Three-Dimensional Chiral Morphogenesis of Active Fluids.

Chirality is an essential nature of biological systems. However, it remains obscure how the handedness at the microscale is translated into chiral morphogenesis at the tissue level. Here, we investigate three-dimensional (3D) tissue morphogenesis using an active fluid theory invoking chirality. We show that the coordination of achiral and chiral stresses, arising from microscopic interactions and energy input of individual cells, can engender the self-organization of 3D papillary and helical structures. The achiral active stress drives the nucleation of asterlike topological defects, which initiate 3D out-of-plane budding, followed by rodlike elongation. The chiral active stress excites vortexlike topological defects, which favor the tip spheroidization and twisting of the elongated rod. These results unravel the chiral morphogenesis observed in our experiments of 3D organoids generated by human embryonic stem cells.

Substrate nesting guides cyst morphogenesis of human pluripotent stem cells without 3D extracellular matrix overlay.

Understanding the principles underlying the self-organization of stem cells into tissues is fundamental for deciphering human embryo development. Here, we report that, without three-dimensional (3D) extracellular matrix (ECM) overlay, human pluripotent stem cells (hPSCs) cultured on two-dimensional soft elastic substrates can self-organize into 3D cysts resembling the human epiblast sac in a stiffness-dependent manner. Our theoretical modeling predicts that this cyst organization is facilitated and guided by the spontaneous nesting of the soft substrate, which results from the adhesion-dependent mechanical interaction between cells and substrate. Such substrate nesting is sufficient for the 3D assembly and polarization of hPSCs required for cyst organization, even without 3D ECM overlay. Furthermore, we identify that the reversible substrate nesting and cyst morphogenesis also require appropriate activation of ROCK-Myosin II pathway. This indicates a unique set of tissue morphomechanical signaling mechanisms that clearly differ from the canonical cystogenic mechanism previously reported in 3D ECM. Our findings highlight an unanticipated synergy between mechanical microenvironment and mechanotransduction in controlling tissue morphogenesis and suggest a mechanics-based strategy for generation of hPSCs-derived models for early human embryogenesis. STATEMENT OF SIGNIFICANCE: Soft substrates can induce the self-organization of human pluripotent stem cells (hPSCs) into cysts without three-dimensional (3D) extracellular matrix (ECM) overlay. However, the underlying mechanisms by which soft substrate guides cystogenesis are largely unknown. This study shows that substrate nesting, resulting from cell-substrate interaction, plays an important role in cyst organization, including 3D assembly and apical-basal polarization. Additionally, actomyosin contractility mediated by the ROCK-Myosin II pathway also contributes to the substrate deformation and cyst morphology. These findings demonstrate the interplay between the mechanical microenvironment and cells in tissue morphogenesis, suggesting a mechanics-based strategy in building hPSC-derived models for early human embryo development.

A three-player game model for promoting enterprise green technology innovation from the perspective of media coverage.

Objective: The objective of this study was to explore the game relationship among enterprise, the government, and the public under the new media environment, so as to provide decision-making reference for improving enterprise green technology innovation and promoting economy high-quality development with new media participation. Methods: This study constructs a three-subject evolutionary game model of enterprise, government, and public based on multi-agent relationship analysis and evolutionary game theory. In addition, the derivation of an evolutionary equilibrium strategy and numerical simulation analysis is carried out to comprehensively explore the evolution trajectory of green technology innovation system under the new media environment. Findings: (1) The system may have four stable evolutionary strategies: (1,0,0), (0,0,1), (1,0,1), and (1,1,1). (2) The initial strategy probability of various actors would affect the system evolution speed but not the evolution result, and the authenticity of new media reports is an important factor determining the system evolution of green technology innovation. (3) Numerical simulation results show that a fair and just new media environment can effectively constrain the traditional production behavior of enterprise, actively guide the public to participate in supervision, and play an alternative role to government regulation to a certain extent. Value: This study explores the evolutionary balance strategy of green technology innovation system under the new media environment, which not only enriches relevant theories of media environment governance but also has important reference value for promoting enterprises' green technology innovation and establishing an environmental governance system jointly governed by government, enterprise, public, and media.

Extracellular Matrix Stiffness Regulates DNA Methylation by PKCα-Dependent Nuclear Transport of DNMT3L.

