Recent Experimental Advances in Characterizing the Self-Assembly and Phase Behavior of Polypeptoids.

Polypeptoids are a family of synthetic peptidomimetic polymers featuring N-substituted polyglycine backbones with large chemical and structural diversity. Their synthetic accessibility, tunable property/functionality, and biological relevance make polypeptoids a promising platform for molecular biomimicry and various biotechnological applications. To gain insight into the relationship between the chemical structure, self-assembly behavior, and physicochemical properties of polypeptoids, many efforts have been made using thermal analysis, microscopy, scattering, and spectroscopic techniques. In this review, we summarize recent experimental investigations that have focused on the hierarchical self-assembly and phase behavior of polypeptoids in bulk, thin film, and solution states, highlighting the use of advanced characterization tools such as in situ microscopy and scattering techniques. These methods enable researchers to unravel multiscale structural features and assembly processes of polypeptoids over a wide range of length and time scales, thereby providing new insights into the structure-property relationship of these protein-mimetic materials.

Brain Correlates of Chinese Handwriting and Their Relation to Reading Development in Children: An fMRI Study.

Handwriting plays an important role in written communication, reading, and academic success. However, little is known about the neural correlates of handwriting in children. Using functional magnetic resonance imaging (fMRI) and a copying task, we investigated regional brain activation and functional lateralization associated with Chinese handwriting in children (N = 36, 9-11 years old), as well as their relations to reading skills. We found significant activation of the bilateral frontal motor cortices, somatosensory cortex, intraparietal sulcus (IPS), fusiform gyrus (FuG), and cerebellum during handwriting, suggesting that an adult-like brain activation pattern emerges by middle childhood. Moreover, children showed left-lateralized and bilateral activation of motor regions and right-lateralized activation of the FuG and cerebellum during handwriting, suggesting that functional lateralization of handwriting is not fully established by this age. Finally, the activation of Exner's area and the lateralization of the IPS and cerebellum during handwriting were correlated with reading skills, possibly representing a neural link between handwriting and reading in children. Collectively, this study reveals the brain correlates of handwriting and their relation to reading development in Chinese children, offering new insight into the development of handwriting and reading skills.

Multiscale Crystalline Structure of Confined Polypeptoid Films: The Effect of Alkyl Side Chain Branching.

We report the effect of alkyl side chain branching on melt-recrystallization of nanoconfined polypeptoid films using poly(N-octyl glycine) (PNOG) and poly(N-2-ethyl-1-hexyl glycine) (PNEHG) as model systems. Upon cooling from the isotropic melt, confined PNOG molecules recrystallize into a near-perfect orthorhombic crystal structure with the board-like molecules stacked face-to-face in the substrate-parallel direction, resulting in long-range ordered wormlike lamellae that occupy the entire film. By contrast, rod-like PNEHG molecules bearing branched N-2-ethyl-1-hexyl side chains stack into a columnar hexagonal mesophase with their backbones oriented parallel to the substrates, forming micron-sized sheaf-like superstructures under confinement, exposing large areas of empty spaces in the film. These findings highlight the effect of alkyl side chain branching on the packing motif and multiscale crystalline structure of polypeptoids under a nanoconfined geometry.

"More control, more conflicts?" Clarifying the longitudinal relations between parental psychological Control and parent-adolescent Conflict by disentangling between-family effects from within-family effects.

INTRODUCTION: Adolescence is a period when adolescents seek autonomy and parent-adolescent conflict appears inevitable. Even though some research found that parental psychological control triggered parent-adolescent conflict, studies clarifying the directionality of effects at the within-family level are scarce. This study investigated the longitudinal relations between parental psychological control and parent-adolescent conflict using a traditional cross-lagged panel model (CLPM) and the random-intercept CLPM (RI-CLPM) framework. METHODS: Data from 2473 Chinese adolescents (Mage Time1 = 13.20 years, standard deviation = 0.52 years; 51.4% male) were collected via a cross-sectional survey across three time points. Adolescents reported on parental psychological control, parent-adolescent conflict, and demographic characteristics at each time point. CLPM and RI-CLPM were utilized. RESULTS: The results from the CLPM analyses suggested a reciprocal effects model. However, the results from the RI-CLPM framework supported a conflict-driven model at the within-family level, wherein if parent-adolescent conflict increased, subsequent parental psychological control would increase as a result. The reverse pattern was not observed. CONCLUSIONS: These findings indicate the maladaptive processes of parent-adolescent conflict that shape parental psychologically controlling behaviors in Chinese families at the within-family level. Practical implications, including how to assist Chinese parents to address parent-adolescent conflict and to reduce psychological control, are discussed.

