A partial least squares (PLS) quantitative chemometric method based on the analysis of the MID-FTIR spectrum of polymer inclusion membranes (PIMs) used for the extraction of Cr(VI) from aqueous media is developed. The system previously optimized considering the variables membrane composition, extraction time, and pH, is characterized in terms of its adsorption isotherm, distribution coefficient, extraction percent and enrichment factor. A Langmuir type adsorption behavior with KL = 21.99 L/mg, qmax = 0.242 mmol/g and 0<RL<1, indicates that metal adsorption is favorable. The characterization of the extraction reaction is performed as well showing an 1:1 Cr(VI):Aliquat 336 ratio, in agreement with solvent extraction data. The principal component analysis (PCA) of the PIMs revels a complex pattern, which is satisfactorily simplified and related to Cr(VI) concentrations through the use of a variable selection method (iPLS) in which bands in the ranges 3451–3500 cm-1 and 3751–3800 cm-1 are chosen. The final PLS model including the 100 wavelengths selected by iPLS and 10 latent variables shows excellent parameter values with RMSEC: 3.73115, RMSECV: 6.82685, Bias: -1.91847e-13, CV Bias: 0.185947, R2 Cal: 0.98145, R2 CV: 0.940902, recovery%: 104.02 ± 4.12 (=0.05), sensitivity%: 0.001547 ppb, γ: 3.8 ppb, γ- 1: 0.6 ppb-1, selectivity: 0.0155, linear range: 5.8–100 ppb, LD: 1.9 ppb, and LQ: 5.8 ppb. The developed PIM sensor is easy to implement as it requires few manipulations and reduced number of chemical compounds in comparison to other similar reported systems.

It is widely reported that the mitochondrial membrane potential, ∆Ψm, is reduced in aging animals. It was recently suggested that the lower ∆Ψm in aged animals modulate mitochondrial bioenergetics and that this effect is a major cause of aging since artificially increased ∆Ψm in C. elegans increased lifespan. Here I review, critically, studies that reported reduction of ∆Ψm in aged animals, including worms, and conclude that many of these observations are best interpreted as evidence that the fraction of depolarized mitochondria is increased in aged cells because of the enhanced activation of the mitochondrial Permeability Transition Pore, mPTP. Activation of the voltage-gated mPTP depolarizes the mitochondria, inhibits oxidative phosphorylation, releases large amounts of calcium and mROS, and depletes cellular NAD+, thus accelerating degenerative diseases and aging. Since the inhibition of mPTP was shown to restore ∆Ψm and retard aging, the reported lifespan extension by artificially generated ∆Ψm in C. elegans is best explained by inhibition of the voltage-gated mPTP. Similarly, the reported activation of the mitochondrial Unfolded Protein Response by reduction of ∆Ψm, and the reported preservation of ∆Ψm in dietary restriction treatment in C. elegans are best explained as a resulting from activation or inhibition of the voltage-gated mPTP, respectively.

Background: Early diagnosis of acute brain injury (ABI) is critical for patients on venoarterial extracorporeal membrane oxygenation (VA-ECMO) to guide anticoagulation strategy; however, neurological assessment in ECMO is often limited by patient sedation. Methods: In this pilot study of adults from June 2018 to May 2019, plasma samples of glial fibrillary acidic protein (GFAP), neurofilament light chain (NFL), and Tau were collected daily after VA-ECMO cannulation and measured using a multiplex platform. Primary outcomes were the occurrence of ABI, assessed clinically, and neurologic outcome, assessed by modified Rankin Scale (mRS). Results: Of 20 consented patients (median age=48.5 years; 55% female), 8 (40%) had ABI and 15 (75%) had unfavorable neurologic outcomes at discharge. 10 (50%) patients were centrally cannulated. The median duration on ECMO was 4.5 days (IQR: 2.5-9.5). Peak GFAP, NFL, and Tau levels were higher in patients with ABI vs. without (AUC = 0.77; 0.85; 0.57, respectively) and in patients with unfavorable vs. favorable neurologic outcomes (AUC = 0.64; 0.59; 0.73, respectively). GFAP elevated first, NFL elevated to the highest degree, and Tau showed limited change regardless of ABI. Conclusion: Plasma biomarkers may facilitate early detection of ABIs in VA-ECMO where neurological exam is limited and assist timely clinical decision-making.

Insufficient oral ridge tissue presents a challenge in the treatment of dental implants. One method to enhance alveolar crest dimensions is guided bone regeneration (GBR); however, existing membranes have certain limitations. To address this issue, we aimed to compare the effectiveness of a resorbable bilayer membrane composed of poly(l-lactic acid) and poly(-caprolactone) （PLACL）with that of a collagen membrane（COL） in a rat GBR model. The rat calvaria was used as an experimental model by placing a plastic cylinder. Forty male Fisher rats underwent surgery, and micro-computed tomography and histomorphometric analyses were performed to assess bone regeneration. The results showed that bone regeneration was similar across all the groups. However, after 24 weeks, the PLACL membrane demonstrated significant resilience, occasional partial degradation, and intermittent air bubble formation. This extended preservation of the barrier effect has great potential to facilitate optimal bone regeneration. In conclusion, this study shows that the PLACL membrane is a promising alternative to GBR. By providing a durable barrier and supporting bone regeneration over an extended period, this resorbable bilayer membrane may address the limitations of the current membranes. Further studies and clinical trials are warranted to validate the efficacy and safety of this drug in humans.

Gold nanoparticles (AuNPs) are promising candidates in various biomedical applications such as sensors, imaging, and cancer therapy. Understanding the influence of AuNPs on lipid membranes is important to assure their safety in the biological environment and to improve their scope in nanomedicine. In this regard, the present study aims to analyze the effects of different concentrations (0.5, 1, and 2 w %) of dodecanethiol functionalized hydrophobic AuNPs on the structure and fluidity of zwitterionic 1-stearoyl-2-oleoyl-sn-glycerol-3-phosphocholine (SOPC) lipid bilayer membranes using Fourier transform infrared (FTIR) spectroscopy and fluorescent spectroscopy. The size of AuNPs was found to be 2.2 ± 1.1 nm using transmission electron microscopy. FTIR results have shown that the AuNPs induced a slight shift in methylene stretching bands, while the band positions of carbonyl and phosphate group stretching were unaffected. Temperature-dependent fluorescent anisotropy measurements have shown that the incorporation of AuNPs up to 2 w % did not affect the lipid order in membranes. Overall, these results indicate that the hydrophobic AuNPs in the studied concentration did not cause any significant alterations in the structure and membrane fluidity, which suggests the suitability of these particles to form liposome-AuNP hybrids for diverse biomedical applications including drug delivery and therapy.

Introduction: Hemostatic dysfunction during extracorporeal membrane oxygenation (ECMO) due to blood-circuit interaction and the consequences of shear stress by flow rates lead to rapid activation of the coagulation cascade and thrombus formation in the ECMO system and blood vessels. In this study, we aimed to identify the incidence and risk factors for cannula-associated arterial thrombosis (CaAT) post-decannulation. Methods: A retrospective study of patients undergoing arterial cannula removal following ECMO. We evaluated the incidence of CaAT and compared clinical characteristics, pre-ECMO severity, and daily hemostasis parameters in patients with and without CaAT. Multivariate analysis revealed the risk factors for CaAT. Results: Forty-seven patients requiring venoarterial ECMO or hybrid methods were recruited to be screened for thrombosis. The median SOFA score was 11 (8-13). CaAT occurred in 29 patients (61.7%), with thrombosis in the superficial femoral artery accounting for 51.7%. Limb ischemia complications in the group with CaAT was 17.2%. In multivariate analysis, an ECMO flow rate of 100 mL/min was determined to be the independent factor for CaAT with an OR of 0.84 (95% CI, 0.73–0.95, p=0.008). Conclusion: In patients successfully weaned from ECMO, the incidence of CaAT was 61.7%. Our study found that a low-flow rate of ECMO was an independent risk factor for CaAT.

A model is proposed that describes the transfer of ions and the process of water dissociation in a system with a bipolar membrane and adjacent diffusion layers. The model considers the transfer of four types of ions: the cation and anion of salt and the products of water dissociation – hydrogen and hydroxyl ions. To describe the process of water dissociation, a model for accelerating the dissociation reaction with the participation of ionogenic groups of the membrane is adopted. The boundary value problem is solved numerically using COMSOL® Multiphysics 5.5 software. An analysis of the results of a numerical experiment shows that, at least in a symmetric electromembrane system, there is a kinetic limitation of the water dissociation process, apparently associated with the occurrence of water recombination reaction at the of the bipolar region. An interpretation of the entropy factor (β) is given as a characteristic length which shows the possibility of an ion that appeared as a result of the water dissociation reaction to be removed from the reaction zone without participating in recombination reactions.

Ion Transport Membrane (ITM) is a well-developed technology for producing O₂ by separating air in its membrane. To decrease energy loss in air separation unit and to increase the overall efficiency of a power generation unit ITM is added with the gasification unit in this model. Ceramic materials are generally used to make ion transport membrane that produces oxygen by conducting oxygen ions at specified temperature. Potential advantages can be gained by integrating ITM technology with power generation units as 99% pure oxygen is produced from ITM. A salient comparison between ITM air separator combined with IGCC and cryogenic air separator combined with IGCC is done in this paper where the total power generation cycle remains same for both cases excluding the air separation units (ITM and cryogenic). Using ITM air separator is more beneficial compared to cryogenic air separation as ITM technology helps to improve IGCC overall efficiency and also reduces plant auxiliaries than that of power generation systems integrated with cryogenic.

The transport of iron(III) from Fe(III)-Mn(II)-HCl mixed solutions through a flat-sheet supported liquid membrane is investigated, being the carrier phase of Cyanex 923 (commercially available phosphine oxide extractant) dissolved in Solvesso 100 (commercially available diluent), as a function of hydrodynamic conditions, concentration of manganese and HCl in the feed phase, and carrier concentration in the membrane phase. A transport model is derived that describes the transport mechanism, consisting of diffusion through a feed aqueous diffusion layer, a fast interfacial chemical reaction, and diffusion of the Fe(III)-Cyanex 923 complex across the membrane phase. The membrane diffusional resistance (Δm) and feed diffusional resistance (Δf) are calculated from the model, and their values are 145 s/cm and 361 s/cm, respectively. It is apparent that the transport of iron(III) is mainly controlled by diffusion through the aqueous feed boundary layer, being the thickness of this layer calculated as 2.9x10-3 cm. Since Mn(II) is not transported through the membrane phase, the present system allows to the purification of this manganese-bearing solutions.

Cesarean Section (CS) is one of the most frequently executed surgical procedures in gynecology and obstetrics. After a cesarean section, surgical site infection (SSI) increases hospital stay, lengthens maternal morbidity, and upsurges treatment costs. The current study determines the prevalence and risk factors for surgical site infection following cesarean section in China. A retrospective study was conducted on 23 cases of pregnant women who underwent cesarean section and incision severe infection and detection from March 2017 to January 2020 at Wuhan Maternal and Child Healthcare Hospital in China as the study group, and 20 cases of uninfected cesarean section during the same period were selected as the control group. Data were compared with the controls based on study variables and the presence of SSI. The mean age was 31±2.6. High fever and blood loss were observed in serous SSI-infected patients. The incidence rate of severe surgical site infection was 0.15 %. SSI was observed to be expected in pregnant women who had premature rupture of membrane before surgery (p < 0.001), who underwent postoperative antibiotic therapy (p < 0.001), and the patients who had gestational diabetes mellitus (p <0.001) and hematoma (p < 0.001) during surgery. Hence, following a cesarean section, surgical site infection is common. This research discovered several modifiable risk factors. SSI is associated with multifactorial rather than a single one. The development and strict implementation of a procedure by all health care practitioners can successfully reduce and prevent infection rates following cesarean section.

Tagetes genus of Composite family consider one of the most favorite floriculture plant. Therefore, of particular interest examine the salt tolerance of this bedding and coloring agent plant. In this research, was report the role of glycinebetaine (GB) in attenuating the adverse impacts of salt stress in African marigold plant, along with their anti-oxidative capacities and biochemical attributes. The salt stressed African marigold (100 and 150 mM NaCl) was treated with GB at 200 mM, beside untreated control plants. According to the obtained results, the growth characters were negatively in salt stressed plants but a mitigate impact of GB were observed in this respect. Obviously, the morphological as well as some physiological characters were reduced with salinity treatments while GB treatment reverses these effects. Overall, the alleviate impact of GB on the negative impact of salt stress was enhanced through improving total phenolic and antioxidant enzyme activity. Further, it is concluded that GB concentration induces the activities of antioxidative enzymes which scavenged ROS increased under saline conditions.

Aim: The aim of this study was to estimate the number of nurses who independently care for pa-tients with severe respiratory failure receiving mechanical ventilation (MV) or veno-venous ex-tracorporeal membrane oxygenation (VV-ECMO). Additionally, the study analyzed the actual role of nurses in the treatment of patients with MV and VV-ECMO. Methods: We conducted a cross-sectional study using postal surveys. The study included 725 Japanese intensive care units (ICUs). Descriptive statistics were conducted. Results: Among the 725 ICUs, we obtained 302 re-sponses (41.7%) and analyzed 282 responses. The median number of nurses per bed was 3.25. The median proportion of nurses who independently cared for patients with MV was 60% [IQR: 42.3-77.3]. The median proportion of nurses who independently cared for patients with VV-ECMO was 46.9 (35.7-63.3%) in the ICU experiencing VV-ECMO use. Concerning task-sharing, 33.8% of ICUs and nurses did not facilitate weaning from MV. Nurses always ti-trated sedatives in 44.5% of ICUs. Conclusion: Nurse staffing might be inadequate in all ICUs, es-pecially for severe respiratory failure. The proportion of competent nurses for caring for severe respiratory failure in ICUs should be considered when determining the work force of nurses.

