Molecular Sites Research Articles

Density functional theory investigation of the contributions of π-π stacking and hydrogen bonding with water to the supramolecular aggregation interactions of model asphaltene heterocyclic compounds

ContextA complex supramolecular process involving electrostatic and dispersion interactions and asphaltene aggregation is associated with detrimental petroleum deposition and scaling that pose challenges to petroleum recovery, transportation, and upgrading. The homodimers of seven heterocyclic model compounds, representative of moieties commonly found in asphaltene structures, were studied: pyridine, thiophene, furan, isoquinoline, pyrazine, thiazole, and 1,3-oxazole. The contributions of hydrogen bonding involving water bridges spanning between dimers and π-π stacking to the total interaction energy were calculated and analyzed. The distance between the planes of the aromatic rings is correlated with the π-π stacking interaction strength. All the dimerization reactions were exothermic, although not spontaneous. This was mostly modulated by the strength of the hydrogen bond of the water bridge and the π-π stacking interaction. Dimers bridged by two water molecules were more stable than those with additional water molecules or without any water molecule in the bridge. Energy decomposition analysis showed that the electrostatic and polarization components were the main stabilizing terms for the hydrogen bond interaction in the bridge, contributing at least 80% of the interaction energy in all dimers. The non-covalent interaction analysis confirmed the molecular sites that had the strongest (hydrogen bond) and weak (π-π stacking) attractive interactions. They were concentrated in the water bridge and in the plane between the aromatic rings, respectively.MethodsThe density functional ωB97X-D with a dispersion correction and the Def2-SVP basis set were employed to investigate supramolecular aggregates incorporating heterocycles dimers with 0, 1, 2, and 3 water molecules forming a stabilizing bridge connecting the monomers. The non-covalent interactions were analyzed using the NCIplot software and plotted as isosurface maps using Visual Molecular Dynamics.

Pioneering molecularly-level Fe sites immobilized on graphene quantum dots as a key activity descriptor in achieving highly efficient oxygen evolution reaction

The emergence of efficient electrocatalysts to facilitate the thermodynamically demanding and kinetically challenging oxygen evolution process (OER), which includes the coordinated transfer of four protons and four electrons, remains an issue. The effective transfer of energy encourages molecular-level control over key redox transitions involving small-molecule substrates (O2, and H2O), at or near electrode surfaces. While many molecular catalysts have been shown highly active for OER, immobilizing those onto the heterogenous solid matrices is challenging. Herein, graphene quantum dots (GQDs), a carbonaceous sub-class, was used as the solid matrices to conjugate the molecular catalyst onto its surface owing to its high surface area and electronic conductivity. Through the coordinated environment of the conjugated material, the molecular Fe sites on the GQDs surface exhibited outstanding OER features, achieving an ultra-low overpotential of 223 mV and 241 mV at a current density of 50 and 100 and mA/cm2, respectively, and excellent stability over 24 h. Our results marked a pioneering step in that through conjugation, these molecular sites were well dispersed at the GQDs matrices and were intrinsically active for OER.

Recognition and separation of artemisinin by two-dimensional GO/MXene laminar imprinted composite membranes constructed based on self-supporting technology

In order to solve the problem that some of the imprinted sites were embedded inside the membranes due to the blending method, resulting in low utilization of the imprinted sites, a two-dimensional click graphene oxide (GO)/MXene self-supported layered imprinted composite membranes (CGMMs) was devised and prepared for the adsorption and efficient discriminative separation of artemisinin. Firstly, MXene was modified by self-polymerization using dopamine (PDA), and PDA hybrid coating was constructed on the surface of MXene, which was effective in improving the oxidation brittleness and hydrophilicity of MXene. Given the structural and hydrophilic similarities between GO and MXene nanosheets, the produced CGMMs exhibit an outstanding hydrophilicity and a characteristic lamellar shape. Subsequently, spherical imprinted polymers based on MXene were successfully constructed on the surface and interlayer of stacked GO/MXene nanosheets. The performance of CGMMs was explored by isothermal adsorption, kinetic adsorption, selective adsorption tests and selective permeation tests. The equilibrium adsorption capacity of CGMMs reached 36.10 mg g−1 with satisfactory selective separation capacity (αArtemisinin/ Artesunate = 4.10 and αArtemisinin/ Dihydroartemisinin = 3.03) and excellent permeation selectivity (βArtesunate/ Artemisinin = 5.71 and βDihydroartemisinin/ Artemisinin = 4.40), which implied the successful construction of effective artemisinin-imprinted sites on CGMMs. An essential aspect of the excellent adsorption property and selectivity exhibited by the prepared CGMMs is that the cross-section of CGMMs is composed of MXene nanosheets and GO nanosheets superimposed on a laminar structure dotted with imprinted polymers, which extends the molecular transport channels and facilitates the construction of more molecular imprinting sites.

