Protein Concentration Research Articles

Comprehensive Proteomics Profiling Identifies Circulating Biomarkers to Distinguish Hypertrophic Cardiomyopathy from Other Cardiomyopathies with Left Ventricular Hypertrophy.

Background: Distinguishing hypertrophic cardiomyopathy (HCM) from other cardiomyopathies with left ventricular hypertrophy (LVH), such as hypertensive LVH, transthyretin amyloid cardiomyopathy (ATTR-CM), and aortic stenosis (AS), is sometimes challenging. Using plasma proteomics profiling, we aimed to identify circulating biomarkers and dysregulated signaling pathways specific to HCM. Methods: In this multicenter case-control study, plasma proteomics profiling was performed in cases with HCM and controls with hypertensive LVH, ATTR-CM, and AS. Two-thirds of patients enrolled earlier in each disease group were defined as the training set, and the remaining one-third as the test set. Protein concentrations in HCM were compared with those in hypertensive LVH (comparison 1), ATTR-CM (comparison 2), and AS (comparison 3). Candidate proteins that meet the following 2 criteria were selected: (1) Higher abundance in HCM throughout all 3 comparisons or lower abundance in HCM throughout all 3 comparisons with univariable P<0.05 and |log2(fold change)| >0.5 in both the training and test sets and (2) Independently associated with HCM with multivariable P<0.05 after adjusting for clinical parameters significantly different between HCM and controls. Using the selected candidate proteins, a logistic regression model to distinguish HCM from controls was developed in the training set and applied to the test set. Finally, pathway analysis was performed in each comparison using proteins with different abundance. Results: Overall, 4,979 proteins in 1,415 patients (HCM, n=879; hypertensive LVH, n=331; ATTR-CM, n=169; AS, n=36) were analyzed. Of those, 5 proteins were selected as candidate proteins. The logistic regression model with these 5 proteins had an area under the receiver-operating-characteristic curve of 0.86 (95% CI 0.82-0.89) in the test set. The MAPK and HIF-1 pathways were dysregulated in HCM throughout the 3 comparisons. Conclusions: This study identified circulating biomarkers that distinguish HCM from other cardiomyopathies with LVH independently from confounders and revealed signaling pathways associated with HCM.

Cicer arietinum phytosome ameliorates hepatosteatosis via downregulation of fatty acid synthase and stearoyl-CoA desaturase 1 in rats

Abstract Background Hepatosteatosis is considered a universal problematic health due to bad lifestyle. Thereby, the current study evaluates the influence of the Cicer arietinum polyunsaturated fatty acids (CAP) and newly synthesized C. arietinum polyunsaturated fatty acids phytosome (CAPP) against non-alcoholic fatty liver disease (NAFLD) persuaded through a high-fat diet (HFD) in addition to tamoxifen (TAM) in male albino rats. Forty-eight rats were separated into eight groups (6 rats/group). Rats of the control group were administered distilled water for 45 consecutive days, while phosphatidyl choline (PC), CAP, and CAPP groups administered distilled water (15 days), afterward administered PC, CAP, and CAPP, respectively (500 mg/kg b.wt), orally for 30 days. All the previous groups fed normal diet for the 45 days, while NAFLD rats feed HFD for 45 days and receive TAM (200 mg/kg b.wt, i.p) daily for 15 days, followed by administration of vehicle, PC, CAP, and CAPP orally for another 30 days. Results Hepatosteatosis was appraised biochemically by significant increase in the concentrations of serum AST, ALT, γGT, LDH, ALP, total bilirubin, total lipid, triglycerides, fatty acid synthase (FAS), stearoyl-CoA desaturase 1 (SCD-1), and LDL-cholesterol, as well as hepatic total lipids and triglycerides. In addition, a significant decline in serum total protein, albumin, and HDL-cholesterol concentrations was observed in comparison with the control group. NAFLD induces oxidative stress by noteworthy increase in hepatic MDA, H2O2, and meaningful reduction in hepatic GSH, SOD, GST, GRD, and CAT levels as compared with the corresponding control group. Liver histological changes were noted in the NAFLD group as compared to the control. Interestingly, CAP and CAPP treatments modulate the abnormal effects of NAFLD in all the previous parameters. For the histological changes caused by NAFLD, the liver tissue appeared nearly normal after the treatment with CAP and CAPP. Conclusion CAP and CAPP administration may have a potential role in alleviating hepatosteatosis. This may relate to its downregulation against FAS, SCD-1, and oxidative stress.