ELK4 promotes the development of gastric cancer by inducing M2 polarization of macrophages through regulation of the KDM5A-PJA2-KSR1 axis.

BACKGROUND: We tried to elaborate the molecular mechanism of ETS-like transcription factor 4 (ELK4) affecting gastric cancer (GC) progression through M2 polarization of macrophages mediated by lysine-specific demethylase 5A (KDM5A)-Praja2 (PJA2)-kinase suppressor of ras 1 (KSR1) axis. METHODS: GC expression dataset was obtained from GEO database, and the downstream regulatory mechanism of ELK4 was predicted. Tumor-associated macrophages (TAMs) were isolated from GC tissues. The interaction among ELK4, KDM5A, PJA2 and KSR1 was analyzed by dual luciferase reporter gene, ChIP and Co-IP assays. The stability of KSR1 protein was detected by cycloheximide (CHX) treatment. After TAMs were co-cultured with HGC-27 cells, HGC-27 cell biological processes were assessed through gain- and loss-of function assays. Tumorigenicity was detected by tumorigenicity test in nude mice. RESULTS: In GC and TAMs, ELK4, KDM5A and KSR1 were highly expressed, while PJA2 was lowly expressed. M2 polarization of macrophages promoted the development of GC. ELK4 activated KDM5A by transcription and promoted macrophage M2 polarization. KDM5A inhibited the expression of PJA2 by removing H3K4me3 of PJA2 promoter, which promoted M2 polarization of macrophages. PJA2 reduced KSR1 by ubiquitination. ELK4 promoted the proliferative, migrative and invasive potentials of GC cells as well as the growth of GC xenografts by regulating KSR1. CONCLUSION: ELK4 may reduce the PJA2-dependent inhibition of KSR1 by transcriptional activation of KDM5A to promote M2 polarization of macrophages, thus promoting the development of GC.

Tumor Inhibitory Effect of Long Non-coding RNA LOC100505817 on Gastric Cancer.

Gastric cancer (GC) is one of the major malignancies worldwide. Emerging evidence has revealed the potential involvement of long noncoding RNA (lncRNA) in human genetic disorders and cancer, but the role of LOC100505817 remains unknown. Thus, in this study, we isolated tissues from GC patients to characterize the functional importance of LOC100505817 in GC tumorigenesis. We also proposed a hypothesis that the regulation of Wnt/ß-catenin pathway by LOC100505817 was regulated by miR-20a-mediated WT1. After the collection of cancer tissues and adjacent tissues were obtained from GC patients, expression of LOC100505817, Wnt/ß-catenin pathway- and EMT-related genes was quantified. Ectopic expression and knockdown experiments were applied in order to investigate the protective role of LOC100505817 in the progression of GC. Subsequently, cell viability, flow cytometry for apoptosis and cell cycle were detected via CCK-8, while migration and invasion were determined using scratch test and Transwell assay respectively. Then interactions among LOC100505817, miR-20a and WT1 were explored by dual luciferase reporter gene assay, RNA pull down assay and RNA binding protein immunoprecipitation (RIP) assay. The results found poor expression LOC100505817 was poorly expressed in GC cells and tissues. Overexpressed LOC100505817 resulted in the significant reduction of cell proliferation, migration and invasion as well as the expression of Wnt2b, ß-catenin, CyclinD1, N-cadherin, Vimentin and snail, while increased cell apoptosis along with the expression of E-cadherin. Wnt/ß-catenin pathway and EMT in GC cells were suppressed by LOC100505817 through miR-20a-inhibted WT1. In summary, our results provided evidence suggesting that LOC100505817 inhibits GC through LOC100505817-mediated inhibition of Wnt/ß-catenin pathway, that leads to the overall restraining of GC cell proliferation, migration and invasion through miR-20a-reduced WT1.

Modulating the Molecular Geometry and Solution Self-Assembly of Amphiphilic Polypeptoid Block Copolymers by Side Chain Branching Pattern.