We propose the physical proof-of-concept of a new simple miniature pressure sensor based on the whispering gallery modes (WGMs) optically excited in a dielectric microsphere placed near a flexible reflective membrane, which acts as an ambient pressure sensing element. WGMs excitation is carried out by free-space coupling of optical radiation to a microsphere. The distinctive feature of proposed sensor design is double excitation of optical eigenmodes by forward and backward propagating radiation reflected from a membrane that causes WGMs interference in particle volume. The optical intensity of resulting resonant field established in the microsphere carries information about the exact position of the pressure-loaded reflecting membrane. The sensitivity of the proposed sensor strongly depends on the quality factor of the excited resonant mode, as well as geometrical and mechanical parameters of the flexible membrane. We propose to register not the displacement of the position of the WGM resonance, but the change in its amplitude under the influence of the change in the distance between the sphere and the mirror under the influence of pressure. Important advantages of the proposed sensor are miniature design (linear sensor dimensions depends only on the membrane diameter) and the absence of a mechanical contact of pressure-sensitive element with WGM resonator.

In recent years, electrochemical methods utilizing reactive electrochemical membranes (REM) have been recognized as the most promising technologies for the removal of organic pollutants from water. In this paper, we propose a 1D convection-diffusion-reaction model concerning the transport and oxidation of oxalic acid (OA) and oxygen evolution in the flow-through electrochemical oxidation system with REM. It allows the determination of unknown parameters of the system by treatment of experimental data and predicts the behavior of the electrolysis setup. There is a good agreement in calculated and experimental data at different transmembrane pressures and initial concentrations of OA. The model provides an understanding of the processes occurring in the system and gives the concentration, current density, potential and overpotential distributions in REM. The dispersion coefficient was determined as a fitting parameter and it is in good agreement with literary data for similar REMs. It is shown, that the oxygen evolution reaction plays an important role in the process even under the kinetic limit, and its contribution decreases with increasing total organic carbon flux through the REM.

Ras is the most frequently mutated oncogene and recent drug development efforts have spurred significant new research interest. Here we will review progress toward understanding how Ras functions in nanoscale, proteo-lipid signaling complexes on the plasma membrane, called nanocluster. We will discuss how G-domain reorientation is plausibly linked to Ras-nanoclustering and -dimerization. We will then look at how these mechanistic features could cooperate in the engagement and activation of RAF by Ras. Moreover, we will show how this structural information can be integrated with microscopy data that provide nanoscale resolution in cell biological experiments. Synthesizing the available data, we propose to distinguish between two types of Ras nanoclusters, an active, immobile RAF-dependent type and an inactive/ neutral membrane anchor-dependent. We conclude that it is possible that Ras reorientation enables dynamic Ras dimerization, while the whole Ras/ RAF complex transits into an active state. These transient di/oligomer interfaces of Ras may be amenable to pharmacological intervention. We close by highlighting a number of open questions including, whether all effectors form active nanoclusters and whether there is an isoform specific composition of Ras nanocluster.

Corona virus disease 2019 (COVID-19) is caused by a Severe Acute Respiratory Syndrome-Coronavirus 2 (SARS-CoV-2), which is a positive strand RNA virus. The SARS-CoV-2 genome and its association to SAR-CoV-1 vary from ca. 66% to 96% depending on the type of betacoronavirdeae family members. With several drugs, viz. chloroquine, hydroxychloroquine, ivermectin, artemisinin, remdesivir, azithromycin considered for clinical trials, there has been an inherent need to find distinctive antiviral mechanisms of these drugs. Curcumin, a natural bioactive molecule has been shown to have a therapeutic potential for various diseases, but its effect on COVID-19 has not been explored. In this study, we show the binding potential of curcumin targeted to a variety of SARS-CoV-2 proteins, viz. spike glycoproteins (PDB ID: 6VYB), nucleocapsid phosphoprotein (PDB ID: 6VYO), membrane glycoprotein (PDB ID: 6M17) along with nsp10 (PDB ID: 6W4H) and RNA dependent RNA polymerase (PDB ID: 6M71) structures. Our results indicate that curcumin has high binding affinity towards nucleocapsid and nsp 10 proteins with potential antiviral activity.

Sterilisation and preservation of vesicle formulations are an important consideration for their viable manufacture for industry applications, particular those intended for medicinal use. Here we undertake an initial investigation of the stability of hybrid lipid – block copolymer vesicles to common sterilisation and preservation processes, with particular interest in how the block copolymer component might tune vesicle stability. We investigate two sizes of polybutadiene-block-poly(ethylene oxide) polymers (PBd12-PEO11 and PBd22-PEO14) mixed with the phospholipid POPC considering the encapsulation stability of a fluorescent cargo and the colloidal stability of vesicle size distributions. We find that autoclaving and lyophilisation cause complete loss of encapsulation stability under the conditions studied here. Filtering through 200 nm pores appears to be viable for sterilisation for all vesicle compositions with comparatively low release of encapsulated cargo, even for vesicle size distributions which extend beyond the 200 nm filter pore size. Freeze-thaw of vesicles also shows promise for preservation of hybrid vesicles with high block copolymer content. We discuss the process stability of hybrid vesicles in terms of the complex mechanical interplay between bending resistance, stretching elasticity and lysis strain of these membranes and propose strategies for future work to further enhance the process stability of these vesicle formulations.

The present protocol described extraction of active polyphenol oxidase and peroxidase from a plant rich in phenolics and chlorophylls in the post-harvest browning syndrome of B. myrtifolia. Initially, general optimisation using conventional enzyme extractions was performed. However, along with membrane-bound proteins, chlorophylls and phenols were also released with Triton X (TTX). With a view to obtaining high enzymatic activity, removal of the released chlorophylls and phenols by formation of TTX-114 micelles in the detergent rich phase after high-temperature induced phase separation was tested.

The structure of existing activated models is inherently deficient in reflecting the major role of the membrane filtration. This study developed and proposed a novel model, MASM, for the membrane activated process. The effective filtration size imposed by the membrane module, entrapping larger size particles was adopted as the basis of the proposed model. The model defined a modified COD fractionation, accounting for the captured COD fractions as additional model components and utilizing related mass balance relationships. It was implemented for testing the fate of soluble hydrolysable COD and system performance of super-fast membrane activated sludge based on real data for the characterization and process kinetics of domestic sewage and denim processing effluents. Model evaluation was carried for parallel systems with gravity settling and membrane filtration operated at a sludge age range of 0.5-2.0 d. Results reflected significantly better performance of super-fast membrane activated sludge system for both wastewaters, underlining that it was crucially important to account for the captured COD fractions to provide an accurate evaluation of system behavior and effluent quality. This should also be identified as the major shortcoming of the ASM models for evaluating and predicting system performance of activated sludge configurations with membrane separation.

The SARS-CoV-2 nucleocapsid protein (N protein) is critical to viral replication by undergoing liquid-liquid phase separation to seed the formation of a ribonucleoprotein (RNP) complex to drive viral genomic RNA (gRNA) translation and in also suppressing both stress granules and processing bodies which is postulated to increase uncoated gRNA availability. The N protein can also form biomolecular condensates with a broad range of host endogenous proteins including RNA binding proteins (RBPs). Amongst these RBPs are proteins that are associated with pathological neuronal and glial cytoplasmic inclusions across several adult-onset neurodegenerative disorders, including TAR DNA binding protein 43 kDa (TDP-43) which forms pathological inclusions in over 95% of amyotrophic lateral sclerosis cases. In this study, we demonstrate that the N protein can form biomolecular condensates with TDP-43 and that this is dependant on the N protein C-terminus domain (N-CTD) and the intrinsically disordered C-terminus domain of TDP-43. This process is markedly accelerated in the presence of RNA. In silico modelling suggests that the biomolecular condensate that formed in the presence of RNA is composed of a N protein quadriplex in which the intrinsically disordered TDP-43 C terminus domain is incorporated.

Polymerase I (Pol I) is at the epicenter of ribosomal RNA (rRNA) synthesis. Pol I is a target for treatment of cancer. Given the many cellular commonalities between cancer and neurodegeneration (i.e., different faces of the same coin) it seems rational to consider targeting of Pol I or, more generally, rRNA synthesis for treatment of disorders associated with the death of terminally differentiated neurons. Principally, ribosomes synthesize proteins and, accordingly, Pol I can be considered the starting point for protein synthesis. Given that cellular accumulation of abnormal proteins such as α-synuclein and tau is an essential feature of neurodegenerative disorders such as Parkinson disease and fronto-temporal dementia, reduction of protein production is now considered as a viable target for treatment of these and closely related neurodegenerative disorders. Abnormalities in polymerase I activity and rRNA production may also be associated with nuclear and nucleolar stress, DNA damage, and childhood onset neuronal death as is the case for the UBTF E210K neuroregression syndrome. Moreover, restraining the activity of Pol I may be a viable strategy to slow aging. Before starting down the road of Pol I inhibition for treating non-cancerous disorders of the nervous system, many questions must be answered. First, how much Pol I inhibition can neurons tolerate and for how long? Should inhibition of Pol I be continuous or pulsed? Will cells compensate for Pol I inhibition by upregulating the number of active rDNAs? At present, we have no effective and safe disease modulatory treatments for Alzheimer disease, α-synucleinopathies, or tauopathies, and novel therapeutic targets and approaches must be explored.

Investigations are currently in progress to assess the potential of elevated FABP3 levels as biomarkers for assessing cardiac and cerebral injury post-stroke. Ongoing research endeavors are concentrated on elucidating the specific mechanisms by which FABPs, particularly FABP3, contribute to the complex processes involved in ischemic stroke. This study employs molecular docking techniques within a Virtual Screening framework to examine the interaction between various natural substances and the active site of human heart fatty acid-binding protein (PDB Code 4TKH). Utilizing Pyrx and Autodock Vina, the research aims to pinpoint compounds demonstrating robust binding interactions, characterized by high binding energy scores (kcal/mol) and the formation of multiple chemical bonds. The anticipated outcomes have the potential to yield valuable insights into the molecular interactions influencing human heart fatty acid-binding protein, suggesting possible implications for therapeutic interventions using these natural substances.From the docking and predicted toxicity results, Resistomycin has demonstrated superior characteristics compared to Morusin.

A defining feature of a productive infection is the co-opting of host cell resources for viral replication. Despite their repertoire of molecular functions, viruses subvert host defenses to take control of cellular factors such as RNA binding proteins (RBPs). RBPs are involved in virtually all steps of mRNA life forming ribonucleoprotein complexes (mRNPs) in a highly ordered and regulated process to control RNA fate and stability in the cell. Thus, the hallmark of this viral takeover is to reshape RNA fate in the cell to modulate host gene expression and evade immune responses. Here we provide an extensive review of work in this area, particularly how the host-viral interplay influences RBP functions to modulate the host cell. Overall, in this review, we highlight the myriad of ways RBPs can regulate RNA stability in either a pro-viral or antiviral manner by gathering novel insights gained from research studies in this field.

The present study investigated the insulin-like growth factors (IGFs) and their receptors and binding proteins among different pig breeds during weaning. Sixty Duroc (DR), Taoyuan black (TB), and Xiangcun black (XB) piglets (20 piglets per breed) were selected at 21 and 24 days of age (three days of post-weaning) to analyze organ indices, plasma concentrations of IGF and IGF-binding proteins (IGFBPs) using ELISA kits, and gene expression of IGF system-related components in different tissues. The plasma IGFBP-3 level in TB piglets was higher (P > 0.05) than in the XB and DR piglets at 21 days of age. At 21 days of age, compared with the DR piglets, the IGF-1 expression was lower (P < 0.05) in the kidney but was higher (P < 0.05) in the spleen of XB and TB piglets. At 24 days of age, the IGF-1 expression was higher (P < 0.05) in the kidney of TB piglets than in the XB and DR piglets, while IGFBP-3 in the stomach and IGFBP-4 in the liver of XB and TB piglets were lower (P < 0.05) compared with the DR piglets. Weaning down-regulated (P < 0.05) the IGF-1 expression in the jejunum, spleen, and liver of piglets, while up-regulated (P < 0.05) IGFBP-3 expression in the stomach, IGFBP-4 in the liver, IGFBP-5 in the ileum, and IGFBP-6 in the jejunum of DR piglets. Spearman’s correlation analysis showed a negative correlation (P < 0.05) between plasma IGFBP-2 and IGFBP-5 and the organ index of piglets. Collectively, there were significant differences in IGF system components among different pig breeds. The IGF system components were altered during weaning, which might be involved in weaning stress to decrease the growth of piglets.

(1) Background: To fight for COVID-19 pandemic, immunity against SARS-CoV-2 should be achieved not only through natural infection but also vaccination. Controversies exist about the effect of COVID-19 vaccination on previously infected persons; (2) Methods: A prospective cohort was undergone to collect sera from unvaccinated survivors and vaccinated persons--with and without COVID-19 pre-infection. The sera were analyzed for the anti-Receptor Binding Domain (RBD) titers by ELISA and for the capacity to neutralize the pseudovirus of the Wuhan-Hu-1 strain by luciferase assays; (3) Results; Neither the antibody titers nor the neutralization capacity was significantly different between the three groups. However, the correlation between the antibody titers and the percentage of viral neutralization derived from sera of unvaccinated survivors was higher than that from vaccinated persons with pre-infection (Spearman correlation coefficient (r) = -0.8558; 95% CI, -0.9259 to -0.7288), p &lt;0.0001 vs -0. 581; 95% CI, -0.7679 to -0.3028; p = 0.0002, respectively), indicating the capacity to neutralize the virus is better among the unvaccinated individuals. (4) Conclusions: Vaccines induced anti-RBD titers as high as the natural infection with lower neutralization capacity, and it did not boost the immunity in pre-infected persons.