Bisphenol a modification and how its structure influences human serum albumin binding force

Bisphenol A (BPA) is an environmental hormone with substantial physiological toxicity to the human body. Three electron-withdrawing derivatives of BPA are synthesized in this study to reduce its toxicity. The interaction mechanism between BPA and its three derivatives with human serum albumin (HSA) is investigated using molecular docking, electrochemistry, circular dichroism spectrum analysis, and fluorescence spectroscopy. Temperature-dependent tests and time-resolved fluorescence spectra reveal that all four compounds dynamically quench the internal fluorescence of HSA. Based on molecular docking and site competition outcomes, four compounds are primarily bound to site I's active pocket. Thermodynamic parameters indicate that the compounds’ interaction with HSA is spontaneous, and introducing weak electron-withdrawing groups changes the action force. Circular dichroism and synchronous fluorescence measurements suggest four compounds impact HSA's structure. The substituents' electron attraction capacity determines their impact. Electrochemical studies examine the effect of electron-absorbing groups on the BPA and HSA binding capacity. Pharmacokinetics showed that nitro-substituted BPA may be a potential superior substitute for BPA. These results indicate crucial practical value, providing theoretical support for future research.

Forward-predictive SERS-based chemical taxonomy for untargeted structural elucidation of epimeric cerebrosides

Achieving untargeted chemical identification, isomeric differentiation, and quantification is critical to most scientific and technological problems but remains challenging. Here, we demonstrate an integrated SERS-based chemical taxonomy machine learning framework for untargeted structural elucidation of 11 epimeric cerebrosides, attaining >90% accuracy and robust single epimer and multiplex quantification with <10% errors. First, we utilize 4-mercaptophenylboronic acid to selectively capture the epimers at molecular sites of isomerism to form epimer-specific SERS fingerprints. Corroborating with in-silico experiments, we establish five spectral features, each corresponding to a structural characteristic: (1) presence/absence of epimers, (2) monosaccharide/cerebroside, (3) saturated/unsaturated cerebroside, (4) glucosyl/galactosyl, and (5) GlcCer or GalCer’s carbon chain lengths. Leveraging these insights, we create a fully generalizable framework to identify and quantify cerebrosides at concentrations between 10−4 to 10−10 M and achieve multiplex quantification of binary mixtures containing biomarkers GlcCer24:1, and GalCer24:1 using their untrained spectra in the models.

In Silico Description of the Direct Inhibition Mechanism of Endothelial Lipase by ANGPTL3.

Angiopoietin-like protein 3 (ANGPTL3) is a plasmatic protein that plays a crucial role in lipoprotein metabolism by inhibiting the lipoprotein lipase (LPL) and the endothelial lipase (EL) responsible for the hydrolysis of phospholipids on high-density lipoprotein (HDL). Interest in developing new pharmacological therapies aimed at inhibiting ANGPTL3 has been growing due to the hypolipidemic and antiatherogenic profile observed in its absence. The goal of this study was the in silico characterization of the interaction between ANGPTL3 and EL. Because of the lack of any structural information on both the trimeric coiled-coil N-terminal domain of ANGPTL3 and the EL homodimer as well as data regarding their interactions, the first step was to obtain the three-dimensional model of these two proteins. The models were then refined via molecular dynamics (MD) simulations and used to investigate the interaction mechanism. The analysis of interactions in different docking poses and their refinement via MD allowed the identification of three specific glutamates of ANGPTL3 that recognize a positively charged patch on the surface of EL. These ANGPTL3 key residues, i.e., Glu154, Glu157, and Glu160, could form a putative molecular recognition site for EL. This study paves the way for future investigations aimed at confirming the recognition site and at designing novel inhibitors of ANGPTL3.