Solution self-assembly of coil-crystalline diblock copolypeptoids has attracted increasing attention due to its capability to form hierarchical nanostructures with tailorable morphologies and functionalities. While the N-substituent (or side chain) structures are known to affect the crystallization of polypeptoids, their roles in dictating the hierarchical solution self-assembly of diblock copolypeptoids are not fully understood. Herein, we designed and synthesized two types of diblock copolypeptoids, i.e., poly(N-methylglycine)-b-poly(N-octylglycine) (PNMG-b-PNOG) and poly(N-methylglycine)-b-poly(N-2-ethyl-1-hexylglycine) (PNMG-b-PNEHG), to investigate the influence of N-substituent structure on the crystalline packing and hierarchical self-assembly of diblock copolypeptoids in methanol. With a linear aliphatic N-substituent, the PNOG blocks pack into a highly ordered crystalline structure with a board-like molecular geometry, resulting in the self-assembly of PNMG-b-PNOG molecules into a hierarchical microflower morphology composed of radially arranged nanoribbon subunits. By contrast, the PNEHG blocks bearing bulky branched aliphatic N-substituents are rod-like and prefer to stack into a columnar hexagonal liquid crystalline mesophase, which drives PNMG-b-PNEHG molecules to self-assemble into symmetrical hexagonal nanosheets in solution. A combination of time-dependent small/wide-angle X-ray scattering and microscopic imaging analysis further revealed the self-assembly mechanisms for the formation of these microflowers and hexagonal nanosheets. These results highlight the significant impact of the N-substituent architecture (i.e., linear versus branched) on the supramolecular self-assembly of diblock copolypeptoids in solution, which can serve as an effective strategy to tune the geometry and hierarchical structure of polypeptoid-based nanomaterials.

Salvia miltiorrhiza solution and its active compounds ameliorate human granulosa cell damage induced by H2O2.

The dried roots or rhizomes of Salvia miltiorrhiza Bge are commonly used in Chinese medicine to promote blood circulation and regulate menstruation. Salvianic acid A and salvianolic acid B are the main active water-soluble compounds in Salvia miltiorrhiza solution. The present study investigated the protective effect of Salvia miltiorrhiza solution and its active compounds in H2O2-induced cell damage of the human ovarian granulosa tumor cell line (KGN) in vitro, as well as its underlying mechanism. Cell viability was detected using a Cell Counting Kit-8 assay. In addition, the levels of malondialdehyde (MDA), superoxide dismutase (SOD), glutathione (GSH) and tumor necrosis factor-α (TNF-α) were measured. Western blotting was performed to detect the protein expression of cleaved caspase-3 and caspase-9. Furthermore, immunocytochemistry was used to detect the expression of TNF-α. It was demonstrated that Salvia miltiorrhiza solution, salvianic acid A and salvianolic acid B did not affect the viability of KGN cells. Additionally, salvianic acid A and salvianolic acid B significantly reduced the H2O2-induced increased MDA levels, and reversed the H2O2-induced suppression of SOD and GSH activities in KGN cells (P<0.05). Treatment with Salvia miltiorrhiza solution, salvianic acid A and salvianolic acid B significantly reduced the overexpression of cleaved caspase-3, cleaved caspase-9 and TNF-α compared with the H2O2-treated group (P<0.05). Therefore, the present results indicated that Salvia miltiorrhiza solution and its main water-soluble compounds, salvianic acid A and salvianolic acid B, ameliorated KGN cell damage induced by H2O2.

microRNA-let-7e in serum-derived exosomes inhibits the metastasis of non-small-cell lung cancer in a SUV39H2/LSD1/CDH1-dependent manner.

Non-small-cell lung cancer (NSCLC) remains the leading cause of cancer-related death worldwide. Accumulating research has highlighted the ability of exosome-encapsulated microRNAs (miRNAs or miRs) as potential circulating biomarkers for lung cancer. The current study aimed to evaluate the clinical significance of serum-derived exosomal miR-let-7e as a biomarker in the metastasis of NSCLC. Initially, the expression of miR-let-7e, SUV39H2, and CDH1 in human NSCLC tissues and exosomes isolated from the serum of NSCLC patients was determined by RT-qPCR, demonstrating that miR-let-7e was downregulated in NSCLC tissues and serum-derived exosomes, while SUV39H2 was upregulated in NSCLC tissues. Kaplan-Meier method revealed that both lower miR-let-7e expression and higher SUV39H2 expression were correlated with a lower survival rate of NSCLC patients. Next, SUV39H2 was predicted and validated to be a target of miR-let-7e using dual-luciferase reporter assay. NSCLC H1299 cells following ectopic expression and depletion experiments of miR-let-7e and SUV39H2 were treated with serum-derived exosomes, after which the viability, migration, and invasion of H1299 cells were detected using CCK-8 and Transwell assays. Further, in vivo experiments were conducted to elucidate the effect of exosomal miR-let-7e on tumorigenesis. Results revealed that miR-let-7e overexpression in serum-derived exosomes inhibited SUV39H2, resulting in impaired cell viability, migration, and invasion in vitro as well as delayed tumor growth in vivo. In conclusion, the key findings of the current study demonstrate that exosomal miR-let-7e from serum possesses anticarcinogenic properties against NSCLC via the SUV39H2/LSD1/CDH1 axis.

