Aggregation Rate Research Articles

The Impact of Polyphosphates on the Colloidal Stability of Laponite Particles.

The effect of polyphosphate (polyP) adsorption on the colloidal properties of disc-shaped laponite (LRD) particles was examined in aqueous dispersions with a focus on elucidating the interparticle forces that govern the colloidal stability of the systems. The charge and aggregation rate data of bare LRD exhibited an ionic strength-dependent trend, confirming the presence of double-layer repulsion and van der Waals attraction as major surface interactions. The charge of LRD particles significantly increased in magnitude at elevated polyP concentrations as a result of polyP adsorption and subsequent overcharging of the positively charged sites on the edges of the LRD discs. A transition from stable to unstable LRD colloids was observed with increasing polyP doses indicating the formation of aggregates in the latter systems due to depletion forces and/or bridging interactions induced by dissolved or adsorbed polyP, respectively. The degree of phosphate polymerization influenced neither the charge nor the aggregation mechanism. The findings clearly confirm that polyP adsorption was the driving phenomenon to induce particle aggregation in contrast to other clay types, where phosphate derivatives act as dispersion stabilizing agents. This study provides valuable insights into the early stages of aggregation in colloidal systems involving LRD and polyPs, which have a crucial role in predicting further material properties that are important to designing LRD-polyP composites for applications such as potential phosphate sources in chemical fertilizers.

Development of monoclonal antibodies in tablet form: A new approach for local delivery

Among the various pharmaceutical forms, tablets offer numerous advantages, like ease of administration, cost-effectiveness in production, and better stability of biomolecules. Beyond these benefits, the tablet form opens up possibilities for alternative routes for the local delivery of biopharmaceuticals such as oral or vaginal administration, thereby expanding the therapeutic applications of these biomolecules and overcoming the inconvenients associated with parenteral administration. However, to date there is limited information on the feasibility of developing biomolecules in the tablet form.In this study, we have evaluated the feasibility of developing monoclonal antibodies in the tablet form while preserving their biological properties. Different excipients and process parameters were studied to assess their impact on the antibody’s integrity during tableting. ELISA results show that applying compression pressure up to 100 MPa is not detrimental to the antibody’s binding properties when formulated from a lyophilized powder containing trehalose or sucrose as the major excipient. This observation was confirmed with SPR and ultracentrifugation experiments, which demonstrated that neither the binding affinity for both Fc and Fab antibody fragments nor its aggregation rate are affected by the tableting process. After compression, the tablets containing the antibodies have been shown to be stable for 6 months at room temperature.

Study on the mechanical properties of recycled brick coarse aggregate concrete based on finite element modeling

In recent years, the use of recycled materials in concrete production has garnered significant attention due to their environmental and economic benefits. To promote the application of recycled aggregates, this study focuses on investigating the utilization of Recycled Brick Coarse Aggregate (RBCA) as a substitute for natural aggregate. This paper presents the development of stochastic convex polygonal RBCA through the utilization of a custom-programmed algorithm and proposes a finite element model designed to simulate the behavior of RBCA concrete under compression and splitting tensile. Numerical simulations were conducted to investigate the effects of brick aggregate Replacement Rate (RR) and porosity on the compressive and splitting tensile properties of RBCA concrete. A strong correlation was found between the Concrete Damage Plasticity (CDP) model developed in this study and experimental results, indicating high reliability. The results indicate that the replacement rate of brick aggregates has a more significant impact on the compressive strength than on the splitting tensile strength of concrete. Furthermore, the distribution of coarse aggregates and pores has a minor influence on the mechanical properties and ultimate failure mode of RBCA concrete but significantly affects the crack distribution pattern. The sequence of damage initiation in RBCA concrete was found to be: pores, old Interfacial Transition Zone (ITZ), old mortar, new ITZ, new mortar, RBCA, and Natural Coarse Aggregate (NCA). These findings contribute to a comprehensive understanding of RBCA's performance and offer valuable insights for optimizing its behavior.

