Hsa_circ_0072765 knockdown inhibits proliferation, activation and migration in transforming growth factor-beta (TGF-β)-induced hepatic stellate cells (HSCs) by the miR-197-3p/TRPV3 axis

Background. Circular RNAs (circRNAs) participate in the progression of diverse human diseases. However, the effects of circRNAs on liver fibrosis are limited. In this study, we aimed to investigate the functions of hsa_circ_0072765 in liver fibrosis. Methods. Transforming growth factor-beta (TGF-β)treated hepatic stellate cells (HSCs) were used as the cell model of liver fibrosis. Quantitative real-time polymerase chain reaction (qRT-PCR) or western blot was performed to determine the expression of hsa_circ_0072765, microRNA-197-3p (miR-197-3p) and transient receptor potential cation channel subfamily V member 3 (TRPV3). 5’-ethynyl-2’-deoxyuridine (EdU) assay, flow cytometry analysis and woundhealing assay were conducted to evaluate cell proliferation, cell cycle and migration. HSC activation was assessed by determining the expression of alphasmooth muscle actin (α-SMA) and type I collagen alpha 1 (Col1A1). Dual-luciferase reporter assay and RNA immunoprecipitation (RIP) were manipulated to analyze the relationship of hsa_circ_0072765, miR-197-3p and TRPV3. The exosome morphology was observed under transmission electron microscopy (TEM). Results. Hsa_circ_0072765 level was increased in TGF-β-induced HSCs. Hsa_circ_0072765 knockdown inhibited cell proliferation, cell cycle, activation and migration in TGF-β-induced HSCs. Hsa_circ_0072765 sponged miR-197-3p and negatively regulated miR-1973p expression. MiR-197-3p inhibition reversed the effects of hsa_circ_0072765 knockdown on TGF-βinduced HSC proliferation, cell cycle, activation and migration. In addition, TRPV3 was the target gene of miR-197-3p and miR-197-3p overexpression inhibited TGF-β-treated HSC proliferation, cell cycle, activation and migration by targeting TRPV3. Besides, we found that exosomal hsa_circ_0072765 was increased in TGFβ-treated HSCs. Conclusion. Hsa_circ_0072765 promoted the progression of TGF-β-treated HSCs by decoying miR197-3p and upregulating TRPV

Serial Monitoring of Circulating Tumor DNA in Patients With Metastatic Colorectal Cancer to Predict the Therapeutic Response

Early biomarkers of therapeutic responses can help optimize the treatment of metastatic colorectal cancers (mCRC). In this prospective exploratory study, we examined serial changes of plasma-circulating tumor DNA (ctDNA) in 41 mCRC patients receiving first-line chemotherapies and tested its association with treatment outcomes according to radiological assessments. Using next-generation sequencing technologies, we profiled somatic mutations in 50 cancer-related genes in ctDNA before each of the first four treatment cycles. We observed mutations in 95.7% of pre-treatment ctDNA samples. Using mutations of the maximal frequency in each pre-treatment plasma ctDNA sample as the candidate targets, we computed log2 fold changes of ctDNA levels between adjacent treatment cycles. We found that ctDNA reductions as early as prior to cycle 2 predicted responses after cycle 4. Log2 fold changes of ctDNA after cycle 1 (ctDNA log2 (C1/C0)) > −0.126 predicted progressive disease, with an accuracy of 94.6%. These patients also showed significantly worse progression-free survival than those with ctDNA log2 (C1/C0) ≤ −0.126 (median 2.0 vs. 9.0 months; P = 0.007). Together, the present exploratory study suggests that early changes in ctDNA levels detected via targeted sequencing are potential biomarkers of future treatment responses in mCRCs

Development and Applications of the Density-based Theory of Chemical Reactivity

Density functional theory well-recognized by its accuracy and efficiency has become the workhorse for modeling the electronic structure of molecules and extended materials in the past decades. Nevertheless, how to establish a density-based conceptual framework to appreciate bonding, stability, function, reactivity, and other physiochemical properties is still an unaccomplished task. In this Perspective, we at first overview the four pathways currently available in the literature to tackle the matter, including orbital-free density functional theory, conceptual density functional theory, direct use of density associated quantities, and information-theoretic approach. Then, we highlight several recent advances of employing these approaches to harvest new understandings for chemical concepts such as covalent bonding, noncovalent interactions, cooperation, frustration, homochirality, chirality hierarchy, electrophilicity, nucleophilicity, regioselectivity, and stereoselectivity. Finally, we provide a few hints for the future development of this relatively uncharted territory. Opportunities are abundant, and they are all ours for the taking

Finite difference representation of information-theoretic approach in density functional theory