Histone deacetylases (HDAC) represent promising epigenetic targets for several diseases including different cancer types. The HDAC inhibitors approved to date are pan-HDAC inhibitors and most show a poor selectivity profile, side effects and especially hydroxamic acid based inhibitors lack good pharmacokinetic profiles. Therefore, the development of isoform-selective non-hydroxamic acid HDAC inhibitors is a highly regarded field in medicinal chemistry. In this study, we analyzed different ligand-based and structure-based drug design techniques to predict the binding mode and inhibitory activity of recently developed alkylhydrazide HDAC inhibitors. Alkylhydrazides have recently attracted more attention as they have shown promising effects in various cancer cell lines. In this work, pharmacophore models and atom-based quantitative structure-activity relationship (QSAR) models were generated and evaluated. The binding mode of the studied compounds was determined using molecular docking as well as molecular dynamics simulations and compared with known crystal structures. Calculated free energies of binding were also considered to generate QSAR models. The models created show a good explanation of in vitro data and were used to develop novel HDAC3 inhibitors.

Climate change and globalization have raised the risk of vector-borne disease (VBD) introduction and spread in various European nations in recent years. In Italy, viruses carried by tropical vectors have been shown to cause viral encephalitis, one of the symptoms of arbovirosis, a spectrum of viral disorders spread by arthropods such as mosquitoes and ticks. Arbovirosis are currently causing alarm and attention, and the World Health Organization (WHO) has released recommendations to adopt essential measures, particularly during the hot season, to restrict the spreading of the infectious agents among breeding stocks. In this scenario, rapid analysis systems are required, because they can quickly provide information on potential virus-host interactions, the evolution of the infection, and the onset of disabling clinical symptoms, or serious illnesses. Such systems include bioinformatics approaches integrated with molecular evaluation. Viruses have co-evolved different strategies to transcribe their own genetic material, by changing the host's transcriptional machinery, even in short periods of time. The introduction of genetic alterations, particularly in RNA viruses, results in a continuous adaptive fight against the host's immune system. We suggest an in silico pipeline method to unravel viral sequences that may interact with host RNA binding proteins (RBPs), which play important roles in RNA metabolism and its several related biological processes. Indeed, viral RNA sequences, able to bind host RBPs may compete with cellular RNAs, altering important metabolic processes. Our findings suggest that the proposed in silico approach, could be a useful and promising tool to investigate the complex and multiform clinical manifestations of viral encephalitis, and possibly identify altered metabolic pathways as targets of pharmacological treatments and innovative therapeutic protocols.

All living organisms require some metal ions for their energy production as well as metabolic and biosynthetic processes. Within cells, metal ions are involved in the formation of adducts interact with metabolites and macromolecules (proteins and nucleic acids). The proteins that require binding to one or more metal ions to be able to carry out their physiological function are called metalloproteins. About one third of all protein structures in the Protein Data Bank involve metalloproteins. Over the past few years there has been a tremendous progress in the number of computational tools and techniques making use of 3D structural information to support the investigation of metalloproteins. This trend has been boosted also by the successful applications of neural networks and deep learning approaches in molecular and structural biology at large. In this review, we discuss recent advances in the development and availability of resources dealing with metalloproteins from a structure-based perspective. We start by addressing tools for the prediction of metal-binding sites (MBSs) using structural information on apo-proteins. Then, we provide an overview of methods for and lessons learned from the structural comparison of MBSs in a fold-independent manner. We then move to describing databases of metalloprotein/MBS structures. Finally, we summarize recent DL applications enhancing the functional interpretation of metalloprotein structures.

Prediction of protein-ligand binding affinities is crucial for computational drug discovery. A number of deep learning approaches have been developed in recent years to improve the accuracy of such affinity prediction. While the predicting power of these systems have advanced to some degrees depending on the dataset used for model training and testing, the effects of the quality and quantity of the underlying data have not been thoroughly examined. In this study, we employed erroneous datasets and data subsets of different sizes, created from one of the largest databases of experimental binding affinities, to train and evaluate a deep learning system based on convolutional neural networks. Our results show that data quality and quantity do have significant impacts on the prediction performance of trained models. Depending on the variations in data quality and quantity, the performance discrepancies could be comparable to or even larger than those observed among different deep learning approaches. In particular, the presence of proteins during model training leads to a dramatic increase in prediction accuracy. This implies that continued accumulation of high-quality affinity data, especially for new protein targets, is indispensable for improving deep learning models to better predict protein-ligand binding affinities.

Thyroid hormones regulate tissue metabolism establishing an energy balance in the cell, in particular by affecting oxidative phosphorylation. Their long-term impact is mainly associated with changes in gene expression, while the short-term effects may differ in mechanism. Our work is devoted to short-term effects of hormones T2, T3, and T4 on mitochondrial cytochrome c oxidase (CcO) mediated by a direct contact with the enzyme. The data obtained indicate the existence of two separate sites of CcO interaction with thyroid hormones differing in location, affinity and specificity to hormone binding. It is shown that T3 and T4 but not T2 inhibit oxidase activity of CcO in solution and on membrane preparations with Кi≈100–200 M. In solution, T3 and T4 compete in a 1:1 ratio with the detergent dodecyl-maltoside for binding to the enzyme. Peroxidase and catalase partial activities of CcO are not sensitive to hormones while electron transfer from heme a to the oxidized binuclear center is affected. We believe that T3 and T4 are ligands of the Bile Acid Binding Site found in the 3D structure of CсO by Ferguson-Miller’s group, and hormone induced inhibition is associated with dysfunction of the K- proton channel. Similar conclusion we made recently with regard to steroid-like compounds. It is found that T2, T3, and T4 inhibit superoxide generation by oxidized CcO in the presence of excess Н2О2. Inhibition is characterized by Ki values of 0.3 – 5 M and apparently affects the formation of О2• at the protein surface. The second binding site for thyroid hormones presumably coincides with the point of tight T2 binding on the Va subunit described in the literature.

The proper regulation of RNA processing is critical for muscle development and the fine-tuning of contractile ability between muscle fiber-types. RNA binding proteins (RBPs) regulate the diverse steps in RNA processing including alternative splicing, which generates fiber-type specific isoforms of structural proteins that confer contractile sarcomeres with distinct biomechanical properties. Alternative splicing is disrupted in muscle diseases such as myotonic dystrophy and dilated cardiomyopathy, and is altered after intense exercise as well as with aging. It is therefore important to understand splicing and RBP function, but currently only a small fraction of the hundreds of annotated RBPs expressed in muscle have been characterized. Here we demonstrate the utility of Drosophila as a genetic model system to investigate basic developmental mechanisms of RBP function in myogenesis. We find that RBPs exhibit dynamic temporal and fiber-type specific expression patterns in mRNA-Seq data and display muscle-specific phenotypes. We performed knockdown with 105 RNAi hairpins targeting 35 RBPs and report associated lethality, flight, myofiber and sarcomere defects, including flight muscle phenotypes for Doa, Rm62, mub, mbl, sbr, and clu. Interestingly, knockdown phenotypes of spliceosome components, as highlighted by phenotypes for A-complex components SF1 and Hrb87F (hnRNPA1), revealed level- and temporal-dependent myofibril defects. We further show that splicing mediated by SF1 and Hrb87F is necessary for Z-disc stability and proper myofibril development, and strong knockdown of either gene results in impaired localization of Kettin to the Z-disc. Our results expand the number of RBPs with a described phenotype in muscle and underscore the diversity in myofibril and transcriptomic phenotypes associated with splicing defects. Drosophila is thus a useful model to gain disease-relevant insight into cellular and molecular phenotypes observed when expression levels of splicing factors, spliceosome components and splicing dynamics are altered.

Bacteria a Microscopic organisms are the most inexhaustible and flexible of microorganisms and constitute a huge division of the whole living earthly biomass, certain microorganisms were found to amass metallic components at a high limit Was Known as Bacterial Bio-sorption Due to their little size, capacity to become under controlled conditions, and their Accommodation to an extensive variety of ecological situations; Potent metal bio-sorbents among microorganisms, at low pH esteems, cell divider ligands are protonated and contend essentially with metals for official. With expanding pH, more ligands, such as amino and carboxyl groups, could be exposed, leading to attraction between these negative charges and the metals, and consequently increment bio-sorption onto the cell surface. Starting with Isolation and identification of heavy metal-resistant bacteria from rock Ore. Studying Factors Affecting Uranium Bio-sorption, Optimization of bacterial growth conditions and optimum for metal uptake by free and immobilized bacterial cells and Desorption ratio of uranium ions adsorbed by Coli. /alginate, All this evidence suggest that functions groups Represented in our study are responsible for metal uptake in our bacterial biomass beside change in peaks position which assigned for it's groups confirm bio-sorption of metal ions from waste due to ions charge interaction comparing with immobilized we found increase in no of binding sites indicate that immobilized bacterial have high efficiency for metal up take which also change in peaks position which assigned for its groups confirm bio-sorption of metal ions from waste due to ions charge interaction, Where the high bio-sorption yield obtained by bacteria, the Uranium & heavy metal bioremediation process expects microorganisms to be joined to a strong surface.

Cells form a bipolar spindle during mitosis to ensure accurate chromosome segregation. Proper spindle architecture is established by a set of kinesin motors and microtubule-associated proteins. In most eukaryotes, kinesin-5 motors are essential for this process, and genetic or chemical inhibition of their activity leads to the emergence of monopolar spindles and cell death. However, these deficiencies can be rescued by simultaneous inactivation of kinesin-14 motors, as they counteract kinesin-5. We conducted detailed genetic analyses in fission yeast to understand the mechanisms driving spindle assembly in the absence of kinesin-5. Here we show that deletion of the nrp1 gene, which encodes a putative RNA-binding protein with unknown function, can rescue temperature sensitivity caused by cut7-22, a fission yeast kinesin-5 mutant. Interestingly, kinesin-14/Klp2 levels on the spindles in the cut7 mutants were significantly reduced by the nrp1 deletion, although the total levels of Klp2 and the stability of spindle microtubules remained unaffected. Moreover, RNA-binding motifs of Nrp1 are essential for its cytoplasmic localization and function. We have also found that a portion of Nrp1 is spatially and functionally sequestered by chaperone-based protein aggregates upon mild heat stress and limits cell division at high temperatures. We propose that Nrp1 might be involved in post-transcriptional regulation through its RNA-binding ability to promote the loading of Klp2 on the spindle microtubules.

Zinc finger proteins (ZFP) play important roles in cellular processes. The DNA binding region of ZFP consists of 3 zinc finger DNA binding domains connected by amino acid linkers, the sequence TGQKP connects ZF1 and ZF2, and TGEKP connects ZF2 with ZF3. Linkers act to tune the zinc finger protein in the right position to bind its DNA target, the type of amino acid residues and length of linkers reflect on ZF1-ZF2-ZF3 interactions and contribute to the search and recognition process of ZF protein to its DNA target. Linker mutations and the affinity of the resulting mutants to specific and nonspecific DNA targets were studied by MD simulations and MM_GB(PB)SA. The affinity of mutants to DNA varied with type and position of amino acid residue. Mutation of K in TGQKP resulted in loss in affinity due to the loss of positive K interaction with phosphates, mutation of G showed loss in affinity to DNA, WT protein and all linker mutants showed loss in affinity to a nonspecific DNA target, this finding confirms previous reports which interpreted this loss in affinity as due to ZF1 having an anchoring role, and ZF3 playing an explorer role in the binding mechanism. The change in ZFP-DNA affinity with linker mutations is discussed in view of protein structure and role of linker residues in binding.

Several animal food allergens assembly into amyloids under gastric-like environments. These aggregated structures provide Gad m 1 with an enhanced IgE interaction due to the amyloid assembly of the epitope regions. However, whether these properties are unique of Gad m 1 or common to other food allergens has not yet been addressed. Using Bos d 5, Bos d 12 and Gal d 2 as food allergen models and Gad m 1 as control, aggregation reactions and the sera of milk, egg and fish allergic patients we have analyzed the IgE interaction of the distinct amyloids. We found that amyloids formed by Bos d 12 and Gal d 2 full-length and truncated chains are recognized by the IgEs of milk and egg allergic patient sera. As with Gad m 1, in most cases amyloid recognition is higher than that of the precursor structure. Bos d 5 was not recognized under any fold by the IgE of the sera studied. These results support that formation of IgE-binding amyloids might be a common feature to animal food allergen.

Emerging paradigms in interferon (IFN) biology suggest a dynamic INF induced interactome that extends through broader Interferon Stimulated Gene (ISG)- induction, which implicates interferon- ISG coordinated cross-talk with mRNA processing, post-translational modification and metabolic processes that underlie pathological (viral, autoimmune and tumor biology) and physiological (stem cell regenerative pathways) processes. INF immune responses can also be triggered by endogenous host-derived molecules that are generated in response to cellular stress or hemostasis imbalance to establish tissue repair and regeneration in first place, however, overactivation or lack of countermeasures can result in host tissue damage. The proteases are integral to viral and tumor pathology, and importantly serine proteases TMPRSS2 and trypsin have been identified as important molecular determinants underlying COVID-19 pathology, and emergence of coronaviruses cultured in vitro, respectively. We propose that pathogen associated proteases can act as novel stress-inducers to facilitate viral- competent immunomodulation. We term it as Protease Induced Transcriptomic/ epi-Transcriptomic Reshaping (PITTR) of host cells to counter cellular stress. We present a novel experimental model and our preliminary findings of trypsin- primed Caco-2 cells (CPT) that result in translational halt comparable to cells grown under serum-starvation conditions (CSS). CPT at escalating trypsin concentration (CPT- EC) induce upregulation of selective proteins that majorly map to ribosomal, RNA transport, and spliceosome ribonucleoproteins (RNPs). The inclusion of proinflammatory IL1-b to CPT (CPT- IL) resulted in global overexpression of proteins comparable to Caco-2 cells cultured in growth-factor rich serum conditions (CFBS), indicating a likely de-repression of trypsin- induced translational halt. Caco-2 cells display abortive interferon proteome under differential trypsin conditions (CPT, CPT-EC and CPT-IL), which is marked by complete lack of INF generation despite induction of intermediate ISGs, suggestive of protease (trypsin)- dependent regulation of INF response. Viruses regulate the proteome of stress granules (SGs) that are induced to cope transient translational halt as a central adaptive response to pathogen induced cellular stress. The integral components of SGs include non-translating mRNA, ribonucleoproteins (RNPs) and RNA binding proteins (RBPs), which together form biological condensates through a biophysical process involving weak electrostatic interactions through intrinsically disordered regions in RBPs resulting in liquid- liquid phase separation. We compared the CPT- EC proteome to the Mammalian Stress Granules Proteome (MSGP) database to explore potential RBPs that could possibly regulate INF response (and could act as potential anti-viral targets). Notably, differentially upregulated RNPs and potential RBPs from ISG family including ADAR and PRKRA, and RNA helicases implicated in viral pathogenesis were found to be upregulated in the CPT- EC proteome further strengthening the role of proteases (trypsin) in regulating INF pathways independent of the pathogen. We propose that the supplementation of viable SARS-CoV-2 viral loads to trypsin- primed host cells could recapitulate an infectious disease model, which may closely phenocopy pathogen- driven inflammation and signaling events. Based on the global downregulation of seven SERPINS (serine protease inhibitors) linked to thromboinflammation in our LCMS profiling data, we support the candidature of serine protease inhibitors for protease mediated viral pathologies. COVID-19 is increasingly linked to coagulopathy and resemblance to Neutrophil Extracellular Trap (NET) related thromboinflammatory features; SERPIN A1AT (alpha 1 antitrypsin) being a potent neutrophil- elastase inhibitor and a negative regulator of coagulation complement pathway may be a promising candidate for establishing hemostasis rebalancing in COVID-19 pathology.

