Introduction: We investigated the potential effect of smoking on pathological staging in clinically low-risk patients. Material-Methods: Data of 59 patients who were diagnosed with a bladder tumor for the first time and had a single lesion radiologically and endoscopically smaller than 3 cm were investigated, retrospectively. A total of 33 patients who currently smoke or smoked were classified as ever smokers group and 26 patients who did not ever smoke were classified as never smokers group. Pathological diagnoses of the patients in both groups were compared. Results: A total of 9 patients (27.3%) in ever smokers group and 18 patients (69.2%) in never smokers group had Ta disease (p<0.05). Morover, 19 patients (57.6%) in ever smokers group and 5 patients (19.2%) in never smokers group had T1 disease (p<0.05). The number of patients with low grade (LG) tumor were 8 (24.2%) and 19 (73.1%) in ever smoking and never smoking groups, respectively (p<0.05). The number of patients with high grade (HG) tumor were 25 (75.8%) and 7 (26.9%) in ever smoking and never smoking groups, respectively (p<0.05). Ta HG was detected in 9 (27.3%) patients in ever smoking group. In contrast, no patients in never smoking group had Ta HG disease (p<0.05). The number of patients with T1 HG was 17 (51.5%) in ever smoking group and 2 (7.69%) in never smoking group (p<0.05). Conclusion:Smoking seems to associate with pathologically worse stage and grade in patients with primary, single, < 3cm bladder cancer.

AbstractWe investigated the effect of cigarette smoking on pathological staging in clinically low-risk patients. Data of 59 patients who were diagnosed with bladder tumor for the first time and had a single lesion radiologically and endoscopically smaller than 3 cm were investigated retrospectively. 33 patients who smoked were classified as Group I, and 26 patients who did not smoke were classified as Group II. Pathological diagnoses of the patients in both groups were compared. The mean age of the patients were 64.8 (20–86) years. In Group II, 5 (19.2%) were female and 21 (80.8%) were male (p < 0.05). Nine patients (27.3%) in Group I and 18 patients (69.2%) in Group II had Ta disease (p < 0.05). Nineteen patients (57.6%) in Group I and 5 patients (19.2%) in Group II had T₁ disease (p < 0.05). The number of patients with low grade (LG) tumor were 8 (24.2%) and 19 (73.1%) in Group I and in Group II, respectively (p < 0.05). The number of patients with high grade(HG) tumor were 25 (75.8%) and 7 (26.9%) in Group I and in Group II, respectively (p < 0.05). TaHG was detected in 9 (27.3%) patients in Group I. In contrast, no patients in Group II had TaHG disease (p < 0.05). The number of patients with T₁HG was 17(51.5%) patients in Group I and 2 (7.69%) patients in Group II (p < 0.05). Smoking is associated with pathologically HG and stage in patients with first time bladder tumor which is single and smaller than 3 cm.

Background: The prevalence of atopic dermatitis in domestic animals is one of the problems of modern veterinary. Treating with standard techniques using chemotherapeutic agents not always leads to a positive result of therapy; moreover, many drugs produce adverse side effects. Methods: Low level laser therapy, in particular, intravenous laser blood illumination (ILBI) has a pronounced and long-lasting impact on the immune system of animals. The combined technique including ILBI-635 (635 nm, 2 mW, 5 min) and LUVBI^® (365 nm, 2 mW, 3 min) every other day provides a positive change in clinical status of cats with allergic dermatitis after the 3rd-4th treatment session. Results: The increased level of erythrocytes and hemoglobin was identified in the course of treatment, and it indirectly indicates increased blood transport activity, which improves trophic provision and microcirculation. A double reduction of leukocytes and a significant decrease of neutrophil cells indicate the immunomodulatory effect of LILI (low-intensity laser illumination). The increase in the percentage of lymphocytes and the decrease of eosinophils and monocytes against the background of basophil concentrations deviations within physiological concentration result in the reduction of inflammatory mediators expression that induce itching. The reduction of total IgE concentration 32 times against control on the 7th day of treatment correlates with the decrease in the quantitative content of peripheral blood eosinophils, indicating the decrease in severity of an allergic process. Conclusion: LLLT is recommended against the background of standard drug therapy to achieve quick clinical outcome together with a long-lasting prolonged effect.

Nonalcoholic fatty liver disease (NAFLD) is a liver metabolism-associated steatohepatitis caused by non-alcoholic factors. NAFLD is currently the most prevalent liver disease in the world, affecting one-fourth of the world's population, and its prevalence increases with age. There are no approved drugs specifically for the treatment of NAFLD, and one important reason hindering drug development is the lack of effective biomarkers. C-reactive protein (CRP), a marker of inflammation, has been linked to NAFLD and aging in recent studies. Coincidentally, hepatocytes are responsible for the major CRP production, and the levels of CRP increase with age. Therefore, CRP is not only a potential marker, but also acts as a key factor driving liver aging and NAFLD. Herein, we reviewed the biological function and production mechanism of CRP and the relationship between CRP and NAFLD. We also comprehensively described the potential molecular mechanisms of CRP-mediated signaling in aging-associated NAFLD. Finally, we proposed possible therapeutic approaches based on the mechanism of CRP signaling in the pathogenesis of NAFLD. We hope this study can provide new insights into the development of aging associated NAFLD biomarkers and suggest that modulation of CRP signaling is a potential therapeutic target.

A 52-day experiment was conducted to determine the crude protein (CP) requirements of juvenile matrinxã Brycon amazonicus, and to evaluate their resulting growth performance, hematological parameters and enzymatic activities. Sixty fish (29.03g ± 1.16g) were distributed in 12 tanks (310 L) with a completely randomized design, and maintained at four dietary crude protein levels (270, 320, 350, 390 g.kg-1) for 52 days. The results revealed that the fish fed diet 390 g.kg-1 CP had the best final weight, weight gain, feed conversion ratio, specific growth rate, protein efficiency ratio and lipid retention rate. The same could be stated for hematocrit, number of circulating erythrocytes, triglycerides and total proteins of the hematological profile (p&lt;0.05). In the whole body composition, dry matter content was lower in the fish fed 390 g.kg-1 CP, while lipid content was higher in the fish fed 350-390 g.kg-1 CP (p&lt;0.05). No differences were observed in CP and ash (p&gt;0.05), or in the activities of digestive enzymes (p&gt;0.05). In short, our findings suggest benefits of the 390 g.kg-1 CP feed for being the most adequate for this species’ juvenile stage.

Polyacrylamide gel electrophoresis (PAGE) is widely used for studying proteins and protein-containing objects. However, it is employed most frequently as a qualitative method rather than a quantitative one. In this paper, we show the feasibility of routine digital image acquisition and mathematical processing of electrophoregrams for protein quantification. Both the well-studied model protein molecules (bovine serum albumin) and more complex real-world protein-based products (casein-containing isolate for sports nutrition), which were subjected to mechanical activation in a planetary ball mill to obtain samples characterized by different protein denaturation degrees, were used as study objects. Protein quantification in the mechanically activated samples was carried out. The degree of destruction of individual protein was shown to be higher compared to that of protein-containing mixture after mechanical treatment for an identical amount of time. The methodological approach used in this study can serve as guidance for other researchers who would like to use electrophoresis for protein quantification both in individual form and in protein mixtures. The findings prove that photographic imaging of gels followed by mathematical data processing can be applied for analyzing the electrophoretic data.

The Rho guanine nucleotide exchange factor (RGNEF) protein encoded by the ARHGEF28 gene has been implicated in the neurodegenerative disease amyotrophic lateral sclerosis (ALS). Biochemical and pathological studies have shown that RGNEF is a component of the hallmark neuronal cytoplasmic inclusions in ALS-affected neurons. Additionally, a heterozygous mutation in ARHGEF28 has been identified in a number of familial ALS (fALS) cases that may give rise to one of two truncated variants of the protein. Little is known about the normal biological function of RGNEF or how it contributes to ALS pathogenesis. To further explore RGNEF biology we have established and characterized a yeast model and characterized RGNEF expression in several mammalian cell lines. We demonstrate that RGNEF is toxic when overexpressed and forms inclusions. We also found that the fALS-associated mutation in ARGHEF28 gives rise to an inclusion-forming and toxic protein. Additionally, through unbiased screening using the split-ubiquitin system, we have identified RGNEF interacting proteins, including two ALS-associated proteins. Functional characterization of other RGNEF interactors identified in our screen suggest that RGNEF functions as a microtubule regulator. Our findings indicate that RGNEF misfolding and toxicity may cause impairment of the microtubule network and contribute to ALS pathogenesis.

Wheat is the essential constituent of cereal-based diets and one of the most significant sources of calories. However, there is an inherently low bioavailability of proteins, mineral, and vitamins in modern wheat grains. Biofortification has earned recognition as an outstanding approach, at the same time as a cure for world hunger. The developments in the identifications of quantitative trait loci (QTL) analysis and understanding of the physiological and molecular basis of QTLs controlling the biofortification traits in wheat has revealed new horizons for the improvement of modern wheat varieties. Within this review, we have compiled the information from the studies carried out in wheat using QTL mapping methodologies that is among the best methods for biofortification traits. We hope this review will serve as an essential reference for the QTLs identified for the several important biofortification traits in wheat.

Nanotechnology is a multidisciplinary science covering matters involving nanoscale level that is being developed for a great variety of applications. Nanomedicine is one of these attractive and challenging uses focused on the employment of nanomaterials in medical applications such as drug delivery. However, the uses of these nanometric systems requires specific parameters to establish the possible advantages and disadvantages in specific applications. This review presents the fundamental factors of nanoparticles and it´s microenvironment that must be considered to make an appropriate design for medical applications: (i) Interactions between nanoparticles and their biological environment, (ii) the interaction mechanisms, (iii) and the physicochemical properties of nanoparticles. On the other hand, the repercussions of the control, alteration and modification of these parameters in the final applications. Additionally, we here briefly report the implications of nanoparticles in nanomedicine and provide perspectives for some particular applications which still are challenged

Surfactant proteins A and D (SP-A and SP-D) belong to the collectin subfamily of C-type oligomeric lectins. They are pattern-recognition molecules (PRM), able to recognise pathogen- or dan-ger-associated molecular patterns (PAMP, DAMP) in the presence of Ca2+ cations. That property enables opsonisation or agglutination of non-self or altered/abnormal self-cells, and contributes to their clearance. Like other collectins, SP-A and SP-D are characterised by the presence of four distinct domains: a cysteine-rich domain (at N-terminus), a collagen-like region, an α-helical neck domain and a globular carbohydrate-recognition domain (CRD) (at C-terminus). Pulmonary sur-factant is a lipoprotein complex, preventing alveolar collapse by reducing surface tension at the air-liquid interface. SP-A and SP-D, produced by type II alveolar epithelial cells, and Clara cells, are not only pattern-recognition molecules but also contribute to the surfactant structure and homeo-stasis. Moreover, they are expressed in a variety of extrapulmonary sites where they are involved in local immunity. The term “cancer” includes a variety of diseases: tumours start from uncontrolled growth of abnormal cells in any tissue which may further spread to other sites of the body. Many cancers are incurable, difficult to diagnose and often fatal. This short review summarises anti- and pro-tumourigenic associations of SP-A and SP-D as well as perspectives of their usefulness in cancer diagnosis and therapy.

Due to the vast conformational space proteins can adopt, accurate and efficient prediction of protein structure remains still a challenging task, coupled with the intricacies of interatomic interactions and the limitations of current computational models in effectively navigating this complex molecular landscape. Additionally, the lack of comprehensive experimental data for all protein structures further exacerbates the difficulty in reliable machine learning-based prediction of the three-dimensional conformations of the proteios building block of life. Geometrically, Cartesian coordinate system (CCS, X, Y and Z) and spherical coordinate system (SCS, ρ, θ and φ) are two interconvertible coordinate systems, and are like two sides of one coin. Since the beginning of Protein Data Bank (PDB) in 1971, CCS has been the default approach to specify atomic positions with X, Y and Z in PDB. In this manuscript, therefore, I present a novel method for the reversible spherical geometric conversion of protein backbone structure coordinate matrices to three independent vectors: ρ, θ and φ. This reversible conversion facilitates lossless extraction of essential structural features from protein backbone structural data, enabling the development of advanced novel algorithms for protein structure prediction in future. In short, this inter-atomic SCS approach offers a comprehensive yet efficient means of representing protein backbone geometry, leveraging spherical coordinates to capture spatial relationships in a compact and intuitive inter-atomic manner, and to provide a robust framework for reversible feature extraction for the ongoing efforts in advancing the field of protein structure prediction, the holy grail of computational structural biology.

Dysregulation of the Cyclin-dependent kinase 8 (CDK8) activity has been associated to many diseases including the colorectal and breast cancer. As usual in the CDK family, the activity of CDK8 is controlled by a regulatory protein called cyclin C (CycC). But while human CDK family members are generally activated in two steps that is, the binding of the cyclin to CDK and the phosphorylation of a residue in the CDK activation loop, CDK8 does not require the phosphorylation step to be active. Another peculiarity of CDK8 is its ability to be associated to CycC while adopted an inactive form. These specificities raise the question of the role of CycC in the complex CDK8-CycC, which appears to be more complex than for the other members of CDK family. Through MD simulations and binding free energy calculations, we investigated the effect of CycC on the structure and dynamics of CDK8 on the one hand, and the structural molecular basis of the protein-protein interaction between the two partners on the other hand. We found that CycC has a stabilizing effect on CDK8 and identified specific interaction hotspots within its interaction surface compared to other human CDK/Cyc pairs. Targeting these specific interaction hotspots could be a promising approach in terms of specificity, to effectively disrupt the interaction between CDK8. The simulation of the conformational transition from the inactive to the active form of CDK8 suggests that the residue Glu99 of the CycC may assume the role of the missing phosphorylation step in the activation mechanism of CDK8. In a more general view, these results point the importance of keeping the CycC in computational studies when studying the human CDK8 protein in both the active and the inactive form.

