Molecular Substances Research Articles

The Role of Extracellular Vesicles in Colorectal Cancer.

Extracellular vesicles (EVs) are a class of spherical vesicles that are produced by active secretion of cells and encapsulated by phospholipid bilayers. In recent years, numerous studies have shown that EVs play pivotal roles in the regulation of intercellular communication between colorectal cancer (CRC) cells and target cells, and can regulate the proliferation, metastasis, and infiltration of tumor cells by regulating the microenvironment of tumor cells. EVs carry specific molecular substances in source CRC cells and are expected to serve as new molecular markers for the detection of cancers. This review highlights the current state of research and progress of potentially incorporating EVs in the diagnosis and treatment of CRC.

Metabolites of extracellular organic matter from Microcystis and Dolichospermum drive distinct modes of carbon, nitrogen, and phosphorus recycling

Algal extracellular organic matter (EOM) metabolites exert considerable impact on the carbon (C), nitrogen (N), and phosphorus (P) cycles mediated by attached bacteria. Field investigations were conducted in two ponds to explore the relationship among EOM metabolites from Microcystis and Dolichospermum, co-occurring microbes, and nutrient recycling from April 2021 to December 2021. Microcystis blooms primarily produced more complex bound EOM (bEOM) metabolites with many amino acid components, which facilitated bacterial colonization and provided sufficient substrates for ammonification. Meanwhile, high abundances of dissimilatory nitrate reduction to ammonium genes from co-occurring microbes such as Rhodobacter have demonstrated their strong N retention ability. Metabolic products of bEOM from Microcystis comprise a large number of organic acids that can solubilize non-bioavailable P. All these factors have collectively resulted in the increase of all fractions of N and P, except for nitrate (NO3−-N) in the water column. In contrast, the EOM metabolite from Dolichospermum was simple, coupled with high abundance of functional genes of α-glucosidase, and produced small molecular substances fueling denitrification. The metabolic products of EOM from Dolichospermum include abundant N-containing substances dominated by heterocyclic substances, suggesting that the metabolic products of Dolichospermum are not conducive to N regeneration and retention. Therefore, the metabolic products of EOM from Microcystis triggered a shift in the attached microbial community and function toward C, N, and P recycling with close mutual coupling. Acquisition of N and P in Dolichospermum is dependent on itself based on N fixation and organic P hydrolysis capacity. This study provides a new understanding of the contribution of algal EOM to the nutrient cycle.

Biomimetically Engineered Amyloid-Shelled Gold Nanocomplexes for Discovering α-Synuclein Oligomer-Degrading Drugs

The assembly of α-synuclein (αS) oligomers is recognized as the main pathological driver of synucleinopathies. While the elimination of toxic αS oligomers shows promise for the treatment of Parkinson's disease (PD), the discovery of αS oligomer degradation drugs has been hindered by the lack of proper drug screening tools. Here, we report a drug screening platform for monitoring the efficacy of αS-oligomer-degrading drugs using amyloid-shelled gold nanocomplexes (ASGNs). We fabricate ASGNs in the presence of dopamine, mimicking the in vivo generation process of pathological αS oligomers. To test our platform, the first of its kind for PD drugs, we use αS-degrading proteases and various small molecular substances that have shown efficacy in PD treatment. We demonstrate that the ASGN-based in vitro platform has strong potential to discover effective αS-oligomer-targeting drugs, and thus it may reduce the attrition problem in drug discovery for PD treatment.

Functional Blood-Brain Barrier Model with Tight Connected Minitissue by Liquid Substrates Culture.

The functional blood-brain barrier (BBB) model can provide a reliable tool for better understanding BBB transport mechanisms and in vitro preclinical experimentation. However, recapitulating microenvironmental complexities and physiological functions in an accessible approach remains a major challenge. Here, a new BBB model with a high-cell spatial density and tightly connected biomimetic minitissue is presented. The minitissue, pivotal functional structure of the BBB model, is fabricated by a novel and easy-to-use liquid substrate culture (LSC) method, which allows cells to self-assemble and self-heal into macrosized, tightly connected membranous minitissue. The minitissue with uniform thickness can be easily harvested in their entirety with extracellular matrix. Attributed to the tightly connected minitissue formed by LSC, the fabricated BBB biomimetic model has 1 to 2 orders of magnitude higher transendothelial electric resistance than the commonly reported BBB model. It also better prevents the transmission of large molecular substances, recapitulating the functional features of BBB. Furthermore, the BBB biomimetic model provides feedback regarding BBB-destructive drugs, exhibits selective transmission, and shows efflux pump activity. Overall, this model can serve as an accessible tool for life science or clinical medical researchers to enhance the understanding of human BBB and expedite the development of new brain-permeable drugs.