Androgen insensitivity syndrome (AIS) is the most common disorder of sex development in people with karyotype 46,XY. Mutations in AR (androgen receptor) gene are found in most individuals with AIS. Exons 4-8, which encode LBD, were shown to be a mutation hotspot. The aim of this study was the search of mutations in the sequence of exons 6-8 which encode LBD of AR gene in patients with different clinical AIS phenotypes from Ukraine. The investigated patients were 4 women with 46,XY karyotype, SRY-positive and clinical features of AIS (2 – CAIS, 2 – PAIS). Serum levels of T, LH, and FSH were quantified by electrochemiluminescence immunoassay (ECLIA) technology. Cytogenetic studies were performed on peripheral blood lymphocytes with further use of standard protocols of chromosomal analysis (GTG-banding). The presence of SRY sequence was confirmed by FISH with LSI SRY probe. Direct Sanger sequencing of 6-8 exons was performed in patients and family members on the PCR products on the matrix of DNA samples isolated from peripheral blood lymphocytes. Detected SNPs were analysed using gnomAD, VEP, MutationTaster, Human Splicing Finder, NetPhorest 2.1, Group-based Prediction System 5.0, and PhosphoPICK bioinformatical resources. Modelling of mutant proteins based on available 3D models was conducted using the open source software UCSF Chimera 1.14rc. We have detected 3 previously described mutations (missense mutation X:67722905 Т>С (rs9332970) in PAIS patient, missense mutation X:67722943 C>T (rs886041132) in CAIS patient and, samesense mutation X:67723745 C>T (rs137852594) in PAIS patient). We determined these mutations as pathogenic using SIFT, PolyPhen, MutationTaster, Human Splicing Finder. Moreover the synonymous mutation X:67723745 C>T (rs137852594) detected in patient with PAIS was determined as mutation affecting processes of splicing. In our study we have identified novel mutation X:67722884 T>G in CAIS patient and family members. This mutation was predicted as a pathogenic using aforementioned bioinformatical tools. STRUM calculations of the protein stability change caused by single-point mutation showed a destabilization effect of the Ile836Ser substitution ΔΔG=-2.6. Possible aberrant phosphorylation analysis revealed the ability of MAPK family, Akt family, CDK1, CDK7, CDK9, PKC kinases to phosphorylate Ser836. Results concerning the pathogenicity of X:67722905 Т>С (rs9332970), X:67722943 C>T (rs886041132), X:67723745 C>T (rs137852594) mutations detected in patients with AIS from Ukraine obtained using bioinformatical resources SIFT, PolyPhen, MutationTaster, Human Splicing Finder correlate with previously published data concerning weaker binding of androgens in patients with the same mutations. This approves informativity of using such resources for mutation pathogenicity analysis. Analysis of the ortholog proteins, subdomain structure, and aberrant phosphorylation of AR-LBD suggests novel X:67722884 T>G mutation to be pathogenic. Based on analysis of mutant protein modelling followed by assessment of free energy change using STRUM it was predicted that mutant protein binds androgens 460 times worse than wild type.

We remind about the dogma initially established with the nucleic acid double helix, i.e. the DNA structure as the primary source of life. However, we bring into the discussion those additional processes that were crucial to enable life and cell evolution. Studying chemosensory proteins (CSPs) and odor binding proteins (OBPs) of insects, we have found a high level of pinpoint mutations on the RNA and peptide sequences. Many of these mutations are found to be tissue-specific and induce subtle changes in the protein structure, leading to a new theory of cell multifunction and life evolution. Here, attention is given to RNA and peptide mutations in small soluble protein families known for carrying lipids and fatty acids as fuel for moth cells. A new phylogenetic analysis of mutations is presented and provides even more support to the pioneer work, i.e. the finding that mutations in binding proteins have spread through moths and various groups of insects. Then, focus is given to specific mechanisms of mutations that are not random, change α-helical profilings and bring new functions at the protein level. In conclusion, RNA and peptide mutations are not seen as representative of a multitude of diseases, but rather as an alternative way by which protocells developed to acquire multifunction and totipotency. This provides a basis for the theory of RNA/peptide mutations for birth and evolution of life on earth’s crust proposed here.

Human NAD(P)H:quinone oxidoreductase 1 (NQO1) is a multi-functional protein whose alteration is associated with cancer, Parkinson´s and Alzheimer´s diseases. NQO1 displays a remarkable functional chemistry, capable of binding different functional ligands that modulate its activity, stability and interaction with proteins and nucleic acids. Our understanding on this functional chemistry is limited by the difficulty of obtaining structural and dynamic information on many of these states. Herein, we have used hydrogen/deuterium exchange monitored by mass-spectrometry (HDXMS) to investigate the structural dynamics of NQO1 in three ligation states: without ligands (NQO1apo), with FAD (NQO1holo) and with FAD and the inhibitor dicoumarol (NQO1dic). We show that NQO1apo has a minimally stable folded core holding the protein dimer and with FAD and dicoumarol ligand binding sites populating binding non-competent conformations. Binding of FAD significantly decreases protein dynamics and stabilizes the FAD and dicoumarol binding sites as well as the monomer:monomer interface. Dicoumarol binding further stabilizes all three functional sites, a result not previously anticipated by available crystallographic models. Our work provides an experimental perspective into the communication of stability effects through the NQO1 dimer, valuable to understand at the molecular level the effects of disease-associated variants, post-translation modifications and ligand binding cooperativity in NQO1.

Substrate binding proteins (SBP) bind to specific ligands in the periplasmic region and bind to membrane proteins to participate in transport or signal transduction. Typical SBPs consist of two α/β domains and recognize the substrate by hinge motion between two domains. Conversely, short length Rhodothermus marinus SBP (named as RmSBP) exists around the methyl-accepting chemotaxis protein. We previously determined the crystal structure of RmSBP consisting of a single α/β domain, but the substrate recognition mechanism is still unclear. To better understand the short length RmSBP, we performed comparative structure analysis, computational substrate docking, and X-ray crystallographic study. RmSBP shares a high level of similarity in α/β domain with other SBP proteins, but it has a distinct topology in the C-term region. The substrate binding model suggested that conformational change in the peripheral region of RmSBP was required to recognize the substrate. We determined the crystal structures of RmSBP at pH 5.5, 6.0, and 7.5. RmSBP showed structural flexibility of the β1-α2 loop, β5-β6 loop, and extended C-term domain based on the electron density map and temperature B-factor analysis. These results provide information that will further the understanding of the function of the short length SBP.

We present simple relations for nuclear stability and nuclear binding energy with respect to three gravitational constants associated with electroweak, strong and electromagnetic interactions.

Echinococcus granulosus is a harmful cestode parasite which could cause Cystic Echinococcosis in humans, various livestock species and wild animals. Calmodulin (CaM), a Ca²⁺ sensor protein, is widely expressed in eukaryotes and mediates a variety of cellular signaling activities. In our study, the CaM in Echinococcus granulosus (rEgCaM) was successfully cloned and the molecular and biochemical characterizations of rEgCaM were identified. The results showed that rEgCaM was a highly conserved calcium-binding protein, consisting of 149 amino acids. Immunoblot analysis revealed that rEgCaM could be identified using E. granulosus infected sheep serum. The usage of rEgCaM as antigen was evaluated by indirect ELISA which exhibited a high sensitivity of 90.3% but low specificity (47.1%). rEgCaM was mainly located in the tegument tissues and parenchymal region of protoscoleces, the tegument and inner body of adult worm and predominantly expressed in the germinal layer. The mRNA expression of rEgCaM in PSCs were gradually decreased with the increase death of PSCs. In electrophoretic mobility tests and ANS assays, rEgCaM showed a typical calcium-binding protein characteristics. This is the first report on CaM from E. granulosus and rEgCaM is considered to be involved in some important biological function of E. granulosus as a calcium-binding protein.

Hydrogen is undoubtedly one of the most promising alternatives for generating energy with low environmental impact. However, most hydrogen produced today is derived from fossil fuels, which negatively impacts the environment. In this context, biomass conversion technologies emerge as a sustainable and environmentally friendly alternative to conventional fossil-based processes for hydrogen production. The main objective of this study is to underscore the potential of biomass-derived hydrogen, as one of the key sustainable energy solutions. This work reviews diverse biological and thermochemical pathways for biomass-derived hydrogen production, noting challenges in technology and feedstock diversity. Biomass offers local availability and economic benefits, potentially yielding negative emissions. Biological methods like bio-photolysis and fermentation promise low-energy, waste-recycling solutions despite operational constraints. Thermochemical processes, influenced by biomass type and energy content, favor economies of scale and conventional gasification for economic viability. Hydrothermal gasification shows promise for high-moisture feedstocks. Overall, while thermochemical processes suit centralized large-scale hydrogen production, biological pathways offer decentralized options, necessitating continued innovation for integration into future energy strategies.

The per capita availability of freshwater resources on a global scale is gradually decreasing due to population growth, rapid urbanization, industrialization, and modern lifestyles. In this situation, wastewater management becomes a major concern. Conventional treatment processes used to treat wastewater discharges are not adequate for the advanced removal of pollutants, especially refractory organic pollutants, which are mainly organic compounds that are not easily biodegradable in the environment. The use of photocatalytic membrane reactors (PMRs) for tertiary wastewater treatment has attracted much interest in recent periods, and various configurations have been investigated. The performance of a PMR using an iron doped titanium photo catalyst and Polysulfone-based polymeric membrane for municipal wastewater treatment was evaluated under natural and simulated solar light. Obtained results proved that solar driven PMRs can remove organic loading (COD) with high efficiencies and may represent a suitable alternative for the tertiary treatment step of municipal wastewater.

The Self-Forming Dynamic Membrane BioReactor (SFD MBR) is a cost-effective alternative to conventional MBR, where the synthetic membrane is replaced by the “cake layer”, an accumulation of the biological suspension over a surface of inert low-cost support, caused by a suction force. Under optimized conditions, the cake layer reveals easy to remove and quick to form again, resulting a “dynamic membrane”. The permeate of SFD MBR has chemo-physical characteristics comparable to those of conventional MBR. In this paper, two nylon meshes with a pore-size of 20 and 50 µm respectively were tested in a bench scale SFD MBR where a periodic air mass load (AML) was supplied tangential to the filtration surface to maintain filtration effectiveness. The SFD MBR equipped with the 20 µm nylon mesh coupled to 5 min of AML every 4 hours showed the best performance both ensuring a permeate with turbidity values always below 3 NTU and revealing no critical fouling. A benchmark test, conducted in the same experimental time, with identical operating conditions, and the only difference of a suction break (relaxation) instead of the AML. This latter test produced a permeate of very good quality, but it needed frequent mesh cleanings, showing that a periodic AML coupled with the use of a 20 µm mesh can be a good strategy for long term operation of SFD MBR.

The presented work is aimed at studying the gas transport characteristics of polymeric hollow-fibre gas separation membranes. Such materials as: polysulfone (PSF), polyphenylene oxide (PFO), polyetherimide (PEI), polyetherimide with polyimide (PEI+PI) were studied on the example of air mixture separation. The values of the permeances of pure gases O2 and N2 and the mixed permeances of oxygen and nitrogen during air separation were obtained. Mathematical models of the gas separation process built on the basis of these values show significant discrepancies. To obtain a gas mixture with 95 mol.% nitrogen from air, taking into account the mixture permeance, 15.8% more PSF membrane area is required than taking into account the permeance of pure gases. For a PPO membrane this value is 13.9%, for PEI 19.8% less area is required, and for PEI+PI 15.9% less. In the design of industrial or semi-industrial membrane installations, such discrepancies can lead to significant errors, including technical and economic ones.

Membrane processes, such as microfiltration, ultrafiltration, and nanofiltration are increasingly used for various applications in both upstream and downstream processing. Membrane-based processes play a critical role in the field of separation/purification of biotechnological products, including protein production/purification. The possibility of using membranes to separate peptides from a chicken byproduct hydrolysate and the effect of the performed downstream processing on the DPP-IV inhibitory activity of MDCR (mechanical deboning chicken residue) has been investigated. The chicken byproduct hydrolysate was prepared by enzymatic hydrolysis followed by MF, UF, NF, and RO separation. The LC-OCD analysis confirmed that NF and RO would retain the bioactive peptides in the concentrate in comparison to MF and UF. Bioactivity was correlated with molecular weight distribution profiles and average molecular weights. Permeates after ultrafiltration showed an IC50 value of 0.75 mg/mL, comparable to other potent DPP-IV inhibitors derived from various food sources, and significantly more potent compared to the microfiltration sample, which showed an IC50 value of 1.04 mg/mL. The average molecular weight of the permeates calculated from the SEC chromatograms was 883 g/mol for UF and 1437 g/mol for MF. Of the four membranes studied, the UF membrane showed the best separation properties with respect to maximizing the yield and up-concentration of the bioactive peptides. Overall, UF was demonstrated to be a feasible technology for the removal of the undesired high molecular weight substances and up-concentration of small molecular weight bioactive peptides from chicken byproduct hydrolysate.