2D magnetic nanoporous carbon with bridge-type aptamer assembly for pesticide detection based on a regenerative field-effect transistor biosensor

Field-effect transistor (FET)-based biosensors have garnered attention due to their sensitivity to surface charge changes and advantages in real-time detection. However, these biosensors often suffer from several disadvantages such as their limited sensitivity and a high cost. Here, we reported an ultra-sensitive and reusable nanoporous-based FET biosensor hybridized with bridge-type aptamers. The sensor consisted of a two-dimensional magnetic iron-cobalt nanoparticle-embedded nanoporous carbon (Fe-Co/NPC) functionalized with bridge-type aptamers. The edges of the nanopores exhibited high surface energy and chemical activity, enabling effective interactions with the aptamers. Moreover, the nanoporous structures provided additional space, which could improve molecular recognition sites and sensor sensitivity. Our sensor could be used to detect organophosphorus pesticides (OPs) in vegetables down to 100 fM in real time and identify OPs from other pesticides. Furthermore, the magnetic properties of Fe-Co/NPC allowed us to reuse a single sensor chip up to 8 times, which significantly reduced the production cost of our sensors. In this respect, our Fe-Co/NPC-FET sensor could be a powerful tool for practical applications such as food safety detection.

Basement membrane diversification relies on two competitive secretory routes defined by Rab10 and Rab8 and modulated by dystrophin and the exocyst complex.

The basement membrane (BM) is an essential structural element of tissues, and its diversification participates in organ morphogenesis. However, the traffic routes associated with BM formation and the mechanistic modulations explaining its diversification are still poorly understood. Drosophila melanogaster follicular epithelium relies on a BM composed of oriented BM fibrils and a more homogenous matrix. Here, we determined the specific molecular identity and cell exit sites of BM protein secretory routes. First, we found that Rab10 and Rab8 define two parallel routes for BM protein secretion. When both routes were abolished, BM production was fully blocked; however, genetic interactions revealed that these two routes competed. Rab10 promoted lateral and planar-polarized secretion, whereas Rab8 promoted basal secretion, leading to the formation of BM fibrils and homogenous BM, respectively. We also found that the dystrophin-associated protein complex (DAPC) and Rab10 were both present in a planar-polarized tubular compartment containing BM proteins. DAPC was essential for fibril formation and sufficient to reorient secretion towards the Rab10 route. Moreover, we identified a dual function for the exocyst complex in this context. First, the Exo70 subunit directly interacted with dystrophin to limit its planar polarization. Second, the exocyst complex was also required for the Rab8 route. Altogether, these results highlight important mechanistic aspects of BM protein secretion and illustrate how BM diversity can emerge from the spatial control of distinct traffic routes.

Salt-assisted construction of hydrophilic carbon nitride photocatalysts with abundant water molecular adsorption sites for efficient hydrogen production

Polymer carbon nitride (PCN), as an affordable and easily prepared photocatalyst, has acquired extensive attention for hydrogen production. However, bulk carbon nitride material exhibits poor dispersibility in water due to the relatively inert surface which limits its quantum efficiency in photocatalytic hydrogen production. In this study, a hydrophilic carbon nitride (HCN) is successfully synthesized by a novel salt-assisted heating process. The heightened water adsorption capacity may contribute additional active sites conducive to the photocatalytic hydrogen production reaction. Meanwhile, potassium ion doping and material size reduction greatly enhance the charge transfer and separation ability of HCN. Consequently, HCN exhibits highly efficient photocatalytic activity for hydrogen production, achieving a rate of 392 μmol·h−1, which is 16 times greater than that of pristine PCN. The simply developed synthetic strategy adopted here provides a novel concept for functionalizing carbon nitride and opening a distinct pathway for the construction of exceptionally efficient photocatalytic systems.