Using density-based quantities to establish a qualitative or even quantitative framework to predict molecular reactivity in density functional theory is of considerable interest in the current literature. Recent developments in information-theoretic approach (ITA) represent such a trend. Traditionally, we represent ITA quantities in terms of the electron density, shape function, and atoms in molecules. In this contribution, we expand the theoretical framework of ITA by introducing a new representation. To that end, we make use of the first-order partial derivative of ITA quantities with respect to the number of total electrons and then approximate them in the finite difference approximation. The new representation has both local (three-dimensional) and global (condensed to atoms) versions. Its close relationship with Fukui function from conceptual density functional theory was derived analytically and confirmed numerically. Extensions of our present approach to include other types of derivatives are discussed. This work not only enriches the theoretical framework of ITA with a new representation, but also provides opportunities to expand its territory as well as the scope of its applicability in dealing with molecular processes and chemical reactivity from a new perspective

On the relationship among Ghosh-Berkowitz-Parr entropy, Shannon entropy and Fisher information

970-977In their seminal work thirty years ago, Ghosh, Berkowitz, and Parr reformulated the ground-state density-functional theory into a local version of thermodynamics, where a new concept, called Ghosh-Berkowitz-Parr entropy, was proposed. Employing the non-interacting kinetic energy density and Thomas-Fermi kinetic energy density, this entropy was formulated like the Sackur-Tetrode equation in classical thermodynamics. Not much has been known about its properties. In this contribution, we investigate its relationship with Shannon entropy and Fisher information from the numerical perspective. To that end, we have examined 36 neutral atoms and 42 molecular systems. We have considered both molecular and atomic contributions with Bader’s zero-flux criterion to partition atoms in molecules. Our results show that these quantities are closely correlated, and yet their correlations might be complicated since no universal relationship among them has been observed

Toward Understanding the Isomeric Stability of Fullerenes with Density Functional Theory and the Information-Theoretic Approach

For a given size of one fullerene molecule, there could exist many different isomers and their energy landscape is remarkably complex. To have a better understanding of the nature and origin of their isomeric stability, as a continuation of our previous endeavors, we systematically dissect the molecular stability of four fullerene systems, C44, C48, C52, and C60, with a total of 2547 structures, using density functional theory and the information-theoretic approach. The total energy decomposition analysis is beneficial to understand the origin and nature of isomeric stability. Our results showcase that the electrostatic potential is the dominant factor contributing to the isomeric stability of these fullerenes, and other contributions such as steric and quantum effects play minor but indispensable roles. This study also finds that the origin of the isomeric stability of these species is due to the spatial delocalization of the electron density. Our work should provide novel insights into the isomeric stability of fullerene molecules, which have found tremendous applications in solar-energy studies and nanomaterial sciences

Baird’s Rule in Substituted Fulvene Derivatives: An Information-Theoretic Study on Triplet-State Aromaticity and Antiaromaticity

Originated from the cyclic delocalization of electrons resulting in extra stability and instability, aromaticity and antiaromaticity are important chemical concepts whose appreciation and quantification are still much of recent interest in the literature. Employing information-theoretic quantities can provide us with more insights and better understanding about them, as we have previously demonstrated. In this work, we examine the triplet-state aromaticity and antiaromaticity, which are governed by Baird’s 4n rule, instead of Hückel’s 4n + 2 rule for the singlet state. To this end, we have made use of 4 different aromaticity indexes and 8 information-theoretic quantities, examined a total of 22 substituted fulvene derivatives, and compared the results both in singlet and triplet states. It is found that cross-correlations of these two categories of molecular property descriptors enable us to better understand the nature and propensity of aromaticity and antiaromaticity for the triplet state. Our results have not only demonstrated the existence and validity of Baird’s rule but also shown that Hückel’s rule and Baird’s rule indeed share the same theoretical foundation because with these cross-correlation patterns we are able to distinguish them from each other simultaneously in both singlet and triplet states. Our results should provide new insights into the nature of aromaticity and antiaromaticity in the triplet state and pave the road toward new ways to quantify this pair of important chemical concepts

The Synergetic and Multifaceted Nature of Carbon-Carbon Rotation Reveals the Origin of Stability for Bulky Alkane Dimers

Designing compounds with as long carbon-carbon bond distances as possible to challenge conventional chemical wisdom is of current interest in the literature. These compounds with exceedingly long bond lengths are commonly believed to be stabilized by dispersion interactions. In this work, we build nine dimeric models with varying sizes of alkyl groups, let the carbon-carbon bond flexibly rotate, and then analyze rotation barriers with energy decomposition and information-theoretic approaches in density functional theory. Our results show that these rotations lead to extraordinarily elongated carbon-carbon bond distances and rotation barriers are synergetic and multifaceted in nature. The dominant factor contributing to the stability of the dimers with bulky alkane groups is not the dispersion force but the electrostatic interaction with steric and exchange-correlation effects playing minor yet indispensable roles