Preparation of Co3O4@carbon nanotubes modified ceramic membrane for simultaneous catalytic oxidation and filtration of secondary effluent

To improve the efficiency of wastewater reclamation, a novel Co3O4@carbon nanotubes modified ceramic membrane (Co3O4@CNT-CM) was prepared in this work for simultaneous catalytic peroxymonosulfate (PMS) oxidation and filtration of secondary effluent. The synthesized Co3O4@CNT catalyst showed better dispersibility with more active sites exposed, and Co3O4@CNT-CM exhibited relatively smooth surface, higher permeate flux and excellent catalytic PMS ability. The antifouling and water purification performance of Co3O4@CNT-CM were systematically investigated in secondary effluent purification. With the dual effect of catalytic oxidation and filtration, the organic pollutants were observably reduced. Fluorescent components were also significantly removed, and more macromolecular substances were degraded into small molecular substances. The flux of Co3O4@CNT-CM was significantly improved, with the reversible and irreversible resistances decreased by 82.5% and 78.6%, individually. With respect to the fouling mechanism, the volume entering the stage of cake filtration dramatically increased. The prepared Co3O4@CNT-CM accelerated the generation of various active species for oxidative degradation of pollutants, thus improving the antifouling performance of membrane. These results demonstrated the application potential of Co3O4@CNT-CM for wastewater treatment and reclamation.

Irregularity molecular descriptors of VC5C7[m,n] and HC5C7[m,n] nanotubes

Scientific organizations are creating carbon nanotube-based composites like VC5C7[m,n] and HC5C7[m,n], which indicate significant response against voltage. Imbalance-based irregularity indices determine the degree of irregularity of a certain molecular structure and, as a result, determine the properties of a molecular substance. In this article, we aim to compute irregularity indices of two nanotubes, VC5C7[m,n] and HC5C7[m,n]. We produce formulas for the irregularity of these two nanotubes, which are functions depending on the parameters of the structure m and n. We compare our results graphically and conclude that VC5C7[m,n] is more irregular than HC5C7[m,n].

Numerical solution of compartment-based reaction/diffusion models with DABOSS algorithm

The intracellular diffusive movement of molecular substances that are buffered by diffusing chelators is often modeled as movement between compartments with constant concentrations within which the buffering occurs. Here, an algorithm to solve such a system of time-dependent differential equations is presented. This Dynamic and Balanced Operator Splitting Scheme (DABOSS) combines dynamic time stepping and operator splitting techniques. The time stepping minimizes the number of time steps while bounding local errors. The balanced operator splitting separates the diffusion and reaction components (each of which is solved efficiently) in a way that preserves the correct steady-state behavior. Analysis shows that DABOSS scales almost linearly in the number of compartments and remains accurate over very long simulations. Moreover, DABOSS works efficiently for nanometer-sized compartments with sources of flux, showing that it is applicable to situations where more spatial resolution is desired.

Explore the mechanism and substance basis of Mahuang FuziXixin Decoction for the treatment of lung cancer based on network pharmacology and molecular docking