Association between Single Nucleotide Polymorphisms of PRKD1 and KCNQ3 Gene and Milk Quality Traits in Gannan Yak (Bos grunniens).

Protein kinase D1 (PRKD1) functions primarily in normal mammary cells, and the potassium voltage-gated channel subfamily Q member 3 (KCNQ3) gene plays an important role in controlling membrane potential and neuronal excitability, it has been found that this particular gene is linked to the percentage of milk fat in dairy cows. The purpose of this study was to investigate the relationship between nucleotide polymorphisms (SNPs) of PRKD1 and KCNQ3 genes and the milk quality of Gannan yak and to find molecular marker sites that may be used for milk quality breeding of Gannan yak. Three new SNPs were detected in the PRKD1 (g.283,619T>C, g.283,659C>A) and KCNQ3 gene (g.133,741T>C) of 172 Gannan lactating female yaks by Illumina yak cGPS 7K liquid-phase microarray technology. Milk composition was analyzed using a MilkoScanTM milk composition analyzer. We found that the mutations of these three loci significantly improved the lactose, milk fat, casein, protein, non-fat milk solid (SNF) content and acidity of Gannan yaks. The lactose content of the TC heterozygous genotype population at g.283,619T>C locus was significantly higher than that of the TT wild-type population (p < 0.05); the milk fat content of the CA heterozygous genotype population at g.283,659C>A locus was significantly higher than that of the CC wild-type and AA mutant populations (p < 0.05); the casein, protein and acidity of the CC mutant and TC heterozygous groups at the g.133,741T>C locus were significantly higher than those of the wild type (p < 0.05), and the SNF of the TC heterozygous group was significantly higher than that of the mutant group (p < 0.05). The results showed that PRKD1 and KCNQ3 genes could be used as candidate genes affecting the milk traits of Gannan yak.

Identification and neuroprotective properties of NA-184, a calpain-2 inhibitor.

Our laboratory has shown that calpain-2 activation in the brain following acute injury is directly related to neuronal damage and the long-term functional consequences of the injury, while calpain-1 activation is generally neuroprotective and calpain-1 deletion exacerbates neuronal injury. We have also shown that a relatively selective calpain-2 inhibitor, referred to as C2I, enhanced long-term potentiation and learning and memory, and provided neuroprotection in the controlled cortical impact (CCI) model of traumatic brain injury (TBI) in mice. Using molecular dynamic simulation and Site Identification by Ligand Competitive Saturation (SILCS) software, we generated about 130 analogs of C2I and tested them in a number of invitro and invivo assays. These led to the identification of two interesting compounds, NA-112 and NA-184. Further analyses indicated that NA-184, (S)-2-(3-benzylureido)-N-((R,S)-1-((3-chloro-2-methoxybenzyl)amino)-1,2-dioxopentan-3-yl)-4-methylpentanamide, selectively and dose-dependent inhibited calpain-2 activity without evident inhibition of calpain-1 at the tested concentrations in mouse brain tissues and human cell lines. Like NA-112, NA-184 inhibited TBI-induced calpain-2 activation and cell death in mice and rats, both male and females. Pharmacokinetic and pharmacodynamic analyses indicated that NA-184 exhibited properties, including stability in plasma and liver and blood-brain barrier permeability, that make it a good clinical candidate for the treatment of TBI.

Study on the evolution characteristics of molecular surface active sites of low-rank coal in low-temperature oxidation stage