The cell surface targeting of neo-synthesized G protein coupled receptors (GPCRs) involves recruitment of receptor into COPII vesicles budding at Endoplasmic Reticulum Exit sites (ERES). This process is regulated for some GPCRs by escort proteins, which facilitate their export, or by gatekeepers that retain the receptors in the ER. PRAF2, an ER gatekeeper of the heterodimeric GABAB receptor protomer GB1, which interacts with a tandem di-leucine / RXR retention motif in the carboxyterminal tail of GB1, also inhibits the plasma membrane export of the chemokine receptor CCR5. PRAF2 / CCR5 interactions involve the transmembrane domains of both proteins. The di-leucine / RXR motif contained in the third intracellular loop of CCR5 does not affect PRAF2-mediated retention but impairs instead the interaction between CCR5 and its private escort protein CD4. PRAF2 and CD4 thus display opposite roles on the cell surface export of CCR5, likely at the level of its recruitment into COPII vesicles, PRAF2 inhibiting and CD4 promoting this process.

Polo-like kinase 1 (PLK1) plays a pivotal role in cell division regulation and emerges as a promising therapeutic target for cancer treatment. Consequently, the development of small-molecule inhibitors targeting PLK1 has become a focal point in contemporary research. The adenosine triphosphate (ATP)-binding site and the polo-box domain in PLK1 present crucial interaction sites for these inhibitors, aiming to disrupt the protein's function. However, designing potent and selective small-molecule inhibitors can be challenging, requiring a deep understanding of protein-ligand interaction mechanisms at these binding sites. In this context, our study leverages the fragment molecular orbital (FMO) method to explore these site-specific interactions in-depth. Through the FMO approach, we used the FMO method to elucidate the molecular mechanisms of small-molecule drug binding to these sites to design PLK1 inhibitors that are both potent and selective. Our investigation further entailed a comparative analysis of various PLK1 inhibitors, each characterized by distinct structural attributes. This comparison enhanced our understanding of the structure-activity relationships of these inhibitors, underscoring the efficacy of the FMO method in identifying critical binding features and predicting binding modes for small-molecule ligands. Furthermore, Our research spotlighted "hot spot" residues instrumental for selective and robust PLK1 binding. Our findings offer profound insights, priming the rational design of innovative potential PLK1 inhibitors with significant implications for developing anticancer therapeutics.

Oyster mushroom( Pleurotus ostreatus) is belong to the group of healthy foods, as they contain high levels of proteins, vitamins and different classes of compounds, it is discovered that oyster mushrooms could play a key role in maintaining good health. Oyster mushroom (Pleurotus sp.) Class Basidiomycetes and Family Agaricaceae are widely known as ‘dhingri’ in India. Pleurotus Ostreatus have several medicinal properties including ; anti-arthritic , antitumor, immune modulatory , antioxidant, anticancer, anti-inflammatory, antigenotoxic, hypo-cholesterolaemic, antihyperglycaemic antihypertensive, antiplatelet aggregating, antiviral and antimicrobial activities.. In this paper studied that effects of chemical constituents of oyster mushroom(Pleurotus sp.) on DNA damaging protein which analyzed its activity of PARP inhibiting or vice – versa.For this analysis we choose the molecular docking technique to check the effects of different chemical constituents of oyster mushroom(Pleurotus sp.) on DNA damaging protein and compare their results to PARP inhibitory drugs which taken as standard . We perform the molecular docking in between chemical constituents of oyster mushroom(Pleurotus sp.) and 4UND protein compare to performance of molecular docking in between standard PARP inhibitory drugs and 4UND protein with the help of PyRx and BIOVIA Discovery studio software.The analysis of molecular docking shows that some chemical constituents of oyster mushroom(Pleurotus sp.) having more binding affinity than standard PARP inhibitory drugs .The Rutin shows better binding affinity than PARP inhibitory drugs on the same protein.

G protein-coupled receptors (GPCRs) are critical drug targets. GPCRs convey signals from the extracellular to the intracellular environment through G proteins. There is evidence that some ligands that bind to the GPCRs activate different downstream signaling pathways. G protein activation or -arrestin biased signaling involves ligands binding to receptors and stabilizing conformations that trigger a specific pathway. Molecular dynamics (MD) simulations are especially valuable for obtaining detailed mechanistic information, including identification of allosteric sites and understanding modulators' interactions between receptors and ligands. Here, we highlight recent simulation studies and methods used to study biased G protein-coupled receptor signaling and their conformational dynamics. We also highlight applications of MD simulations to drug discovery.

VpStyA1 and VpStyA2B of Variovorax paradoxus EPS is annotated and characterized as the first representative of an E2-type styrene monooxygenase of proteobacteria. It comprises a single epoxidase (VpStyA1) and a fusion protein (VpStyA2B) which serves mainly as NADH:FAD-oxidoreductase. VpStyA2B had a Km of 33.6 ± 4.0 µM for FAD and a kcat of 22.3 ± 1.1 s-1. VpStyA2B and VpStyA1 showed monooxygenase activity on styrene of 0.14 U mg-1 and 0.46 U mg-1 as well as on benzyl methyl sulfide of 1.62 U mg-1 and of 3.11 U mg-1. A putative fusion region at position 408 (AREAV) was mutated to provide insights on VpStyA2B-function. The best mutant (408-AAAAA) obtained showed a 6.6-times higher affinity for FAD while keeping the NADH-affinity and -oxidation activity. Corresponding epoxidase activity increased (1.6-times). But, other mutants showed still NADH:FAD-oxidoreductase activity, but lost mostly their epoxidase activity indicating effects on the monooxygenase-part as well. Thus, this monooxygenase system represents an interesting candidate for biocatalyst development.

Hyper-radiosensitivity (HRS) is the increased sensitivity to low doses of ionizing radiation observed in most cell lines. We previously demonstrated that HRS is permanently abolished in cells irradiated at a low dose rate (LDR), in a mechanism dependent on transforming growth factor β3 (TGF-β3). In this study, we aimed to elucidate the activation and receptor binding of TGF-β3 in this mechanism. T-47D cells were pre-treated with inhibitors of potential receptors and activators of TGF-β3, along with addition of small extracellular vesicles (sEVs) from LDR primed cells, before their radiosensitivity was assessed by the clonogenic assay. The protein content of sEVs from LDR primed cells was analyzed with mass spectrometry. Our results show that sEVs contain TGF-β3 regardless of priming status, but only sEVs from LDR primed cells remove HRS in reporter cells. Inhibition of the matrix metalloproteinase (MMP) family prevents removal of HRS, suggesting an MMP-dependent activation of TGF-β3 in the LDR primed cells. We demonstrate a functional interaction between TGF-β3 and activin receptor like kinase 1 (ALK1), by showing that TGF-β3 removes HRS through ALK1 binding, independent of ALK5 and TGF-βRII. These results are an important contribution to a more comprehensive understanding of the mechanism behind TGF-β3 mediated removal of HRS.

The goal of this paper is to present a low-cost, low-power prototype of a pulsed Ultra Wide Band UWB) oscillator and an UWB elliptical dipole antenna integrated on the same Radio Frequency (RF) Printed Circuit Board (PCB) and its digital control board for Real Time Locating System (RTLS) applications. The design is compatible with IEEE 802.15.4 high rate pulse repetition UWB standard being able to work between 6 GHz and 8.5 GHz with 500 MHz bandwidth and with a pulse duration of 2 ns. The UWB system has been designed using the CST Microwave Studio transient Electro-Magnetic (EM) circuit co-simulation method. This method integrates the functional circuit simulation together with the full wave (EM) simulation of the PCB’s 3D model allowing fast parameter tuning. The PCB has been manufactured and the entire system has been assembled and measured. Simulated and measured results are in excellent agreement with respect to the radiation performances as well as the power consumptions.

All life on Earth uses three integrated molecular systems in which genetic information contained in DNA base sequences is transmitted to ribosomes by RNA and a genetic code, then translated into the amino acid sequences of structural and catalytic proteins. Therefore, the most important point for understanding the origin of life is to determine how such systems could emerge from random processes on the early Earth. In this review, two alternatives are compared: the RNA world hypothesis and the [GADV]-protein world hypothesis. [GADV] refers to four amino acids, Gly [G], Ala [A], Asp [D] and Val [V] that are conserved in the amino acid sequences of many common proteins. Here I will argue that the origins of the three primary processes required for life to begin can be better explained by the GADV hypothesis than the RNA world hypothesis. The GADV hypothesis also incorporates a conversion process by which random polymers can evolve into proteins with ordered sequences.

Uterine leiomyosarcoma (LMS) is a rare and aggressive form of uterine cancer, with a poor prognosis and high number of uterine cancer-related deaths. Chimeric Antigen Receptor (CAR) T-cell therapy is an immunotherapy approach to antigen specific of cancer cell, thereby enhancing the immune system's ability to target and destroy cancer cells. This study aims to investigate the potential of targeting differentially expressed genes (DEGs) as a novel therapeutic strategy using CAR T-cell technology in LMS. Genome datasets were obtained from NCBI-GEO database, Of the five datasets, genes that experienced significant overexpression in at least three datasets were categorized as DEGs, and DEGs were evaluated for protein localization, Gene Ontology, bioactivity, interaction, and overexpression. The results identified 25 DEGs, with ten of them expressed on the plasma membrane; four of them—HMMR, KIF20A, PRC1, and ZWINT—were part of the main protein network derived from the 25 DEGs. The dominant bioactivity of these PMGs involves influencing the cell cycle, particularly processes related to chromosome segregation. In conclusion, HMMR, KIF20A, PRC1, and ZWINT are high-potential DEGs as candidates for tumor-associated antigen CAR T-cell therapy. Further research, both in vitro and in vivo, is needed to enhance the validity of these findings.

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

Neurodegenerative protein conformational diseases are characterized by misfolding and aggregation of metastable proteins encoded within the host genome. The host is also home to thousands of proteins encoded within exogenous genomes harbored by bacteria, fungi, and viruses. Yet, their contributions to host protein-folding homeostasis, or proteostasis, remain elusive. Recent studies, including our previous work, suggest that bacterial products contribute to toxic aggregation of endogenous host proteins. We refer to these products as bacteria-derived protein aggregates (BDPAs). Furthermore, antibiotics were recently associated with increased risk for neurodegenerative diseases, including Parkinson’s disease and amyotrophic lateral sclerosis  possibly by virtue of altering the composition of the human gut microbiota. Other studies have shown a negative correlation between disease progression and antibiotic administration, supporting their protective effect against neurodegenerative diseases. These contradicting studies emphasize the complexity of the human gut microbiota, the gut-brain axis, and the effect of antibiotics. Here, we further our understanding of bacteria’s effect on host protein folding using the model Caenorhabditis elegans. We employed genetic and chemical methods to demonstrate that the proteotoxic effect of bacteria on host protein folding correlates with the presence of BDPAs. Furthermore, the abundance and proteotoxicity of BDPAs are influenced by gentamicin, an aminoglycoside antibiotic that induces protein misfolding, and by butyrate, a short-chain fatty acid that we previously found to affect host protein aggregation and the associated toxicity. Collectively, these results increase our understanding of host-bacteria interactions in the context of protein conformational diseases.

Hypoplastic left heart syndrome (HLHS) is a severe congenital heart disease (CHD) affecting 1 in 5,000 newborns. We constructed the interactome of 74 HLHS-associated genes identified from a large-scale mouse mutagenesis screen, augmenting it with 408 novel protein-protein interactions (PPIs) using our High-precision Protein-Protein Interaction Prediction (HiPPIP) model. The interactome is available on a webserver with advanced search capabilities (http://severus.dbmi.pitt.edu/wiki-HLHS). 364 genes including 73 novel interactors were differentially regulated in tissues/iPSC-derived cardiomyocytes of HLHS patients. Novel PPIs facilitated the identification of TOR signaling and endoplasmic reticulum stress modules. 60.5% of the interactome consisted of housekeeping genes that may harbor large-effect mutations and drive HLHS etiology but show limited transmission. Network proximity of diabetes, Alzheimer’s disease, and liver carcinoma-associated genes to HLHS genes suggested a mechanistic basis for their comorbidity with HLHS. Interactome genes showed tissue-specificity for sites of extracardiac anomalies (placenta, liver and brain). The HLHS interactome shared significant overlaps with the interactomes of ciliopathy and microcephaly-associated genes, with the shared genes respectively enriched for genes involved in intellectual disability and/or developmental delay, and neuronal death pathways. This supported the increased burden of ciliopathy variants and prevalence of neurological abnormalities observed among HLHS patients with developmental delay and microcephaly respectively.