Stimulation of Saliva Affects the Release of Aroma in Wine: A Study of Microbiota, Biochemistry, and Participant Origin.

Saliva influences the release of aroma in the oral cavity. The composition of human saliva varies depending on stimulation and host's origin; however, the compositional differences of saliva and their influences on aroma release have not been fully evaluated. In this study, we recruited 30 healthy adults (15 Australians and 15 Chinese) and collected saliva samples at three stages: before, during, and after stimulation. Salivary samples were characterized by the flow rate, total protein concentration, esterase activity, microbiome composition by full-length 16S rRNA gene sequencing, and the ability to release aroma from wine by headspace solid-phase microextraction gas chromatography-mass spectrometry (HS-SPME-GC-MS). Differences in salivary composition and specific wine volatiles were found between Australian and Chinese participants and among the three stimulation stages. Significant correlations between the relative abundance of 3 bacterial species and 10 wine volatiles were observed. Our results confirm the influence of participant's geographic origin and stimulation on the salivary composition, highlighting the role of salivary components, especially salivary bacteria, on the release of aroma from wine.

Fe/Co-modified Enteromorpha bio-hydrochar enhanced anaerobic digestion of chicken manure with sulfadimethazine: focusing on synergistic mechanism and microbial community succession

Abstract Residual antibiotics in chicken manure may interfere with the stability of anaerobic digestion (AD) and inhibit resource utilization efficiency. In this study, we aimed to enhance chicken manure bio-methanation in AD with high-concentration of sulfamethazine (SMZ) by adding metal (Fe, Co)-modified Enteromorpha-based hydrochar (Co-HC, Fe-HC). The results showed that Fe-HC and Co-HC increased the degree of acidogenesis by 1.25 times and 1.58 times, respectively. The maximum protein concentration in EPS was increased by 47.64% and 72.5% after adding Fe-HC and Co-HC. However, only Co-HC demonstrated notable improvements in both methane production and SMZ removal efficiency. Electrochemical analysis showed that Co-HC possessed a richer variety of oxygen and nitrogen functional groups, along with superior electron exchange capabilities compared to Fe-HC. Furthermore, microbiological assessments revealed that Co-HC enriched syntrophic bacteria (such as Syntrophomonas and Mesotoga), facilitating direct interspecies electron transfer (DIET) and subsequently enhancing biomethane production. The abundance of genes involved in electron transfer increased significantly with Co-HC, with a maximum increase of 75.86% in Co1.5-HC treatment. Additionally, the elimination of antibiotic resistance genes (sul1, sul2) increased by 65.66% in the Co1.5-HC treatment. This study offers a theoretical foundation and empirical support for the synergistic improvement of livestock and poultry manure containing high antibiotic concentrations, thereby helping to overcome challenges posed by recalcitrant substances. Graphical Abstract

Spectroscopic and Molecular Docking Studies on the Influence of Inulin on the Interaction of Sophoricoside with Whey Protein Concentrate

The influence of inulin on the interaction of sophoricoside (Sop) with whey protein concentrate (WPC) was investigated using various spectroscopic methods, including fluorescence spectroscopy (intrinsic fluorescence, synchronous fluorescence, and three-dimensional fluorescence), ultraviolet-visible (UV–Vis) spectroscopy, Fourier transform infrared (FTIR) spectroscopy, and molecular docking. Sop was found to quench the intrinsic fluorescence of WPC by a static mechanism, both with and without the addition of inulin, and to enhance the antioxidant capacity of the protein. The addition of inulin slightly increased the binding distance between WPC and Sop, while reducing the number of binding sites from two to one. Non-covalent interactions, predominantly van der Waals forces and hydrogen bonding, were maintained between Sop and the protein. Synchronous fluorescence spectroscopy revealed that Sop prevents the exposure of hydrophobic groups on tryptophan residues, leading to increased surface hydrophilicity of the WPC complex. This aligns with the decreased protein surface hydrophobicity measured by 8-Anilino-1-naphthalenesulfonic acid (ANS) binding assays. With inulin, the overall hydrophobicity of the protein was lower than in the system without inulin, suggesting that both inulin and Sop improve the solubility of WPC. Three-dimensional fluorescence spectral analysis showed a reduction in fluorescence intensity and a red shift in the presence of both Sop and inulin. FTIR spectroscopy indicated a slight increase in the secondary structure ordering of WPC following the addition of both Sop and inulin, suggesting structural stabilization under heating conditions. Molecular docking highlighted the potential for hydrogen bond formation between Sop and WPC.

