Microbial bionic nano-aromatic drugs for prevention of depression induced by chronic stress.

Depression is a mood disorder mainly clinically characterized by significant and persistent low spirits. Chronic stress is the leading cause of depression. However, traditional medicine has severe side effects in treating depression, ineffective treatment, and easy recurrence. Therefore, it is of great significance to prevent depression in the environment of chronic stress. In this study, aromatherapy was used for the prevention of depression. To solve the defects of intense volatility and inconvenience in using essential oils, we designed bionic nano-aromatic drugs and adhered them to the wallpaper. Inspired by the moldy wallpaper, we successively prepared the morphology-bionic nano-aromatic drugs, the function-bionic nano-aromatic drugs, and the bionic plus nano-aromatic drugs by referring to the morphology of microorganisms and substances in bacterial biofilms. Bionic nano-aromatic drugs remarkably promoted their adhesion on wallpaper. Molecular dynamics simulation explored its molecular mechanism. The essential oils, which were slowly released from the bionic nano-aromatic drugs, showed excellent biosecurity and depression prevention. These sustainedly released essential oils could significantly increase monoamine neurotransmitters in the brain under a chronic stress environment and had excellent neuroprotection. Besides, the bionic nano-aromatic drugs with simple preparation process and low cost had excellent application potential.

Physiological and transcriptional regulation in Taxodium hybrid 'Zhongshanshan' leaves in acclimation to prolonged partial submergence.

MAIN CONCLUSION: Taxodium 703 leaves activate fermentation, amino acids metabolism and ROS detoxification, and reduce TCA cycle and ABA biosynthesis in acclimation to prolonged partial submergence stress. Taxodium hybrid 'Zhongshanshan 703' (T. mucronatum × T. distichum; Taxodium 703) is a highly flooding-tolerant woody plant. To investigate the physiological and transcriptional regulatory mechanisms underlying its leaves in acclimation to long-term flooding, we exposed cuttings of Taxodium 703 to either non-flooding (control) or partial submergence for 2 months. The leaf tissues above (AL) and below (BL) flooding-water were separately harvested. Partial submergence decreased concentrations of chlorophyll (a + b) and dehydroascorbate (DHA) and lactate dehydrogenase (LDH) activity in AL, and reduced biomass, concentrations of succinic acid, fumaric acid and malic acid, and transcript levels of genes involved in tricarboxylic acid (TCA) cycle in BL. Under partial submergence, concentrations of starch, malondialdehyde and abscisic acid (ABA) decreased, and also mRNA levels of nine-cis-epoxycarotenoid dioxygenases that are involved in ABA biosynthesis in AL and BL of Taxodium 703. Partial submergence increased O2- content in AL, and improved concentrations of pyruvate and soluble sugars and activities of LDH and peroxidase in BL. In addition, partial submergence increased concentrations of ethanol, lactate, alanine, γ-aminobutyric acid, total amino acids and ascorbic acid (ASA), and ASA/DHA, activities of alcohol dehydrogenases (ADH) and ascorbate peroxidase, as well as transcript levels of ADH1A, ADH1B and genes involved in alanine biosynthesis and starch degradation in AL and BL of Taxodium 703. Overall, these results suggest that Taxodium 703 leaves activate fermentation, amino acids metabolism and reactive oxygen species detoxification, and maintain a steady supply of sugars, and reduce TCA cycle and ABA biosynthesis in acclimation to prolonged partial submergence stress.

Dynamics of the spin-boson model: The effect of bath initial conditions.

The dynamics of the (sub-)Ohmic spin-boson model under various bath initial conditions is investigated by employing the Dirac-Frenkel time-dependent variational approach with the multiple Davydov D1 Ansatz in the interaction picture. The validity of our approach is carefully checked by comparing the results with those of the hierarchy equations of motion method. By analyzing the features of nonequilibrium dynamics, we identify the phase diagrams for different bath initial conditions. We find that for the spectral exponent s < sc, there exists a transition from coherent to quasicoherent dynamics with increasing coupling strengths. For sc < s ≤ 1, the coherent to incoherent crossover occurs at a certain coupling strength and the quasicoherent dynamics emerges at much larger couplings. The initial preparation of the bath has a considerable influence on the dynamics.

Optimization of Isolation and Transformation of Protoplasts from Uncaria rhynchophylla and Its Application to Transient Gene Expression Analysis.