Study of RNA-protein interactions and identification of RNA targets are among the key aspects of understanding the RNA biology. Currently, various methods are available to investigate these interactions, in particular, RNA pulldown assay. In the present paper, a method based on the HaloTag technology is presented that is called Halo-RPD (HaloTag RNA PullDown). The proposed protocol uses plants with stable fusion protein expression and the MagneBeads magnetic beads to capture RNA-protein complexes directly from the cytoplasmic lysate of transgenic A. thaliana plants. The key stages described in the paper are as follows: 1) preparation of the magnetic beads 2) tissue homogenization and collection of control samples 3) precipitation and wash of RNA-protein complexes; 4) evaluation of protein binding efficacy; 5) RNA isolation; 6) analysis of the obtained RNA. Recommendations for better NGS assay designs are provided.

The present Feature Paper highlights the application of bacterial surface (S-) layer proteins as versatile components for the fabrication of biosensors. One technologically relevant feature of S‑layer proteins is their ability to self-assemble on many surfaces and interfaces to form a crystalline 2D protein lattice. The S-layer lattice on the surface of a biosensor becomes part of the interface architecture, linking the bioreceptor to the transducer interface, which may cause signal amplification. The S-layer lattice as ultrathin, highly porous structure with functional groups in a well-defined special distribution and orientation and an overall anti-fouling characteristics can significantly raise the limit in terms of variety and ease of bioreceptor immobilization, compactness of bioreceptor molecule arrangement, sensitivity, specificity, and detection limit for many types of biosensors. The present paper discusses and summarizes examples for the successful implementation of S-layer lattices on biosensor surfaces in order to give a comprehensive overview on the application potential of these bioinspired S-layer protein-based biosensors.

Following the detection of highly pathogenic avian influenza (HPAI) virus in countries bordering Kenya to the west, we conducted surveillance among domestic and wild birds along the shores of Lake Victoria. In addition, between 2018 and 2020, we conducted surveillance among poultry and poultry workers in live bird markets and among wild migratory birds in various lakes that are resting sites during migration to assess introduction and circulation of avian influenza viruses in these populations. We tested 7,464 specimens (oropharyngeal and cloacal swabs) from poultry and 6,531 fresh fecal specimens from wild birds for influenza A viruses by real-time RT-PCR. Influenza was detected in 3.9% (n=292) of specimens collected from poultry and 0.2% (n=10) of fecal specimens from wild birds. On hemagglutinin subtyping, most of the influenza A positives from poultry (274/292, 93.8%) were H9. Of 34 H9 specimens randomly selected for further subtyping, all were H9N2. On phylogenetic analysis, these viruses were genetically similar to other H9 viruses detected in East Africa. Only two of the ten influenza A positive specimens from the wild bird fecal specimens were successfully subtyped; sequencing analysis of one specimen collected in 2018 was identified as low pathogenicity avian influenza H5N2 virus of the Eurasian lineage and the second specimen, collected in 2020, was subtyped as H11. A total of 18 OP/NS swabs from poultry workers with ARI (12%) were collected; none were positive for influenza A virus. We observed significant circulation of H9N2 influenza viruses in poultry in live bird markets in Kenya. During the same period, low pathogenic H5N2 virus was detected in a fecal specimen collected in a site hosting a variety of migratory and resident birds. Although HPAI H5N8 was not detected in this survey, these results highlight the potential for introduction and establishment of highly pathogenic avian influenza viruses in poultry populations and the associated risk of spillover to human populations.

Frequently Asked Questions (FAQs) systems rely on semantic symmetry similarity measuring between two sentences. To address the challenges of insufficient training data and limited domain-specific understanding in low-resource FAQs, this paper proposes a general framework, PDAMF-FAQ, to solve these issues. Firstly, we propose a paraphrasing-based data augmentation model that integrates syntactic information and edit vectors. Using a rule-based approach, it retrieves template sentences from a corpus and masks relevant words with special characters. Edit vectors between the original and paraphrase sentences are added to a pre-trained model's encoding layer to enhance the model's ability to learn the differences between the original and reference paraphrase sentences. Additionally, this paper presents a mixed-feature semantic matching model based on SimBERT. The model extracts keyword features from the text, replacing these keywords with special characters to construct intent features. These intent features, along with the user question and keyword features, are then concatenated to form the model's input. Experiments were conducted respectively on the paraphrasing-based data augmentation model, mixed-feature semantic matching model and their comprehensive application in a low-resource domain-specific FAQ. The experimental results show that the proposed framework effectively improve the performance of domain-specific FAQ system.

With the widespread use of new equipment such as distributed photovoltaics, distributed energy storage, electric vehicles, and distributed wind power, the control of low-voltage distribution networks (LVDNs) has become increasingly complex. Acquiring the most recent topological structure is essential for conducting accurate analysis and real-time control of LVDNs. The signal-injection-based topology identification algorithm is favored for its speed and efficiency. This study proposes a new signal-injection-based topology identification algorithm aimed at solving the issues of reduced completeness and correctness of identification caused by missing feature signal records (FSRs). By analyzing the correlations between FSRs of different positions, the algorithm employs vertical and horizontal completion methods to effectively address missing data, combined with inclusion detection algorithms, to identify the topology of LVDNs. Based on the study of actual LVDN data, the results indicate that the algorithm not only significantly improves the completeness and correctness of topology identification for LVDNs but can also increase the number of devices in operation by evaluating the status of topological equipment, further enhancing the topology identification performance.

In the process of climate change mitigation and adaptation, the focus on climate risk driven by transition innovations has received widespread attention from governments, regulators, and investors. Based on the identification of low-carbon patents through the Green and Low-carbon Technology Inventory in China, this study constructs low-carbon innovation measurements of listed firms in China from 2015 to 2021. Then, an empirical model is used to investigate the impact and mechanism of climate transition innovations on the default risk. The baseline regression model shows that low-carbon innovations can mitigate the default risk of listed firms. Moreover, our findings are supported by instrumental variable regressions that use the time costs of innovation. Finally, the mediation effect demonstrates that investor attention, total factor productivity, and technology spillovers are paths through which transition innovations can affect the default risk. This study reveals that low-carbon technological advances have a positive effect on climate transition risks.

This review provides a comprehensive and updated information on chalcones, presenting their sources, methods of identification and properties putting emphasis on applications in agricultural industry. Vast exploitation of synthetic pesticides led to the weed and pest resistance issue, causing economic loss but more importantly health risk due to pesticide overuse. Because one of the aim of the European Green Deal 2030 is the Farm to Fork strategy which targets on reducing by 50% the use of chemical pesticides by 2030, and push towards natural pesticides which are more environmentally friendly and restore natural resources, chalcones and their derivatives seem to fit perfectly. They have herbicidal, fungicidal, bactericidal and antiviral properties. Moreover, chalcones are naturally occurring substances, known for their favorable health effect for years, working on many areas. This review is complementary to the previous ones describing chalcones use in agriculture, updates them but additionally shows methods of detection.

Public housing stock, called Social Housing, in Italy developed between the 1950s and the 1980s. As of today, the first residential developments are almost nearing their end-of-life age, in need of urgent and intensive renovation. The European Commission, with the Renovation Wave, has set a goal of doubling the rate of building renovation over the next 10 years, reducing emissions, improving energy performance, and promoting decarburization. Renovation interventions, including structural, functional, energy, plant upgrading, etc., are to be preferred over integral demolition and reconstruction interventions, which have significant repercussions in terms of managerial and social discomfort. The case studies examined concern renovation interventions aimed at energy efficiency, functional adaptation of housing as well as facade restyling. The design variants analyzed were evaluated in terms of CO2e emissions, according to LCI (Life Cycle Inventory) and EPD (Environmental Product Declaration) approaches. This approach has a twofold purpose: to propose design guidelines, with low CO2e emissions, through hypotheses of variants to the case studies, and to propose, to the Economic Operators, economically advantageous bidding scenarios, in the procurement process.

For the last two decades, an increasing demand for low-cost adsorbents for drinking water treatment has been challenged in the rural areas of developing countries that have problems with arsenic (As) contamination. In this work, spent bleaching earth (SBE), a residual material that is formed during the process of refining vegetable oil, has been utilized to prepare the new magnetic adsorbent Fe-SBE/C by modifying its surface area through calcination and co-precipitation with iron. The experimental results demonstrate that Fe-SBE/C exhibits a substantial adsorption capacity towards both arsenite (As(III)) and arsenate (As(V)). Optimal pH conditions were found to be pH 10 for As(III) and pH 3 for As(V), resulting in adsorption percentages of 76.7% and 94.1%, respectively. Other experimental parameters such as calcination conditions, adsorbent dosage, iron-loading ratio, and the presence of co-existing ions were thoroughly investigated. The kinetic study revealed that the adsorption processes follow the Elovich and intraparticle diffusion models, suggesting a combined adsorption mechanism of boundary layer control and chemisorption. Furthermore, the isotherm followed the Langmuir model with a maximum adsorption capacity of 202.61 μg g-1 for As(III) and 187.61 μg g-1 for As(V). Through thermodynamic analysis and reinforcement by activation energy data, this research validates that the observed adsorption process is indicative through chemisorption. The regeneration study revealed the potential for multiple cycles of arsenic removal, highlighting the practical applicability of Fe-SBE/C in environmental contexts. In conclusion, the findings of this study underscore the efficacy of Fe-SBE/C in arsenic removal and present it as a promising and environmentally friendly solution for mitigating arsenic pollution.

Background. Implementing mammogram screening means that clinicians are seeing many breast cancers that will never develop metastases. The purpose of this study was to identify subgroups of breast cancer patients who did not present events related to long-term breast cancer mortality, taking into account diagnosis at breast screening, absence of palpability and axillary involvement, and genomic analysis with PAM50. Patients and Methods. To identify them, a retrospective observational study was carried out selecting patients without palpable tumour, without axillary involvement, and a genomic analysis was performed with PAM50. Results. The probability of distant metastasis-free interval (DMFI) of 337 patients was 0.92 (95% CI, 0.90-0.93) at 20 years and 0.96 (95% CI, 0.92-1.00) in 95 patients (28%) with available PAM50 tests. In 22 (23.15%) luminal A tumours and in 9 (9.47%) luminal B tumours smaller than 1 cm and in HER2 and basal type tumours there were no metastatic events (20-year DMFI of 1.00). Conclusion. Patients with nonpalpable breast cancer found at screening with negative nodes are at very low risk. It is possible to identify subgroups without metastatic events by determining the intrinsic subtype and tumour size less than 1 cm. De-escalation of treatment should be considered.

This paper is an extended version of a previously reported conference paper regarding low power design for NAND Flash. As the number of bits per NAND Flash die increases with cost scaling, IO datapath speed increases to minimize the page access time with scaled CMOS in IOs. The power supply for IO buffers, namely VDDQ, has decreased from 3V to 1.2V, accordingly. In this paper, how a reduction in VDDQ can contribute to power reduction in BL path is discussed and validated. Conventionally, BL voltage of about 0.5V has been supplied from a supply voltage source (VDD) of 3V. BL path power can be reduced by a factor of VDDQ to VDD when BL voltage is supplied from VDDQ. To maintain a sense margin at sense amplifiers, the supply source for BLs is switched from VDDQ to VDD before sensing. As a result, power reduction and equivalent sense margin can be realized at the same time. The overhead of implementing this operation is an increase in BL access time of about 2% for switching the power supply from VDDQ to VDD and an increase in die size of about 0.01% for adding the switching circuit, both of which are not significant in comparison with a significant power reduction in BL path power of NAND die of about 60%. The BL path was designed in 180nm CMOS to validate the design. When the cost for powering SSD becomes quite significant especially for data center, an additional lower voltage supply such as 0.8V dedicated to BL charging for read and program verify operations may be the best option for the future.

forging a resilient path towards a low carbon future, this research delves deep into the intricate dynamics of the petroleum and petrochemical industries. By uncovering the challenges posed by transitioning to a low carbon economy, this study emphasizes their transformative potential as catalysts for growth. Through an in-depth analysis of the oil and natural gas sector, it not only sheds light on the carbon footprint of Nigeria's petroleum and petrochemical industries but also identifies the opportunities for sustainable transformation within these sectors. Ultimately, this research aims to pave the way for a greener future by unraveling the complexities and intricacies of building a low carbon economy."By incorporating the unique attributes of the petroleum and petrochemical industries and considering the evolving domestic and global context, this research investigates the challenges and prospects associated with the shift towards a low-carbon economy. It delves deep into the complexities of the sector, taking into consideration the distinct characteristics of petroleum and petrochemical production. Through a comprehensive analysis, this study aims to uncover the potential barriers and opportunities that arise from the pursuit of a sustainable and low-carbon future within the petroleum and petrochemical industries. In addition, this research thoroughly examines the current global and local conditions, shedding light on the opportunities for growth and transformation within the petroleum and petrochemical sectors. By presenting insightful perspectives and recommendations, the study aims to provide valuable guidance for fostering the development of a low-carbon economy within these industries. Ultimately, the research seeks to drive positive change by offering actionable insights and strategies to propel the transition towards a sustainable future.