Canadian Organic Wheat Breeding with On-farm Selection: A Case Study using Landrace and Modern Parents

Participatory plant breeding (PPB) has the potential to be an alternative to a centralized breeding model for niche markets that are historically underserved. Our objectives were to evaluate the performance of two parental cultivars from a Canadian PPB program: a modern spring wheat (Triticum aestivum L.) cultivar (5602HR) and a landrace (Red Fife) - with the progeny of the cross when selected by two farmers located 1800 km apart (denoted Farm1 and Farm2) and evaluate progeny differences from each other under organic conditions. Red Fife was 18 cm taller, matured 5 days later, had greater lodging susceptibility, greater seed mass, and 3.5% lower protein concentration than 5602HR. Farmer genotypes were similar to 5602HR in protein concentration and lodging severity, and similar to Red Fife in plant height (14 cm taller than 5602HR) and seed mass. Farmer genotypes did not yield differently from either parent. Farmer genotypes did not differ from each other in most parameters measured, however, Farm1 had greater lodging resistance under high fertility conditions than Farm2 despite similar plant height. This research provides a proof of concept for the role that farmer selectors can play in selecting for positive traits for organic production and provide insight into organic farmers’ preferences. The research also demonstrated that using an older landrace (ie., Red Fife) allowed positive features such as tall stature to be incorporated into the resulting progeny.

Pharmacodynamic effects of semorinemab on plasma and CSF biomarkers of Alzheimer's disease pathophysiology.

Semorinemab, an anti-tau monoclonal antibody, was assessed in two Phase II trials for Alzheimer's disease (AD). Plasma and cerebrospinal fluid (CSF) biomarkers provided insights into the drug's potential mechanism of action. Qualified assays were used to measure biomarkers of tau, amyloidosis, glial activity, neuroinflammation, synaptic function, and neurodegeneration from participant samples in Tauriel (NCT03289143) and Lauriet (NCT03828747) Phase II trials. Plasma phosphorylated Tau 181 (pTau181) and CSF chitinase-3-like protein 1 (YKL-40) increased following semorinemab treatment in both studies. In Lauriet, increasing plasma glial fibrillary protein (GFAP) concentrations stabilized with semorinemab, while this was not observed in Tauriel. Other AD pathophysiology biomarkers showed no consistent response to semorinemab. Increases in CSF YKL-40 suggest that semorinemab may stimulate microglia activation in the presence of AD-associated Tau pathology, but not in healthy controls. Stabilization of plasma GFAP in Lauriet indicates a possible impact on reactive gliosis in mild-to-moderate AD. Tauriel ClinicalTrials.gov Identifier: NCT03289143. Lauriet ClinicalTrials.gov Identifier: NCT03828747. Phase 1 ClinicalTrials.gov Identifier: NCT02820896. AD pathophysiology biomarkers were measured to assess the mechanism of action. Semorinemab increased CSF YKL-40 in participants with AD but not in healthy controls. Semorinemab possibly stabilized plasma GFAP in the Lauriet trial. Semorinemab treatment may activate microglia and moderate reactive gliosis.

Insights into larval development and protein biochemical alterations of Agrotis ipsilon (Hufnagel) (Lepidoptera: Noctuidae) following Beauveria bassiana and Solanum lycopersicum treatments

BackgroundThe polyphagous notorious pest, black cutworm, Agrotis ipsilon (Hufnagel) (Lepidoptera: Noctuidae), cause significant production losses due to its distinctive feeding and hiding behavior, making it particularly challenging to control it with conventional methods. Therefore, sustainable agriculture demands more effective and environmentally safe pest control solutions. This study aimed to investigate the toxicity of two insecticide alternatives, the entomopathogenic fungus (EPF) Beauveria bassiana and Solanum lycopersicum extract (Tomato plant crude extract, TPCE), using two bioassay methods: the poisoned bait method and the leaf dipping method. In addition, the impact of these biological tools on larval development and protein profiles was evaluated.ResultsThe bait application of both tested materials exhibited higher toxicity than the leaf dipping method, as indicated by the toxicity index. The LC50 values for B. bassiana were 1.6 × 10⁸ and 1.8 × 10⁶ conidia ml−1 using the leaf dipping method and poisoned baits method, respectively. For TPCE, the LC50 values were 4.35 and 1.51 mg ml−1 for the same methods, respectively. In addition, sublethal concentrations of both materials altered the larval and pupal durations. B. bassiana significantly reduced the concentration of larval hemolymph protein. A maximum of 12 protein bands in the control sample, with molecular weights (Mw) ranging between 35 and 120 kDa, were detected by sodium dodecyl sulfate–polyacrylamide gel electrophoresis (SDS–PAGE). In B. bassiana-treated larvae, ten bands were detected with Mw ranging from 35 to 120 kDa. At least seven bands were detected in TPCE-treated larvae, with Mw ranging from 35 to 97 kDa.ConclusionsThe findings of this study can be integrated into management programs for A. ipsilon. In addition, the availability of B. bassiana and TPCE in Egypt and their cost-effectiveness as insecticide alternatives support their use in the management programs of this critical pest. These methods are particularly effective when applied in bait form.Graphical

