.

Image fusion is a useful tool for producing a high-resolution multispectral image to be used for land use and land cover mapping. In this study, we use nine pansharpening algorithms namely Color Normalized (CN), Gram-Schmidt (GS), Hyperspherical Color Space (HCS), High Pass Filter (HPF), Nearest-Neighbor Diffusion (NND), Principal Component Analysis (PCA), Resolution Merge (RM), Stationary Wavelet Transform (SWT), and Wavelet Resolution Merge (WRM) to fusion Worldview-3 multispectral Bands and panchromatic band. In spectral and spatial fidelity, several image quality metrics are used to evaluate the performance of pansharpening algorithms. The SWT and PCA algorithms showed better results compared to other pansharpening algorithms while GS and CN algorithms showed the worst results for the original image fusion. The effect of fusion on each band was separately investigated and according to the calculations, we found that the CoastalBlue band and the Blue band showed the best result and the NIR-1 band and NIR-2 band show the worst result for the original image fusion. In the end, we conclude that the choice of fusion method depends on the requirement of remote sensing application.

Bacterial indole-3-acetic acid (IAA), an effector molecule in microbial physiology, plays an important role in plant growth-promotion. Here, we comprehensively analyzed about 7282 prokaryotic genomes representing diverse bacterial phyla, combined with root-associated metagenomic data to unravel the distribution of tryptophan-dependent IAA synthesis pathways and to quantify the IAA synthesis-related genes in the plant root environments. We found that 82.2% of the analyzed bacterial genomes were potentially capable of synthesizing IAA from tryptophan (Trp) or intermediates. Interestingly, several phylogenetically diverse bacteria showed a preferential tendency to utilize different pathways and tryptamine and indole-3-pyruvate pathways are most prevalent in bacteria. About 45.3% of the studied genomes displayed multiple coexisting pathways, constituting complex IAA synthesis systems. Furthermore, root-associated metagenomic analyses revealed that rhizobacteria mainly synthesize IAA via IAM and tryptamine (TMP) pathways and might possess stronger IAA synthesis abilities than bacteria colonizing other environments. The obtained results refurbished our understanding of bacterial IAA synthesis pathways and provided a faster and less labor-intensive alternative to physiological screening based on genome collections. The better understanding of IAA synthesis among bacterial communities could maximize the utilization of bacterial IAA to augment the crop growth and physiological function.

Nowadays, network simulators are very useful to model a communications system. In this technical note we will focus in the creation of a new error model in NS-3 network simulator. This note describes the main steps to create or modify an Wi-Fi error model in this network simulator. In our case, we have created a new error model to included the approach of [1] to compute PER (Packet Error Rate) for vehicular environments.

We show that given a Lie superalgebra and an element of its dual space one can construct the 3-Lie superalgebra. We apply this approach to Lie superalgebra of (m,n)-block matrices taking supertrace of a matrix as the element of dual space. Then we also apply this approach to commutative superalgebra and the Lie superalgebra of its derivations to construct 3-Lie superalgebra. The graded Lie brackets are constructed by means of a derivation and involution of commutative superalgebra, and we use them to construct 3-Lie superalgebras.

Rett syndrome (RTT), a neurodevelopmental disorder, is mainly caused by mutations in methyl CpG-binding protein 2 (MECP2), which alter the functions of domains to either bind to methylated DNA or interact with a transcriptional co-repressor complex. It has been established that alterations in cyclin-dependent kinase-like 5 (CDKL5) or forkhead box protein G1 (FOXG1) correspond to distinct neurodevelopmental disorders, given that a series of studies have indicated that RTT is also caused by alterations in either one of these genes. We tried to elucidate RTT through evolution and structure assessment of MeCP2, CDKL5, and FOXG1, by focusing on their binding partners and disordered structures. Here, we provide insight into the similarities of the FOXG1 and MECP2 binding partners evolution and function. On the other hand, we suggest that CDKL5 could be a potential candidate for a classical RTT treatment, particularly based on its disordered structure that spans after the catalytic domain to the C-terminus, which shows abundant linear motifs that can bind to molecules with divergent structures of similar affinity. Additionally, we provide insight into the relationship between disordered structure and disease.

The enzyme-linked immunosorbent assay (ELISA) coupled with surface-enhanced Raman spectroscopy (SERS) detection is a growing area of analytical chemistry emerged as a solution to a problem of sensitivity improvement. SERS-based ELISA with horseradish peroxidase as an enzymatic label, o-phenylenediamine (oPD) substrate, and 2,3-diaminophenazine (DAP) enzymatic product was one of the first examples of such systems. Surprisingly, the full potential of this long-known approach has not been revealed yet. The current study addresses a previously neglected problem of SERS detection stage performance. Using silver nanoparticles and model mixtures of oPD and DAP, the effects of pH, concentration of aggregating agent, and particle surface chloride stabilizer were extensively evaluated. At optimal mildly acidic pH of 3, 0.93 to 1 M citrate buffer, and AgNPs stabilized with 20 mM chloride, at least two orders of magnitude advantages in the detection limits of SERS over colorimetry both for DAP and HRP were demonstrated. We suppose that this improved detection system could become a useful tool for the development of SERS-based ELISA protocols.