Background. The purpose of the study was to evaluate the intensity and frequency of low back pain (LBP) in people with multiple sclerosis (PwMS) and the patient's knowledge of physiotherapeutic methods of combating. Methods. In this study, patients with confirmed multiple sclerosis were selected. The study was carried out using an original survey questionnaire and a numerical pain intensity scale (Visual Analogue Scale). PwMS were divided into 3 age groups: 18-30 years, 31-50 years, and over 50 years. Results. Ninety PwMS (68 women and 22 men) aged 18 to 60 years were included in the study. The mean duration of the disease was 9.5±4.9 years, and the mean EDSS was 3.5±1.6. Most of the patients had a relapse-remitting form. 68.9% of PwMS felt lower back pain (n = 62). The relationship tested was statistically significant (p=0.0000012), and the strength of the relationship was high (rc=0.695). The average level of low back pain among PwMS was 4.7 out of 10 on the VAS scale. The prevalence of LBP was higher in female patients (p<0.001), with a secondary progressive form (p<0.001) and with a longer duration of the disease (p=0.023). The most widely used methods of LBP therapy were kinesitherapy and manual therapy. Conclusions. LBP is common in multiple sclerosis. A female sex, a secondary progressive form of MS, and a longer duration of the disease increased the risk of LBP. It is important to implement properly planned physiotherapy activities and educate patients on how to combat LBP.

Camera malfunctions or loss of storage elements in imaging devices may lead to loss of important image information or random impulse noise interference. Low rank is one of the important prior information in image optimization processing. This paper uses different low-rank constraint models of the image matrices to recover the impulse interference satellite images. Firstly, an overview of image inpainting models based on nuclear norm, truncated nuclear norm, weighted nuclear norm, and matrix-factorization-based F-norm is presented, and corresponding optimiza-tion iterative algorithms are provided. Then, we conducted experiments under three types of pulse interference and provided visual and numerical results. Finally, it is concluded that the WSVT_ADMM method based on the weighted nuclear norm can obtain the best image inpainting results; The UV_ADMM method based on F norm of matrix factorization has the least computa-tion time and can be used for large-scale low-rank matrix computation; The WSVT_ADMM method based on weighted nuclear norm and the TSVT_ ADMM method based on truncated nuclear norms can significantly improve the repair effect compared to the nuclear norm-based methods such as SVT, SVP, and n_ADMM.

In the context of post-harvest pest management in agricultural products, the adoption of modified atmospheres presents an eco-friendly alternative to conventional pesticides. This study focuses on nitrogen gas as a potential agent for insect control in stored commodities, utilizing computational simulations to investigate its penetration and distribution within two common storage configurations: chamber-contained pallets and silos. By employing the convection-diffusion equation, the simulations reveal insights into nitrogen distribution dynamics and duration required for oxygen reduction. The results highlight the influence of boundary conditions, commodity porosity, and convection effects on nitrogen dispersion. In chamber scenarios, boundary condition type significantly affects oxygen reduction time, while in silos, convection and diffusion interact to establish a consistent diffusion layer thickness. This research enhances the understanding of modified atmosphere techniques and their potential for sustainable pest management. It provides practitioners with valuable quantitative insights, paving the way for optimized modified atmosphere strategies in real-world agricultural contexts.

A Gem-quality rubies and sapphires are often commercially heat treated at about 800°C or higher temperatures to enhance their colour and clarity, and hence quality. For this study, selected corundum samples containing diaspore- and goethite inclusions were heated step-by-step to a maximum of 1000 °C with the aim to monitor the dehydration and phase transformation of these oxyhydroxides to corundum and hematite during heating. Based on our experiments and in agreement with literature, the dehydration of diaspore in corundum occurs between 525 to 550 °C, whereas goethite transforms to hematite already between 300 and 325 °C. As both, diaspore and goethite are common inclusions in rubies, sapphires, and other corundum varieties, these dehydration reactions and phase transformations can be considered important criteria to separate unheated stones from heated ones, specifically in cases in which other methods (e.g. microscopy, FTIR) are unsuccessful.

One of the strategies to reduce the contents of the low density lipoproteins (LDLs) in a blood is a hemoperfusion, in which case they are selectively retracted from plasma by an adsorber located outside the patient body. Recently, a photo-controllable smart surface was developed for this purpose characterised by high selectivity and reusability [C.Guo et al., ACS Applied Materials &amp; Interfaces 2022, DOI:10.1021/acsami.2c07193]. We present a mesoscopic model for such a setup involving the azobenzene-containing polymer brush and the model LDL particles. The latter comprise an uniform spherical core covered by a shell of elongated particles representing phospholipids. The system is studied using the coarse-grained molecular dynamics simulation. We examined the dependences of the binding energy on both the length of polymer chains and the grafting density of a brush, and established optimal conditions for the adsorption. These are explained by a competition between the concentration of azobenzenes and phospholipids in the same spatial region, flexibility of polymer chains, and excluded volume effects.

Torulaspora delbrueckii showed renewed interest in recent years in the fermentation of wine, for its biotechnological potential linked to the ability to enhance flavor and aroma and it probably is the non-Saccharomyces yeast currently widely used in winemaking. On the base of this, sequential fermentations with a selected native strain of T. delbrueckii (DiSVA 130) and low sulfite native strain of Saccharomyces cerevisiae (DiSVA 709) were carried out to establish their contribution in biocontrol and aroma profile. A first set trials, carried out in winery, were set up to establish the effect of the sulfur dioxide addition on pure and T. debrueckii/S. cerevisiae sequential fermentations. A second set of sequential fermentations without SO₂ addition were conducted in the same conditions, to evaluate the biocontrol and aromatic effectiveness of the T. delbrueckii native strain and a commercial one. The effective biocontrol action of native T. delbrueckii inoculated in sequential fermentation was shown, indeed without SO₂ addition the presence of native T. delbrueckii revealed an effective fungistatic action in the first two days of fermentation. Moreover, the native T. delbrueckii strain seems to have fermentative performances comparable to those of T. delbrueckii commercial strain showing a more evident biocontrol action (wild yeasts reduced by c.a. 1 Log at 2^nd day) and its presence did not negatively affect S. cerevisiae fermentation activity. Finally, the combination of both native and commercial T. delbrueckii/S. cerevisiae trials led distinctive aromatic profile of wines with a significant enhancement of isoamyl acetate, phenyl ethyl acetate, supported by positive appreciations, from the tasters, for ripe and tropical fruits, citrus and balance. The whole results indicate that the proposed strain could be a potential biocontrol tool toward wild yeasts in the first phase of fermentation also contributing to improve and differentiate the final aroma wine.

Highly efficient, broadband and distinctively structured electromagnetic wave (EMW) absorption materials exhibit huge exceptions with multi-functions in both military and civilian fields. Searching the relationship between structural and EMW performance is beneficial to develop outstanding microwave absorption materials, and has become an attractive research topic. In this study, we briefly reviewed the different EMW absorption mechanisms and key influence factors, then, present the latest developments in low-dimensional (LD) EMW absorption materials. We provide a comprehensive discussion of remarkable examples and summarize the main information related to the structure-function relationship of dimensional design and structural engineering in order to facilitate the rapid evolution of this fascinating field.

Low back pain (LBP) is a health problem that affects 70-80% of the population in Western countries. Because of the biomechanical relationship between the lumbar region and the hip, it is thought that strengthening the muscles of this joint could improve the symptoms of people with LBP. The objective of the study is to evaluate the current evidence on the efficacy of hip strengthening exercises to reduce pain and disability in people with LBP. Clinical trials were collected from PubMed, PEDro, and Scopus databases published up to September 2022. Based on Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) guidelines and using CASpe and PEDro tools for methodological quality assessment, we selected studies that included hip strengthening exercises as part of LBP treatment and measured pain and/or disability parameters. Among the 966 records identified in the search, a total of 7 studies met the established selection criteria. Overall, participants who performed hip strengthening exercises had significantly improved in pain and disability. The methodological quality of the included studies was assessed as “good”. In conclusion, the addition of hip muscle strengthening exercises iterating LBP effectively improving pain and disability.

Our understanding of the long-term consequences of chronic ionising radiation for living organisms remains scarce. Modern molecular biology techniques are helpful tools for researching pollutant effects on biota. To reveal the molecular phenotype of plants growing under chronic radiation exposure, we sampled Vicia cracca L. plants in the Chernobyl Exclusion Zone and in areas with normal radiation backgrounds. We performed a detailed analysis of soil and gene expression patterns, and made coordinated multi-omics analyses of plant samples, including transcriptomics, proteomics, and metabolomics. Chronic exposure to ionising radiation induced complex and multidirectional changes, including significant alterations in the metabolism and gene expression patterns of irradiated plants. We revealed profound changes in carbon metabolism, nitrogen reallocation, and photosynthesis. These plants were characterised by increased DNA damage, redox imbalance, and stress response reactions. The upregulation of histones, chaperones, peroxidases, and secondary metabolism were noted.

Drowning is a serious public health concern. Low middle income countries are mostly affected, as they carry 90% of the global drowning burden. The purpose of this epidemiological study is to provide a comprehensive overview of fatal drownings in South Africa between 2016 and 2021. The data used for the study was obtained from the South African Police Service. Descriptive statistics were used to summarise data. Statistical analysis included a t-test and chi-square test. The results indicate that the average fatal drownings per annum is 1477 in South Africa, with a drowning rate of 2.54 per 100 000 population from 2016 - 2021. The KwaZulu-Natal province had the highest incidence of drowning. The 0 – 4-year category has a high prevalence of drowning amongst all the age categories. More males drowned in South Africa compared to females. The study highlights key areas of concern these include age, sex, race, province, type of water body and time of day. This information is crucial to inform drowning prevention initiatives in South Africa.

Low-grade glioma (LGG) is a highly aggressive disease in the skull. On the other hand, anoikis, a specific form of cell death induced by the loss of cell contact with the extracellular matrix, plays a key role in cancer metastasis. In this study，anoikis-related genes (ANRGs) were used to identify LGG subtypes and to construct a prognostic model for LGG patients. In addition, we explored the immune microenvironment and enrichment pathways between different subtypes. We constructed an anoikis-related gene signature using the TCGA cohort and investigated the differences in clinical features, mutational landscape, immune cell infiltration, etc. between different risk groups. Kaplan-Meier analysis showed that the characteristics of ANRGs in the high-risk group were associated with poor prognosis in LGG patients. The risk score was identified as an independent prognostic factor. The high-risk group had higher immune cell infiltration, tumor mutation load, immune checkpoint gene expression, and ICB treatment response. Functional analysis showed that these high- and low-risk groups had different immune statuses and drug sensitivity. Risk scores were used together with LGG clinicopathological features to construct a nomogram, and DCA analysis showed that the model could enable patients to benefit from clinical treatment strategies.

Reduced glutathione (GSH) is an antioxidant in plants and is one of the important ways for plants to combat low-temperature stress. In this paper, Eriobotrya japonica Lindl. cv. Zaozhong No. 6 seedlings were used to study the effects of exogenous 5-aminolevulinic acid (ALA) application on glutathione synthesis and cyclic metabolism of loquat seedlings under low-temperature stress and to explore the regulatory mechanism of ALA on loquat cold tolerance. The results showed that ALA treatment could increase the content of GSH and the reduced glutathione/oxidized glutathione (GSH/GSSG) ratio in loquat leaf slices under low-temperature stress; reduce the electrolyte leakage rate and GSSG, H₂O₂ and MDA contents in leaf tissues; and alleviate the peroxidation damage caused by low temperature. ALA treatment increased the activity of γ-glutamine synthetase (γ-ECS) in loquat leaf slices under low-temperature stress and promoted the biosynthesis of reduced glutathione, thereby increasing the GSH content in leaf tissues. On the other hand, ALA treatment could also improve the activities of glutathione reductase (GR), glutathione S-transferase (GST) and glutathione peroxidase (GPX) and promote the cyclic regeneration of GSH, accordingly maintaining a high GSH/GSSG ratio, promoting the removal of reactive oxygen species (ROS), and enhancing the antioxidant capacity of leaves. The regulatory effect of ALA on enhancing the antioxidant capacity of loquat seedlings under low-temperature stress can be inhibited by L-buthionine-sulfoximine (BSO, GSH biosynthesis inhibitor). The results showed that ALA improved the antioxidant capacity of loquat seedlings under low-temperature stress, and GSH was involved in the regulation of the antioxidant effect of ALA on loquat seedlings under low-temperature stress.

Urban floods are typical urban disasters that threaten the economy and development of cities. Sponge cities can improve the flood resistance ability and reduce the floods by setting low-impact development measures (LID). Evaluating the floods reduction benefits is the basic link in the construction of sponge cities. Therefore, it is of great significance to evaluate the benefits of sponge cities from the perspective of different rain patterns. In this study, we investigated the urban runoff of various rainfall patterns in Mianyang city using the Strom Water Management Model (SWMM). We employed 2–100-year return periods and three different temporal rainfall downscaling methods to evaluate rain patterns and simulate urban runoff in Mianyang, with and without the implementation of sponge city measures. After calibration, model performance was validated using multi-source data concerning flood peaks and inter-annual variations in flood magnitude. Notably, the effects of peak rainfall patterns on historical floods were generally greater than the effects of synthetic rainfalls generated by temporal downscaling. Compared to the rainfall patterns of historical flood events, the flood protection capacities of sponge cities tended to be overestimated when using the synthetic rainfall patterns generated by temporal downscaling. Overall, an earlier flood peak was associated with better flood sponge city protection capacity.

Computer systems that operate in remote locations such as satellites, remote weather stations and autonomous robots are highly limited in the availability of energy for their operation. This work aims to employ artificial intelligence algorithms in energy management in order to obtain the maximum energy yield and the prediction of energy availability to the system. The work presents the main types of algorithms used in artificial intelligence and presents the creation of a prototype that will operate as a low power system powered by batteries and a small solar plate, the prototype will perform inferences on the LSTM neural network algorithm in order to predict the future availability of energy, consequently the management system will carry out the energy distribution in order to obtain the maximum operation of the prototype without total discharge of the batteries. So that the artificial intelligence system could be embedded in the prototype, the TensorFlow Lite framework was used, which allows the inference to be carried out in devices with low consumption and limited processing power.