Dengue Fever in Pregnant Women with a Favorable Outcome

Dengue fever is a viral infectious disease, it manifests itself from mild to severe severity, in some cases to fatal outcomes. The number of cases of dengue fever has been increasing in recent years. The results of many studies have also shown adverse effects on pregnant infected women. This article describes the clinical course of Dengue fever in pregnant women, which occurred in moderate severity and without complications. Dengue fever in a pregnant woman manifested itself in the form of complaints of pain in the epigastric region, bleeding gums and petechial hemorrhages within 1 day. She had a high fever for 5 days before going to the hospital. Upon admission, her body temperature was 37 °C, blood pressure was 110/80 mmHg, pulse rate was 80 beats per minute, respiratory rate was 20 beats per minute. She had mild dehydration, normal breathing and heartbeat. The height of the bottom corresponds to the gestation period of 31 weeks, and the fetal heart rate was 144 beats per minute. Petechiae measuring at least 1-2 m in diameter were found around her face, forearms and both basal areas. In a laboratory study, the results showed changes in the number of platelets in the form of thrombocytopenia, leukocytopenia and in the biochemical analysis of blood by increasing the concentration of C-reactive protein and the detection of antibodies in serum during serological analysis. Although many studies have shown that Dengue during pregnancy increases the risk of preeclampsia, hemorrhagic dengue fever (HLD), fetal distress, premature birth, cesarean section and maternal mortality and intrauterine development delay and stillbirth consequences. This clinical case concludes with favorable outcomes. But the physiological effects of dengue fever during pregnancy (for both mother and child), depending on the trimester, as well as research and treatment methods require further study, especially in the region of endemic zones and India.

Implemention of Innovative Process Analytical Technologies to Characterize Critical Quality Attributes of Co-Formulated Monoclonal Antibody Products.

Characterizing co-formulated monoclonal antibodies (mAbs) poses significant challenges in the pharmaceutical industry. Due to the high structural similarity of the mAbs, traditional analytical methods, compounded by the lengthy method development process, hinder product development and manufacturing efficiency. There is increasing critical need in the pharmaceutical industry to streamline analytical approaches, minimizing time and resources, ensuring a rapid clinical entry and cost-effective manufacturing. This study investigates the application of process analytical technologies (PAT) to address such challenges. Our investigation introduces two complementary technologies, on-line ultra-performance liquid chromatography (online UPLC) and multimode fluorescence spectroscopy (MMFS), as potential PAT tools tailored for characterizing critical quality attributes (CQA) in co-formulated mAb products. Specifically, the CQAs under evaluation include the total protein concentration of the mAbs within the co-formulation and the ratio of mAb A to mAb B. Online UPLC enables direct and automated measurement of the CQAs through physical separation, while MMFS determines them in a non-destructive and more swift manner based on chemometric modeling. We demonstrate these technologies' comparable performance to conventional methods, alongside substantial benefits such as reduced analytical turnaround time and decreased laboratory efforts. Ultimately, integrating them as innovative PAT tools expedites the delivery of therapeutic solutions to patients and enhances manufacturing efficiency, aligning with the imperative for swift translation of scientific discoveries into clinical benefits.