Reinforcing the photocatalytic removal of ibuprofen antibiotic over S-scheme 2D/1D Bi12O17Cl2/V2O5 heterojunction under solar light illumination

In our work, the Bi12O17Cl2/V2O5 hybrid with a favorable S-scheme mechanism was prepared via a simple self-assembly procedure for ibuprofen (IBF) oxidation under solar light energy. The 2D Bi12O17Cl2 provides abundant active sites to immobilize 1D V2O5 nanorods, enhancing the interaction between two semiconductors. The establishment of the 2D/1D structure reflected a positive effect on the surface area of Bi12O17Cl2/V2O5-10 %, which was linked to the reduction in the aggregation rate of V2O5 nanorods. Amazingly, optimal Bi12O17Cl2/V2O5 photocatalysts achieved exceptional IBF degradation capacities of 88.6 % and 71.3 % under LED and direct solar light irradiation, respectively. Among the samples, the optimized Bi12O17Cl2/V2O5-10 % reflected the best IBF oxidation kinetic with a reaction constant of 0.03894 min− 1, which is stronger than pristine Bi12O17Cl2 (0.00885 min− 1) and V2O5 (0.0119 min− 1) by 4.4 and 3.27 times, respectively. The promoted catalytic activity was correlated to the S-scheme heterojunction between Bi12O17Cl2 and V2O5 that could upgrade the solar light absorbance, facilitate the separation and transportation of charge carriers, and strengthen the redox potential of Bi12O17Cl2/V2O5. Furthermore, the parameters revealed the best IBF treatment at a catalyst dosage of 0.6 g/L and a pH value of 7. Besides, Bi12O17Cl2/V2O5-10 % recorded outstanding catalytic stability in six cycles without notable alteration in its structure, morphology, or optical properties. On the other hand, the radical quenching tests declared that •O2− and •OH play major contributions in IBF photooxidation over Bi12O17Cl2/V2O5-10 %. Finally, our work offers vital guidance towards designing robust bismuth-based heterojunctions for efficient degradation of IBF antibiotics in a sustainable and cost-effective strategy.

Efficacy and Hemorheology of Ginkgo biloba Extract (EGb 761) in the Treatment of Sudden Sensorineural Hearing Loss: A Retrospective Study.

This study aimed to analyze the therapeutic effect of Ginkgo biloba extract (EGb 761) on sudden sensorineural hearing loss (SSNHL) and its influence on hemorheology. The clinical data of patients diagnosed with SSNHL and admitted to the Wendeng Hospital of Traditional Chinese Orthopedics and Traumatology of Shandong Province from May 2020 to May 2023 were retrospectively analyzed. Based on different clinical treatment protocols, patients were divided into a control group (treated with routine treatment) and an administration group (treated with routine treatment + EGb 761). Both groups underwent drug treatment for 10 days. Subsequently, the hearing threshold, hemorheological parameters (blood high shear viscosity, blood low shear viscosity, plasma viscosity, and platelet aggregation rate) and inflammatory factors and serum levels (C-reactive protein, interleukin-6, tumor necrosis factor-α and soluble vascular cell adhesion molecule-1) of these groups were compared. This study comprised 120 patients, with 66 cases in the control group and 54 cases in the administration group. Following treatment, the total effective rate of the administration group was significantly higher than that of the control group (90.74% vs. 72.73%) (P-value < 0.05). The hearing threshold, hemorheological parameters, inflammatory factors, and serum levels were significantly lower in the administration group than in the control group (P-value < 0.05). Compared with routine treatment, joint EGb 761 in the SSNHL treatment may improve the hearing threshold and hemorheological indexes of patients, inhibit the inflammatory response, and promote the recovery of hearing function. Moreover, no serious adverse reactions are observed, indicating adequate safety.

Impact of Discontinuing Contact Precautions for Multidrug-resistant Gram-negative Enterobacteriaceae in a Large Health System