Protoplast-based engineering has become an important tool for basic plant molecular biology research and developing genome-edited crops. Uncaria rhynchophylla is a traditional Chinese medicinal plant with a variety of pharmaceutically important indole alkaloids. In this study, an optimized protocol for U. rhynchophylla protoplast isolation, purification, and transient gene expression was developed. The best protoplast separation protocol was found to be 0.8 M D-mannitol, 1.25% Cellulase R-10, and 0.6% Macerozyme R-10 enzymolysis for 5 h at 26 °C in the dark with constant oscillation at 40 rpm/min. The protoplast yield was as high as 1.5 × 107 protoplasts/g fresh weight, and the survival rate of protoplasts was greater than 90%. Furthermore, polyethylene glycol (PEG)-mediated transient transformation of U. rhynchophylla protoplasts was investigated by optimizing different crucial factors affecting transfection efficiency, including plasmid DNA amount, PEG concentration, and transfection duration. The U. rhynchophylla protoplast transfection rate was highest (71%) when protoplasts were transfected overnight at 24 °C with the 40 µg of plasmid DNA for 40 min in a solution containing 40% PEG. This highly efficient protoplast-based transient expression system was used for subcellular localization of transcription factor UrWRKY37. Finally, a dual-luciferase assay was used to detect a transcription factor promoter interaction by co-expressing UrWRKY37 with a UrTDC-promoter reporter plasmid. Taken together, our optimized protocols provide a foundation for future molecular studies of gene function and expression in U. rhynchophylla.

Regional differences and convergence of green innovation efficiency in China.

Green innovation facilitates high-quality economic development and ecological environmental protection. Herein, the minimum distance to strong efficient frontier (MinDS) model was used to measure green innovation efficiencies (GIEs) of 30 Chinese provinces over a period of 21 years (2000-2020). Gini coefficient decomposition and kernel density estimation methods were used to analyze the regional differences of GIE. Spatial correlation was estimated to analyze spatial-spillover effects and spatial convergence of the GIE. China's GIE has shown an increasing trend with significant spatial differences in GIE among provinces. Regional differences and transvariation intensity are the primary sources of spatial differences in GIE. Regional differences in GIE have decreased, except for eastern regions. The results of spatial convergence estimation suggest spatial absolute and conditional convergence in all regions. Therefore, for the GIE improvement in China, the effects of economic level, industrial structure, and environmental regulations must be considered.

Emission spectral non-Markovianity in qubit-cavity systems in the ultrastrong coupling regime.

We study the emission spectra of the dissipative Rabi and Jaynes-Cummings models in the non-Markovian and ultrastrong coupling regimes. We have derived a polaron-transformed Nakajima-Zwanzig master equation (PTNZE) to calculate the emission spectra, which eliminates the well-known limitations of the Markovian approximation and the standard second-order perturbation. Using the time-dependent variational approach with the multiple Davydov ansatz as a benchmark, the PTNZE is found to yield accurate emission spectra in certain ultrastrong coupling regimes where the standard second-order Nakajima-Zwanzig master equation breaks down. It is shown that the emission spectra of the dissipative Rabi and Jaynes-Cummings models are, in general, asymmetric under various initial conditions. Direct comparisons of spectra for the two models illustrate the essential role of the qubit-cavity counter-rotating term and the spectral features under different qubit-cavity coupling strengths and system initial conditions.

Genome-Wide Identification and Characterization of NAC Family in Hibiscus hamabo Sieb. et Zucc. under Various Abiotic Stresses.

NAC transcription factor is one of the largest plant gene families, participating in the regulation of plant biological and abiotic stresses. In this study, 182 NAC proteins (HhNACs) were identified based on genomic datasets of Hibiscus hamabo Sieb. et Zucc (H. hamabo). These proteins were divided into 19 subfamilies based on their phylogenetic relationship, motif pattern, and gene structure analysis. Expression analysis with RNA-seq revealed that most HhNACs were expressed in response to drought and salt stress. Research of quantitative real-time PCR analysis of nine selected HhNACs supported the transcriptome data's dependability and suggested that HhNAC54 was significantly upregulated under multiple abiotic stresses. Overexpression of HhNAC54 in Arabidopsis thaliana (A. thaliana) significantly increased its tolerance to salt. This study provides a basis for a comprehensive analysis of NAC transcription factor and insight into the abiotic stress response mechanism in H. hamabo.