Low-energy Coulomb excitation is capable of providing unique information on static electromagnetic moments of short-lived excited nuclear states, including non-yrast states. The process selectively populates low-lying collective states and is therefore ideally suited to study phenomena such as shape coexistence and development of exotic deformation (triaxial or octupole shapes). Historically, these experiments were restricted to stable isotopes. However, the advent of new facilities providing intense beams of short-lived radioactive species has opened the possibility to apply this powerful technique to a much wider range of nuclei. We discuss the observables that can be measured in a Coulomb-excitation experiment, their relation to nuclear structure parameters with an emphasis on the nuclear shape, and present some recent examples of Coulomb-excitation studies that provided outcomes relevant for the Shell Model.

Pain is an unpleasant emotional and sensory experience. For many years orthodontists have been looking for an effective method of reducing this feeling of discomfort. In recent years, low-level laser therapy (LLLT) has taken hold in the orthodontic field. Among the countless advantages it can modulate the painful feeling. The aim of this research is to identify the use of photobiomodulation in subjects undergoing fixed orthodontic treatment, to reduce the pain and discomfort that it causes. The research was conducted from the Web of Science, Pubmed and Scopus databases. Only 14 of all articles met the inclusion and exclusion criteria and were therefore used to conduct the research. The different studies compared, in most cases, patients whose mouth was divided into a part treated with laser therapy and a placebo part. The results show a statistically significant difference in perceived pain between the irradiated arch and the non-irradiated arch. Three authors didn’t find statistically significant results in favour of low-laser therapy, but it is important to remember that they used different parameters. To obtain generally valid studies, with consistent and reproducible results, it is necessary to standardize the different parameters used that are independent by operator performing the procedure.

We report a very frugal microscope building method from easily realizable parts. We show a highly portable field ready compound type microscope with bright field, dark field and projection microscopy capabilities. It has good resolution and magnification for multiple aspects of education and diagnosis. We demonstrate that such a system can be built from simple lenses in laser pointers and camera modules with no specific 3d printed parts or costly lenses. We show all the parts of the system like stage, coarse and fine focussing system, microscope body, even slides can be built from commonly available materials like soda bottle and DVD disks. We list alternate, safer and easily available staining methods and chemicals. The microscope is developed with a target that it can be self-developed even in rural areas of the world with only resources at one’s disposal with very little education. This features a stable focussing and panning system for comfortable viewing through eyes and also easy imaging with a smartphone. We show its utility for microorganism analysis and potential for clinical diagnosis.

This paper focuses on processing low oversampling echo data of staggered synthetic aperture radar (SAR). In staggered mode, the non-uniformly sampling and irregular loss of echo data cause azimuth ambiguity which severely degrades the imaging quality. To solve this problem, we propose a compressed sensing (CS) method in which the non-uniform fast Fourier transform (NUFFT) technique is adopted to obtain uniform azimuth spectrum, and the fast iterative shrinkage thresholding algorithm (FISTA) is utilized to efficiently reconstruct the ambiguity-free image from in-complete echo data. Simulation results demonstrate the proposed method can effectively suppress the azimuth ambiguity in the vicinity of targets.

Population concentration in cities brings new risks as an increase in pollution, which causes urban health problems. In order to address this problem, traffic reduction measures are being implemented, as pedestrianization areas and the definition of Low Emissions Zones (LEZ). When the effectiveness of these types of measures is in doubt, smart city tools provide data that can be used to scientifically asses their impact. This article analyzes the situation of Madrid Central (Spain), a LEZ subject to controversy. We apply statistical and regression analyses to evaluate the effectiveness of this measure to reduce air pollution and outdoor noise. According to the results, this LEZ was able to significantly reduce NO$_2$, PM$_{2.5}$, and PM$_{10}$ concentration locally, having the same positive impact in the rest of the city. In terms of noise, this measure is able to mitigate background noise levels generated by the road traffic.

The aim of this survey is to review some recent developements in devising efficient preconditioners for sequences of linear systems A x = b. Such a problem arise in many scientific applications, such as discretization of transient PDEs, solution of eigenvalue problems, (Inexact) Newton method applied to nonlinear systems, rational Krylov methods for computing a function of a matrix. Full purpose preconditioners such as the Incomplete Cholesky (IC) factorization or approximate inverses are aimed at clustering eigenvalues of the preconditioned matrices around one. In this paper we will analyze a number of techniques of updating a given IC preconditioner (which we denote as P0 in the sequel) by a low-rank matrix with the aim of further improving this clustering. The most popular low-rank strategies are aimed at removing the smallest eigenvalues (deflation) or at shifting them towards the middle of the spectrum. The low-rank correction is based on a (small) number of linearly independent vectors whose choice is crucial for the effectiveness of the approach. In many cases these vectors are approximations of eigenvectors corresponding to the smallest eigenvalues of the preconditioned matrix P0 A. We will also review some techniques to efficiently approximate these vectors when incorporated within a sequence of linear systems all possibly having constant (or slightly changing) coefficient matrices. Numerical results concerning sequences arising from discretization of linear/nonlinear PDEs and iterative solution of eigenvalue problems show that the performance of a given iterative solver can be very much enhanced by the use of low-rank updates.

The establishment of low carbon assessment initiatives is a crucial task especially at the city level. The determination of which source of carbon contributed more require robust data set and strategic approach. Hence, by using the campus as a small city approach, the establishment of carbon assessment and its’ reduction initiatives was required to keep track of the hotspot of the carbon source. The substantial amount of carbon source from campus operations such as energy consumption in the building, waste generation, and water consumption were identified. Moreover, as institutions of higher education, the execution of low carbon campus was initiated structurally involves the triangulation of research activities, teaching & learning and as well as campus operations or known as campus living lab approach. The application of low carbon cities framework, LCCF and assessment system enables to strategize the low carbon campus initiatives through the use of carbon footprint concept and the LCCF carbon track.

Carburizing of stainless steels at low temperatures (below 500°C) develops a high content carbon layer, known for its high hardness. X-ray Diffraction investigation indicates that carburization treatment does not impact the structure of substrate; however, introduced carbon causes expansion in the carburized layer through the increase in d-spacing. Characterization of carbon concentration and hardness profiles indicate that carbon content gradually decreases while moving further into the substrate; and the origin of the increased hardness of the expanded layer arises from the super-saturated carbon content, following the solid solution strengthening theory. An area that is not well understood is in regard to the carburized layer’s relation to the substrate and the significance in their differences. Using two grades of stainless steel, AISI 316L and PH 17-4, it was observed that the carburized layer is not a separate layer, but a higher carbon content version of the substrate,

Carbon concrete PAN/lignin-based CF composites are a new promising material class for the building industry. The replacement of the traditional heavy and corroding steel reinforcement by carbon fiber (CF) based reinforcements offers many significant advantages: a higher protection of environmental resources because of lower CO2 consumption during cement production, a longer lifecycle and thus muss less damage in structural components and a higher degree of design freedom because lightweight solutions can be realized. However, due to cost pressure in civil engineering, completely new process chains are required to manufacture CF based reinforcement structures for concrete. The article describes the necessary process steps in order to develop CF reinforcement: (1) the production of cost-effective CF using novel carbon fiber lines, (2) the fabrication of CF rebars with different geometry profiles. It was found that PAN/lignin-based CF is currently the most promising material in order to meet the future market demands. However, significant research needs to be undertaken in order to improve the properties of lignin-based and PAN/lignin-based CF, respectively. The CF can be manufactured to CF-based rebars using different manufacturing technologies which have been developed on prototype level in this study.

We conducted an in-situ crystal structure analysis of ferroselite at non-ambient conditions. The aim is to provide a solid ground to further the understanding of the properties of this material in a broad range of conditions. Ferroselite, marcasite-type FeSe2, was studied under high pressures up to 46 GPa and low temperatures, down to 50 K using single-crystal microdiffraction techniques. High pressure and low temperatures were generated using a diamond anvil cell and a cryostat. We found no evidences of structural instability in the explored P-T space. The deformation of the orthorhombic lattice is slightly anisotropic. As expected, the compressibility of the Se-Se dumbbell, the longer bond in the structure, is larger than that of the Fe-Se bonds. Less obvious is the behavior of the octahedral bonds, the shorter bond is the most compressible determining a small increase in the octahedron distortion with pressure. We also achieved a robust structural analysis of ferroselite at low temperature in the diamond anvil cell. Structural changes upon temperature decrease are small but qualitatively similar to those produced by pressure.

The consumer’s acceptability of hamburgers elaborated with the flank of culling cows in which the content of salt or fat had been partially replaced was studied. A mixture of potassium chloride, potassium ferrocyanide and sodium ferrocyanide was used as substitutes for the salt. Oat flakes or a mixture of chia and flax seeds were used as substitutes for the fat. The hamburgers were tasted by 34 consumers. Consumers did not detect significant differences between the control and the rest of the formulations. Neither the gender nor the age of the consumers influenced the sensory appraisal. However, many comments regarding texture failures were recorded. Therefore, the substitution of salt and / or fat in the composition of hamburgers made with the flank of cows is a viable alternative for the commercialization of these pieces of low commercial value as long as the texture of the same is adjusted to resemble it to the control.

Air pollution has created a lot of problems in the developed and developing countries. To avoid or reduce these problems, constant monitoring of the air should be ensured. The conventional techniques is costly because it requires a lot of money and time consuming. Biomonitoring has been the alternative method. Moss, lichens and plants are biomonitors available to entrap air pollutants. The aim of this paper is to discuss one of the ways of monitoring air pollution – Moss bag technique. To do this, types, choice, preparation, handling of bags after preparation of moss were discussed. From the literatures consulted, it was discovered that there were differences in the techniques used by the researchers. In all, the use of mosses with emphasis on the employment of moss bag have proved to be a powerful tool in airborne particulate and toxic elements. To conclude, developing countries should focus more on this technique because it will reduce cost of air monitoring.

A low-cost bio-mass-derived carbon substrate has been employed to synthesize MoS₂@carbon composites through a hydrothermal method. Carbon fibers derived from natural cotton provide a three-dimensional and open framework for the uniform growth of MoS₂ nanosheets, thus constructing hierarchically coaxial architecture. The unique structure could synergistically benefit fast Li-ion and electron transport from the conductive carbon scaffold and porous MoS₂ nanostructures. As a result, the MoS₂@carbon composites, when served as anodes for Li-ion batteries, exhibit a high reversible specific capacity of 820 mAh g^-1, high-rate capability (457 mAh g^-1 at 2 A g^-1), and excellent cycling stability. The superior electrochemical performance makes the MoS₂@carbon composites to be low-cost and promising anode materials for Li-ion batteries.

The development effect of water flooding in ultra-low permeability reservoir was poor due to its poor physical property and high shale content, the experimental study of air flooding which help to complement producing energy was carried out. Based on the Accelerating Rate Calorimeter experimental results, the crude oil of N block in L oilfield can produce low-temperature oxidation reaction, which was the basic condition of air flooding. Three groups of experiment natural cylinder core were designed for oil displacement, water flooding and air flooding were used respectively, and the relationship of differential pressure, oil recovery, injection capacity with injection volume was investigated. It has been showed on the result that the recovery efficiency improved sharply than water flooding, the effect of depressurization and augmented injection was obvious, and the air displacement was validation.

This article focuses on the current state-of-the-art in the area of cellular and molecular biotechnology for over-production of clinically relevant therapeutic growth factors and how the technology can be used for the treatment of osteoarthritis (OA). Transfected and irradiated protein packaging cell lines may be used as “cellular factories” for large-scale production of therapeutic proteins and pro-anabolic growth factors, particularly in the context of cartilage matrix regeneration. We discuss the potential for new innovations in regenerative medicine for degenerative diseases of synovial joints using mammalian protein production platforms, specifically protein packaging cell lines, for over-producing growth factors for cartilage tissue regeneration and give recent examples. Mammalian protein production platforms that incorporate protein packaging cell lines are superior to bacterial expression systems and are likely to have a significant impact on the development of new biological therapies for treating focal cartilage defects and more generally for the treatment of degenerative joint diseases such as OA.