Background: Contact precautions (CP) to prevent transmission of multidrug-resistant gram-negative (MDRGN) Enterobacteriaceae are recommended, although studies of discontinuation of CP (DcCP) have found no change in healthcare associated infections (HAI) due to extended-spectrum beta-lactamase (ESBL) producing Enterobacteriaceae. Limited data exists on DcCP for MDRGN in a large health system. Methods: We performed a retrospective observational study analyzing the relationship between use of CP and HAI due to two definitions of MDRGN Enterobacteriaceae: ESBL, and non-susceptibility to ≥3 drug classes (3DC-GNR), with carbapenem resistant Enterobacteriaceae (CRE) serving as control. The study included all inpatient admissions from 2/2017 through 9/2022 at 21 acute care hospitals. Hospitals had latitude to determine CP practices based on local risk assessment, but in 2/2018, system-wide transmission-based precautions guidance was updated to recommend DcCP for MDRGN Enterobacteriaceae and in 12/2019 was updated to clarify DcCP specifically for ESBL and 3DC-GNR while continuing CP for carbapenem-resistant organism carriage. We interviewed infection preventionists to define when CP were used for CRE, ESBL, and 3DC-GNR Enterobacteriaceae. HAI were defined using National Healthcare Safety Network criteria including all HAI categories. We compared the incidence rate of HAI attributable to the two MDRGN types in hospital months with and without use of CP, with HAI due to CRE as a comparison group since all hospitals used CP for CRE throughout the study period. Results: The periods of CP use, by hospital, are shown in Figure 1. Throughout the study period, there were 987 HAI attributed to ESBL Enterobacteriaceae, 579 due to 3DC-GNR Enterobacteriaceae, and 329 due to CRE. Figure 2 shows the unadjusted aggregate rate of HAI for each of the three MRGN types, including among hospitals with and without CP in each month, for ESBL and 3DC-GNR. In months with and without CP, the rate of HAI was 1.482/10,000 and 1.093/10,000 patient days (incidence rate ratio [IRR], 1.356 [95% confidence interval, 1.195-1.540]) for ESBL Enterobacteriaceae. In months with and without CP, the rate of HAI was 1.071/10,000 and 0.493/10,000 patient days (IRR,2.173[95% confidence interval, 1.838-2.569]) for 3DC-GNR Enterobacteriaceae. Conclusion: DcCP was not associated with an increase in HAI due to ESBL and 3DC-GNR Enterobacteriaceae in aggregated facilities that self-selected for DcCP. Facilities that used CP were associated with significantly higher rates of ESBL and 3DC-GNR Enterobacteriaceae, a relationship that did not change as hospitals DcCP for these MDRGN. Further analyses are necessary to assess for a causal relationship.

The effect of agitating buffy coats on platelet quality before soft spin

BackgroundPlatelet plays a vital role in both physiological and pathological processes. However, the limited storage time of platelet in vitro poses an immense challenge for its applications because of the increased risk of bacterial contamination and platelet storage lesions. Agitation can inhibit lesions by facilitating continuous oxygenation of platelets and permitting excess carbon dioxide to be removed during storage. However, it is still not known whether agitating BCs gives a positive effect on platelet quality. Objectives: To evaluate the quality difference between platelet concentrates (PCs) from buffy coats (BCs) held rest and agitation. MethodsSamples were withdrawn for cell count, blood gas analysis, free hemoglobin level, hypotonic shock response, maximum aggregation rate, activation marker expression (CD62P and CD42b) and coagulation function. Results: We found the PCs prepared from the agitating BCs had fewer residual WBCs, exhibited a better gas exchange ability, slower metabolism (higher pH, higher content glucose, and lower lactic acid levels), better hypotonic shock response, and lower levels of CD62P. The TEG-PC assays showed no difference in coagulation function. Conclusion: Our findings showed that BC can be agitated overnight before a soft spin.

Effect of partial substitution of NaCl by KCl on aggregation behavior and gel properties of beef myosin

Based on the three typical gels under KCl substitution groups, the effect of partial substitution of NaCl by KCl (groups: T 1:0.6 M NaCl; T 2: 0.3 M NaCl +0.3 M KCl; T 3: 0.2 M NaCl +0.4 M KCl; T 4:0.6 M KCl) on the aggregation behavior and gel characteristics of myosin was evaluated. The significant changes in hydrophobicity and sulfhydryl content (P < 0.05) indicate KCl substitution enhances myosin aggregation through hydrophobic interactions and disulfide bonds. According to Ca2+-ATP, scanning electron microscopes (SEM) and the rheological results, T2 had a smoother network structure at about 75 °C. Noticeably, T3 had high water holding capacity (WHC), but its gel had some visible cavities. T4 had a gel structure with several irregular aggregates due to a greater aggregation rate. Thus, appropriate partial substitution of NaCl by KCl could enhance beef myosin gel properties and heat-induced aggregation behavior

Patient Comments and Patient Experience Ratings Are Strongly Correlated With Emergency Department Wait Times.