Acute phase responses in clinically healthy multiparous Holsteins with and without calcium dysregulation during the early postpartum period

Patterns of calcium dysregulation resulting in low total serum calcium concentrations (tCa) at 4 DIM, known as dyscalcemia, commonly occur in multiparous Holsteins. Dyscalcemia is associated with risk of disease, decreased production, and poor reproductive performance. Inflammation is well-documented early in lactation and is associated with similarly suboptimal outcomes. The acute phase response produces markers and mediators of inflammation; therefore, the objective of our case-control study was to evaluate postpartum patterns of 3 positive acute phase proteins in cows with and without dyscalcemia. We hypothesized that dyscalcemic cows would experience more activated inflammation than eucalcemic cows and that inflammation would precede dyscalcemia diagnosis. Multiparous Holstein cows at 2 commercial dairy farms in central New York were enrolled from a parent study based on tCa at 4 DIM, at a 2:1 ratio of eucalcemic (tCa >2.3 mmol/L; n = 32) to dyscalcemic cows (tCa <2.2 mmol/L; n = 16). Blood was collected 1 to 3 d before parturition and once every 24 h postpartum through 4 DIM. Samples were analyzed for 3 acute phase proteins, serum amyloid A (SAA), haptoglobin and lipopolysaccharide binding protein (LBP). Patterns of protein concentrations in blood over time were compared using linear mixed effects models including fixed effects of calcium status group, time, parity group, farm, relevant 2-way interactions, and the random effect of cow. Overall, dynamics of acute phase proteins showed that dyscalcemic cows experienced increased acute phase responses compared with eucalcemic cows, and that these responses preceded dyscalcemia diagnosis at 4 DIM. Dyscalcemic cows had elevated concentrations of SAA beginning at 2 DIM (eucalcemic: mean = 13.88 µg/mL, 95% CI = 11.34 to 16.99 µg/mL; dyscalcemic: mean = 32.95 µg/mL, 95% CI = 24.55 to 44.21 µg/mL). and continuing through 4 DIM (eucalcemic: mean = 8.14 µg/mL, 95% CI = 6.66 to 9.95 µg/mL; dyscalcemic: mean = 30.01 µg/mL, 95% CI = 22.60 to 39.83 µg/mL). Haptoglobin concentrations were also elevated in the blood of dyscalcemic cows from 2 DIM (eucalcemic: mean = 0.39 g/L, 95% CI = 0.31 to 0.49 g/L; dyscalcemic: mean = 1.11 g/L, 95% CI = 0.79 to 1.56 g/L) through 4 DIM (eucalcemic: mean = 0.27 g/L, 95% CI = 0.21 to 0.34 g/L; dyscalcemic: mean = 1.65 g/L, 95% CI = 1.19 to 2.28 g/L). Concentrations of LBP exhibited a different pattern with a small difference between groups at 3 DIM (eucalcemic: mean = 4.67 µg/mL, 95% CI = 4.02 to 5.42 µg/mL; dyscalcemic: mean = 7.91 µg/mL, 95% CI = 6.49 to 9.63 µg/mL) that became larger at 4 DIM (eucalcemic: mean = 4.88 µg/mL, 95% CI = 4.22 to 5.64 µg/mL; dyscalcemic: mean = 10.79 µg/mL, 95% CI = 8.84 to 13.17 µg/mL). Our work supports the hypothesis that dyscalcemia and inflammatory activity are associated in dairy cows under naturally occurring postpartum conditions. While the causal structure of this relationship remains unknown, improved understanding of inflammation and dyscalcemia may provide insight into mechanisms by which some cows experience maladaptation during the early postpartum period.

SARS-CoV-2 and HSV-1 Induce Amyloid Aggregation in Human CSF Resulting in Drastic Soluble Protein Depletion.

The corona virus (SARS-CoV-2) pandemic and the resulting long-term neurological complications in patients, known as long COVID, have renewed interest in the correlation between viral infections and neurodegenerative brain disorders. While many viruses can reach the central nervous system (CNS) causing acute or chronic infections (such as herpes simplex virus 1, HSV-1), the lack of a clear mechanistic link between viruses and protein aggregation into amyloids, a characteristic of several neurodegenerative diseases, has rendered such a connection elusive. Recently, we showed that viruses can induce aggregation of purified amyloidogenic proteins via the direct physicochemical mechanism of heterogeneous nucleation (HEN). In the current study, we show that the incubation of HSV-1 and SARS-CoV-2 with human cerebrospinal fluid (CSF) leads to the amyloid aggregation of several proteins known to be involved in neurodegenerative diseases, such as APLP1 (amyloid β precursor like protein 1), ApoE, clusterin, α2-macroglobulin, PGK-1 (phosphoglycerate kinase 1), ceruloplasmin, nucleolin, 14-3-3, transthyretin, and vitronectin. Importantly, UV-inactivation of SARS-CoV-2 does not affect its ability to induce amyloid aggregation, as amyloid formation is dependent on viral surface catalysis via HEN and not its ability to replicate. Additionally, viral amyloid induction led to a dramatic drop in the soluble protein concentration in the CSF. Our results show that viruses can physically induce amyloid aggregation of proteins in human CSF and result in soluble protein depletion, thus providing a potential mechanism that may account for the association between persistent and latent/reactivating brain infections and neurodegenerative diseases.