The increase in fungal infections, accompanied by adverse effects and acquired resistance associated with the use of antifungal agents used for their clinical management, have facilitated the search for new substances with antifungal properties. Naphthoquinones have been investigated due to their multiple biological activities, including their significant antifungal potential. This study aimed at evaluating the antifungal potential of naphthoquinones against opportunistic fungi and dermatophytes and to assess the impact of a selected naphthoquinone on the formation of the cell wall, ergosterol membrane, and cellular membrane of Candida albicans ATCC 60193. Additionally, cytotoxicity in the MRC-(Medical Research Council-)5 cell lineage, Artemia salina, and tomato as well as arugula seeds was evaluated. The antifungal activity of four naphthoquinones was assessed using well-characterized fungal strains, the minimum inhibitory concentration (MIC) was determined applying the microdilution assay technique. Antifungal activity of the assessed naphthoquinones could be confirmed, particularly for 2,3-DBNQ (2,3-dibromo-1,4-naphthoquinone), which showed prominent antifungal activity (MIC of &lt;1.56 - 6.25 µg/mL) in all chosen test settings. However, its toxicity in MRC-5 cells (IC50 = 15.44 µM), a recorded 100% mortality in A. salina at a concentration of 50 µg/mL, as well as inhibition of 94.8% of the tomato seeds at a concentration of 400 µg/mL and inhibition of 64.1% of arugula seeds at a concentration of 200 µg/mL may limit hypothetical therapeutic applications. It was demonstrated that the likely mechanism of action of 2,3-DBNQ involves interfering with fungal membrane permeability, leading to increased leakage of nucleotides. This study adds to available knowledge on antifungal effects of naphthoquinones, especially of 2,3-DBNQ, against opportunistic yeasts and dermatophytes. However, the observed cytotoxicity in the MRC-5 cell lineage, A. salina, as well as tomato and arugula seeds highlights a need for further research to optimize the selectivity and safety profile of naphthoquinones like 2,3-DBNQ before potential clinical use may be assessed.

(1) Background: The Gárdos channel (KCNN4) and Piezo1 are the best-known ion channels in the red blood cell (RBC) membrane. Nevertheless, the quantitative electrophysiological behavior of RBCs and its heterogeneity are still not completely understood.; (2) Methods: Here we use state-of-the-art biochemical methods to probe for the abundance of the channels in RBCs. Furthermore, we utilize automated patch-clamp, based on planar chips, to compare the activity of the two channels in reticulocytes and mature RBCs. Besides this characterization, we performed membrane potential measurements to demonstrate the effect of channel activity and interplay on the RBC properties.; (3) Results: Both, Gárdos channel and Piezo1, albeit their average copy number of activatable channels per cell is in the single digit range, can be detected by transcriptome analysis of reticulocytes. Proteomics analysis of RBCs could only detect Piezo1 but not the Gárdos channel. Furthermore, they can be reliably measured in the whole-cell configuration of the patch-clamp method. While for the Gárdos channel the activity is higher in reticulocytes compared to mature RBCs, for Piezo1 the tendency is the opposite. While the interplay between Piezo1 and Gárdos channel cannot be followed using the patch-clamp measurements, it could be proved based on membrane potential measurements in populations of intact RBCs.; (4) Conclusions: We discuss the Gárdos channel and Piezo1 abundance, interdependencies and interactions in the context of their proposed physiological and pathophysiological functions, which are the passing of small constrictions, e.g., in the spleen, and their active participation in blood clot formation and thrombosis.

Single-particle cryo-electron microscopy (cryo-EM SPA) has recently emerged as an exceptionally well-suited technique for determining the structure of membrane proteins (MPs). Indeed, in the last years, it was observed a huge increase in the number of MPs solved by cryo-EM SPA at a resolution better than 3.0 Å in the Protein Data Bank (PDB). However, sample preparation remains a significant challenge in the field. Here, we evaluated in the MPs solved by cryo-EM SPA deposited in the PDB in the last two years at a resolution below 3.0 Å the most critical parameters for sample preparation: i) the surfactant used for protein extraction from the membrane, ii) the surfactant, amphiphiles, nanodiscs or other molecules present in the vitrification step, iii) the vitrification method employed, and iv) the type of grids used. The aim is not to provide a definitive answer on the optimal sample conditions for cryo-EM SPA of MPs, but rather assess the current trends in the MP structural biology community towards obtaining high-resolution cryo-EM structures.

F-type ATP synthases play a key role in oxidative and photophosphorylation processes producing adenosine triphosphate (ATP) for most biochemical reactions in living organisms. In contrast to the mitochondrial FOF1-ATP synthases those of chloroplasts are known to be mostly monomers with approx. 15% fraction of oligomers interacting presumably non-specifically in a thylakoid membrane. To shed light to the nature of this difference we studied interactions of the chloroplast ATP synthases using small-angle X-ray scattering (SAXS) method. Here, we report evidence of I-shaped dimerization of solubilized FOF1-ATP synthases from spinach chloroplasts at different salinity. The structural data were obtained by SAXS and showed dimerization in response to changes in ionic strength. The best model describing SAXS data was two ATP-synthases connected through F1/F1’ parts, presumably via their δ-subunits, forming dimers with the “I” shape. Such I-shaped dimers might possibly connect the neighboring lamellae in thylakoid stacks assuming that the FOF1 monomers comprising such dimers are embedded in different thylakoid membranes. If this type of dimerization exists in nature, it might be one of the pathways of inhibition of chloroplast FOF1-ATP synthase for preventing of ATP hydrolysis in dark, when salinity in plant chloroplasts is rising. Together with a redox switch inserted into a γ-subunit of chloroplast FOF1 and lateral oligomerization, an I-shaped dimerization might comprise a subtle regulatory process of ATP synthesis and stabilize the structure of thylakoid stacks in chloroplasts.

Zeolitic imidazolate frameworks (ZIFs) have potential for various gas and ion separations due to their well-defined pore structure and relatively easy fabrication process compared to other metal-organic frameworks. As a result, many reports have focused on preparing polycrystalline and continuous ZIF layers on porous supports. In this study, we investigated how humidity and chamber temperature influence the structure of a ZIF-8 layer prepared by the hydrothermal method. We controlled the chamber temperature (ranging from 50 °C to 70 °C) and relative humidity (ranging from 20 % to 100 %) using a thermos-hygrostat chamber. We found that as the chamber temperature increased, ZIF-8 preferentially grew into particles rather than forming a continuous polycrystalline layer. By measuring the temperature of the reacting solution based on chamber humidity, we discovered that the heating rate of the reacting solution varied with humidity, even at the same chamber temperature. At higher humidity, thermal energy transfer was accelerated as water vapor delivered more energy to the reacting solution. Therefore, a continuous ZIF-8 layer could be formed more easily at low humidity ranges (ranging from 20 % to 40 %), while micron ZIF-8 particles were synthesized at a high heating rate. Our findings suggest that controlling the heating rate of the reacting solution is critical to preparing a continuous ZIF-8 layer, particularly for future scale-up of ZIF-8 membranes.

One of the most broadly used models for membrane fouling is the Hermia model, which separates this phenomenon into four blocking mechanisms, each with an associated parameter n. These mechanisms are complete blocking (n=2), intermediate blocking (n=1), standard blocking (n=3/2), and cake formation (n=3/2). The original model, which was obtained through experimental data, is given by an Ordinary Differential Equation (ODE) dependent on n. At the time, this ODE was only solved for these four values of n, which limits the effectiveness of the model when adjusted to experimental data. This paper aims to not only mathematically prove the original Hermia model but also to broaden the scope of this model for any real number n by using the original ODE, the equations of fluid mechanics, and the properties of single and multivariable calculus. The extended Hermia model (EHM) is given by a power law for any n≠2 and is given by an exponential function at n=2. To better test the model, we have performed the model fitting of the EHM and compared its performance to the original four pore-blocking mechanisms in 6 micro- and ultrafiltration examples. In all examples, the EHM performed consistently better than the four original pore-blocking mechanisms. Changes in the blocking mechanisms concerning transmembrane pressure (TMP), crossflow rate (CFR), crossflow velocity (CFV), membrane composition, and pretreatments are also discussed.

Chronic venous insufficiency (CVI) is a lifelong, moribund, and debilitating disease process with tremendous personal and financial costs. At its core, CVI involves blood pooling in the lower extremities secondary to inadequate venous blood return, resulting in venous hypertension and incompetence of the one-way valves in the lower extremity veins. As venous circulation slows, metabolic demands of the cells in the lower extremities increase, leading to stasis dermatitis, infection, cellular death, and venous ulceration. This case study aims to report the efficacy of dehydrated amniotic membrane allograft (DAMA) applications to a chronic right lateral ankle ulcer resulting from chronic venous insufficiency. The patient in this study received DAMA applications weekly for six weeks. Upon examination at the initial application, the wound was wet and macerated due to drainage with significant hemosiderosis and lipodermatosclerosis consistent with a Venous Clinical Severity Score (VCSS) of 2. Upon inspection at the final visit, the wound was closed, with a VCSS of 0. This case study demonstrates that the application of DAMA has the potential to act as an effective barrier to cover and accelerate wound closure time. Future non randomized and randomized controlled trials may further establish standardized protocols for DAMA application in venous ulceration, help create treatment algorithms to predict wound closure endpoints, and encourage innovation that may further accelerate healing time.

This article is a followup to an earlier review which outlined some of the interesting features of the soliton/wave-action potential (AP) model, and noted the need to test its key aspects; including the need to test if its presumed lipid phase transition is actually happening during AP firings in excitable cells. The intent here is to point out the sort of tests, and evidence from them, that might be needed if the soliton/wave-AP model is to be accepted broadly by biologists. Here, after an overview of the modern electrophysiological-AP model and of the soliton/wave-AP model, there are three areas considered. First, possible compositional influences on membrane properties relative to the soliton/wave-AP model are presented. Including questions with regard to the soliton/wave-AP model’s assumption that changes in surface potentials influence the transmembrane potential. Second, some recent work from the good folks who advocate for the soliton/wave-AP model concerning the occurrence of lipid phase transitions in neurons or in extracts from nervous tissues are examined. Here it is noted that there is a need to consider whether these lipid phase transitions happen within normal physiological conditions or not. Third, and finally, the advocates for the soliton/wave-AP model have adopted a thermodynamic/theory-based philosophical approach in their studies. It is argued that this philosophical approach is a radical departure from the philosophical approach used under the scientific method. The features of this new approach, and implications its use, are examined.

Although there is a common physiological notion that the origin of the membrane potential is attributed to transmembrane ion transport, it is theoretically possible to explain its generation by the mechanism of ion adsorption. It was previously suggested that the ion adsorption mechanism led even to the potential formulas which are even identical to either the famous Nernst equation or Goldman-Hodgkin-Katz equation. Our further analysis shown in this paper indicates that the potential formula based on the ion adsorption mechanism leads to one equation which is the function of material surface charge density and the material surface potential. Furthermore, we confirmed that the equation holds in all the different experimental systems we studied. Although we have not succeeded in elucidating why such an equation is established, the equation appears to be the key equation governing the characteristics of the membrane potential regardless of the systems in question.

It is known that ammonium has a higher permeability through anion-exchange and bipolar membranes compared to K+ cation that has the same mobility in water. However, the mechanism of this high permeability is not clear enough. We develop a mathematical model based of the Nernst-Planck and Poisson equations for diffusion of ammonium chloride through an anion-exchange membrane; proton exchange reactions between ammonium, water and ammonia are taken into account. It is assumed that ammonium, chloride and OH− ions can only pass through membrane hydrophilic pores, while ammonia can also dissolve in membrane matrix fragments not containing water and diffuse through these fragments. It is found that due to the Donnan exclusion of H+ ions as coions, the pH in the membrane internal solution increases when approaching the membrane side facing distilled water. Consequently, there is a change in the principal nitrogen-atom carrier in the membrane: in the part close to the side facing the feed NH4Cl solution (pH&lt;8.8), it is the NH4+ cation, and in the part close to distilled water, NH3 molecules. The concentration of NH4+ reaches almost zero at a point close to the middle of the membrane cross-section, which approximately halves the effective thickness of the diffusion layer for the transport of this ion. When NH3 takes over the nitrogen transport, it only needs to pass through the other half of the membrane. Leaving the membrane, it captures an H+ ion from water, and the released OH− goes towards the membrane side facing the feed solution to meet the NH4+ ions. The comparison of the simulation with experiment shows a satisfactory agreement.

Current physiology attributes the mechanism of membrane potential generation to transmembrane ion transport, but ion adsorption could just as well play this fundamental role. The evidence shows that the ion adsorption mechanism accurately reproduces the experimentally measured membrane potential. The Goldman-Hodgkin-Katz equation (GHK eq.) and the Nernst equation (Nernst eq.) are the typical mathematical formulas representing the membrane potential in current physiology. However, the authors were able to show that the potential formulas by ion adsorption mechanism give identical results to GHK eq. and Nernst. eq. Our experimental and theoretical analyses suggest that there is a special relationship between the membrane potential and the membrane surface charge density, and this unique equation inevitably leads to the establishment of a GHK eq and/or a Nernst eq. The authors found that the unique equation is the foundation of thermodynamics “Boltzmann distribution”. Thus, the GHK eq. and the Nernst eq. are simply the natural consequence of thermodynamics from the view of the ion adsorption mechanism.

We report cyclic growth/retraction phenomena observed for saline droplets placed on the cured PDMS membrane with the thickness of 7.8±0.1 µm floating on pure water surface. Osmotic mass transport across the micro-scaled floating PDMS membrane provided the growth of the sessile saline droplets followed by evaporation of the saline droplets. The observed growth/retraction cycle was reversible. The model of the osmotic mass transfer across the cured PDMS membrane is suggested. The model explains semi-quantitatively the time evolution of a droplet.