The article introduces a new solution approach to grid-connected single-stage three-phase PV inverter whereby a dc-link voltage can successfully achieve the desired performance. As a single-stage, the variable output of perturb and observe maximum power point tracking (P&O based-MPPT) is fully utilized as dc-link voltage reference in inverter control scheme. As a result, it is challenging for the dc-link voltage to preserve energy balance by tracking its variable dc-link voltage reference under unpredictable environmental changes. To overcome this challenge, an adaptive reference proportional-integral (ARPI) controller, self-tuning, is designed and implemented to compel the dc-link voltage tracking its voltage reference to be equal as closely as possible; hence, the capability of the dc-link under abnormal events substantially guarantees the best energy balance and transient performance enhancement. To verify the validity of the method, simulation results for multiple events scenarios on 250 KW single-stage grid-connected PV systems show the effectiveness of the ARPI controller compared with PI controller.

Our goal was to determine the cellular immune response (CIR) among a random sample of the Borriana COVID-19 cohort (Spain) to identify its associated factors and their relationship with infection, reinfection and sequelae. We conducted a nested case-control study using a randomly selected sample of 225 individuals age 18 and older, including 36 individual naïve to SARS-CoV-2 infection, and 189 infected patients. We employed flow cytometry-based immunoassays for intracellular cytokine staining, utilizing Wuhan and BA.2 antigens and chemoluminescence microparticle immunoassay for detection SARS-CoV-2 antibodies. Logistic regression models were used. A total of 215 (95.6%) participants exhibited T-cell response (TCR) to at least one antigen. Positive responses of CD4+ and CD8+ T cells were 89.8% and 85.3% respectively. No difference in CIR was found for naïve and infected patients. Patients who experienced sequelae exhibited higher CIR than those without. A positive correlation was observed between TCR and Anti-Spike IgG levels. Factors positive associated with TCR included A-blood group, number of SARS-CoV-2 vaccine doses received, and Anti-N IgM; factors inversely related were the time elapsed since the last vaccine dose or infection, and B-blood group. These findings contribute valuable insights into the nuance immune landscape shaped by SARS-CoV-2 infection and vaccination.

Vaccine-induced immune thrombotic thrombocytopenia (VITT) is a rare but severe adverse event that was first observed during the global vaccination campaign against SARS-CoV-2 infection, specifically in those receiving adenoviral vector-based vaccines for Coronavirus disease 2019 (COVID-19). VITT develops 4 to 42 days post-vaccination and is characterized by the development of platelet-activating anti-platelet factor 4 (PF4) antibodies, leading to thrombocytopenia and thrombosis at unusual sites. The rise in awareness and subsequent prompt recognition of VITT was paramount in reducing mortality. Moreover, as vaccination campaigns around the world continue, a better understanding of VITT not only has important clinical implications but is also crucial for future vaccine development. In this review, we summarize the clinical features, pathophysiology, and incidence rates of VITT as well as highlight other anti-PF4 antibody-mediated disorders of growing clinical significance.

This prospective study provides data on long-term humoral immunogenicity of a heterologous off-label vaccine regimen combining the adenoviral vectored ChAdOx1 nCoV-19 from Astra-Zeneca (ChAd) with the mRNA-1273 vaccine from Moderna (m1273) in comparison to two different homologous mRNA vaccine schedules. Of the 316 COVID-19 naïve adult health care workers (HCW) included to complete a survey on vaccine-associated symptoms (VAS), 197 had received the homologous BNT162b2 mRNA vaccine from Pfizer/BioNTech (BNT/BNT), 76 the homologous m1273/m1273, and 43 the heterologous ChAd/m1273 vaccine regimen. Concentration of antibodies against SARS-CoV-2 spike protein in plasma 5-7 months after the second vaccine dose was higher in the m1273/m1273 and ChAd/m1273 than the BNT/BNT vaccine group. The frequency of systemic VAS after first vaccine dose was 86% after ChAd compared to 35% and 39% after BNT and m1273, respectively (p &lt; 0.0001), and after second vaccine dose highest (89%) in the m1273/m1273 group (p &lt; 0.001). Individuals with systemic VAS achieved higher levels of antibodies irrespective of vaccine regimen. In conclusion, VAS serve as a strong predictor of long-term humoral immune response, and the heterologous ChAd/m1273 vaccine regimen provides an at least equal long-term humoral immune response compared with the standard vaccine regimens used in Denmark.