Compared with other coal types of coal, low - metamorphic coal contains numerous active sites, making it susceptible to spontaneous combustion and posing significant risks during production, transportation, and storage. To further reveal the evolution characteristics and laws of low-rank coal's active sites during the process of low-temperature oxidation of coal (LTOC), X-ray photoelectron spectroscopy (XPS), 13C nuclear magnetic resonance (13C NMR), and Fourier transform infrared (FTIR) experiments were used to determine the basic structural parameters such as the valence state of non-carbon features, types of carbon elements in coal macromolecules, and structure and quantity of functional groups. Combined with molecular modelling software (GaussView 6.0) and macromolecular calculation software (Grimme-XTB), macromolecular models of coal at different temperature points were constructed, and the surface energy field distribution was calculated. The number and energy change information of chemical and physical adsorption sites of low-rank coal during heating were obtained. The results show that during the LTOC, the chemical adsorption sites such as aliphatic hydrocarbons (-CH3/-CH2) have higher reactivity and can be converted into oxygen-containing functional groups (-CHO, –OH, –COOH); the number of physical adsorption sites increased first and then decreased, and reached the maximum at 50 °C. Coal exhibited a higher affinity for O2 at this temperature. The peroxide (-C-O-O-H) undergoes thermal decomposition, leading to H2O and weight loss of coal. The –CO and –COO structures undergo decarboxylation to generate CO, CO2, and other gases. This study comprehensively revealed the evolution of active sites through two key coal oxygen processes, physical and chemical adsorption, based on the gradual temperature elevation of low-rank coal. This holds immense significance for improving and enriching the understanding of the mechanism of coal spontaneous combustion(CSC), preparing more targeted CSC inhibition, and formulating efficient fire prevention and extinguishing measures.

Rutin promotes M2 phenotype microglia polarization by suppressing the JAK/STAT3 signaling to protect against retinal ischemia-reperfusion injury.

We aimed to investigate the neuroprotective effect of rutin on retinal ganglion cells (RGCs) under ischemia-reperfusion (I/R) conditions and the underlying mechanisms involving microglia polarization and JAK/STAT3 signaling. RGCs isolated from C57/Bl6 mice were co-cultured with BV2 microglial cells under normal or in vitro oxygen-glucose deprivation and reoxygenation (OGD/R) conditions. Rutin's effects were evaluated by assessing cell viability, apoptosis rates, cytokine levels, microglial polarization markers and JAK/STAT3 phosphorylation levels. The specific target is confirmed through the inhibitory effect of rutin on the respectively activated signaling factors. Furthermore, molecular docking analyses elucidated rutin-JAK1 interactions. OGD/R conditions significantly reduced RGC viability, exacerbated by BV2 co-culture. However, both 1 μM and 5 μM rutin treatment dose-dependently enhanced RGC viability, reduced apoptosis, and suppressed pro-inflammatory cytokine levels. Western blot analysis indicated that rutin promoted the M2 microglial phenotype and suppressed JAK/STAT3 signaling. Notably, rutin selectively inhibited JAK1 phosphorylation without affecting STAT3. Molecular docking highlighted potential interaction sites between rutin and specific JAK1 pseudokinase domain. Rutin exerts neuroprotective effects against retinal I/R injury by promoting M2 microglial polarization, potentially through the selective inhibition of JAK1 phosphorylation within the JAK/STAT3 signaling pathway. These findings provide a foundation for the therapeutic potential of rutin in retinal I/R injuries.

Selection of epigenetically privileged HIV-1 proviruses during treatment with panobinostat and interferon-α2a

CD4+ Tcells with latent HIV-1 infection persist despite treatment with antiretroviral agents and represent the main barrier to a cure of HIV-1 infection. Pharmacological disruption of viral latency may expose HIV-1-infected cells to host immune activity, but the clinical efficacy of latency-reversing agents for reducing HIV-1 persistence remains to be proven. Here, we show in a randomized-controlled human clinical trial that the histone deacetylase inhibitor panobinostat, when administered in combination with pegylated interferon-α2a, induces a structural transformation of the HIV-1 reservoir cell pool, characterized by a disproportionate overrepresentation of HIV-1 proviruses integrated in ZNF genes and in chromatin regions with reduced H3K27ac marks, the molecular target sites for panobinostat. By contrast, proviruses near H3K27ac marks wereactively selected against, likely due to increased susceptibility to panobinostat. These data suggest that latency-reversing treatment can increase the immunological vulnerability of HIV-1 reservoir cells and accelerate the selection of epigenetically privileged HIV-1 proviruses.