Pomegranate extract (PG-E) has been reported to exert a protective effect in skin due to its antioxidant activity. Ingredients rich in phenolic compounds are unstable in extract solutions and, therefore, the use of a suitable nanosystem to encapsulate this type of extract could be necessary in different biotechnological applications. Thus, we investigated the capacity of Brassica oleracea L. (cauliflower) inflorescence vesicles (CI-vesicles) to encapsulate PG-E and determined the stability and the antioxidant capacity of the system over time. In addition, the protective effect against UV radiation and heavy metals in HaCaT cells was also tested. The CI-vesicles had an entrapment efficiency around 50% and accelerated stability tests did not show significant changes in the parameters tested. The results for the HaCaT cells show the non-cytotoxicity of the CI-vesicles containing PG-E and their protection against heavy metals (lead acetate and mercuric chloride) and UV-B radiation through a reduction of oxidative stress. The reduction of the percentage of deleted mtDNA (mtDNA4977, “common deletion”) in UV-treated HaCaT cells due to the presence of CI-vesicles containing PG-E indicates the mechanism of protection. Therefore, the effects of CI-vesicles loaded with PG-E against oxidative stress support their utilization as natural cosmeceuticals to protect skin health against external damage from environmental pollution and UV radiation.

By the use of the tertiary amine A327 and 1 M HCl solution as precursors, the ionic liquid A327H+Cl- was generated and used to investigate its performance in the transport of Au(III) form hydrochloric acid medium. The influence of the stirring speed (600-1800 min-1), ionic liquid concentration (1.25-50% v/v) in the membrane phase and gold concentration (0.01-0.15 g/L) in the feed phase on metal transport have been investigated. An equation which included both equilibrium and kinetics parameters was derived, and the membrane diffusional resistance (Δm) and feed phase diffusional resistance (Δf) was estimated as 9.5x106 s/cm and 307 s/cm, respectively. At carrier concentrations in the 5-50% v/v range and gold concentrations in the 0.01-0.15 g/L range, metal transport is controlled by diffusion of metal species through the feed boundary layer, whereas at the lowest carrier concentrations, membrane diffusion is predominant. From the receiving solutions, gold can be recovered as gold nanoparticles.

The chemistry and electrochemistry basic fields have been active since the last two decades of the past century studying how surface modification of electrodes by coating with conductive films enhances their activity and performance. In the light of the development of alternative sustainable ways of energy storage and carbon dioxide conversion by electrochemical processes, these research studies have jumped in the 21st century to more applied fields such as chemical engineering, energy and environmental science and engineering. The huge amount of literature on experimental works dealing with the development of CO2 electroreduction processes addresses electrocatalyst development. Membranes can help understanding and controlling the mass transport limitations of current electrodes and reactors designs. The present bibliometric review addresses the papers published in the 21st century regarding membrane coated electrodes and electrocatalysts to enhance electrochemical reactor performance and viability with a special focus on the urgent issue of carbon dioxide capture and utilization.

The use of bacteriophage is reemerging as a tool for combatting multi-drug resistant bacterial infections. In our previous study, we showed that colistin resistant carbapenem-resistant Klebsiella pneumoniae (ColR-CRKP) is more susceptible to killing by lytic tailed phages, including ФNJS1 specific for nonmucoid K. pneumoniae. Although we demonstrated that alteration on surface charges of ColR-CRKP promotes phage adherence and infection, the receptor for ФNJS1 was still unknown. In current study, we identified O-antigen was involved in the reversible adsorption, and outer membrane protein (OMP) FepA may be served as one of the irreversible receptors for ФNJS1. We firstly found accelerated reversible phage adsorption to ColR-CRKP cells, and that periodate treatment of bacteria inhibited the phage binding, indicating LPS may be involved in phage reversible adsorption. ФNJS1-resistant bacterial mutants screening revealed that mutants in ∆wecG(mTn5) and ∆wecA(mTn5), two genes responsible for LPS biosynthesis, affected phage adsorption capacity and phage infectivity. The loss of wzyE encoding O-antigen polymerase showed no significant difference in phage adsorption but increased phage infectivity, suggesting the long chain length of O-antigen may also be a barrier for bacteriophage infection. Among four OMP mutants including ∆fepA, ∆fhuA, ∆ompA and ∆ompC, only ∆fepA slowed phage lysis rate, suggesting FepA may be as one of irreversible receptors for ФNJS1. The results are helpful to better understand why ColR-CRKP sensitizes phage infection and to combat multi-drug resistant K. pneumoniae infections in the future.

Recent COVID-19 outbreak has come into prominence the pathogenetic mechanisms underlying the Biology and Biochemistry of viral infections. COVID-19 illness is brought about by infection with the severe acute respiratory syndrome coronavirus SARS-CoV-2 [1,2], an enveloped positive single stranded RNA virus (ssRNA+). From a lipidomics viewpoint, there is a variety of mechanisms involving virus infection that encompass virus entry, disturbance of host cell lipid metabolism, and the role played by diverse lipids in regard to the infection effectiveness. All these aspects have currently been tackled separately as independent issues and focusing on the function of proteins. Here we review the role of cholesterol and other lipids in in ssRNA+ and SARS-COV-2 infection.

Within the micro and nano world, tiny membrane-enclosed bits of material are more or less free to move and act as communication tools within cells, between cells, between different tissues and between organisms in global environment. Based on the mechanism of membrane budding and vesiculation that includes all types of cells, in this review, we attempted to present a review on SARS-CoV-2 virus actions in compartments of different scales (cells and their surroundings, tissues, organisms and society). Interactions of the virus with cells on a molecular level, with neural system, endothelium, hematopoietic system, gastrointestinal system and genitourinary system. Transmission route between organisms and between mother and fetus are considered. Also, transmission of virus through contact with materials and with environment, the suggested measures to prevent contamination with the virus and to support the organism against the disease are given.

There are different treatment options in modern dentistry for the replacement of lost dentition. Of these the most upcoming and acceptable treatment option is Dental implants. The common problem usually with immediate implant placement in the anterior region is the post-operative soft tissue contour as a part of the bone modelling during healing. Hurzeler et al in 2010 introduced a new technique called the “socket shield technique”. This technique has been used as an alternative treatment modality for immediate implant placement in the aesthetic zone.This review articles provides a detailed information regarding the clinical concept of Root membrane technique.

The transport of indium(III), from HCl solutions, across a supported liquid membrane in flat-sheet configuration was investigated, being the carrier the ionic liquid HA324H+Cl- (derived from the tertiary amine Hostarex A324 and hydrochloric acid). Different variables affecting the metal transport: hydrodynamic conditions in the source and receiving phases, metal and HCl concentrations in the source phase, and carrier concentration in the membrane phase, were investigated. Also the transport of indium(III) using carriers of various nature: ionic liquids, alcohol, ketone, phosphine oxide and phosphoric ester, was compared. The metal transport was modelled describing the transport mechanism as: diffusion across the source diffusion layer, a fast interfacial chemical reaction, and diffusion of the InCl4--carrier complex through the membrane support. Diffusional parameters for the transport of indium(III), from the experimental data and the model, were estimated.

Membrane materials are most widely applied in construction engineering with small mass and high flexibility, it presents strong geometric nonlinearity in the process of vibration. In the paper, an improved multi-scale perturbation method is used to solve the aeroelastic stability of closed and open membrane roofs for quantify the effect of geometric nonlinearity on the single-mode aeroelastic instability wind speed of membrane roofs. The results show that the critical wind speed values of the two models are small when the geometrical nonlinearity of membrane material is neglected. In addition, under normal wind load, the influence of geometrical nonlinearity of membrane on the aerodynamic stability of roof can be neglected, However, under strong wind load, when the roof deformation reaches 3% of the span, the influence of geometric nonlinearity should be considered and the influence increases with the decrease of transverse and downwind span of membrane roof. The results obtained in this paper have important theoretical reference value for the design the membrane structures.

We have studied on the stress measurement by making use of salivary nitrate, which can be a candidate of stress markers, with ion-selective field-effect transistors (ISFETs). ISFETs are suitable for on-site single-drop analysis of salivary nitrate within 10 seconds. However, when ISFETs are used for salivary nitrate, ISFETs have a problem which is called the initial drift. The initial drift makes it difficult for determination of an accurate nitrate monitoring. Thus, the purpose of this study is to suppress an initial drift and to search for new easy polymer to possess more performance of sensor responses than conventional matrix membrane such as PVC. In this research, we investigated ISFETs using specific matrix membrane for example, KP-13, Pellethane^® and P7281-PU. The initial drift was evaluated from the fluctuation of the response values generated by ISFETs which are immersed in saliva or aqueous solution. As a result, P7281-PU showed its suppression effect for the initial drift in the whole saliva and various solutions. Furthermore, the cause of drift may be H⁺ diffusion, and drift suppression effect of P7281-PU may be affected by urethane bond capturing H⁺ in ion-selective membrane. This result suggests a continuous nitrate monitoring and development of wearable sensors.

Fouling by activated sludge in membrane bioreactor (MBR) processes for wastewater treatment can be reduced using several strategies such as backflushing, relaxation, and chemical cleaning. Some proprietary systems such as Avanti’s RPU-185 Flexidisks MBR use novel circular rotating, flat sheet membranes to assist in limiting this fouling. An attempt has already been made to model this novel rotating fouling process by developing a simulation model based on first principles and traditional fouling mechanisms. In order to directly compare the potential benefits of rotational MBR system, a follow-up study was carried out using Avanti’s newly developed static (non-rotating) Flexidisks MBR system. This new process uses the same proprietary and patented membrane modular arrangement as used in the circular rotational unit, but is configured instead as a static square-shaped unit which is in-line with the more traditional and popular format used for submerged flat sheet MBR systems. During this study, the results from operating the static pilot unit were simulated and modelled using a standard fouling model coupled with a viscosity to mixed liquor relationship model. These results were then compared with those obtained from running the rotating MBR model however with rotational switching functions turned off and rotational parameters set to a static mode. This comparison was done to ascertain whether the basic premise of the developed rotational model was sound in empirical terms when compared to a standard MBR flux model. The study concluded that relatively good agreement was reached between the two types of models, thus vindicating the usage of a complex rotational MBR model. Follow on studies will now compare results from the rotating MBR system using rotational models developed by other researchers to ascertain the effectiveness rotating MBR modelling approach.

Background. A rat model of chronic tympanic membrane perforation was developed to be used in the search of new materials for the sealing of these perforations. Methods. A longitudinal study was carried out in rats subjected to incisional myringotomy followed by the application of mitomycin C alone or with dexamethasone. Rats were checked at days 3, 7, 10, 14 and weekly thereafter until perforation closure, for up to 6 months. Results. The addition of dexamethasone is a key component in order to obtain a chronic opening. Myringotomies treated with saline had a mean healing time of 8.5 days. At 8 weeks, 70.5% of these remained perforated and at 6 months this number fell to 21.4%. Conclusion. This technique is able to maintain more than 70% of tympanic membrane perforations patent for at least 8 weeks. This rat model is adequate for its use in preclinical or translational research.

Drug-target binding is a crucial parameter in drug discovery and design, ensuring drug efficacy and specificity. Semaglutide, a potent GLP-1 receptor agonist, is widely used to treat type 2 diabetes mellitus by regulating blood glucose levels and promoting weight loss. This study introduces a novel approach utilizing the concept of a general intermolecular binding affinity calculator (GIBAC) for designing semaglutide analogues with enhanced binding affinity to GLP-1R. For the first time, a Val27-Arg28 exchange was manually introduced to strengthen the semaglutide-GLP-1R binding affinity. A comprehensive structural and biophysical analysis was conducted to explore the semaglutide-GLP-1R sequence space, leading to the identification of promising analogues. Among these, one semaglutide analogue demonstrated a binding affinity to GLP-1R that is more than two orders of magnitude (113.3 times) higher than native semaglutide, achieving a Kd of 3.0 x 10^-8 M compared to the Kd of 3.4 x 10^-6 M for native semaglutide. This article proposes a promising structural biophysical approach for developing GLP-1 receptor agonists with improved efficacy. The prototype GIBAC, termed semaGIBAC, represents a paradigm shift in precise drug discovery and design, advocating for the construction of a full-scale GIBAC to be prioritized within the drug discovery and design community.

In the domain of drug discovery and design, the acquisition of precise structural and intermolecular Kd data for biological molecules is paramount. However, conventional methods for obtaining such data are often beset by challenges including high costs, time intensiveness, and inherent limitations in scalability and diversity. This article puts forward a high-throughput approach for in silico generation of structural and intermolecular binding affinity (Kd) data, which keeps exploring the uncharted territories of drug discovery & design by harnessing computational methodologies to synthetically generate diverse datasets. Through a meticulously designed workflow encompassing molecular structural modeling, structural biophysics-based calculations of intermolecular binding affinity (Kd), this innovative methodology transcends the constraints of traditional experimentation, offering a cost-effective, scalable, and efficient alternative. By simulating molecular interactions and binding interfaces and predicting binding affinities with reasonable accuracy, this approach not only expedites the drug development process but also enables the exploration of vast molecular space, thereby facilitating the discovery of novel therapeutics beyond conventional drug modality as a form factor. Moreover, the versatility of synthetic data extends beyond virtual screening and lead optimization, encompassing applications such as dataset augmentation, model validation, and benchmarking against experimental data. This article elucidates the conceptual underpinnings, methodological intricacies, validation strategies, and potential ramifications of in silico generated data, heralding a paradigm shift in drug discovery paradigms. By fostering synergy between computational and experimental research domains, this innovative approach promises to accelerate the pace of drug discovery, enhance the robustness of predictive models, and pave the way for transformative advancements in the entire pharmaceutical industry.