BackgroundMahuang FuziXixin Decoction (MFXD) is a classic Chinese herbal formula for the treatment of lung cancer. However, its mechanisms of action are unclear. In present study, network pharmacology and molecular docking technology were employed to investigate the molecular mechanism and substance basis of MFXD for the treatment of lung cancer. MethodThe active compounds and corresponding targets of MFXD were collected through the TCMSP database. OMIM and GeneCards databases were applied to filter the targets of lung cancer. The protein-protein interaction (PPI) were acquired through the STRING platform. Metascape and the Bioinformatics server were used for the visualization of GO and KEGG analysis. The tissue and organ distribution of targets was evaluated based on the BioGPS database. The binding affinity between potential targets and active compounds was evaluated by molecular docking. ResultA total of 51 active compounds and 118 targets of MFXD were collected. The target with a higher degree were identified through the PPI network, namely AR, RELA, NCOA1, EGFR, FOS, CCND1, ESR1 and HSP90AA1. GO and KEGG analysis suggested that MFXD treatment of lung cancer mainly involves hormone and response to inorganic substance, transcription regular complex, transcription factor binding and Pathways in cancer. Experimental validation showed that MFXD treatment inhibited the proliferation of NSCLC cells through downregulation the expression of EGFR, HIF1A, NCOA1 and RELA. Moreover, molecular docking revealed that hydrogen bond and hydrophobic interaction contribute to the binding of the compounds to targets. ConclusionOur findings comprehensively elucidated the actives, potential targets, and molecular mechanisms of MFXD against lung cancer, providing a promising strategy for the scientific basis and therapeutic mechanism of traditional Chinese medicine prescriptions for the treatment of the disease.

Pair entropy and universal viscosity scaling for molecular systems via molecular dynamics simulations

The scaling between the excess entropy and transport coefficients of liquids is an interesting property found by Rosenfeld in atomistic simulations. Later, Dzugutov proposed to estimate the excess entropy on the basis of the pair entropy. That approach has been shown to work well for atomic liquids and rigid molecules, but there is a problem of pair entropy definition for molecular substances in general. In this work, we propose a new method of estimation of the pair contribution to the excess entropy for hydrocarbon liquids. We present the results on viscosity-pair entropy Rosenfeld scaling for linear alkanes and an aromatic compound in two different force fields, and compare the results with the available experimental and correlation data. We show that our method accounts for 75–90% of excess entropy changes in molecular liquid, comparable to the pair entropy contribution in atomic liquids. The universal nearly-univariate dependence of the scaled viscosity and pair entropy is observed for each compound at different temperatures, and the scaling is shown to be transferable between the force fields models.

Setup for precision optical studies of supercritical fluids in a wide temperature range at high pressures up to 1 GPa

A setup with a working volume of more than 10mm3 has been fabricated to experimentally study the optical properties of gases, liquids, and solutions in a wide range of temperature (from 200 to 500K) at hydrostatic pressures up to 1GPa. The experimental parameters can be maintained with an accuracy of 0.1K and 1.5 MPa for up to 3-4 h. To introduce laser radiation and to record spectra, high-temperature optical fibers of increased strength in a metal sheath are introduced directly into the working chamber. The primary goal of experiments is to study the Raman radiation at vibron frequencies in supercritical fluids of molecular substances (N2, CO2, CH4, etc.).

Biotransformation of sulfamethoxazole (SMX) by aerobic granular sludge: Removal performance, degradation mechanism and microbial response

Aerobic granular sludge (AGS) is a promising biotechnology for the treatment of antibiotic−rich wastewater. However, little is known about the antibiotics degradation mechanism and microbial response in a sulfamethoxazole (SMX)-loaded AGS system. Herein, the results of a continuous 240 days test suggested that 0.5–5 mg/L of SMX could be thoroughly removed by AGS via adsorption and degradation. The degradation pathway of SMX involved the hydrolysis of the sulfonamide bond and cleavage of NS or CS bonds, subsequently leading to the production of small molecular substances (e.g. benzene and 5-methyl-isoxazole). In terms of the AGS system, it exhibited a strong resistance to 0.5 mg/L of SMX, while 1 and 5 mg/L of SMX significantly inhibited the microbial growth, declined the nitrification efficiency, weakened the sludge settleability, and triggered the excessive growth of filamentous bacteria. Besides, the secretion of extracellular polymer substances was suppressed by 57.3% when increasing the SMX concentration from 0.5 to 5 mg/L, which was not conducive to the system stability. The long−term presence of SMX enhanced the proliferation of antibiotics resistance genes (sul1and sul2) and exerted a strong selection pressure on the microbial community, especially with Thiothrix being the dominating genus. Overall, this study elucidated that AGS qualified promising application prospects in the removal of SMX present in wastewater, but SMX at high concentrations posed great adverse impacts on the performance of the AGS system, which causes concern when treating SMX rich wastewaters.