Covalent Attachment of Functional Proteins to Microfiber Surfaces via a General Strategy for Site-Selective Tetrazine Ligation.

Surface modification of materials with proteins has various biological applications, and hence the methodology for surface modification needs to accommodate a wide range of proteins that differ in structure, size, and function. Presented here is a methodology that uses the Affinity Bioorthogonal Chemistry (ABC) tag, 3-(2-pyridyl)-6-methyltetrazine (PyTz), for the site-selective modification and purification of proteins and subsequent attachment of the protein to trans-cyclooctene (TCO)-functionalized hydrogel microfibers. This method of surface modification is shown to maintain the functionality of the protein after conjugation with proteins of varying size and functionalities, namely, HaloTag, NanoLuc luciferase (NanoLuc), and fibronectin type III domains 9-10 (FNIII 9-10). The method also supports surface modification with multiple proteins, which is shown by the simultaneous conjugation of HaloTag and NanoLuc on the microfiber surface. The ability to control the relative concentrations of multiple proteins presented on the surface is shown with the use of HaloTag and superfolder GFP (sfGFP). This application of the ABC-tagging methodology expands on existing surface modification methods and provides flexibility in the site-selective protein conjugation methods used along with the rapid kinetics of tetrazine ligation.

Study of the nutritional quality of peas (Pisum sativum L.) under different conservation conditions

Peas (Pisum sativum L.) are among the most widely cultivated legumes, known for their adaptability to dry and warm environments and their high nutritional value. This research aimed to investigate the biochemical diversity of proteins, polyphenols, flavonoids, tannins, and antioxidant activity in a local population of peas from the Mareth oasis in Tunisia under different preservation methods: fresh, frozen, canned, and dried. The hypothesis was that preservation methods significantly impact the nutritional quality of peas, with fresh peas retaining the highest levels of essential nutrients. The results showed that fresh peas had superior nutritional quality, demonstrating the highest concentrations of protein (39 mg/g MF), polyphenols (0.17 mg GAE/g MF), flavonoids (0.086 mg QE/mg MF), and antioxidants (52%). In contrast, dried peas exhibited the lowest nutrient levels, particularly in protein and antioxidant activity. The study highlighted that freezing is an effective method for preserving the nutritional integrity of peas compared to canning and drying, which significantly reduce essential nutrient levels. Understanding the effects of various preservation techniques is crucial for maintaining the nutritional quality of peas. These findings have significant implications for consumers and the food industry, advocating for practices that prioritize the retention of nutrients in preserved peas. This research contributes to the ongoing discourse on food preservation methods and their impact on nutritional quality, providing insights that support better choices in food processing and consumption.

Recent Advances in Simulation Studies on the Protein Corona

When flowing through the blood stream, drug carriers such as nanoparticles encounter hundreds of plasma proteins, forming a protein layer on the nanoparticle surface, known as the “protein corona”. Since the protein corona influences the size, shape, and surface properties of nanoparticles, it can modulate their circulating lifetime, cytotoxicity, and targeting efficiency. Therefore, understanding the mechanism of protein corona formation at the atomic scale is crucial, which has become possible due to advances in computer power and simulation methodologies. This review covers the following topics: (1) the structure, dynamics, and composition of protein corona on nanoparticles; (2) the effects of protein concentration and ionic strength on protein corona formation; (3) the effects of particle size, morphology, and surface properties on corona formation; (4) the interactions among lipids, membranes, and nanoparticles with the protein corona. For each topic, mesoscale, coarse-grained, and all-atom molecular dynamics simulations since 2020 are discussed. These simulations not only successfully reproduce experimental observations but also provide physical insights into the protein corona formation. In particular, these simulation findings can be applied to manipulate the formation of a protein corona that can target specific cells, aiding in the rational design of nanomedicines for drug delivery applications.

Systemic immune-inflammation mediates the association between Klotho protein and metabolic syndrome: findings from a large-scale population-based study.