Hospitals and clinicians increasingly are reimbursed based on quality of care through financial incentives tied to value-based purchasing. Patient-centered care, measured through patient experience surveys, is a key component of many quality incentive programs. We hypothesize that operational aspects such as wait times are an important element of emergency department (ED) patient experience. The objectives of this paper are to determine (1) the association between ED wait times and patient experience and (2) whether patient comments show awareness of wait times. This is a cross-sectional observational study from January 1, 2019, to December 31, 2020, across 16 EDs within a regional health care system. Patient and operations data were obtained as secondary data through internal sources and merged with primary patient experience data from our data analytics team. Dependent variables are (1) the association between ED wait times in minutes and patient experience ratings and (2) the association between wait times in minutes and patient comments including the term wait (yes/no). Patients rated their "likelihood to recommend (LTR) an ED" on a 0 to 10 scale (categories: "Promoter"=9-10, "Neutral"=7-8, or "Detractor"=0-6). Our aggregate experience rating, or Net Promoter Score (NPS), is calculated by the following formula for each distinct wait time (rounded to the nearest minute): NPS=100* (# promoters - # detractors)/(# promoters+ # neutrals+ # detractors). Independent variables for patient age and gender and triage acuity, were included as potential confounders. We performed a mixed-effect multivariate ordinal logistic regression for the rating category as a function of 30minutes waited. We also performed a logistic regression for the percentage of patients commenting on the wait as a function of 30minutes waited. Standard errors are adjusted for clustering between the 16 ED sites. A total of 50 833 unique participants completed an experience survey, representing a response rate of 8.1%. Of these respondents, 28.1% included comments, with 10.9% using the term "wait." The odds ratio for association of a 30-minute wait with LTR category is 0.83 [0.81, 0.84]. As wait times increase, the odds of commenting on the wait increase by 1.49 [1.46, 1.53]. We show policy-relevant bubble plot visualizations of these two relationships. Patients were less likely to give a positive patient experience rating as wait times increased, and this was reflected in their comments. Improving on the factors contributing to ED wait times is essential to meeting health care systems' quality initiatives.

Navigating the complexities of online opinion formation: An insight into consumer cognitive heuristics

Few studies have considered changes in consumer perceptions when faced with multiple levels of review ratings. Drawing on availability heuristic theory, we aim to explore the synergistic effects of different levels of review ratings on consumers' cognitive processes. Using a longitudinal dataset of reviews from 4637 restaurants on Yelp, we conducted an empirical study using individual and time-dual fixed-effects models. Our findings indicate that easy-to-retrieve (review) rating is better than aggregate ratings in predicting consumer purchase decisions. The inconsistency between easy-to-retrieve and aggregate ratings influences consumers' cognitive heuristic when interpreting online reviews. Additionally, inconsistencies and proportional changes in expert and amateur reviews influence consumer perceptions of different levels of information. Furthermore, we conducted two online experiments to validate the distinguishing impact of aggregate versus easy-to-retrieve ratings on consumers. These findings provide insightful implications for understanding consumers’ cognitive heuristics in online consumption contexts.

5G wavelength-division-multiplexing-based bidirectional optical wireless communication system with signal remodulation employing cascaded reflective semiconductor optical amplifiers

Compared with previous generations, fifth-generation communications can provide faster download and upload speeds and support a greater number of connected devices. Integrating fifth-generation signals with optical wireless communication systems provides promising ways to afford higher transmission rates and faster wireless connectivity. Here we report a fifth-generation wavelength-division-multiplexing-based bidirectional optical wireless communication system with signal remodulation employing cascaded reflective semiconductor optical amplifiers to effectively remove the downstream data for uplink transmission. It shows a fifth-generation wavelength-division-multiplexing-based bidirectional optical wireless communication system using four wavelengths for communication. The uplink performance is substantially enhanced by using two reflective semiconductor optical amplifiers to remove the downstream data. The system achieves an aggregate transmission rate of 36.4 Gbit/s for both downlink and uplink transmissions over a 100-m optical wireless link. This demonstrated fifth-generation wavelength-division-multiplexing-based bidirectional optical wireless communication system employing cascaded reflective semiconductor optical amplifiers holds great potential for enhancing fifth-generation advanced communication capabilities.