Sawdust biomass promotes aquathermolysis of extra-heavy oil

The application of biomass to the enhanced oil recovery of extra-heavy oil is a promising technology. In this paper, the promoting effect of sawdust on the viscosity reduction of extra-heavy oil was discussed. During the experiment, sawdust and extra-heavy oil were co-aquathermolysis. The experimental results showed that the viscosity of extra-heavy oil can be reduced from 145 Pa·s to 10.42 Pa·s at 553 K for 24 h and the feedstock ratio of sawdust: extra-heavy oil: water is 1:50:50. Elemental analysis of extra-heavy oil showed that the H/C increased from 1.4347 to 1.6296, and the oxygen content increased from 2.05 wt% to 5.61 wt%. Compared with the upgrading oil without sawdust, the viscosity decreased by 11.03 Pa·s and the H/C increased by 0.0832. The GC–MS results show that the dehydrogenation and deoxidation reactions of small molecular substances generated by sawdust provide hydrogen and oxygen sources for the upgrading of extra-heavy oil.

An inter-laboratory effort to harmonize the cell-delivered in vitro dose of aerosolized materials

Air-liquid interface (ALI) lung cell models cultured on permeable transwell inserts are increasingly used for respiratory hazard assessment requiring controlled aerosolization and deposition of any material on ALI cells. The approach presented herein aimed to assess the transwell insert-delivered dose of aerosolized materials using the VITROCELL® Cloud12 system, a commercially available aerosol-cell exposure system. An inter-laboratory comparison study was conducted with seven European partners having different levels of experience with the VITROCELL® Cloud12. A standard operating procedure (SOP) was developed and applied by all partners for aerosolized delivery of materials, i.e., a water-soluble molecular substance (fluorescence-spiked salt) and two poorly soluble particles, crystalline silica quartz (DQ12) and titanium dioxide nanoparticles (TiO2 NM-105). The material dose delivered to transwell inserts was quantified with spectrofluorometry (fluorescein) and with the quartz crystal microbalance (QCM) integrated in the VITROCELL® Cloud12 system. The shape and agglomeration state of the deposited particles were confirmed with transmission electron microscopy (TEM).Inter-laboratory comparison of the device-specific performance was conducted in two steps, first for molecular substances (fluorescein-spiked salt), and then for particles. Device- and/or handling-specific differences in aerosol deposition of VITROCELL® Cloud12 systems were characterized in terms of the so-called deposition factor (DF), which allows for prediction of the transwell insert-deposited particle dose from the particle concentration in the aerosolized suspension. Albeit DF varied between the different labs from 0.39 to 0.87 (mean (coefficient of variation (CV)): 0.64 (28%)), the QCM of each VITROCELL® Cloud 12 system accurately measured the respective transwell insert-deposited dose. Aerosolized delivery of DQ12 and TiO2 NM-105 particles showed good linearity (R2 > 0.95) between particle concentration of the aerosolized suspension and QCM-determined insert-delivered particle dose. The VITROCELL® Cloud 12 performance for DQ12 particles was identical to that for fluorescein-spiked salt, i.e., the ratio of measured and salt-predicted dose was 1.0 (29%). On the other hand, a ca. 2-fold reduced dose was observed for TiO2 NM-105 (0.54 (41%)), which was likely due to partial retention of TiO2 NM-105 agglomerates in the vibrating mesh nebulizer of the VITROCELL® Cloud12.This inter-laboratory comparison demonstrates that the QCM integrated in the VITROCELL® Cloud 12 is a reliable tool for dosimetry, which accounts for potential variations of the transwell insert-delivered dose due to device-, handling- and/or material-specific effects. With the detailed protocol presented herein, all seven partner laboratories were able to demonstrate dose-controlled aerosolization of material suspensions using the VITROCELL® Cloud12 exposure system at dose levels relevant for observing in vitro hazard responses. This is an important step towards regulatory approved implementation of ALI lung cell cultures for in vitro hazard assessment of aerosolized materials.