This study utilized large-scale population data from the National Health and Nutrition Examination Survey (NHANES) to elucidate the relationship between the Klotho protein and metabolic syndrome along with its components. We further investigated the possible mediating effect of inflammation on these relationships. Our objective was to identify biomarkers for risk stratification and potential therapeutic targets for metabolic syndrome. This study enrolled 13,119 participants aged 40-79 years, spanning five NHANES cycles from 2007 to 2016, with complete information on metabolic syndrome and the Klotho protein. The definition of metabolic syndrome followed the criteria of the National Cholesterol Education Program-Adult Treatment Panel III. Survey-weighted logistic regression and subgroup analysis were used to explore the associations between serum Klotho protein levels and metabolic syndrome, along with its components. Mediation analysis was performed to investigate the mediating effects of inflammation-related markers, including white blood cells, neutrophils, lymphocytes, monocytes, the neutrophil-to-lymphocyte ratio (NLR), the platelet-to-lymphocyte ratio (PLR), the systemic immune-inflammation index (SII) and the monocyte-to-HDL ratio (MHR), with the aim of elucidating how the Klotho protein influences the onset and progression of metabolic syndrome. The study participants had an average age of 56.06 years (95% CI: 55.76-56.37), with a Klotho protein concentration of 798.10 pg/ml (95% CI: 656.50-980.50) and a 43.77% prevalence of metabolic syndrome (n = 5742). In the crude model, Klotho was negatively correlated with metabolic syndrome and its components, including central obesity, hypertension, and hypertriglyceridemia. After adjusting for all confounding factors, Klotho was demonstrated to be negatively associated only with metabolic syndrome (OR: 0.82, 95% CI: 0.70-0.97), hypertension (OR: 0.83, 95% CI: 0.70-0.98), and hypertriglyceridemia (OR: 0.78, 95% CI: 0.67-0.91). Subgroup and interaction analyses revealed significant interactions between age, sex, race/ethnicity, body mass index, and Klotho. Additionally, mediation analysis demonstrated that leukocytes, neutrophils and monocytes accounted for 34.78%, 31.91% and 7.13%, respectively, of the associations between Klotho and metabolic syndrome. The serum concentration of Klotho protein was negatively associated with metabolic syndrome, with the relationship being partly mediated by systemic immune inflammation. The findings of this research revealed that the Klotho protein may be a valuable biomarker for risk stratification and a potential therapeutic target for metabolic syndrome.

Effect of abamectin on haemolymph and ovarian proteins during the reproductive cycle of female Argas (Persicargas) arboreus (Acari: Argasidae)

AbstractThe avian tick Argas (Persicargas) arboreus is a vector of pathogens infecting the nestlings of the agriculturally beneficial bird, the buff-backed heron in Egypt. The topical treatment of the fed-mated (engorged) female A. (P.) arboreus with a sublethal dose of abamectin (10 µl 10 ppm/female) on the 3rd day after feeding (daf), reduced the concentration of total protein in the haemolymph (HL) by 13–66%, in the ovary by 30–54%, and in freshly deposited eggs by 11–16%, compared to untreated females during vitellogenesis and oviposition. However, the treatment did not prevent vitellogenesis and oviposition but reduced the number of mature oocytes (stages III–V) and deposited eggs. Additionally, it delayed the onset and slowed the progress of each process in the treated females. The application of abamectin at the onset of vitellogenesis (on the 3rd daf) in normal female and the prominent decrease inHL total protein concentration in treated female on the 4th daf pointed to a probable interference of abamectin with the release of the vitellogenesis-inducing factor (VIF) and/or other subsequent hormone(s) known to regulate vitellogenesis in this argasid tick species. Graphical abstract

Antimicrobial Activity of Diffusible Substances Produced by Lactococcus lactis Against Bacillus cereus in a Non-Contact Co-Culture Model

The symptoms of foodborne illness caused by Bacillus cereus often go unreported, complicating the effectiveness of conventional chemical and physical methods used to inhibit its growth in food production. This challenge, combined with the increasing use of lactic acid bacteria (LAB) in the food industry and consumer preference for minimally processed products, prompted this study. The antibacterial activity of diffusible substances produced by Lactococcus lactis ATCC 11454 against Bacillus cereus NC11143 and Escherichia coli K-12 MG1655 was investigated using a non-contact co-culture model utilising deMann Rogosa and Sharpe broth, with glucose as a carbon source. This study employed plate counting and flow cytometry to assess the impact of these substances on bacterial growth and to analyse their composition and antimicrobial efficacy. The co-culture of Lactococcus lactis ATCC 11454 resulted in the production of a stable antimicrobial peptide, which was heat resistant and acid tolerant. Purification was achieved via ammonium sulphate precipitation and preparative HPLC, yielding a peptide with a molecular mass of 3.3 kDa, with daughter ion fractions similar to nisin A. Antimicrobial activity studies demonstrated that the diffusible substances effectively inhibited B. cereus growth over a period of eight days and exhibited bactericidal activity, killing 99% of the B. cereus cells. Additionally, these substances also inhibited Escherichia coli K-12 MG1655 grown under similar conditions. Comparative analysis revealed that in the co-culture assay, L. lactis produced a 50% higher yield of the antimicrobial peptides compared to pure cultures. Similarly, the specific growth rate of L. lactis was four times higher. With respect to protein purification and concentration, ammonium sulphate precipitation coupled with solid phase extraction was most effective in the purification and concentration of the diffusible substances. The findings provide a basis for utilising bacteriocin-producing strains as a preservation method, offering an alternative to traditional chemical and physical control approaches especially for the food industry.