When water molecules or other particles collide with protein molecules in a solution, the protein molecules absorb some of the momentum and deform, forming a certain molecular potential energy. When a protein molecule in a high-energy state changes to a stable state, if there is a suitable substrate binding and the potential energy of the protein molecule is greater than the energy required to break the substrate chemical bond, catalytic action will occur. The α-helices and β-folds in protein molecules play a major role in converting the kinetic energy of water molecules into their own potential energy due to the large number of amino acids involved and their regular structure. The internal structural deformation of proteins caused by the impact of water molecules on α-helices and β-folds also has a profound impact on the structure of substrates. ‌

Alzheimer’s disease (AD) is an age-associated neurodegenerative disorder. A wealth of evidence indicates that the amyloid β (Aβ) aggregates result from dyshomeostasis between Aβ production and clearance, which plays a pivotal role in the pathogenesis of AD. Consequently, therapies targeting Aβ reduction represent a promising strategy of AD intervention. Tetramethylpyrazine nitrone (TBN) is a novel tetramethylpyrazine derivative with the potential for the treatment of AD. Previously, we demonstrated that TBN markedly improved cognitive functions and reduced Aβ, APP, BACE 1 and hyperphosphorylated tau levels in 3 × Tg-AD mice. However, the mechanism by which TBN inhibits Aβ deposition still unclear. In this study, we employed the APP/PS1 mice treated with TBN (60 mg/kg, ig, bid) for six months and N2a/APP695swe cells treated with TBN (300 μM) to explore the mechanism of TBN on the Aβ reduction. Our results indicated that TBN significantly alleviated cognitive impairment and reduced Aβ depositions in APP/PS1 mice. Further investigation of the underlying mechanisms revealed that TBN decreased the expression of APP and BACE1, activated the AMPK/mTOR/ULK1 autophagy pathway and inhibited the PI3K/AKT/mTOR/ULK1 autophagy pathway, as well as decreased the phosphorylation levels of JNK and ERK in APP/PS1 mice. Moreover, TBN was found to significantly reduce the mRNA levels of APP and BACE1, as well as those of SP1, CTCF, TGF-β, and NF-κB, transcription factors involved in regulating gene expression. Additionally, TBN was observed to decrease the level of miR-346 and increase the levels of miR-147 and miR-106a in the N2a/APP695swe cells. These findings indicate that TBN may reduce Aβ levels likely via reducing APP expression by regulating APP gene transcriptional factors and miRNAs, reducing BACE1 expression, and promoting autophagy activities.

Sea cucumber peptides are small molecular peptides with biological function obtained from fresh sea cucumber as feedstock, which were hydrolyzed by protease, separated ,and purified. As the main product of sea cucumber refinement, it more accurately expresses the nutritional effect of sea cucumber and has a wide range of potential applications. It has been demonstrated that sea cucumber has a certain value-added effect on bone mineral density regulation, but the differences in bone mineral density regulation of extracts from different parts of sea cucumber and the techniques contributing to the efficient isolation of bone sea cucumber peptides have not been reported. Firstly, the aim of this study was to reveal the differences in osteogenic activities of enzymatic peptides from three major parts of sea cucumber: the body wall, the egg protein, and the intestinal protein. Then, the bone-enhancing sea cucumber peptides were isolated based on the characteristics of the dif-ferences in molecular weight distribution, hydrophilicity, and ionisation degree of sea cucumber, and to explore the possible mechanisms of their action. The findings indicated that sea cucumber peptides extracted from three distinct sites exhibited a dose-dependent enhancement of osteoblast proliferation and differentiation. Upon evaluating the three methods of sea cucumber peptide separation based on molecular weight distribution, hydrophilicity, and ionization, it was observed that the fraction isolated by hydrophobicity and

In this comprehensive survey, we delve into the multifaceted role of palmitoylation across vari-ous cell death modalities in the oncological context. From its intricate correlations with tumor-igenesis, steered by the DHHC family, to the counter-process of depalmitoylation mediated by enzymes like PPT1. Innovations in detection methodologies have paralleled our growing under-standing, transitioning from rudimentary techniques to sophisticated modern methods. Central to our discourse are agents like GNS561 and DC661, promising heralds in palmitoylation-targeted cancer therapy. Collectively, this review accentuates palmitoylation's transformative potential in oncology, foreshadowing groundbreaking therapeutic strategies and deepening our molecular comprehension of cancer dynamics.

Bioactive peptides are promising cosmetic active ingredients that can improve skin health and appearance. They exhibit a broad spectrum of activity, including anti–ageing, antioxidant, antimicrobial and anti–inflammatory. The aim of this study was to develop a safe, stable and efficacious environmentaly friendly ("green") emulsion using milk protein hydrolysate as a model active ingredient. Potential emulsions were formulated with biodegradable emollients, stabilised with a naturally-derived mixed emulsifier and prepared by cold process. They were evaluated for rheological behavior (continuous rotation and oscillation tests), physical stability (dynamic mechanical thermal analysis - DMTA test) and texture profiles, as well as for cytotoxic, antioxidant and antimicrobial effects. Rheological characterization revealed shear-thinning flow behaviour with yield point from continuous rotation tests and predominantly elastic character from oscillation (amplitude and frequency sweep) tests, with small structural change detected in the DMTA test. These results implied satisfactory rheological properties and good stability. Texture analysis revealed acceptable spreadability and substantivity of the emulsions. The protein hydrolysate showed antioxidant activity. The developed emulsions showed low antibacterial activity against selected microorganisms, but this was due to the action of preservatives, not peptides. All potential emulsions showed desirable safety profile. The results obtained provide the basis for the next stage of formulation development, i.e. in vivo efficacy tests.

Adenoviruses are associated with respiratory tract, gastrointestinal or, less frequently, other involvement. Epidemics of adenovirus infections occur globally, in communities and in closed or crowded settings. In our institution, an outbreak of Adenovirus infection in infants and children was recently observed. Two main patterns of clinical presentation were observed: 68 patients had mainly respiratory symptoms (pharyngitis n=67, cough n=44; tonsillar exudate n=17; other respiratory signs n=4) while 26 patients showed prevalent gastrointestinal involvement (diarrhea n=26, vomiting n=8). Patients with respiratory symptoms had a significantly higher count of WBC, PMN and platelets, while CRP level approached statistical significance (p=0.07) for higher values in the patients with diarrhea. In order to explore the impact of selected presenting features, possible association between level of CRP and presence of pharyngeal exudate, cough, vomiting, diarrhea, duration of fever, number of neutrophils, and administration of antibiotics was analyzed. Patients falling in the tertile with more elevated CRP values had significantly more often tonsillar exudate and diarrhea, while those in the lower tertile had a 4.4 days duration of fever, vs. ≥5.0 days in the remaining patients. Antibiotic therapy was administered more frequently to patients with higher values of CRP (p=0.006). Duration of hospitalization was not associated with the CRP level. The median time from the receipt of positive adenovirus PCR test result to patient discharge was 1 day in 73% of cases. The number of copies of adenovirus detected by PCR ranged between 47 million and 15/L. Falling in the highest terzile of copy number was significantly associated with pharyngitis. The 24 patients with evidence of viral coinfection had no difference in the demographics or presenting features, with the only exception of a significantly higher leukocyte count. Rapid turn-around of results of molecular testing of adenovirus genome on pharyngeal swab allowed us to rapidly diagnose adenovirus infection, allowing stopping antibiotic therapy and immediate discharge, with reduced discomfort for the families and more appropriate use of hospital beds. A high copy number of adenovirus from pharyngeal swab should not be taken as an indicator of worse prognosis, thus allowing preferential use of qualitative rather than quantitaive assay.

Huntington's disease (HD) is caused by an expansion of a CAG repeat in the gene that encodes the huntingtin protein (HTT). The exact function of HTT is still not fully understood, and previous studies have mainly focused on identifying proteins that interact with HTT to gain insights into its function. Numerous HTT-interacting proteins have been discovered, shedding light on the functions and structure of HTT. Most of these proteins interact with the N-terminal region of HTT. Among the various HTT-interacting proteins, huntingtin-associated protein 1 (HAP1) and HTT-interacting protein 1 (HIP1) have been extensively studied. Recent research has uncovered differences in the distribution of HAP1 in monkey and human brains compared to mice. This finding suggests that there may be species-specific variations in the regulation and function of HTT-interacting proteins. Understanding these differences could provide crucial insights into the development of HD. In this review, we will focus on the recent advancements in the study of HTT-interacting proteins, with particular attention to the differential distributions of HTT and HAP1 in larger animal models.

Background: Chagas disease is still a neglected disease considered a public health problem. Early diagnosis of cases is important to improve the prognosis of infected patients and prevent transmission. Serological tests are the method of choice for diagnosis. However, two serological tests are currently recommended to confirm positive cases. In this sense, more sensitive and specific serological tests need to be developed to overcome the problems currently faced. This study aimed to develop a new recombinant multiepitope protein for the diagnosis of Chagas disease, hereafter named rTC. Methods: The rTC was constructed based on amino acid sequences from different combinations of Trypanossoma cruzi antigens in the same polypeptide and tested in ELISA for detecting different Chagas disease. Results: rTC1 was able to discriminate between indeterminate (IND) and cardiac (CARD) cases and cross-reactive diseases, and healthy samples, with 96.6% sensitivity and 97.96% specificity, respectively. Conclusion: These data suggest a preliminary study that rTC1 has the po-tential to be tested in future studies against a larger serological panel for the diagnosis of Chagas disease.

The COVID-19 pandemic has highlighted the importance and urgent need of rapid and accurate diagnostic tests for detection and screening of this infection. In our proposal, a biosensor based on the ELISA immunoassay was developed for monitoring antibodies against SARS-CoV-2 in human serum samples. The SARS-CoV-2 nucleocapsid protein (N-protein) was selected as a specific receptor for the detection of SARS-CoV-2 nucleocapsid immunoglobulin G. Thus, the N-protein was immobilized on surface of screen-printed carbon electrode (SPCE) modified with carboxylated graphene (CG). The IgG-SARS-CoV-2 nucleocapsid concentration was quantified using a secondary antibody labelled with horseradish peroxidase (HRP) (anti-IgG-HRP) catalyzed by 3,3’,5,5’-tetramethylbenzidine (TMB) mediator by chronoamperometry. A linear response was obtained in the range of 1:1000-1:200 v/v in phosphate buffer solution (PBS) and the limit of detection calculated was of 1:4947 v/v. The chronoamperometric method showed electrical signals directly proportional to antibody concentrations due to Ag-Ab specific and stable binding reaction.

Hepatitis C virus (HCV) core protein is a multifunctional protein that is involved in proliferation, inflammation and apoptosis mechanism of hepatocytes. HCV core protein genetic variability has been implicated in various outcomes of HCV pathology and treatment. In the present study, we aimed to analyze the role of HCV core protein in tumor necrosis factor α (TNFα)-induced death under the viewpoint of HCV genetic variability. Immortalized hepatocytes (IHH), and not the Huh7.5 hepatoma cell line, stably expressing HCV subtype 4a and HCV subtype 4f core proteins showed that only HCV 4a core protein could increase sensitivity to TNFα-induced death. Development of two transgenic mice expressing the two different core proteins under the liver-specific promoter of transthyretin (TTR) allowed for the in vivo assessment of the role of core in TNFα-induced death. Using the TNFα-dependent model of lipopolysaccharide/D-galactosamine (LPS/Dgal) we were able to recapitulate the in vitro results in IHH cells in vivo. Transgenic mice expressing HCV 4a core protein were more susceptible to the LPS/Dgal model while mice expressing HCV 4f core protein had the same susceptibility as their littermate controls. Transcriptome analysis in liver biopsies from these transgenic mice gave insights into HCV core molecular pathogenesis, while linking HCV core protein genetic variability to differential pathology in vivo.

A model for parasitic motility has been proposed in which parasite filamentous actin (F-actin) is attached to surface adhesins by a large component of the glideosome, known as the glideosome-associated connector protein (GAC). This large 286 kDa protein interacts at the cytoplasmic face of the plasma membrane with the phosphatidic acid-enriched inner leaflet and cytosolic tails of surface adhesins to connect them to the parasite actomyosin system. GAC is observed initially to the conoid at the apical pole and re-localised with the glideosome to the basal pole in gliding parasite. GAC presumably functions in force transmission to surface adhesins in the plasma membrane and not in force generation. Proper connection between F-actin and the adhesins is as important for motility and invasion as motor operation itself. This notion highlights the need for new structural information on GAC interactions, which has eluded the field since its discovery. We have obtained crystals that diffracted to 2.6-2.9 Å for full-length GAC from Toxoplasma gondii in native and selenomethionine-labelled forms. These crystals belong to space group P212121, cell dimensions are roughly a=119 Å, b=123Å, c=221Å, α=90, β=90, γ=90 with 1 molecule per asymmetric unit, suggesting a more compact conformation than previously proposed.

In antimicrobial-peptide/protein engineering, understanding the peptide/protein’s adaptability to harsh environmental conditions such as urea, proteases, fluctuating temperatures, high salts provide enormous insight into the pharmacokinetics and pharmacodynamics of the engineered peptide/protein and its ability to survive the harsh internal environment of the human body such as the gut or the harsh external environment to which they are applied. A previous work in our laboratory demonstrated that our cloned Eɛ34 TSP showed potent antimicrobial activity against Salmonella newington, and more so, could prevent biofilm formation on decellularized tissue. In this work, the effects of urea-acid on the Eɛ34 stability is studied, and the results demonstrates that at lower pHs of 3 and 4 with urea the protein was denatured into monomeric species. However, the protein withstood urea denaturation above pH of 5 and thus remained as trimeric protein. The mechanism of denaturation of Eɛ34 TSP seems to show that urea denatures proteins by depleting hydrophobic core of the protein by directly binding to the amide units via hydrogen bonds. The results of our in-silico investigation determined that urea binds with Eɛ34 TSP with relative free energies range of -3.4 to -2.9 kcal/mol at the putative globular head binding domain of the protein. The urea molecules interacts with with the protein’s predicted hydrophobic core, thus, disrupting and exposing the shielded hydrophobic moieties of Eɛ34 TSP to the solvent. We further showed that after the unfolding of Eɛ34 TSP via urea-acid, renaturation of the protein to its native conformation was possible within few hours. This unique characteristic of refolding of Eɛ34 TSP which is similar to that of the P22 phage tailspike protein is of special interest to protein scientists and can also be exploited in antimicrobial-protein engineering.