The superconductivity of CaC6 as a function of pressure and of abundant Ca isotopes is revisited using DFT calculations on a 2c – double hexagonal superlattice. The introduction of superlattices is motivated by previous synchrotron absorption and Raman spectroscopy results on other superconductors that show evidence of superlattice vibrations at low (THz) frequencies. A 2c superlattice for CaC6 is illustrative of atomic orbital symmetry and periodicity, including bonding and antibonding s-orbital character implied by cosine modulated electronic bands. Inspection of the cosine band reveals that the cosine function has a small (meV) energy difference between bonding and antibonding regions relative to a midpoint non-bonding energy. Fermi surface nesting is apparent in an appropriately folded Fermi surface using a superlattice construct. Nesting relationships identify phonon vectors for conservation of energy and for phase coherency between coupled electrons at opposite sides of the Fermi surface. Detailed analysis of this Fermi surface nesting provides accurate estimates of the superconducting gaps for CaC6 with change in applied pressure. Recognition of superlattices within a rhombohedral or hexagonal representation provides consistent mechanistic insight on superconductivity and electron−phonon coupling in CaC6.

Mitochondria are semiautonomous organelles, which are pivotal for the energy metabolism of eukaryotic cells. These organelles contain their own genetic system (mtDNA, mitogenome) that encodes to some structural RNAs and organellar proteins. The biogenesis and function of mitochondria is tightly regulated by nuclear-encoded protein cofactors. The mtDNAs of land plants are characteristically large, with a complex mode of gene organization and expression, in particularly at the post-transcriptional level. To become functional, the primary organellar transcripts undergo extensive maturation steps, which include endo- and exo-nucleolytic cleavage, RNA-base editing, and both ‘cis’- and ‘trans’-splicing events. These essential processing steps rely on the activities of a large set of nuclear-encoded factors. Among these, the RNA helicases serve as key players in organellar (mt-)RNA metabolism. This review summarizes the important roles played by these factors in regulating the highly dynamic processes of transcription, RNA processing, and translation within the mitochondria of land plants. We further discuss recent advancements in understanding how dysregulation of mitochondrial RNA helicases affects the organellar gene expression, respiratory functions, and hence the growth, development and physiology of land plants.

Background and Objectives: Non-alcoholic fatty liver disease (NAFLD) is highly prevalent world-wide. It progresses from simple steatosis to non-alcoholic steatohepatitis (NASH). Fibrosis is often present during NAFLD progression; however, factors determining which subjects develop NASH or fibrosis are unclear. Insulin-like growth factor binding proteins (IGFBP) is a family of secreted proteins involved in senescence and scarring mainly synthetized in the liver. Here we aimed to study the association of IGFBP and its induced senescence with the progression of NAFLD and liver fibrosis. Materials and Methods: 16 weeks old male C57BL/6 mice weighing 23 ± 3 g were fed either Methionine-Choline Deficient or control diet for 2, 8 or 12 weeks. Blood and liver samples were collected; histological assessment of NAFLD and fibrosis was performed. Fat contents were measured. Cellular senescence was evaluated in the liver. IGFBP levels were assessed in liver and serum. Data was expressed as Mean ± SD and analyzed by one-way ANOVA followed Tukey’s test. Lineal regression models were applied for NAFLD and fibrosis progression. p

mRNA vaccines have attracted widespread research attention with clear advantages in terms of molecular flexibility, rapid development, and potential for personalization. However, current mRNA vaccine platforms have not been optimized for induction of CD4/CD8 T cell responses. In addition, mucosal administration of mRNA based on lipid nanoparticle technology faces challenges in clinical translation. In contrast, adenovirus-based vaccines induce strong T-cell responses and have been approved for intranasal delivery. To leverage the inherent strengths of both the mRNA and adenovirus platforms, we developed a novel modular adenoviral mRNA delivery platform based on Tag/Catcher bioconjugation. Specifically, we engineered adenoviral vectors integrating Tag/Catcher proteins at specific locales on the Ad capsid proteins, allowing us to anchor mRNA to the surface of engineered Ad viruses. In proof-of-concept studies, the Ad-mRNA platform successfully mediated mRNA delivery and could be optimized via the highly flexible modular design of both the Ad-mRNA and protein bioconjugation systems.

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

Demonstrating biosimilarity entails comprehensive analytical evaluations, clinical pharmacolo-gy profiling, and efficacy testing for at least one medical indication in patients. These require-ments are stipulated by the U.S. Biologics Price Competition and Innovation Act (BPCIA). The costliest element—efficacy testing—can be waived if other compliance benchmarks are satisfied, including comparing functional pharmacodynamic (PD) biomarkers, even when they do not di-rectly correlate with clinical outcomes. Most biological drugs, such as monoclonal antibodies (mAbs), lack identifiable PD biomarkers. The FDA has employed various 'omics' technologies to identify potential PD biomarkers, including proteomics, glycomics, transcriptomics, genomics, epigenomics, and metabolomics. Although these efforts provide a robust scientific basis for estab-lishing biosimilarity, they are neither practical nor necessarily superior to existing functional biomarkers, such as receptor binding and mode-of-action outcomes. As we report for the first time, these functional biomarkers can effectively serve as PD indicators for all FDA-licensed bio-logical drugs. We recommend that the FDA consider officially listing these functional biomarkers to expedite and reduce the cost of biosimilar development, thereby increasing the accessibility of biological drugs. PD surrogates, like the receptor binding and pharmacokinetic profiles, are more robust and offer a rational solution to finding PD markers to compare for establishing biosimi-larity.

Objective: Obstructive sleep apnea syndrome (OSAS) is a common sleep disorder that is caused by the reduction or cessation of airflow in the upper airway. Irisin, retinol-binding protein-4 (RBP-4), and adiponectin are the three significant factors in the metabolic process of the human body. The objective of this study was to investigate whether plasma irisin, RBP-4, and adiponectin levels are associated with the severity of OSAS. Methods: According to inclusion and exclusion criteria, 125 patients with OSAS and 46 healthy, gender matched controls were included to the study. The patients were classified according to the apnea hypopnea index (AHI) as 14 mild cases (5<AHI<15), 23 moderate OSAS cases (15<AHI<30) and 88 severe OSAS cases (AHI>30). The plasma irisin, RBP-4 and adiponectin levels were measured and compared between groups. Results: RBP-4 levels were higher in severe OSAS compared to moderate (p<0.05) and mild (p<0.001) OSAS groups, irisin levels were significantly lower compared to moderate (p<0.05) and mild (p<0.001) OSAS groups. There was a negative correlation between irisin and RBP-4 (r=-0.379; p<0.001) and AHI (r=-0.834; p<0.001) and a positive correlation with minimum oxygen saturation (MOS) (r=0.341; p<0.001) in the patient group. In the patient group, there was a negative correlation between adiponectin and BMI (r=-0.682; p<0.001), RBP-4 (r=-0.292; p<0.01) and AHI (r=-0.179; p<0.05) and a positive correlation with MOS (r=0.397; p<0.001). In the patient group, there was a positive correlation between RBP-4 and BMI (r=0.406; p<0.001) and AHI (r=0.473; p<0.001) and a negative correlation with MOS (r=-0.805; p<0.001). As a predictor of OSAS, adiponectin showed the highest specificity (84.8%) and RBP-4 the highest sensitivity (92.0%). Conclusion: The results of the present study demonstrated that the severity of OSAS causes more metabolic problems, including decreased plasma irisin and adiponectin levels and an increased plasma RBP-4 level. As a result, patients with an AHI score greater than thirty should be closely monitored for metabolic and cardiovascular abnormalities.

Changes in epitranscriptome with N6‐methyladenine (m6A) modification could be involved in the development of multiple diseases, which might be a prevalent modification of messenger RNAs (mRNAs) in eukaryotes. The m6A modification might be performed through the action of methyltransferases, demethylases, and methylation-binding proteins. Importantly, the m6A methylation may be associated with various neurological disorders including Alzheimer's disease (AD), Parkinson's disease (PD), depression, aging related diseases, and/or aging itself. In addition, the m6A methylation might functionally regulate the eukaryotic transcriptome by influencing splicing, export, subcellular localization, translation, stability, and decay of mRNAs. Neurodegenerative diseases may possess a wide variety of phenotypes depending on the neurons that degenerate at occasions. Interestingly, increasing number of evidences have indicated that m6A modification could modulate the expression of autophagy-related genes and promote autophagy in neuronal cells. Oxidative stresses such as reactive oxygen species (ROS) could stimulate the m6A RNA methylation, which may be also related to the regulation of autophagy and/or the development of neurodegenerative diseases. Both m6A modification and autophagy could also play critical roles in regulating health condition of neurons. Therefore, a comprehensive understanding of the m6A and autophagy relationship in human diseases may benefit in developing therapeutic strategies in the future. This paper reviews advances in the understanding of the regulatory mechanisms of m6A modification in the occurrence and development of neurodegenerative diseases and/or aging, discussing the possible therapeutic procedures related to mechanisms of m6A RNA methylation and autophagy.

Wheat has a large and diverse repertoire of NLRs involved in disease resistance, with over 1,500 NLRs detected in some studies. These NLR genes occur as singletons or clusters containing copies of NLRs from different phylogenetic clades. The number of NLRs and cluster size can differ drastically among ecotypes and cultivars. Primarily, duplication has led to the evolution and diversification of NLR genes. Among the various mechanisms, whole genome duplication (WGD) is the most intense and leading cause, contributing to the complex evolutionary history and abundant gene set of hexaploid wheat. Tandem duplication or recombination is another major mechanism of NLR gene expansion in wheat. The diversity and divergence of duplicate NLR genes are responsible for the broad-spectrum resistance of most plant species with limited R genes. Understanding the mechanisms underlying the rapid evolution and diversification of wheat NLR genes will help improve disease resistance in crops. The present review focuses on the diversity and divergence of duplicate NLR genes and their contribution to wheat disease resistance. Moreover, we provide an overview of disease resistance-associated gene duplication and the underlying strategies in wheat.

Development of methods and algorithms to predict the effect of mutations on protein stability, protein-protein, and protein-DNA/RNA binding is necessitated by the needs of protein engineering and for understanding the molecular mechanism of disease-causing variants. The vast majority of the leading methods are either methods with adjustable parameters or machine learning algorithms, both requiring a database of experimentally measured folding and binding free energy changes. These databases are collections of experimental data taken from scientific investigations typically aimed at probing the role of particular residue on the above-mentioned thermodynamics characteristics, i.e., the mutations are not introduced at random and do not necessarily represent mutations originating from single nucleotide variant (SNV). Thus, the reported performance of the leading algorithms assessed on these databases or other limited cases, may not be applicable for predicting the effect of SNVs seen in the human population. Indeed, we demonstrate that the SNVs and non-SNVs are not equally presented in the corresponding databases and the distribution of the free energy changes are not the same. Furthermore, the Pearson correlation coefficients (PCCs) obtained on cases involving SNVs are less impressive than for non-SNVs, indicating that caution should be used in applying them to reveal the effect of human SNVs. All methods are found to underestimate the energy changes by roughly a factor of 2.

The substrate N1, N3, N5 -tris(2-hydroxyphenyl)benzene-1,3,5-tricarboxamide (Sensor A) was prepared in the reaction of 1,3,5-benzenetricarboxylic acid (trimesic acid) and o-aminophenol in ethanol. The prepared organic sensor fulfills the chemiluminescent requirements including luminophore, spacer, and suitable binding receptor that distress the probe's luminescent features, providing selective and sensitive detection of mercury and iron ions in aqueous solutions. The sensor selectively detects mercury and iron ions in a water matrix containing various metal ions including sodium, calcium, magnesium, zinc, and nickel. Strong and immediate binding was observed between mercury ions and the substrate at pH 7.0 with a binding affinity toward Hg (II) enhanced by nine folds higher than that observed for iron sensor binding affinity, which makes the substrate a distinctive luminescence sensor for mercury detection at ambient conditions. The sensor shows a linear response toward Hg (II) in the concentration range from 4.2 x 10-5 to 2.0 x 10-8 M with a limit of detection of 1.0 x 10-8 M. Further, Sensor A provides linear detection for iron ions in the range from 1.5 x 10-3 to 1.5 x 10-8 M. The measured adsorption capacity of Sensor A toward mercury ions ranged from 1.25 to 1.97 mg/g and the removal efficiency from water samples reached 98.8% at pH 7.0. The data demonstrate that Sensor A is an excellent probe for detecting and removing mercury ions from water bodies.

Head and neck squamous cell carcinoma (HNSCC) arise from the mucosal epithelium in the oral cavity, pharynx, sino-nasal region, and larynx. Laryngeal squamous cell carcinoma (LSCC) represents one-third of all head and neck cancers. Dysregulated RNA-related pathways define an important molecular signature in this aggressive carcinoma. The Survival Motor Neuron (SMN) protein regulates fundamental aspects of the RNA metabolism but, curiously, its role in cancer is virtually unknown. For the first time, here we focus on SMN in cancer context. We conducted a pilot study in a total of 20 patients with LSCC where SMN was found overexpressed at both the protein and transcript levels. By a cellular model of human laryngeal carcinoma, we demonstrated that SMN impacts cancer-relevant behaviors and perturbs key players of cell migration, invasion, and adhesion. Furthermore, in LSCC we showed a physical interaction between SMN and the epidermal growth factor receptor (EGFR), whose overexpression is an important feature in these tumours. This study candidates SMN as novel therapeutic target in LSSC, and likely in the whole spectrum of HNSCC. Overall, we provide the first analysis of SMN in human cancer.

The eugenol derivative, ethyl 4-(2-methoxy-4-(oxiran-2-ylmethyl)phenoxy)butanoate 1, with promising insecticidal capability was encapsulated in liposomal formulations of egg-phosphatidylcholine/cholesterol (Egg-PC:Ch) 70:30 and of 100% dioleoylphosphatidylglycerol (DOPG). Compound-loaded Egg-PC:Ch liposomes exhibit small hydrodynamic diameters (below 100 nm), high encapsulation efficiency (88.8% ± 2.7%), higher stability and a more efficient compound release, being chosen for assays in Sf9 insect cells. Compound 1 elicited a loss of cell viability up to 80% after 72h of incubation. Relevantly, encapsulation maintained the toxicity of compound 1 towards insect cells, while it lowered toxicity towards human cells, thus showing the selectivity of the system. Structure based inverted virtual screening was used to predict the most likely targets and molecular dynamics simulations and free energy calculations were used to demonstrate that this molecule can form a stable complex with insect odorant binding proteins and/or acetylcholinesterase.