Long noncoding RNA LINC00982 upregulates CTSF expression to inhibit gastric cancer progression via the transcription factor HEY1.

Upregulating the expression of long noncoding RNA LINC00982 controlled cell proliferation in gastric cancer, but the regulatory molecular mechanisms are yet to be expounded. We here aimed to elaborate how LINC00982 regulated the malignancy of gastric cancer cells. RT-qPCR and Western blot analysis were used to detect the expression of LINC00982 and cathepsin F (CTSF) in gastric cancer tissues and cells. Modulatory effect of LINC00982 on gastric cancer cells was assessed by CCK-8, colony formation, Transwell migration, and invasion assays. The relationship between LINC00982, YRPW motif 1 (HEY1), and CTSF was examined by RNA-binding protein immunoprecipitation, luciferase assay, and chromatin immunoprecipitation, and their interaction in the regulation of gastric cancer cellular functions was analyzed by performing gain-of-function and rescue assays. The nude mouse model of tumor formation was developed to examine the effects of LINC00982 on tumorigenesis. LINC00982 was lowly expressed in gastric cancer tissues, whereas its overexpression impaired the proliferative, migratory, and invasive properties of gastric cancer cells. Furthermore, LINC00982 could bind to transcription factor HEY1 and inhibited its expression. Through blocking the binding of HEY1 to CTSF promoter, LINC00982 promoted the expression of CTSF. Overexpression of HEY1 or inhibition of CTSF could reverse the antitumor effects of LINC00982 on gastric cancer, which were further demonstrated in vivo. All these taken together, LINC00982 acted as a tumor suppressor in gastric cancer, which is therefore suggested to be a potential antitumor target for gastric cancer.NEW & NOTEWORTHY We identified LINC00982 as a promising antitumor target for the treatment of patients with gastric cancer. We also determined a regulatory network involved in the pathophysiology of gastric cancer wherein LINC00982 could bind to HEY1 to impair its binding to cathepsin F (CTSF) promoter and hence promote CTSF expression, which aids in better understanding of molecular mechanisms related to gastric tumorigenesis.

Cyclic Topology Enhancing Structural Ordering and Stability of Comb-Shaped Polypeptoid Thin Films against Melt-Induced Dewetting.

We investigated the effect of cyclic chain topology on the molecular ordering and thermal stability of comb-shaped polypeptoid thin films on silicon (Si) substrates. Cyclic and linear poly(N-decylglycine) (PNDG) bearing long n-decyl side chains were synthesized by ring-opening polymerization of N-decylglycine-derived N-carboxyanhydrides. When the spin-coated thin films were subjected to thermal annealing at temperatures above the melting temperature (T > T m), the cyclic PNDG films exhibited significantly enhanced stability against melt-induced dewetting than the linear counterparts (l-PNDG). When recrystallized at temperatures below the crystallization temperature (T < T c), the homogeneous c-PNDG films exhibit enhanced crystalline ordering relative to the macroscopically dewetted l-PNDG films. Both cyclic and linear PNDG molecules adopt cis-amide conformations in the crystalline film, which transition into trans-amide conformations upon melting. A top-down solvent leaching treatment of both l/c-PNDG films revealed the formation of an irreversibly physisorbed monolayer with similar thickness (ca. 3 nm) on the Si substrate. The physisorbed monolayers are more disordered relative to the respective thicker crystalline films for both cyclic and linear PNDGs. Upon heating above T m, the adsorbed c-PNDG chains adopt trans-amide backbone conformation identical with the free c-PNDG molecules in the molten film. By contrast, the backbone conformations of l-PNDG chains in the adsorbed layers are notably different from those of the free chains in the molten film. We postulate that the conformational disparity between the chains in the physically adsorbed layers versus the free chains in the molten film is an important factor to account for the difference in the thermal stability of PNDG thin films. These findings highlight the use of cyclic chain topology to suppress the melt-induced dewetting in polymer thin films.

Novel Cucurbitane Triterpenes from the Tubers of Hemsleya amabilis with Their Cytotoxic Acitivity.

Chemical research of the medicinal plant Hemsleya amabilis (Cucurbitaceae) yielded five new cucurbitane-type triterpenes hemslelis A⁻E (1⁻5) by silica gel column, ODS column, and semi-HPLC techniques. Their structures were determined by spectroscopic analysis and examined alongside existing data from prior studies. Compounds 1⁻5 were evaluated for their cytotoxic activities against three human tumor cell lines, Hela, HCT-8, and HepG-2, with the IC50 ranging from 5.9 to 33.9 µM compared to Cisplatin.