Theoretical study on molecular charge populations of 1D π-stacked multimers in neutral and electron oxidation states

Abstract We theoretically investigated molecular charge populations of 1D π-stacked multimers consisting of π-conjugated molecules in the neutral and electron oxidation states based on the valence-bond (VB) theory. Qualitative analysis for a π-stacked trimer model based on the VB mixing diagram suggested that the inner monomer site tends to be more positively charged than the outer sites in the monocationic π-stacked trimer. Spatial expansion of each molecular site orbital toward the stacking direction is predicted to enhance the difference of positive charge populations between the inner and outer monomers. In contrast, an opposite tendency for the site charges was expected in the dicationic π-stacked trimer, primarily due to the hole–hole Coulomb repulsions. To generalize the results of the trimer to π-stacked N-mers, 1D N-site VB configuration interaction models were constructed considering the orbital expansion effects between the sites. We examined how the number of monomers (N), stacking distance (R), and characteristic orbital exponent for the monomers (ζ) affected the molecular charge populations in the monocationic and dicationic π-stacked N-mers through the parameters χij characterizing the orbital expansion effect. The results are expected to help establish design strategies for novel electronic functional materials based on discrete stacks of π-conjugated molecules.

Molecular docking and dynamics simulation studies uncover the host-pathogen protein-protein interactions in Penaeus vannamei and Vibrio parahaemolyticus.

Shrimp aquaculture contributes significantly to global economic growth, and the whiteleg shrimp, Penaeus vannamei, is a leading species in this industry. However, Vibrio parahaemolyticus infection poses a major challenge in ensuring the success of P. vannamei aquaculture. Despite its significance in this industry, the biological knowledge of its pathogenesis remains unclear. Hence, this study was conducted to identify the interaction sites and binding affinity between several immune-related proteins of P. vannamei with V. parahaemolyticus proteins associated with virulence factors. Potential interaction sites and the binding affinity between host and pathogen proteins were identified using molecular docking and dynamics (MD) simulation. The P. vannamei-V. parahaemolyticus protein-protein interaction of Complex 1 (Ferritin-HrpE/YscL family type III secretion apparatus protein), Complex 2 (Protein kinase domain-containing protein-Chemotaxis CheY protein), and Complex 3 (GPCR-Chemotaxis CheY protein) was found to interact with -4319.76, -5271.39, and -4725.57 of the docked score and the formation of intermolecular bonds at several interacting residues. The docked scores of Complex 1, Complex 2, and Complex 3 were validated using MD simulation analysis, which revealed these complexes greatly contribute to the interactions between P. vannamei and V. parahaemolyticus proteins, with binding free energies of -22.50 kJ/mol, -30.20 kJ/mol, and -26.27 kJ/mol, respectively. This finding illustrates the capability of computational approaches to search for molecular binding sites between host and pathogen, which could increase the knowledge of Vibrio spp. infection on shrimps, which then can be used to assist in the development of effective treatment.

Molecularly Detailed View of Strong Coupling in Supramolecular Plexcitonic Nanohybrids.

Plexcitons constitute a peculiar example of light-matter hybrids (polaritons) originating from the (strong) coupling of plasmonic modes and molecular excitations. Here we propose a fully quantum approach to model plexcitonic systems and test it against existing experiments on peculiar hybrids formed by Au nanoparticles and a well-known porphyrin derivative, involving the Q branch of the organic dye absorption spectrum. Our model extends simpler descriptions of polaritonic systems to account for the multilevel structure of the dyes, spatially varying interactions with a given plasmon mode, and the simultaneous occurrence of plasmon-molecule and intermolecular interactions. By keeping a molecularly detailed view, we were able to gain insights into the local structure and individual contributions to the resulting plexcitons. Our model can be applied to rationalize and predict energy funneling toward specific molecular sites within a plexcitonic assembly, which is highly valuable for designing and controlling chemical transformations in the new polaritonic landscapes.

Unveiling a pH-Responsive Dual-Androgen-Blocking Magnetic Molecularly Imprinted Polymer for Enhanced Synergistic Therapy of Prostate Cancer.