Extracellular matrix (ECM) stiffness has profound effects on the regulation of cell functions. DNA methylation is an important epigenetic modification governing gene expression. However, the effects of ECM stiffness on DNA methylation remain elusive. Here, it is reported that DNA methylation is sensitive to ECM stiffness, with a global hypermethylation under stiff ECM condition in mouse embryonic stem cells (mESCs) and embryonic fibroblasts compared with soft ECM. Stiff ECM enhances DNA methylation of both promoters and gene bodies, especially the 5' promoter regions of pluripotent genes. The enhanced DNA methylation is functionally required for the loss of pluripotent gene expression in mESCs grown on stiff ECM. Further experiments reveal that the nuclear transport of DNA methyltransferase 3-like (DNMT3L) is promoted by stiff ECM in a protein kinase C α (PKCα)-dependent manner and DNMT3L can be binding to Nanog promoter regions during cell-ECM interactions. These findings unveil DNA methylation as a novel target for the mechanical sensing mechanism of ECM stiffness, which provides a conserved mechanism for gene expression regulation during cell-ECM interactions.

Recent Advances on Polymeric Beads or Hydrogels as Embolization Agents for Improved Transcatheter Arterial Chemoembolization (TACE).

Transcatheter arterial chemoembolization (TACE), aiming to block the hepatic artery for inhibiting tumor blood supply, became a popular therapy for hepatocellular carcinoma (HCC) patients. Traditional TACE formulation of anticancer drug emulsion in ethiodized oil (i.e., Lipiodol®) and gelatin sponge (i.e., Gelfoam®) had drawbacks on patient tolerance and resulted in undesired systemic toxicity, which were both significantly improved by polymeric beads, microparticles, or hydrogels by taking advantage of the elegant design of biocompatible or biodegradable polymers, especially amphiphilic polymers or polymers with both hydrophilic and hydrophobic chains, which could self-assemble into proposed microspheres or hydrogels. In this review, we aimed to summarize recent advances on polymeric embolization beads or hydrogels as TACE agents, with emphasis on their material basis of polymer architectures, which are important but have not yet been comprehensively summarized.

miR396-OsGRFs Module Balances Growth and Rice Blast Disease-Resistance.

Fitness cost is a common phenomenon in rice blast disease-resistance breeding. MiR396 is a highly conserved microRNA (miRNA) family targeting Growth Regulating Factor (OsGRF) genes. Mutation at the target site of miR396 in certain OsGRF gene or blocking miR396 expression leads to increased grain yield. Here we demonstrated that fitness cost can be trade-off in miR396-OsGRFs module via balancing growth and immunity against the blast fungus. The accumulation of miR396 isoforms was significantly increased in a susceptible accession, but fluctuated in a resistant accession upon infection of Magnaporthe oryzae. The transgenic lines over-expressing different miR396 isoforms were highly susceptible to M. oryzae. In contrast, overexpressing target mimicry of miR396 to block its function led to enhanced resistance to M. oryzae in addition to improved yield traits. Moreover, transgenic plants overexpressing OsGRF6, OsGRF7, OsGRF8, and OsGRF9 exhibited enhanced resistance to M. oryzae, but showed different alteration of growth. While overexpression of OsGRF7 led to defects in growth, overexpression of OsGRF6, OsGRF8, and OsGRF9 resulted in better or no significant change of yield traits. Collectively, our results indicate that miR396 negatively regulates rice blast disease- resistance via suppressing multiple OsGRFs, which in turn differentially control growth and yield. Therefore, miR396-OsGRFs could be a potential module to demolish fitness cost in rice blast disease-resistance breeding.

Anion-Responsive Metallopolymer Hydrogels for Healthcare Applications.

Metallopolymers combine a processable, versatile organic polymeric skeleton with functional metals, providing multiple functions and methodologies in materials science. Taking advantage of cationic cobaltocenium as the key building block, organogels could be simply switched to hydrogels via a highly efficient ion exchange. With the unique ionic complexion ability, cobaltocenium moieties provide a robust soft substrate for recycling antibiotics from water. The essential polyelectrolyte nature offers the metallopolymer hydrogels to kill multidrug resistant bacteria. The multifunctional characteristics of these hydrogels highlight the potential for metallopolymers in the field of healthcare and environmental treatment.

Toxicity of Graphene Quantum Dots in Zebrafish Embryo.