Development and engineering of protein crystals regarding mechanical stability and crystallizability occurs on a small scale. Later in the process chain of industrial production however, filtration properties are important to separate the crystals from mother liquor. Many protein crystals are sensitive to mechanical stress which is why it is important to know the filtration behavior early on. In this study we analyze settling and filtration behavior of isometric, rod-like and needle shaped lysozyme and rod-like alcohol dehydrogenase (ADH) crystals on a small scale using an optical analytical centrifuge. Needle shaped lysozyme and rod-like ADH crystals show compressible material behavior. With the results from settling and filtration experiments the flux density function is calculated and modeled which can be used to describe the whole settling and permeation process in dependency of the solids volume fraction. This is also an issue for simulations of industrial processes.

89Zr-radiolabelled proteins functionalised with desferrioxamine B are a cornerstone of diagnostic positron emission tomography. In the clinical setting, 89Zr-labelled proteins are produced manually. Here, we explore the potential of using a microfluidic photochemical flow reactor to prepare 89Zr-radiolabelled proteins. The light-induced functionalisation and 89Zr-radiolabelling of human serum albumin ([89Zr]ZrDFO-PEG3-Et-azepin-HSA) was achieved by flow photochemistry with a decay-corrected radiochemical yield (RCY) of 31.2±1.3% (n = 3) and radiochemical purity &gt;90%. In comparison, a manual batch photoreactor synthesis produced the same radiotracer in a decay-corrected RCY of 59.6±3.6% (n = 3) with an equivalent RCP &gt;90%. The results indicate that photoradiolabelling in flow is a feasible platform for the automated production of protein-based 89Zr-radiotracers, but further refinement of the apparatus, and optimisation of the method is required before the flow process is competitive with manual reactions.

Proteases catalyse irreversible posttranslational modifications that often alter a biological function of the substrate. The protease dipeptidyl peptidase 4 (DPP4) is a pharmacological target in type 2 diabetes therapy primarily because it inactivates glucagon-like protein-1. DPP4 also has roles in steatosis, insulin resistance, cancers and inflammatory and fibrotic diseases. In addition, DPP4 binds to the spike protein of MERS virus, causing it to be the human cell surface receptor for that virus. DPP4 has been identified as a potential binding target of SARS-CoV-2 spike protein, so this question requires experimental investigation. Understanding protein structure and function requires reliable protocols for production and purification. We developed such strategies for baculovirus generated soluble recombinant human DPP4 (residues 29-766) produced in insect cells. Purification used differential ammonium sulphate precipitation, hydrophobic interaction chromatography, dye affinity chromatography in series with immobilised metal affinity chromatography, and ion exchange chromatography. The binding affinities of DPP4 to the SARS-CoV-2 full-length spike protein and its receptor binding domain (RBD) were measured using surface plasmon resonance and ELISA. This optimised DPP4 purification procedure yielded 1 to 1.8 mg of pure fully active soluble DPP4 protein per litre of insect cell culture with specific activity >30 U/mg, indicative of high purity. No specific binding between DPP4 and CoV-2 spike protein was detected by surface plasmon resonance or ELISA. In summary, a procedure for high purity high yield soluble human DPP4 was achieved and used to show that, unlike MERS-CoV, SARS-CoV-2 does not bind human DPP4.

Wild game consumption has been associated with health benefits, but the influence on protein metabolism remains unknown. We compared the feeding-induced response to 2 oz of free-range reindeer (FR) versus commercial beef (CB) using stable isotope methodology. Seven male and female participants (age: 38±12 years; body mass index: 24±3 kg/m2) completed two studies using a randomized, crossover design in which they ingested 2 oz of FR or CB. L-[ring 2H5]phenylalanine & L-[ring 2H2]tyrosine were delivered via primed, continuous intravenous infusion. Blood samples were collected during the basal period and following consumption of FR or CB. Feeding-induced changes in whole body protein synthesis (PS), protein breakdown (PB), and net protein balance (NB) were determined via analysis of plasma samples for phenyalanine and tyrosine enrichment by gas chromatography mass spectrometry; plasma essential amino acid concentrations were determined by liquid chromatography-electrospray ionization-mass spectrometry. Plasma post-prandial essential amino acid (EAA) concentrations were higher with the ingestion of FR compared to CB (P=0.02). The acute feeding-induced response in PS was not different in either trial, but PB was reduced with the ingestion of FR compared to CB (P<0.0001). The difference in PB contributed to a superior level of NB (P<0.0001). When protein kinetics were normalized relative to the amino acids ingested, PB/EAAs and total amino acids ingested were reduced (P<0.01 and 0.001, respectively) in FR compared to CB; contributing to greater NB/total amino acid ingested (P<0.0001) between FR and CB. We conclude that the nutrient profiles of FR may have a more favorable benefit on protein metabolism compared to CB. These data support the potential health benefits of wild game in the preservation of whole-body protein.

The current framework of evolutionary theory postulates that evolution relies on random mutations generating a diversity of phenotypes on which natural selection acts. This framework was established using a top-down approach as it originated from Darwinism, which is based on observations made on complex multicellular organisms, and then modified to fit a DNA-centric view. In this article, I argue that, based on a bottom-up approach starting from the physicochemical properties of nucleic and amino acid polymers, we should reject the facts that: i) natural selection plays a dominant role in evolution, and ii) the probability of mutations is independent of the generated phenotype. I will show that the adaptation of a phenotype to an environment does not correspond to organism fitness but rather corresponds to maintaining the genome stability and integrity. In a stable environment, the phenotype maintains the stability of its originating genome, and both (genome and phenotype) are reproduced identically. In an unstable environment (i.e., corresponding to variations in physicochemical parameters above a physiological range), the phenotype no longer maintains the stability of its originating genome but instead influences its variations. Indeed, environment- and cellular-dependent physicochemical parameters define the probability of mutations in terms of frequency, nature and location in a genome. Evolution is non-deterministic because it relies on probabilistic physicochemical rules, and evolution is driven by a bidirectional interplay between genome and phenotype, the phenotype ensuring the stability of the genotype in a cellular and environment physicochemical parameter-depending manner.

A model of the early RNA world is proposed. Nearly self-complementary sequences that could adopt double-stranded, smallhairpin-like (shRNA), structures would be selected for due to their greater hydrolytic stability. These would be phosphorylated attheir 5' ends. We suppose that dehydrating conditions arise (perhaps intermittently) in the early environment allowing amino acidsto condense with these RNA molecules. The resulting phosphate-amino acid anhydrides would play the role of early, charged,tRNAs. A crude genetic code could emerge owing to the greater resistance of some amino acid-shRNA pairings to hydrolysisrelative to others. Early on there is no division of labor between mRNAs and tRNAs; the same molecules perform both functions.But the first systems would have encoded little in the way of protein sequence information. Rather they would have served as catalysts for the random polymerization of amino acids. It is speculated that the selective advantage inhering in such systems lay intheir ability to supply raw materials for the formation of coacervates within which the various molecules essential to proto-lifecould be concentrated. This would greatly facilitate the necessary chemistries. The evolution of homochiral protein and RNA populations is discussed. An appealing feature of this model is its ability to explain the transition from phosphorylated amino acids to the 3' ester-linked aminoacyl-tRNAs employed by modern life.

This study was conducted to investigate the effect of supplementing different types of methionine (L and D-type) and its precursor (HMBi) on milk protein synthesis using immortalized bovine mammary epithelial cell line (MAC-T Cell); D-methionine (D-Met), L-methionine (L-met) and 2-hydroxy-4-methylthiobutanoic acid I (HMBi), an isopropyl ester of the hydroxy analogue precursor of methionine. The underlying mechanism of milk protein synthesis by adding D- and L-type amino acid as well as HMBi was elucidated through omics analysis to verify the metabolism pathway. Results showed that HMBi group showed the highest beta casein mRNA expression levels compared to D- and L-Met groups and highest medium protein although not different with the L-Met treatment. The observed upregulated (>2 protein expression vs. control) and downregulated (<0.5 protein expression vs. control) proteins in L-Met, D-Met and HMBi treated groups were: 39, 77; 46, 68; and 40, 78, respectively. Interestingly, based on protein pathway analysis, L-Met treated group stimulated the ATP synthesis, PI3 kinase and pyruvate metabolism. On the other hand, the D-Met group stimulated fructose-galactose metabolism, glycolysis pathway, PI3 kinase and pyruvate metabolism. And lastly HMBi-treated group stimulated pentose phosphate pathway and glycolysis pathway. Metabolite analysis revealed that L-Met treated group resulted in the increase in 11 metabolites. On the other hand, D-Met treated group showed increase in 7 metabolites and decreased of uridine monophosphate (UMP). HMBi supplementation caused increases of 3 metabolites and decreased of UMP and N-acetyl-L-glutamate Addition of different isoforms of Met stimulated the production of intermediate metabolites for energy production. Addition of L-Met stimulated the production of energy metabolites such as pyruvate, malate, and fumarate, well-known as intermediates of Krebs cycle. On the other hand, HMBi supplementation resulted in increases of energy metabolite glucose 1-phosphate and 6-phosphogluconate. Results showed that HMBi-treated group exhibited highest expression of β-casein mRNA expression by stimulating proteins and metabolites as well as protein and metabolic pathways involved in protein and energy synthesis. As a result, HMBi-treated group resulted in highest protein concentration but not significantly different with L-Met. Both the D- and L-isoforms has considerably the same medium protein concentration and β-casein mRNA expression higher than the control. So, D- and L-Met isoforms can be used alternatively without any significant change in protein synthesis efficiency in bovine mammary epithelial cells.

Abnormal filamentous aggregates formed by tangled tau protein turn out to be classic amyloid fibrils, meeting all criteria defined under the fuzzy oil drop model in the context of amyloid characterization. The model recognizes amyloids as linear structures where local hydrophobicity minima and maxima propagate in an alternating manner along the fibril’s long axis. This distribution of hydrophobicity differs greatly from the classic monocentric hydrophobic core observed in globular proteins. Rather than becoming a globule, the amyloid instead forms a ribbonlike (or cylindrical) structure, which can be thought of as a distorted spherical micelle, which in limit form appears to be the ribbon-like micelle.

The mitochondrial network is a dynamic organization within eukaryotic cells that participates in a variety of essential cellular processes, such as ATP synthesis, central metabolism, apoptosis and inflammation. The mitochondrial network is balanced between rates of fusion and fission that respond to pathophysiologic signals to coordinate appropriate mitochondrial processes. Mitochondrial fusion and fission are regulated by proteins that either reside or translocate to the inner or outer mitochondrial membranes or are soluble in the inter-membrane space. Mitochondrial fission and fusion are performed by GTPases on the outer and inner mitochondrial membranes with the assistance of other mitochondrial proteins. Due to the essential nature of mitochondrial function for cellular homeostasis regulation of mitochondrial dynamics is under strict control. Some of the mechanisms used to regulate the function of these proteins are post-translational proteolysis and/or turnover and this review will discuss these mechanisms required for correct mitochondrial network organization.

Glioblastoma multiforme (GBM) is the most frequent and aggressive primary brain tumor. GBM is formed by a very heterogeneous astrocyte population, neurons, neovascularization and infiltrating myeloid cells (microglia and monocyte derived macrophages). The IQGAP1 scaffold protein interacts with components of the cytoskeleton, cell adhesion molecules, and several signaling molecules to regulate cell morphology and motility, cell cycle and other cellular functions. IQGAP1 overexpression and delocalization has been observed in several tumors, suggesting a role for this protein in cell proliferation, transformation and invasion. IQGAP1 has been identified as a marker of amplifying cancer cells in GBMs. To determine the involvement of IQGAP1 in the onco-biology of GBM, we performed immunohistochemical confocal microscopic analysis of the IQGAP1 protein in human GBM tissue samples using cell type-specific markers. IQGAP1 immunostaining and subcellular localization was heterogeneous; the protein was located in the plasma membrane and, at variable levels, in nucleus and/or cytosol. Moreover, IQGAP1 positive staining was found in podosome/invadopodia-like structures. IQGAP1⁺ staining was observed in neurons (Map2⁺ cells), in cancer stem cells (CSC; nestin⁺) and in several macrophages (CD31⁺ or Iba1⁺). Our results indicate that the IQGAP1 protein is involved in normal cell physiology as well as oncologic processes.

In tissue engineering scaffolds take the place of the natural extra cellular matrix (ECM). The natural ECM is the extracellular part of animal tissue that usually provides structural support to the animal cells in addition to performing various other important functions. The design aspect along with the choice of the material for the artificial scaffold is very crucial to cell differentiation, adhesion, proliferation, and the transport of the growth factors or other bio molecular signals. In addition to the material and design of the scaffolds, it is necessary to replicate the normal physiological situation if the scaffold has to function as an implant. The cells have to be located in the porous scaffold to form a three dimensional assembly. The article discusses the important factors to be considered while designing a scaffold for tissue engineering and regenerative medicine.

Protein dynamics play a crucial role in biological function, encompassing motions ranging from atomic vibrations to large-scale conformational changes. Recent advancements in experimental techniques, computational methods, and artificial intelligence have revolutionized our understanding of protein dynamics. Nuclear magnetic resonance spectroscopy provides atomic-resolution insights, while molecular dynamics simulations offer detailed trajectories of protein motions. The integration of machine learning, exemplified by AlphaFold2, has accelerated structure prediction and dynamics analysis. These approaches have revealed the importance of protein dynamics in allosteric regulation, enzyme catalysis, and intrinsically disordered proteins. The shift towards ensemble representations of protein structures and the application of single-molecule techniques have further enhanced our ability to capture the dynamic nature of proteins. Understanding protein dynamics is essential for elucidating biological mechanisms, designing drugs, and developing novel biocatalysts, marking a significant paradigm shift in structural biology and drug discovery.