“Racial mortality inversion”: Black-white disparities in mortality among people experiencing homelessness in the United States

Disparities in mortality between Black and White people have long been observed. These disparities persist at all income levels. However, similar patterns in racial mortality disparities are not observed among people experiencing homelessness. Instead, studies in a handful of cities show a reversal in the Black-White mortality disparity in the United States: Black people experiencing homelessness are less likely to die compared to White people experiencing homelessness. We propose a theory of “racial mortality inversion” and test whether inverted Black-White mortality patterns are observable in homeless populations throughout the United States. Using a novel dataset of 18,618 homeless decedents in 20 localities across 10 states and the District of Columbia, we find consistent evidence for “racial mortality inversion” across time and place. Between 2015 and 2020, the aggregate White homeless mortality rate was 67.8%–138.4% higher than the rate for the Black homeless population. Inverted racial mortality rates were observed in all 20 localities and in nearly every year. Across the entire sample, higher average ages of death were also observed for Black people compared to White people experiencing homelessness in 5 of 6 years, though racial inversion in age was not consistent across localities. These findings offer novel insight into racial health disparities among people experiencing homelessness and may inform policies and programs that seek to prevent homelessness and homeless mortality across racial groups.

Fisheries and aquaculture by-products: Case studies in Norway, United States, and Vietnam

Fishmeal and fish oil (FMFO) have historically come from capture fisheries, although supply from capture fisheries is constrained and demand for FMFO is increasing. Fish production losses and by-products are an alternative raw material for FMFO, however, there is little systematic data collected on the use of these raw materials and limited knowledge about barriers to their use in FMFO production. This study collected data on production losses and by-products from seven fisheries and aquaculture sectors that are important in supplying the US seafood market. From 2019–2021, quantitative surveys (n=47 businesses), semi-structured qualitative interviews (n=31 businesses), and secondary data were collected for the study period of 2014–2018. There was significant variation in utilization of production losses and by-products across sectors (range: 37–99 %), and overall, the aggregate utilization rate was 72 %. Scale appeared to be the most important factor leading to use of production losses and by-products. Aquaculture industries in this study had a large and relatively steady supply of by-products year-round, which made investments in FMFO plants worthwhile and led to moderate to high rates of by-product utilization. Wild-caught fisheries in this study had lower rendering rates due to short fishing seasons, smaller scales, operations in remote locations, and regulations that allow dumping of by-products. There were several examples of companies that invested in rendering plants because it was profitable to sell the rendered waste, while other sectors and industries require better coordination and policy supports to make use of this valuable resource.

Influence of natural organic matter on the aggregation dynamics of biochar colloids derived from various feedstocks

Abundant biochar colloids (BCs) produced from a wide range of feedstocks, resulting from forest fires, agricultural production, and environmental restoration, exhibit varying aggregation behaviors influenced by feedstock type and natural organic matter. However, the impact of natural organic matter on the colloidal stability of BCs derived from different feedstocks remains poorly understood. In this study, six selected biochars were derived from various feedstocks as follows: sewage sludge (SS), rice husk (RH), oil seed rape straw pellets (OSR), wheat straw pellets (WS), miscanthus straw pellets (MS) and softwood pellets (SW). The colloidal stability of BCs, with the exogenous addition of organic matter, was further determined. The order of critical coagulation concentrations (CCCs) of BCs with the presence of humic acid (HA) was as follows: RH (989.48 mM) < MS (1084.69 mM) < SS (1149.76 mM) < WS (1338.99 mM) < OSR (2402.98 mM) < SW (3151.32 mM). This order was significantly positively correlated with the specific surface area and negatively correlated with the ash content of the bulk biochar. Compared to HA, bovine serum albumin (BSA) more effectively inhibited the aggregation behavior of BCs due to steric hindrance. The initial aggregation rate constant (k) of BCs at 3000 mM NaCl was as follows: MS (0.238 nm/s) > OSR (0.142 nm/s) > WS (0.128 nm/s) > SS (0.126 nm/s) > RH (0.118 nm/s) > SW (0.112 nm/s). The stabilizing effects of BSA on biochar colloids were independent of the physicochemical properties of bulk biochar. In the presence of BSA, a thin layer of protein corona significantly enhanced the stability of biochar colloids, particularly the BCs derived from MS. Our results underscore the importance of considering feedstock resources and natural organic matter type when assessing the aggregation and potential risks of BCs in aquatic systems.

Mechanical properties of recycled aggregate concrete containing brick particles

To investigate the mechanical properties of recycled aggregate concrete containing brick particles (RACB), compressive strength tests were conducted on RACBs with different water/cement ratios and recycled fine aggregate substitution rates. The changes in compressive strength, elastic modulus and peak strain of RACB were analysed as a function of the proportion of substituted recycled fine aggregate, and a stress–strain equation was established. A damage model was established using ultrasonic non-destructive testing technology to reveal the damage mechanism of RACB. Results show that the basic mechanical properties of RACB are best when the replacement proportion of recycled fine aggregate (r) is 30%. The model parameter a of the stress–strain curve equation is consistent with the change of elastic modulus with r. The model parameter b has a quadratic function relationship with r, reflecting the brittleness of RACB. The initial damage of RACB is relatively large, and cracks penetrate the recycled coarse aggregate, leading to specimen failure.