OBJECTIVE: To evaluate the bio-safety of graphene quantum dots (GQDs), we studied its effects on the embryonic development of zebrafish. METHODS: In vivo, biodistribution and the developmental toxicity of GQDs were investigated in embryonic zebrafish at exposure concentrations ranging from 12.5-200 µg/mL for 4-96 h post-fertilization (hpf). The mortality, hatch rate, malformation, heart rate, GQDs uptake, spontaneous movement, and larval behavior were examined. RESULTS: The fluorescence of GQDs was mainly localized in the intestines and heart. As the exposure concentration increased, the hatch and heart rate decreased, accompanied by an increase in mortality. Exposure to a high level of GQDs (200 µg/mL) resulted in various embryonic malformations including pericardial edema, vitelline cyst, bent spine, and bent tail. The spontaneous movement significantly decreased after exposure to GQDs at concentrations of 50, 100, and 200 µg/mL. The larval behavior testing (visible light test) showed that the total swimming distance and speed decreased dose-dependently. Embryos exposed to 12.5 µg/mL showed hyperactivity while exposure to higher concentrations (25, 50, 100, and 200 µg/mL) caused remarkable hypoactivity in the light-dark test. CONCLUSION: Low concentrations of GQDs were relatively non-toxic. However, GQDs disrupt the progression of embryonic development at concentrations exceeding 50 µg/mL.

Maternal circulating concentrations of tumor necrosis factor-alpha, leptin, and adiponectin in gestational diabetes mellitus: a systematic review and meta-analysis.

Gestational diabetes mellitus (GDM) is one of the most common pregnancy complications. Inflammation may play a role in the pathogenesis of GDM. We performed a systematic review and meta-analysis to determine whether maternal serum concentration of tumor necrosis factor-alpha (TNF-α), leptin, and adiponectin were associated with GDM. A systematic search of PubMed and Medline was undertaken. In total, 27 trials were evaluated by meta-analyses using the software Review Manager 5.0. The results showed that maternal TNF-α (P = 0.0003) and leptin (P < 0.00001) concentrations were significantly higher in GDM patients versus controls. However, maternal adiponectin (P < 0.00001) concentration was significantly lower in GDM patients compared with controls. Subgroup analysis taking in consideration the effect of obesity on maternal adipokine levels showed that circulating levels of TNF-α and leptin remained elevated in GDM patients compared to their body mass index (BMI) matched controls, and adiponectin level remained depressed in GDM individuals. Our findings strengthen the clinical evidence that GDM is accompanied by exaggerated inflammatory responses.

[Spectra and structural analysis of high boiling solvent lignin from Bagasse].

Bagasse high boiling solvent lignin is a polymer prepared by high boiling solvent pulping process. In the IR spectra, the absorbance of HBS lignin at 1700 and 1 328 cm(-1) is present. It is showed that the nonconjugated carbonyl existed. The strong absorbance of UV spectra of HBS lignin is about 201 nm for n-->pi electron transition, which indicates that the HBS lignin is an unsaturated polymer. Judged from the 1H NMR, the syringyl and guaiacyl group in the lignin is present. The element composition and the content of OCH3 group were investigated. The empirical C9-formula of the lignin is C9H9.79O2.58(OCH)0.75 according to dealing with the experiment data. The weight-average molecular weight of the HBS lignin is 2674 g x mol(-1).

[Genetic mapping of the intergenomic translocated "taigu" genic sterility gene (Ms2)].

The "Taigu" genic sterility gene Ms2 located on the short arm of the 4D chromosome of common wheat (AABBDD) originally incorporated into hexoploid triticale (AABBRR) and durum wheat (AABB) through intergenomic translocation in distant hybridization was introduced back into the genomes of common wheat. The dominant male sterility was expressed normally in the new "Taigu" genic sterile wheat carrying the intergenomically translocated Ms2, and the female fertility mechanism in its male sterile plants was normal as well. Observation of the chromosome configuration at meiosis of pollen mother cells (PMC) of the young ears of the sterile plants showed that they were euploid plants (2n = 42). No configurations different from those of the "Taigu" genic sterility gene located at the original locus were noticed of the Ms2 intergenomically translocated back into the common wheat. In systematic test crosses with marker genes the intergenomically translocated gene Ms2 was found to be linked with the dominant dwarf marker in common wheat Rht3 and, consequently, remapped and located on the short arm of the 4B chromosome of common wheat with a distance of 9.7 cM from Rht3. The new locus was designated as Ms2 (4BS). Discussions are given of the fate of Ms2 during translocation in the hexoploid triticale, the exchange of the names for 4A and 4B chromosomes in common wheat and the possible exploitation of the new locus Ms2 (4BS), and the following speculations are made: (a) In genic genes of allopolyploid organisms the donor chromosomes tend to be intergenomically translocated to their physiologically and evolutionarily close chromosomes with the same order number and the same arm; (b) it is confirmed that the 7th International Conference of Wheat Genetics was right to exchange the names between chromosomes 4A and 4B of common wheat in 1988; and (c) as a new genetic marker and a breeding tool for all the chromosome B-carrying species in the tribe of Triticeae, Ms2(4BS) may have wide application in building and expanding the gene pool of germplasm resources of various species of wheat.