Initially, retinol-binding protein (RBP), was thought to be a biomarker for proximal convoluted tubule dysfunction could be important in chronic kidney diseases (CKD). Membranous glomerulonephritis (MGN) is an important cause of CKD and end-stage renal disease (ESRD). Therefore, monitoring MGN patients using urinary RBP is important in effective treatment decision making and prognostication of MGN patients. Enzyme-linked immunosorbent assay (ELISA) technique was used to detect the RBP in the urine samples of 69 MGN patients comprising 47 primary and 22 secondary MGN, at the end of the follow-up period. The test for the urinary biomarker gave the following results: urinary RBP was detected in 27 (39.1%) and 6 (8.7%) of the primary and secondary MGN patients, respectively. The correlation analysis demonstrated a significant relationship between urinary RBP and renal function test parameters, in addition to a logistic regression analysis that proved urinary RBP as a prognostic non-invasive biomarker for primary MGN. Therefore, urinary RBP could be employed to monitor and provide effective prognosis and early treatment decisions in primary MGN.

Amyotrophic Lateral Sclerosis (ALS) is an irreversible neurodegenerative disease with no known cure. Recent studies suggest a strong metabolic component in ALS pathogenesis and have shown an inverse relationship between leptin levels and ALS progression, although the effects of leptin as a treatment have not yet been studied. Therefore, we aim to examine whether the acute treatment with leptin has beneficial effects on brain pathology and cognitive function in the transgenic TDP43A315T line of ALS. Mice were treated intranasally (IN) with 0.03mg/kg of leptin or vehicle (VH) daily for 7 days. Data showed a progressive decline in body weight and motor coordination in TDP43A315T mice. Moreover, Lep-treated TDP43A315T mice showed an earlier disease onset, along with an improvement in motor performance. Altered levels of some of the adipokines and metabolic proteins studied were found in TDP43A315T mice, which were differently expressed among Lep-treated and VH-treated animals. Furthermore, some correlations were found among the serum levels of this proteins in WT and TDP43A315T mice. As far as we know, this is the first pilot study to provide evidence of the therapeutic effect of leptin treatment in a mice model of ALS, although further studies are needed to expound on the underlying mechanisms.

Fragile X syndrome (FXS) is a neurodevelopmental disorder associated with a wide range of cognitive, behavioral and medical problems. It arises from the silencing of the fragile X mental retardation 1 (FMR1) gene, and consequently, in the absence of its encoded protein, FMRP (Fragile X Mental Retardation Protein). FMRP is a ubiquitously expressed and multifunctional RNA-binding protein, primarily considered as a translational regulator. Pre-clinical studies of the past two decades have therefore focus on this function to relate FMRP’s absence to the molecular mechanisms underlying FXS physiopathology. Based on these data, successful pharmacological strategies were developed to rescue fragile X phenotype in animal models. Unfortunately, these results did not translate into human, as clinical trials using same therapeutic approaches did not reach the expected outcomes. These failures highlight the need to put into perspectives the different functions of FMRP in order to get a more comprehensive understanding of FXS pathophysiology. In this review, FMRP’s involvement on noteworthy molecular mechanisms are pointed out; ultimately contributing to various biochemicals alterations composing the fragile X phenotype.

HIF-1α is a master regulator of oxygen homeostasis involved in different stages of cancer development. Thus, HIF-1α inhibition represents an interesting target for anti-cancer therapy. It was recently shown that HIF-1α interaction with NQO1 inhibits its proteasomal degradation, thus suggesting that targeting the stability of NQO1 could led to destabilization of HIF-1α as a therapeutic approach. Since the molecular interactions of NQO1 with HIF-1α are beginning to be unraveled, we review here our current knowledge on the intracellular functions and stability of NQO1, its pharmacological modulation by small ligands, and the molecular determinants of its roles as a chaperone of many different proteins including cancer-associated factors such as p53 and p73α. This knowledge is then discussed in the context of potentially targeting the intracellular stability of HIF-1α by acting on its chaperone, NQO1. This could result in novel anti-cancer therapies.

The transnational spread of coronavirus (2019-nCoV) first detected in Wuhan is causing global panic; thus, accelerated research into clinical intervention is of high necessity. The spike glycoprotein structure has been resolved, and its affinity to human angiotensin-converting enzyme 2 (ACE-2) has been experimentally validated. Here, using computational methods, a metastable conformation of 2019-nCoV-RBD/ACE-2 complex has been revealed and FDA-database of approved drugs have been docked into the interface. Darunavir has been discovered as high ligand affinity candidate capable of disrupting communication between 2019-nCoV-RBD and ACE-2. Darunavir, in addition to its previously known anti-HIV protease inhibitor is now repurposeable for the treatment 2019-nCoV disease acting via disruption of cellular recognition, binding and invasion.

Amino acid sequences of native proteins are generally not palindromic. The protein molecule obtained as a result of reading the amino acid sequence backwards, i.e., a retro-protein, having the same amino acid composition and the same hydrophobicity profile as the native sequence may behave as a different molecule. Here we have used R4, a directed evolution product of Scfv-13, a protein that binds β-galactosidase, and report the properties of the retro-R4 (rR4). rR4 remains a binding protein and its new target is Glutamine-fructose-6-phosphate aminotransferase (GLMS), a native E. coli protein. Additionally, a tight junction immunoglobulin domain- containing membrane protein, junctional adhesion molecule A (JAMA) retro-protein retains the ability to drive cell-cell interactions. Thus, protein engineering suggests a new potential application to retro-proteins of the immunoglobulin superfamily.

PgRMC1 (progesterone receptor membrane component 1) is a progesterone-binding protein highly expressed in various cancer cells. Its expression has been associated with cancer development, chemoresistance, and poor prognosis in breast cancer through the regulation of drug and sterol metabolism, cell cycle, and apoptosis. However, the precise functions of PgRMC1 remain unclear. We examined PgRMC1 expression in breast cancer tissues and analyzed its correlation with clinicopathological characteristics and treatment response (n=112). PgRMC1 expression was detected in breast cancer tissue, while no immunoreactivity for PgRMC1 was observed in normal breast tissue. Notably, PgRMC1 expression levels were high in the HER2 subtype. Among patients treated with neoadjuvant chemotherapy, those with a poor pathological response had significantly higher PgRMC1 expression than those with a good response. PgRMC1 overexpression in breast cancer cell lines reduced chemosensitivity. Real-time qPCR analyses revealed that PgRMC1 induced the expression of differentiation markers, including CDH1 and KRT19, indicating that PgRMC1 is involved in the suppression of epithelial-mesenchymal transition and mammary luminal epithelial differentiation. Our findings suggest that PgRMC1 may contribute to chemoresistance and serve as a putative biomarker for assessing neoadjuvant chemotherapy sensitivity.

The new hybrid composite materials for PEM fuel cell were synthesized by UV-polymerization of acrylic monomers (acrylonitrile (AN), acrylic acid (AA), ethylene glycol dimethacrylate (EGDMA)) and sulfo aromatic monomer – sodium styrene sulfonate (SSS), and tetraethoxysilane/3-methacryloxypropyltrimethoxysilane (TEOS/MAPTMS)-based sol-gel system. By means of X-ray spectroscopy fractal structure of the obtained materials was characterized. Proton conductivity and viscoelastic properties of the materials were investigated depending on the content of inorganic component in nanocomposites. On the basis of impedance studies, an equivalent scheme is proposed that successfully describes the proton conductivity in the synthesized composite electrolyte membranes.

Antibodies are important tools for the study of membrane proteins in biological, biophysics and structural analyses. However, the production of purified membrane proteins is still a formidable challenge due to the amphipathic character and inherent instability of these proteins. In this work, we tested a strategy for producing antibodies against an ATP-Binding Cassette (ABC) transporter without the need to produce the full membrane complex. Instead, just the extra cytoplasmic regions of the ABC-type transporter Rv1819c from Mycobacterium tuberculosis were presented in the RAD-display, a scaffold system based on the engineered Pyrococcus furiosus RadA protein developed for exposition of peptides. The RadA scaffold protein is highly stable, can tolerate long insertions and easy to produce in Escherichia coli. Based on the three-dimensional structure of Rv1891c, we selected two versions of the main extracellular loops of the permease to use as test cases for this approach. Rv1819c-derived peptides displayed on RAD display system were used for immunization of mice and production of polyclonal antibodies. These antibodies were able to recognize the transporter in M. tuberculosis cell extracts, on intact cells by flow cytometry and as purified protein. The results showed the approach can be a useful tool for in vitro analyses, screening, and evaluation of different epitopes in membrane proteins.

The vagina is an essential component of the female reproductive system and is responsible for providing female sexual satisfaction. Vaginal smooth muscle contraction plays a crucial role in various physiological processes, including sexual arousal, childbirth, and urinary continence. In pathophysiological conditions such as pelvic floor disorders, aberrations in vaginal smooth muscle function can lead to urinary incontinence and pelvic organ prolapse. A set of cellular and sub-cellular physiological mechanisms regulates the contractile properties of the vaginal smooth muscle cells. Calcium influx is a crucial determinant of smooth muscle contraction, facilitated through voltage-dependent calcium channels and calcium release from intracellular stores. Comprehensive reviews on smooth muscle biophysics are relatively scarce within the scientific literature, likely due to the complexity and specialized nature of the topic. The objective of this review is to provide a comprehensive description of alterations in the cellular physiology of vaginal smooth muscle contraction. The benefit associated with this particular approach is that conducting a comprehensive examination of the cellular mechanisms underlying contractile activation will enable the creation of more targeted therapeutic agents to control vaginal contraction disorders.

Helicobacter pylori is a gastric oncopathogen that infects over half of the world’s human population. It is a Gram-negative, microaerophilic, helix-shaped bacterium that is equipped with flagella, which provide high motility. Colonization of the stomach is asymptomatic in up to 90% of people but is a recognized risk factor for developing various gastric disorders such as gastric ulcers, gastric cancer and gastritis. Invasion of the human stomach occurs via numerous virulence factors such as CagA and VacA. Similarly, outer membrane proteins (OMPs) play an important role in H. pylori pathogenicity as a means to adapt to the epithelial environment and thereby facilitate infection. While some OMPs are porins, others are adhesins. The epithelial cell receptors SabA, BabA, AlpA, OipA, HopQ and HopZ have been extensively researched to evaluate their epidemiology, structure, role and genes. Moreover, numerous studies have been performed to seek to understand the complex relationship between these factors and gastric diseases. Associations exist between different H. pylori virulence factors, the co-expression of which appears to boost pathogenicity of the bacterium. Improved knowledge of OMPs is a major step towards combatting this global disease. Here, we provide a current overview of different H. pylori OMPs and discuss their pathogenicity, epidemiology and correlation with various gastric diseases.

This paper describes new horizons in the diversity and taxonomy of negev-like viruses encoding the membrane-embedded SP24 protein. First, our data extend the known host range of SP24-encoding negev-like viruses to include brown algae, fungi, green plants, the phylum Entoprocta, the phylum Mollusca, and vertebrates. Second, our phylogenetic analysis suggests that the evolution of the SP24 gene family may have involved frequent events of inter-order virus genome shuffling. Third, the identification of 2-3 copies of SP24 protein genes in some virus RNAs shows that virus genomes may have acquired additional SP24 genes during the evolutionary process due to duplications or new acquisition steps. Forth, the broad host specificity of some SP24-encoded viruses may be related to an important adaptive role of SP24. Fifth, insect and nematode genomes may acquire viral SP24 genes by putative horizontal transfer from negev-like viruses known to infect species of both taxa.

N-maleimide-derivatized phospholipids are often used to facilitate protein anchoring to membranes. In autophagy studies, this is applied to the covalent binding of Atg8, an autophagy protein, to a phosphatidylethanolamine (PE) in the nascent autophagosome. However, the question remains on how closely the N-maleimide PE derivative (PE-mal) mimicks the native PE in the bilayer. In the present paper, spectroscopic and calorimetric techniques have been applied to vesicles containing either PE or PE-mal (together with other phospholipids) to compare the properties of the native and derivatized forms of PE. According to differential scanning calorimetry, and to infrared spectroscopy, the presence of PE-mal did not perturb the fatty acyl chains in the bilayer. Fluorescence spectroscopy and microscopy showed that PE-mal did not alter bilayer permeability either. However, fluorescence emission polarization of Laurdan and DPH probes indicated an increased order, or decreased fluidity, in the bilayers containing PE-mal. In addition, infrared spectral data from the phospholipid phosphate region revealed a PE-mal-induced conformational change of the polar heads, accompanied by an increased hydration. Globally considered, the results suggest that PE-mal would be a reasonable substitute for PE in model membranes containing reconstituted proteins.

It is important to develop new antibacterial drugs since the emergence of bacterial resistance to available antibiotics. Metal nanoparticles have the potential to combat antibiotic resistance and are effective antibacterial agents. Here, we demonstrate the biogenic production of zinc nanoparticles using Rhododendron arboreum stem bark. The biosynthesized ZnNPs were characterized through different analytical techniques such as UV-vis, FTIR, EDX, SEM, and XRD. Clinical isolates such as E. coli, S. aureus, and K. pneumonia were used to check the antibacterial efficacy of the biosynthesized zinc nanoparticles. The MIC and MBC values against K. pneumonia, S. aureu, and E. coli were found to be 34±0.21 and 11.71±0.47, 47±0.11 and 23.86±0.84 and 94±0.18 and 40.43±0.16 µg/mL, respectively. It dramatically decreased the integrity of the cell membrane and markedly increased the permeability of both inner and outer membranes. The green synthesized ZnNPs have good catalytic activity. It degraded 65% of methyl orange dye within 6h when the mixture was kept in direct sunlight, thus demonstrating good photodegradation potential and can be employed as a good photocatalyst. According to these results, biosynthesized zinc nanoparticles could be a potential therapy option for controlling bacterial pathogenesis and an effective photocatalyst for the elimination of hazardous water contaminants.