Yeast two-hybrid approaches, which are based on fusion proteins that must co-localise to the nucleus to reconstitute the transcriptional activity of GAL4 have greatly contributed to understand the nitrogen interaction network of cyanobacteria, whose main hubs are the trimeric PII and the monomeric PipX regulators. The bacterial two-hybrid system, based on the reconstitution in the E. coli cytoplasm of the adenylate cyclase of Bordetella pertussis, should provide a relatively faster and presumably more physiological assay for cyanobacterial proteins than the yeast system. Here we use the bacterial two-hybrid system to gain additional insights into the cyanobacterial PipX interaction network while simultaneously assessing the advantages and limitations of the two most popular two-hybrid systems. Comprehensive mutational analysis of PipX and bacterial two-hybrid assays were performed to compare outcomes between yeast and bacterial systems. We detected interactions previously recorded in the yeast two-hybrid system as negative as well as a “false positive”, the self-interaction of PipX, which is rather an indirect interaction dependent on PII homologs from the E. coli host, a result confirmed by Western analysis with relevant PipX variants. This is, to our knowledge, the first report of the molecular basis of a false positive in the bacterial two-hybrid system.

The knowledge of COVID-19 impact on the human body has increased rapidly. Although many people recover from COVID-19, some continue to experience persistent symptoms that have been identified as Long COVID. This condition can have a severe impact on quality of life, and it remains a significant concern for medical professionals and researchers. One of the key components of the SARS-CoV-2 virus that enables it to enter human cells is the spike (S) protein. Recent studies have revealed a complex network of interactions between G proteins, spike (S) protein, and the Renin-Angiotensin System (RAS) may be responsible, at least in part, for long COVID. SARS-CoV-2 can also affect the brain, leading to neurological symptoms such as confusion, memory loss, and fatigue. Increasing evidence suggests that COVID-19 is not just a respiratory illness since it is likely that the virus could influence signal transduction pathways such as G-protein-coupled receptor (GPCR), among others, in the brain, either directly or indirectly, affecting neural functions. These interactions with the spike (S) protein and RAS, alongside the brain, are complex and require deep research to understand their implications for Long COVID-19 manifestation fully. While recent research has shed light on the complex interactions between G proteins, spike (S) protein, the brain, and the angiotensin system, this article explores these interconnected pathways and their implications for long COVID-19 manifestations. The present review summarises current research on different molecular mechanisms in Long COVID pathophysiology and may help identify possible targets or new strategies for the diagnosis and treatment.

Noncoding RNAs (ncRNAs) including circular RNAs (circRNAs) and N6-methyladenosine (m6A) have been shown to play a critical role in the development of various diseases including obesity and metabolic disorder-associated fatty liver disease (MAFLD). Obesity is a chronic disease considered by excessive fat accumulation in the body, which has been increased lately and is the foremost risk factor for the MAFLD. Causes of obesity may involve the interaction of genetic, behavioral, and social factors. The m6A RNA methylation might add a novel inspiration for understanding the development of obesity and MAFLD with post-transcriptional regulation of gene expression. In particular, circRNAs, microRNAs (miRNAs) and m6A might be implicated in the progression of MAFLD. Interestingly, m6A modification could modulate the translation, degradation, and other functions of ncRNAs. miRNAs/circRNAs could also modulate m6A modifications by affecting writers, erasers, and readers. In turn, ncRNAs could modulate the expression of m6A regulators in different ways. However, there is limited evidence on how these ncRNAs and m6A interact to affect the promotion of liver diseases. M6A has been appeared to occur in DNA, RNA and proteins, which may be associated with several biological properties. This study would provide a mechanistic understanding of the m6A modification and ncRNAs in the association on liver diseases, especially for MAFLD. Comprehension of the association between m6A modification and ncRNAs may contribute to the development of treatment tactics for MAFLD.

Replication protein A (RPA) is a heterotrimeric protein complex and the main single-stranded DNA (ssDNA) binding protein in eukaryotes. RPA has key functions in most of the DNA-associated metabolic pathways and DNA damage signalling. Its high affinity for ssDNA helps to stabilise ssDNA structures and prevents the DNA sequence from nuclease attacks. RPA consists of multiple DNA-binding domains which are oligonucleotide/oligosaccharide-binding (OB)-folds, responsible for DNA binding, and interactions with proteins. These RPA-ssDNA and RPA-protein interactions are crucial for DNA replication, DNA repair, DNA damage signalling, and the conversation of the genetic information of cells. Proteins such as ATR use RPA to locate to regions of DNA damage for DNA damage signalling. Recruitment of nucleases and DNA exchange factors to sites of double strand breaks are also an important RPA function to ensure effective DNA recombination to correct these DNA lesions. Due to its high affinity to ssDNA, RPA’s removal from ssDNA is of central importance to allow these metabolic pathway to proceed and processes to exchange RPA against downstream factors are established in all eukaryotes. These facetted and multi-layered functions of RPA will be discussed in detail in the review. RPA is also a major player in a variety of human diseases, which will be discussed.

Polycystic ovary syndrome (PCOS) is an insulin resistant state, compensated by hyperinsulinemia. More than 50% of the women with PCOS are obese, and/or have metabolic syndrome. Weight loss improves both metabolic and reproductive outcomes. Not only the energy content, but also the nutrient composition of a diet may be important. This article will present a series of studies from our research comparing effects of dietary protein vs. simple-carbohydrates (CHO). Results of the acute challenge studies demonstrate that simple-CHO intake causes reactive hypoglycemia in one third of the women with PCOS, especially among obese and insulin resistant individuals. Symptoms of hypoglycemia are associated with secretion of cortisol and adrenal androgens. Simple-CHO suppresses the hunger signal ghrelin for a shorter period. During weight loss, women who receive protein supplementation achieve larger amounts of weight- and fat-mass losses. Amino acid compositions of the protein supplements do not affect the improvements in weight and insulin resistance. It is plausible that simple-CHO intake leads to weight gain, or interferes with weight-loss, by causing reactive hypoglycemia, triggering adrenal steroid secretion, and leading to snacking. Since obese women with PCOS are more susceptible to reactive hypoglycemia, a vicious cycle establishes. Restriction of simple-CHO may break this cycle.

Chronic Kidney Disease (CKD) is a major public health concern with an increasing proportion of sufferers progressing to renal replacement therapy (RRT). Early identification of those at risk of disease progression could be key in improving outcomes. We hypothesise that urinary liver-type fatty acid binding protein (uL-FABP) may be a suitable biomarker for CKD progression and can add value to currently established biomarkers such as urinary protein to creatinine ratio (uPCR) 583 participants with CKD 1-5 (not receiving renal replacement therapy) entered a 2-yr prospective longitudinal study. UPCR and uL-FABP were measured at baseline and CKD progression was defined as either i) a decline in eGFR of >5ml/min/1.73m2 or an increase in serum creatinine by 10% at 1-yr or ii) a decline in eGFR of >6 ml/min/1.73m2, or an increase in serum creatinine by 20% at 2-yrs or iii) the initiation of RRT. A combined outcome of initiating RRT or death was also included. Approximately 40% of participants showed CKD progression. UL-FABP predicted CKD progression at both years 1 and 2 (OR 1.01, p<0.01). Sensitivity and specificity were comparable to those of uPCR (AUC 0.623 v 0.706) and heat map analysis suggested that uL-FABP in the absence of significant proteinuria can predict an increase in serum creatinine of 10% at 1yr and 20% at 2yr. The risk of the combined outcome of initiating RRT or death was 23% higher in those with high uL-FABP (p<0.01) independent of uPCR. UL-FABP appears to be a highly sensitive and specific biomarker of CKD progression. The use of this biomarker could enhance the risk stratification of CKD and its progression and should be assessed further.

The expression of the Fasciola hepatica Carboxylesterase type B (CestB) gene is induced in response to the anthelmintic triclabendazole (TCBZ), resulting in a significant increase in enzymatic specific activity. Furthermore, the amino acid sequence of CestB exhibits variations that could lead to substantial amino acid substitutions at the ligand-binding site. These substitutions have the potential to affect the interaction between the ligand and the protein, as well as the catalytic properties of the enzyme. The objective of this study was to identify new CestB polymorphisms in TCBZ-resistant parasites using 3D modeling against the metabolically oxidized form of the anthelmintic TCBZSOX. Our aim was to observe the formation of TCBZSOX-specific binding pockets that could potentially explain the resistance to anthelmintic agents. We identified a CestB polymorphism in a TCBZ-resistant strain of parasites exhibiting three radical amino acid substitutions at positions 147, 215, and 243, resulting in the formation of a TCBZSOX-affinity pocket capable of binding the anthelmintic drug. Additionally, our 3D modeling analysis revealed that these amino acid substitutions also had an impact on the configuration of the CestB catalytic site, affecting the enzyme's interaction with chromogenic carboxylic ester substrates and altering its catalytic properties; however, the identified TCBZSOX-binding pocket was located far from the enzyme's catalytic site, making the enzymatic hydrolysis of TCBZSOX theoretically impossible. Nonetheless, the increased affinity for the anthelmintic may explain a drug-sequestration type of anthelmintic resistance and lays the foundation for the development of a molecular diagnostic tool for identifying anthelmintic resistance in F. hepatica.

Begomoviruses, which belong to the Geminiviridae family, are intracellular parasites transmitted by whiteflies to dicotyledonous plants, significantly damaging agronomically relevant crops. These nucleus-replicating DNA viruses need to move intracellularly from the nucleus to the cytoplasm and then, like other plant viruses, spread systemically throughout the plant to cause dis-ease. The transport proteins of begomoviruses play a crucial role in recruiting host components for the movement of viral DNA within and between cells while exhibiting functions that suppress the host's immune defense. Pioneering studies on species of the Begomovirus genus have identified specific viral transport proteins involved in intracellular transport, cell-to-cell movement, and systemic spread. Recent research has primarily focused on viral movement proteins and their interaction with the cellular host transport machinery, significantly expanding our understanding of viral infection pathways. This review focuses on three main aspects: (i) the role of viral transport proteins, specifically movement proteins (MPs) and nuclear shuttle proteins (NSPs), (ii) their ability to recruit host factors for intra- and intercellular viral movement, and (iii) suppress antiviral immunity, with a particular emphasis on bipartite begomoviral movement proteins.

Protein-protein interactions (PPIs) are associated with various diseases; hence, they are important targets in drug discovery. However, the physicochemical empirical properties of PPI-targeted drugs are distinct from those of conventional small molecule oral pharmaceuticals, which adhere to the ”rule of five (RO5).” Therefore, developing PPI-targeted drugs using conventional methods, such as molecular generation models, is difficult. In this study, we propose a molecule generation model based on deep reinforcement learning, specialized for generating PPI inhibitors. By introducing a scoring function that can represent the properties of PPI inhibitors, we successfully generated potential PPI inhibitor compounds. The generated virtual compounds possess the desired properties for PPI inhibitors, and show similarity to commercially available PPI libraries. These generated virtual compounds are freely available as a virtual library.

As a result of the growing demand for foods with reduced animal protein content, many new alternative diets are now emerging. Nevertheless, recent studies have shown that the Western population is unprepared for drastic changes and is disinclined to accept foods based on alternative proteins. However, hybrid products might become a good transitional offer. This study used a desirability-based mixture design to model hybrid spreadable cheese analogues (SCAs). The design combined the dairy protein (MPC), Tenebrio molitor (IF) and faba bean (FBP) flours. Nine SCAs with different MPC/FBP/IF ratios were formulated, representing 0, 50 and 100% MPC replacement (7.1% of the formula). Incorporating the IF negatively impacted the desirable texture properties. The FBP flour improved the texture (achieving increased firmness and stickiness and decreased spreadability), but only when combined with MPC. Changing the MPC/FBP/IF ratio affected the colour of SCAs. Sensory analysis showed that hybrid SCAs (≤ 50% MPC) had a more characteristic cheesy flavour than the commercial plant-based reference, and sample C2 had a texture profile similar to the dairy reference. Samples containing IF showed a better flavour profile than the products without IF. The SCAs had higher protein and lower saturated fat, starch and sugar con-tent than commercial analogues.This study demonstrates that the inclusion of alternative proteins can be effective as a strategy to reduce dairy protein content in hybrid product formulations.

Directed evolution methods are becoming increasingly popular, as they are extremely powerful toward developing new biomolecules with altered/novel activities, e.g., proteins with new catalytic functions or substrate specificities, and nucleic acids that recognize an intended target. Especially useful are systems that have incorporated continuous evolution, where the protein to be evolved undergoes continuous mutagenesis to evolve a desired trait with little to no input from the researcher once the system is started. However, continuous evolution methods can be challenging to implement in the lab and daunting for researchers to invest time and resources. Our intent is to provide basic information and helpful suggestions that we have gained from our experience with bacterial phage-assisted continuous evolution (PACE). Specifically, we review factors to consider before adopting PACE for a given evolution scheme, different types of selection circuits that can be utilized with particular focus on the PACE-B1H selection system, what optimization of a PACE selection circuit may look like using directed evolution of ME47 as a case study, and additional techniques that may be incorporated into a PACE experiment. With this information, researchers will be better equipped to determine if PACE is a valid strategy to use to evolve their proteins and how to set up a valid selection circuit.