Topological Co-Indices of Molecular Structure of Porphyrazine Network

Topological co-indices are used to measure the strength of a relationship between molecular substance and its properties. A topological co-index is a mathematical representation of a molecular structure that integrates specific physical features of the basic molecular structure and its mathematical representation. Mathematical chemistry uses molecular graphs, which include edges that represent bonds between molecules and vertices that represent atoms, to integrate graph theory with science. Topological co-indices are a type of topological indices that considers separate vertices configurations that are numerical values of the atomic structures, which are used to describe and analyze the various chemical structures. Chemical graph theory brings up more possibilities for scientists. Topological co-indices are frequently used because through this we can save time by determining the topological indices instead of doing time-consuming tests in a research laboratory. In this article, we computed different topological co-indices for the chemical structure of Porphyrazine Network MCIPz(n).

Fishhook characteristics of biodiesel lubricity during autoxidation

The effects of light, ventilation and antioxidant on biodiesel performance and the corresponding influence mechanisms are investigated during long-term storage. The biodiesel exhibits slow autoxidation and its physical/chemical properties change during storage. Light and ventilation conditions can accelerate the oxidation of biodiesel, thereby aggravating its degradation. During the autoxidation process of biodiesel, the grinding spot diameter firstly decreases from 165.01 μm to 131.45 μm and then increases to 362.5 μm, similar to the shape of a fishhook. During the initial storage stage, the fatty acid methyl ester in biodiesel is decomposed into carboxylic acid and small molecular substances such as aldehydes and ketones, thereby improving the lubricity of biodiesel and reducing the grinding spot diameter. After long-term storage, insoluble resins and sediments are generated, causing an increase in the grinding spot diameter. Specifically, the kinematic viscosity of biodiesel is increased to 4.407 mm2/s even under dark and sealed storage conditions.

Mechanisms of Myocardial Damage Due to Hyperlipidemia: A Review of Recent Studies.

Myocardial injury and necrosis caused by hyperlipidemia have been investigated by several researchers. Their pathogenesis and molecular basis are different from those of the more common clinical ischemic myocardial injury. Hyperlipidemia leads to peroxide accumulation in the cardiomyocytes, causes lipid overload, decreases the antioxidant capacity of the body, and promotes the inflammatory response. Furthermore, hyperlipidemia causes changes in the structure and function of mitochondria in the cardiomyocytes, which results in their injury and necrosis. Many previous studies have shown that metabolic diseases (eg, obesity and diabetes) and chemical poisoning can lead to hyperlipidemic myocardial injury and necrosis. Moreover, it has been observed that this pathological process can be inhibited by many small molecular substances. In the clinic, myocardial damage can be prevented or reduced by lowering the levels of triglyceride and cholesterol. Myocardial damage can also be regulated via the molecular pathway of myocardial injury caused by hyperlipidemia so that the disease can be treated. The present article reviewed the recent findings reported on the mechanisms of myocardial damage due to hyperlipidemia.

Calcined hydroxyapatite powders with increased chemical stabilities and dispersibility

Biocompatible hydroxyapatite (HAp) powders have thermodynamically driven tendencies to lower their surface areas due to the formation of irreversible aggregates. To address this challenge, HAp hybrid powders are herein prepared by using a traditional wet-precipitation method with subsequent hydrothermal carbonization for surface modification. The crystallite size, crystallite degree and area ratio of the infrared peak assigned to bonding water against those of free water are determined to investigate the variation of HAp crystallization with processing parameters. The crystallization of HAp is facilitated by enriched water in a stealth layer with water molecules evolved by citrate, nitrogen (N)-containing methylene blue (MB), hydrogen-group-rich β-cyclodextrin (CD) and oxygen-containing organic carbon shells. The low surface areas result in fabrication of nano-sized HAp powders with a uniform size distribution, well-dispersed morphologies and smooth surfaces through calcination of HAp-CD-MB@C. The pH values of acidic buffers increase slowly during incubation of HAp-CD-MB@C powders with chemical stability and a large grain size after calcination at 550°C for 2 h. The present study will shed light on the preparation of nano-sized inorganic powders with a uniform size distribution, well-dispersed morphologies and modulated chemical stability for potential applications as carriers of small molecular substances and fillers in composite materials.