Flexibility and sensitivity in gene regulation out of equilibrium

Cells adapt to environments and tune gene expression by controlling the concentrations of proteins and their kinetics in regulatory networks. In both eukaryotes and prokaryotes, experiments and theory increasingly attest that these networks can and do consume biochemical energy. How does this dissipation enable cellular behaviors forbidden in equilibrium? This open question demands quantitative models that transcend thermodynamic equilibrium. Here, we study the control of simple, ubiquitous gene regulatory networks to explore the consequences of departing equilibrium in transcription. Employing graph theory to model a set of especially common regulatory motifs, we find that dissipation unlocks nonmonotonicity and enhanced sensitivity of gene expression with respect to a transcription factor's concentration. These features allow a single transcription factor to act as both a repressor and activator at different concentrations or achieve outputs with multiple concentration regimes of locally enhanced sensitivity. We systematically dissect how energetically driving individual transitions within regulatory networks, or pairs of transitions, generates a wide range of more adjustable and sensitive phenotypic responses than in equilibrium. These results generalize to more complex regulatory scenarios, including combinatorial control by multiple transcription factors, which we relate and often find collapse to simple mathematical behaviors. Our findings quantify necessary conditions and detectable consequences of energy expenditure. These richer mathematical behaviors-feasibly accessed using biological energy budgets and rates-may empower cells to accomplish sophisticated regulation with simpler architectures than those required at equilibrium.

Phytochemical Composition and Functional Properties of Brassicaceae Microgreens: Impact of In Vitro Digestion.

The aim of this study was to compare the concentration of phenolic compounds, glucosinolates, proteins, sugars and vitamin C between kohlrabi (Brassica oleracea var. acephala gongylodes), Savoy cabbage (B. oleracea sabauda), Brussels sprouts (B. oleracea gemmifera), cauliflower (B. oleracea botrytis), radish (Raphanus sativus) and garden cress (Lepidium sativum) microgreens for their antioxidant and hypoglycemic potential. In addition, we applied an in vitro-simulated system of human digestion in order to track the bioaccessibility of the selected phenolic representatives, and the stability of the microgreens' antioxidant and hypoglycemic potential in terms of α-amylase and α-glucosidase inhibition after each digestion phase. Using spectrophotometric and RP-HPLC methods with statistical analyses, we found that garden cress had the lowest soluble sugar content, while Savoy cabbage and Brussels sprouts had the highest glucosinolate levels (76.21 ± 4.17 mg SinE/g dm and 77.73 ± 3.33 mg SinE/g dm, respectively). Brussels sprouts were the most effective at inhibiting protein glycation (37.98 ± 2.30% inhibition). A very high positive correlation (r = 0.830) between antiglycation potential and conjugated sinapic acid was recorded. For the first time, the antidiabetic potential of microgreens after in vitro digestion was studied. Kohlrabi microgreens best inhibited α-amylase in both initial and intestinal digestion (60.51 ± 3.65% inhibition and 62.96 ± 3.39% inhibition, respectively), and also showed the strongest inhibition of α-glucosidase post-digestion (19.22 ± 0.08% inhibition). Brussels sprouts, cauliflower, and radish had less stable α-glucosidase than α-amylase inhibitors during digestion. Kohlrabi, Savoy cabbage, and garden cress retained inhibition of both enzymes after digestion. Kohlrabi antioxidant capacity remained unchanged after digestion. The greatest variability was seen in the original samples, while the intestinal phase resulted in the most convergence, indicating that digestion reduced differences between the samples. In conclusion, this study highlights the potential of various microgreens as sources of bioactive compounds with antidiabetic and antiglycation properties. Notably, kohlrabi microgreens demonstrated significant enzyme inhibition after digestion, suggesting their promise in managing carbohydrate metabolism and supporting metabolic health.