Tubulin-binding region alters tau-lipid interactions and changes toxicity of tau fibrils formed in the presence of phosphatidylserine lipids.

Alzheimer's disease is the fastest-growing neurodegenerative disease that affects over six million Americans. The abnormal aggregation of amyloid β peptide and Tau protein is the expected molecular cause of the loss of neurons in brains of AD patients. A growing body of evidence indicates that lipids can alter the aggregation rate of amyloid β peptide and modify the toxicity of amyloid β aggregates. However, the role of lipids in Tau aggregation remains unclear. In this study, we utilized a set of biophysical methods to determine the extent to which phospatidylserine (PS) altered the aggregation properties of Tau isoforms with one (1N4R) and two (2N4R) N terminal inserts that enhance the binding of Tau to tubulin. We found that the length and saturation of fatty acids (FAs) in PS altered the aggregation rate of 2N4R isoform, while no changes in the aggregation rate of 1N4R were observed. These results indicate that N terminal inserts play an important role in protein-lipid interactions. We also found that PS could change the toxicity of 1N4R and 2N4R Tau fibrils, as well as alter molecular mechanisms by which these aggregates exert cytotoxicity to neurons. Finally, we found that although Tau fibrils formed in the presence and absence of PS endocytosed by cells, only fibril species that were formed in the presence of PS exert strong impairment of the cell mitochondria.

Recycling of Waste Plastic PET on Asphalt Concrete (AC) by Using Application of Response Surface Methodology: Effect of PET on AC Formulated by Duriez Model

The wet recycling process of plastic waste was used to design a composite material (asphalt concrete) following the Duriez method. This process aims to improve the rheological performance of asphalt concrete by transforming PET on powdery and added to bitumen. To attend this objective, Doehlert&amp;apos; surface plane was used to assess how the asphalt rate, the PET rate and size, and then the aggregate rate affected the stability (wet and dry) and, in turn, the immersion/compression strength index (RI/C), the absorption capacity, the compactness as well as the void that could be filled by the 0/10 AC (asphalt concrete). All quadratic multivariate polynomial models with interactions were obtained and validated in order to optimize the responses. Thus, the physical characterization made it possible to obtain an asphalt concrete with good mechanical characteristics. In addition, it was observed that the selected factors had a different impact on the responses, which are: IR/C; the water absorption capacity, compactness and void filled by the binder by significantly increasing or decreasing them in simple, quadratic and interaction contributions. From the multi-response optimization, the objective was to obtain a composite material (Asphalt-PET-Aggregates) with has the best rheological characteristic, resulted in the following compromise: Bitumen rate 7%, PET 6% of asphalt, PET size 0,5mm; Aggregate content 93%. The simulated optimal values yielded the following responses were: 0.77 RI/C, immersion/compressive strength (Y.&amp;lt;SUB&amp;gt;RI/C&amp;lt;/SUB&amp;gt;); 2.9%, absorption capacity (Y.&amp;lt;SUB&amp;gt;WAC&amp;lt;/SUB&amp;gt;); 94%, compactness (Y.&amp;lt;SUB&amp;gt;C&amp;lt;/SUB&amp;gt;); 71% void filled by asphalt (Y.&amp;lt;SUB&amp;gt;VFA&amp;lt;/SUB&amp;gt;)

A Practical Guide to All-Atom and Coarse-Grained Molecular Dynamics Simulations Using Amber and Gromacs: A Case Study of Disulfide-Bond Impact on the Intrinsically Disordered Amyloid Beta.