[Early cardiac injury in patients with obstructive sleep apnea].

OBJECTIVE: To evaluate the early cardiac injury caused by obstructive sleep apnea (OSA) before the development of cardiovascular symptoms of OSA. METHODS: Ninety-two patients without any known cardiovascular disorders who underwent polysomnography (PSG) were enrolled in the study. Subjects were divided into mild, moderate, and severe OSA groups by their apnea hypopnea index (AHI), and 25 healthy individuals were identified as controls. After PSG examination, fasting blood samples for the evaluation of N-terminal pro-brain natriuretic peptide (NT-proBNP) and heart-type fatty acid binding protein (h-FABP) were collected in the morning, and left ventricular(LV) functions were assessed by using echocardiographic methods. Thirty moderate and severe OSA patients were treated with continuous positive airway pressure respectively (CPAP). RESULTS: The levels of h-FABP and NT-proBNP were obviously higher in all OSA groups than those in the control group (P<0.01), and were positively correlated with AHI (P<0.01). The Em/Am values of all OSA groups and E/A values of the moderate and severe OSA groups were significantly reduced (P<0.01). The difference in Em/Am values among the groups was statistically significant (P<0.01). Compared with those before treatment, h-FABP and NT-BNP levels in serum of OSA patients after CPAP treatment were significantly reduced (P<0.01), and Em/Am and E/A values were significantly increased (P<0.01). CONCLUSIONS: Left ventricular diastolic dysfunction and early myocardial microtrauma are major manifestations of early heart damage in patients with OSA. CPAP therapy could significantly improve early cardiac damage in OSA patients.

Characterization and structure-activity relationship of natural flavonoids as hERG K+ channel modulators.

OBJECTIVES: Flavonoids are present in varying concentrations in plant foods and have been reported to have numerous pharmacological activities, such as anti-cancer, antioxidant, anti-inflammatory, hepatoprotective, and vasodilator effects. We found that quercetin, fisetin, and some related flavonoid derivatives could inhibit human ether-à-go-go-related gene (hERG) K+ channels. KEY FINDINGS: In this study, we tested the effects of a series of flavonoids on the hERG K+ channel expressed in HEK293 cells. For the first time, we demonstrate that quercetin and fisetin (Fise) are potent hERG current blockers. The 50% inhibiting concentration (IC50) and maximum efficacy (Emax) of quercetin were 11.8±0.9µM and 82±2%, while those of fisetin were 38.4±6µM and 100±6%, respectively. Luteolin (Lute) was a less potent inhibitor of hERG current (48±1% at 100µM). Galangin, kaempferol, and isorhamnetin (100µM) showed weaker activity on the hERG currents. CONCLUSION: These results suggest that quercetin, fisetin, and luteolin are potent hERG K+ channel inhibitors and reveal the structure-activity relationship of natural flavonoids.

Clerodens E-J, antibacterial caffeic acid derivatives from the aerial part of Clerodendranthus spicatus.

Six new caffeic acid derivatives, Clerodens E-J (1-6) were isolated from the aerial part of Clerodendranthus spicatus. Their structures were elucidated by extensive spectroscopic analysis, including NMR, MS, and ECD data. Compound 1 showed moderate antibacterial activities against drug-resistant strains of bacteria in vitro.

[Solitary median maxillary central incisor syndrome:a case of report].

Solitary median maxillary central incisor (SMMCI) is a rare dental anomaly characterized by a symmetric central incisor of normal size, developed and erupted precisely in the midline of the maxilla in both primary and permanent dentitions. SMMCI may occur alone or be associated with other midline structures defects of the body or other systemic disorders. The best known association is holoprosencephaly (HPE). This paper reported a case of SMMCI that companied with other midline structures defects of the body.

A survey on evolutionary algorithm based hybrid intelligence in bioinformatics.

With the rapid advance in genomics, proteomics, metabolomics, and other types of omics technologies during the past decades, a tremendous amount of data related to molecular biology has been produced. It is becoming a big challenge for the bioinformatists to analyze and interpret these data with conventional intelligent techniques, for example, support vector machines. Recently, the hybrid intelligent methods, which integrate several standard intelligent approaches, are becoming more and more popular due to their robustness and efficiency. Specifically, the hybrid intelligent approaches based on evolutionary algorithms (EAs) are widely used in various fields due to the efficiency and robustness of EAs. In this review, we give an introduction about the applications of hybrid intelligent methods, in particular those based on evolutionary algorithm, in bioinformatics. In particular, we focus on their applications to three common problems that arise in bioinformatics, that is, feature selection, parameter estimation, and reconstruction of biological networks.