This study investigates the long-term stability of the Suomi National Polar-orbiting Partnership (S-NPP) Visible Infrared Imaging Radiometer Suite (VIIRS) moderate-resolution Thermal Emissive Bands (M TEBs; M12 – M16) covering a period from February 2012 to August 2020. It also assesses inter-sensor consistency of the VIIRS M TEBs among three satellites-S-NPP, NOAA-20, and NOAA-21 over eight months spanning from March 18 to November 30, 2023. The field of interesting is limited to the ocean surface between 60°S and 60°N, specifically under clear-sky conditions. Taking radiative transfer modeling (RTM) as the transfer reference, we employed the Community Radiative Transfer Model (CRTM) to simulate VIIRS TEB brightness temperature (BTs), incorporating European Centre for Medium-range Weather Forecasts (ECMWF) reanalysis data as inputs. Our results reveal two key findings. Firstly, the reprocessed S-NPP VIIRS TEBs exhibit a robust long-term stability, as demonstrated through analyses of the observation minus background BT differences (O-B ∆BTs) between VIIRS measurements (O) and CRTM simulations (B). The drifts of the O-B BT differences are consistently less than 0.105 K/Decade across all S-NPP VIIRS M TEB bands. Notably, observations from VIIRS M14 and M16 stand out with drifts well within 0.04 K/Decade, reinforcing their exceptional reliability for climate change studies. Secondly, excellent inter-sensor consistency among these three VIIRS instruments is confirmed through the double-difference analysis method (O-O). This method relies on the O-B BT differences obtained from daily data. The mean inter-VIIRS O-O BT differences remain within 0.08 K for all M TEBs, except for M13. Even in the case of M13, the O-O BT differences between NOAA-21 and NOAA-20/S-NPP have values of 0.312 K and 0.234 K, respectively, which are comparable to the 0.2 K difference between some TEBs among VIIRS and MODIS. These disparities are primarily attributed to the significant differences in the Spectral Response Function (SRF) of NOAA-21 compared to NOAA-20 and S-NPP. Our study confirms the RTM-based TEB quality evaluation method’s versatility and effectiveness in assessing long-term sensor stability and inter-sensor consistency. The double-difference approach effectively mitigates uncertainties and biases inherent to CRTM simulations, establishing itself a robust mechanism for assessing inter-sensor consistency. In addition, we’ve observed that, except for M13, M12 always exhibits larger spatial variations of O-O BT differences with greater uncertainties compared to the other M TEBs. The influence of solar contribution through sea surface reflection on the Top of Atmosphere (TOA) radiance measurements during daytime in M12 should not be underestimated.

Introduction: Despite more than one year passed since the first cases of SARS-CoV-2 were reported, there is still no consensus on the definition and clinical management of post-acute-COVID-19. The condition has heterogeneously been named as Chronic COVID syndrome, Post COVID-19 Syndrome, post-acute sequela of SARS-CoV-2 (PASC), and the more familiar long COVID. Method: In order to capture all relevant published studies, we undertook a multi-step search with no language restriction. The following four-step search strategy was utilized: First, a preliminary (limited) search was conducted on January 20, 2021, in Google Scholar and PubMed to identify the appropriate keywords. Then, on January 30, 2021, we adopted a search strategy of electronic databases from Cochrane Library, PsycINFO, PubMed, Embase, Scopus, and Web of sciences, using those keywords. Then, after duplicate removal, we screened all titles, abstracts, and full texts. This resulted in 66 eligible studies. Subsequently, after a forward and backward search of their references and citations an additional 54 publications were found, resulting in a total of 120 publications that formed the basis of the present analysis. The titles, abstracts, and full-texts of non-English articles were translated using Google Translate for further evaluation. We conducted our scoping review based on the PRISMA-ScR Checklist.Results: We found only one randomized clinical trial in our search. Of the 67 original studies, 22 were cohort and 28 were cross-sectional studies totaling 74.6% of the original studies. Of the total of 120 publications, 59 (49.1%) focused on signs and symptoms, 28 (23.3%) were focused on management, and 13 (10.8%) focused on pathophysiology. Ten (9%) publications focused on imaging studies. Ninety-one percent of the original investigations came from high and upper-middle-income countries, highlighting the scarcity of reports originating from low-income and lower-middle-income countries.Conclusion: The predominant symptoms among those with the so-called “Long COVID” were: fatigue, breathlessness, arthralgia, sleep difficulties, and chest pain. Recent reports also point to the risk of long-term sequela with cutaneous, respiratory, cardiovascular, musculoskeletal, mental health, neurologic, and renal involvement in those who survive the acute phase of the illness. The ambiguity and controversies in its definition have impaired proper recognition and management of those requiring additional support following the resolution of the acute phase of this infection. This has resulted in long-standing distress for the patients and their families. Our findings highlight the need for a multidisciplinary approach, support, and rehabilitation for these patients in terms of long-term mental and physical health.

In the case of long-stator linear drive, unlike rotative drives for which speed or position sensors are a single unit attached to the shaft, these sensors extend along the guideway. The position signals transmitted from maglev vehicle can’t meet the need of the real-time propulsion control in the on-ground inverter power substations. In this paper the design of the propulsion inverter control system with a position estimator for driving long-stator synchronous motor in high speed maglev train is proposed. The experiments have been carried out at the 150m long guideway in O-song test track. To investigate the performance of the position estimator, the propulsion control system with and without the position estimator are compared. The result confirms that the proposed strategy can meet the dynamic property need of propulsion inverter control system for driving long-stator linear synchronous motors