Intrinsically disordered proteins (IDPs) pose challenges to conventional experimental techniques due to their large-scale conformational fluctuations and transient structural elements. This work presents computational methods for studying IDPs at various resolutions using the Amber and Gromacs packages with both all-atom (Amber ff19SB with the OPC water model) and coarse-grained (Martini 3 and SIRAH) approaches. The effectiveness of these methodologies is demonstrated by examining the monomeric form of amyloid-β (Aβ42), an IDP, with and without disulfide bonds at different resolutions. Our results clearly show that the addition of a disulfide bond decreases the β-content of Aβ42; however, it increases the tendency of the monomeric Aβ42 to form fibril-like conformations, explaining the various aggregation rates observed in experiments. Moreover, analysis of the monomeric Aβ42 compactness, secondary structure content, and comparison between calculated and experimental chemical shifts demonstrates that all three methods provide a reasonable choice to study IDPs; however, coarse-grained approaches may lack some atomistic details, such as secondary structure recognition, due to the simplifications used. In general, this study not only explains the role of disulfide bonds in Aβ42 but also provides a step-by-step protocol for setting up, conducting, and analyzing molecular dynamics (MD) simulations, which is adaptable for studying other biomacromolecules, including folded and disordered proteins and peptides.

Hydrogen Sulfide Promotes Platelet Autophagy via PDGFR-α/PI3K/Akt Signaling in Cirrhotic Thrombocytopenia.

The role of platelet autophagy in cirrhotic thrombocytopenia (CTP) remains unclear. This study aimed to investigate the impact of platelet autophagy in CTP and elucidate the regulatory mechanism of hydrogen sulfide (H2S) on platelet autophagy. Platelets from 56 cirrhotic patients and 56 healthy individuals were isolated for in vitro analyses. Autophagy markers (ATG7, BECN1, LC3, and SQSTM1) were quantified using enzyme-linked immunosorbent assay, while autophagosomes were visualized through electron microscopy. Western blotting was used to assess the autophagy-related proteins and the PDGFR/PI3K/Akt/mTOR pathway following treatment with NaHS (an H2S donor), hydroxocobalamin (an H2S scavenger), or AG 1295 (a selective PDGFR-α inhibitor). A carbon tetrachloride-induced cirrhotic BALB/c mouse model was established. Cirrhotic mice with thrombocytopenia were randomly treated with normal saline, NaHS, or hydroxocobalamin for 15 days. Changes in platelet count and aggregation rate were observed every three days. Cirrhotic patients with thrombocytopenia exhibited significantly decreased platelet autophagy markers and endogenous H2S levels, alongside increased platelet aggregation, compared to healthy controls. In vitro, NaHS treatment of platelets from severe CTP patients elevated LC3-II levels, reduced SQSTM1 levels, and decreased platelet aggregation in a dose-dependent manner. H2S treatment inhibited PDGFR, PI3K, Akt, and mTOR phosphorylation. In vivo, NaHS significantly increased LC3-II and decreased SQSTM1 expressions in platelets of cirrhotic mice, reducing platelet aggregation without affecting the platelet count. Diminished platelet autophagy potentially contributes to thrombocytopenia in cirrhotic patients. H2S modulates platelet autophagy and functions possibly via the PDGFR-α/PI3K/Akt/mTOR signaling pathway.

Experimental Study of Mechanical Properties and Theoretical Models for Recycled Fine and Coarse Aggregate Concrete with Steel Fibers.

With diminishing natural aggregate resources and increasing environmental protection efforts, the use of recycled fine aggregate is a more sustainable approach, although challenges persist in achieving comparable mechanical properties. Exploration into the incorporation of steel fibers with recycled aggregate has led to the development of steel-fiber-reinforced recycled aggregate concrete. This study investigates the shrinkage performance and compressive constitutive relationship of steel fiber recycled concrete with different steel fibers and recycled aggregate dosages. Initially, based on different replacement rates of recycled coarse aggregate and different volume contents of steel fiber, experimental results demonstrate that as the replacement rate of recycled coarse aggregate increases, shrinkage also increases, while the addition of steel fiber can mitigate this effect. An empirical shrinkage model for steel fiber recycled concrete under natural curing conditions is also proposed. Subsequently, based on the uniaxial compression test, findings indicate that with an increasing replacement rate of recycled fine aggregate, the peak stress and elastic modulus of concrete decrease, accompanied by an increase in peak strain, and the addition of steel fiber limits concrete crack development and enhances its brittleness while the peak stress and strain of recycled fine aggregate concrete are enhanced. However, the steel fiber volume percentage has a negligible effect on the elastic modulus. A constitutive relationship for concrete considering the effects of recycled fine aggregate and steel fiber is also proposed. This finding provides foundational support for the influence patterns of steel fiber dosage and recycled aggregate ratio on the mechanical properties of steel fiber recycled concrete.