Effect of hapten structures on development of novel antibody against capsaicin and dihydrocapsaicin

• Three novel capsaicinoids haptens were synthesized, and the antibody-eliciting properties of four hapten-protein conjugations were investigated. • Novel polyclonal antibodies against capsaicinoids were prepared, and the important role of molecular structure and electrostatic potential in producing specific antibodies was verified. • A competitive indirect ELISA (icELISA) was established for capsaicinoids detection in spicy foods. Capsaicinoids content as a basis for the evaluation of spicy taste has attracted much attention. Antibody, as an important component of immunoassay, plays an important role in the detection of capsaicinoids levels. The molecular structure of the hapten is the key factor affecting the quality of small molecule antibodies. In our study, six capsaicinoids haptens were selected with different junction arm of length and structure to analyzed immune effect by geometric structure and electrostatic potential (ESP). Among them, three haptens were capsaicinoids structural analogues, and others were designed and synthesized. The results showed that the retention of amide bond (–NH–CO–) and hydroxyl group in the benzene ring of capsaicinoids hapten as well as rigid spacer arm that linked proteins to hapten had a positive effect on the affinity of the antibody. It provided a theoretical basis for rapid screening of small molecular substance haptens. To test our hypothesis, four kinds of haptens were used to synthesize antigens and immunize animals. Comparing 28 antiserum/coating conjugates combinations tested by indirect competitive enzyme-linked immunosorbent assay (icELISA) method for capsaicinoids (i.e., capsaicin and dihydrocapsaicin), the homologous combination of Pa-B2/OVA-hapten B had been shown to be most suitable for the determination of capsaicin and dihydrocapsaicin, which was consistent with the ESP analysis. In short, ESP analysis can speed up haptens screening and reduce the workload while producing high-quality antibodies. Thus, an icELISA based on hapten B polyclonal antibody was developed with IC 50 value of 0.36 μg mL −1 and the limit of detections (LODs) of 20 µg kg −1 in spicy food samples. Moreover, these results were also validated by high performance liquid chromatography (HPLC), and showed good agreements.

Metabolomic profiling upon external digestion in larvae of diving beetles: Cybister Curtis, 1827, Dytiscus Linnaeus, 1758, and Hydaticus Leach, 1817 (Coleoptera: Dytiscidae)

The SDS–PAGE analysis of prey animals (fly larvae) during external digestion by aquatic predators, the larvae of selected species in dytiscid genera, showed a major component of protein with a molecular weight of ca. 20 kDa. In addition, the analysis of third instar larvae of Cybister brevis Aubé, 1838, by nanoLC–ESI–Q-TOF/MS/MS revealed that the digested body fluid includes a polypeptide with a sequence of 97 amino acids corresponding to hemocyanin N (51% matched by Mascot and BLAST searches) and hemocyanin M (12% matched) derived from flies. We also found evidence indicating that beetle larvae repeatedly release digestive enzymes at least twice while consuming the fly bodies. These results suggest that the digested polypeptides were derived from ubiquitous high molecular substances such as arylphorin subunit C223 precursor included in the body fluid of the fly (Calliphora vicina Robineau-Desvoidy, 1830) that were produced during external digestion by diving beetle larvae.

Exploration of the phytohormone regulation of energy storage compound accumulation in microalgae

AbstractMicroalgal energy storage compounds (carbohydrates, lipids, etc.) can serve as renewable feedstocks for biofuels and biobased chemicals. Traditional methods of inducing the accumulation of energy storage compounds in microalgae, such as abiotic stress (high light intensity, high salinity, nutrient limitation, heavy metals, etc.), can affect the growth of microalgae and limit their efficient accumulation of energy storage materials. Plant hormones are a class of small molecular substances that act as chemical messengers to coordinate plant cell activities and regulate the physiological and metabolic activities of microalgae, including promoting microalgal cell proliferation, improving stress resistance, and enhancing photosynthetic activity, thereby increasing algal biomass and lipid, chlorophyll and protein content. This paper reviews the recent research progress on regulation of the accumulation of energy storage compounds in microalgae by adding exogenous plant hormones combined with abiotic stress, discusses the mechanism of plant hormones regarding the accumulation of energy storage compounds in microalgae, and proposes future research needs.