Prostate cancer is the most common malignancy diagnosed in men. Androgens are directly related to its pathogenesis. Inhibition of the androgen receptor (AR) is considered to be the most promising therapeutic approach for the treatment of prostate cancer. In this study, a new type of pH-responsive dual androgen-blocking nanodrug (FASC MIPs) based on a molecularly imprinted polymer has been designed and synthesized. The nanodrug could selectively sequester testosterone from the prostate tumor through specific molecular imprinting sites and simultaneously deliver the AR inhibitory drug bicalutamide, which ultimately leads to enhanced synergistic therapy of prostate cancer. FASC MIPs demonstrate excellent pH responsiveness in a simulated tumor microenvironment due to the presence of chitosan and significantly inhibit the growth of prostate cancer cells (LNCaP cells) by blocking the G1 phase of cytokinesis. Additionally, the nanodrug also displayed excellent antitumor properties in a xenograft mouse model of prostate cancer without any sign of detrimental effects on healthy tissues and organs. Both in vitro and in vivo studies verified the augmented and synergistic therapeutic effects of FASC MIPs, and the proposed dual-androgen-blocking strategy could explore novel avenues in prostate cancer treatment.

Characterization of multi-copy C3 genes and association analysis of C3.1 polymorphism with GCRV resistance traits in Ctenopharyngodon idella

Molecular-assisted breeding plays an essential role in the selection of high disease -resistant fish in grass carp (Ctenopharyngodon idella) aquaculture. Complement 3 (C3) is a central molecule in the complement cascade and plays a polyfunctional role in immune defense, complement activation, and the inflammatory response. In this study, 9 copies of the C3 gene (named C3.1-C3.9) were identified in C. idella, and their structure, genomic location, phylogeny, expression patterns, and genetic characteristics were systematically analyzed. Phylogenetic analysis indicates that nine copies of grass carp C3 (hereafter called CiC3) cluster in the branch of Osteichthyes together with that of other fish, forming a different evolutionary branch distinct from other vertebrates. CiC3 are constitutively expressed in all examined tissues, among which CiC3.1 is the dominant C3 molecule. At 14 days of grass carp reovirus (GCRV) challenge, the CiC3s expression patterns share a similar expression trend. Furthermore, the comparison of the level of C3 protein, the mRNA expression level of dominant CiC3 (C3.1), and the mortality after GCRV challenge between the Xiangjiang River and Yangtze River grass carp indicate that the C3 protein exhibits distribution of polymorphism in a population, and the expression level of C3 is heritable and positively correlated with GCRV resistance. Furthermore, we identified 10 SNPs (named SNP1–10) of the C3.1 gene between GCRV-resistant and GCRV-susceptible grass carp groups. Inspiringly, SNP7 (g.76773C/T), SNP8 (g.76945 T/C), SNP1 (g.7065C/T), SNP9 (g.77153 A/C) and SNP10 (g.77252 T/C) have been verified to be significantly associated with the GCRV-resistant trait. Collectively, our findings provide potential molecular markers and relevant SNP sites for future grass carp breeding with respect to GCRV resistance.

Boiling, critical, and freezing temperatures in light of molecular descriptors: correlation and causation.

In the pursuit of tracking some physicochemical properties of fluids down to the molecular level, ab initio molecular surface analyses were performed on 169 molecules. This included electrostatic potential (EP), average local ionization energy (ALIE), and electron localization function (ELF) mapped onto an electron density isosurface value of 0.001 au. Using stepwise linear regression (SLR) analysis, it was found that besides the well-studied EP, ALIE and ELF played important roles in determining the normal boiling and freezing points and critical temperatures of fluids. Apparently, the ALIE and ELF were relevant to the attractive polarization forces and repulsive Pauli forces, respectively, between molecules. To further demonstrate and rationalize this assumption, a localized molecular orbital energy decomposition analysis (LMO-EDA) was carried out. In the LMO-EDA analysis, the complexes of the helium atom, He, and ClCl, ClBr, ClI, OCO, OCS, OCSe, and CO/OC molecules were investigated, where the helium atom faced different molecular sites in each molecule. Fortunately, the results showed that lower the ALIE value on a molecular site, the stronger (i.e., more attractive) the polarization interaction energy. The results also indicated that higher the ELF value on a molecular site, the stronger (i.e., more repulsive) the Pauli interaction. The work is aimed to present novel molecular-based rationales to physical chemists, chemical engineers, and materials scientists.