Reversible Micrometer-Scale Spiral Self-Assembly in Liquid Crystalline Block Copolymer Film with Controllable Chiral Response.

The spiral is a fundamental structure in nature and spiral structures with controllable handedness are of increasing interest in the design of new chiroptical materials. In this study, micrometer-scale spiral structures with reversible chirality were fabricated based on the assembly of a liquid crystalline block copolymer film assisted by enantiopure tartaric acid. Mechanistic insight revealed that the formation of the spiral structures was closely related to the liquid crystalline properties of the major phase of block copolymer under the action of chiral tartaric acid. The chiral spiral structures with controllable handedness were easily erased under ultraviolet light irradiation and restored via thermal annealing. This facile thermal treatment method provides guidance for fabrication of chiral micrometer-scale spiral structures with adjustable chiral properties.

Construction of a Mex3c Gene-Deficient Mouse Model to Study C-FOS Expression in Hypothalamic Nuclei and Observe Morphological Differences in Embryonic Neural Tube Development.

BACKGROUND This study utilized CRISPR/Cas9 gene editing technology to construct a Mex3c gene-deficient mouse model, and studied C-FOS expression in hypothalamic nuclei. MATERIAL AND METHODS Thirty Mex3c-/+ mice, 30 mice in the normal group, and 30 Mex3c-/+ mice were randomly divided into control, leptin, and ghrelin groups according to different intraperitoneal injections. HE and Nissl staining were performed to observe the morphology of hypothalamic nerve cells. The C-FOS expression in hypothalamic nuclei of each group was analyzed by immunohistochemical techniques. HE staining was used to observe neural tube morphology, and LFB staining was used to observe nerve myelin sheath morphology. TEM was used to observe neuronal ultrastructure and immunohistochemical techniques were utilized to analyze nestin expression. RESULTS C-FOS expression was lower in the normal control group than in the leptin and ghrelin groups. The Mex3c control group and the leptin group had higher C-FOS expression than the ghrelin group. In neural tube studies, no significant differences were found in the neural tube pathological sections of E14.5-day embryos in each group. Nestin results demonstrated lower expression in the normal group and there was little difference between the HD and Mex3c groups. CONCLUSIONS Mex3c appears to participate in the regulation of energy metabolism by inducing C-FOS expression in the hypothalamus. The neural tubes of the offspring of Mex3c-/+ mice had defects during development.

Positively Charged Polyprodrug Amphiphiles with Enhanced Drug Loading and Reactive Oxygen Species-Responsive Release Ability for Traceable Synergistic Therapy.

Due to the vast differences in chemical properties among small molecule drugs, nucleotide drugs, and superparamagnetic iron oxide nanocubes (SPIONs), such as charge and hydrophobicity, entrapment of these within a single carrier for traceable synergistic therapy has been proven difficult. Herein, we synthesize positively charged polyprodrug amphiphiles. The hydrophobic polyprodrug unit of the amphiphiles is positively charged, which can simultaneously load hydrophobic SPIONs and absorb negative let-7b antisense oligonucleotide to construct traceable co-delivery nanoparticles (NPs). This characteristic avoids the use of inert materials and enhances drug loading of the traceable NPs. The traceable NPs can achieve controlled release of drugs to reduce the differentiation of exogenous neural stem cells (NSCs) and enhance their secretion of brain-derived neurotrophic factor (BDNF) synergistically. Exogenous NSCs treated with the NPs significantly rescue the memory deficits in 2xTg-AD mice. In addition, the transplantation site and migration of exogenous NSCs can be traced using the SPIONs with high r2 value for magnetic resonance imaging. Therefore, traceable NPs self-assembled from the positively charged polyprodrug amphiphiles may have the potential to open up a new avenue for treatment of Alzheimer's disease (AD), as well as other neurodegenerative disorders.

Microenvironment-Responsive Three-Pronged Approach Breaking Traditional Chemotherapy to Target Cancer Stem Cells for Synergistic Inoperable Large Tumor Therapy.

Three-pronged nanoparticles (NPs) that can efficiently prohibit the proliferation of large tumor are developed for inoperable large tumor therapy. The NPs achieve spatially and temporally controlled release of drugs in target sites. The NPs induce the apoptosis of differentiated cancer cells, cancer stem cells, and vascular niches simultaneously. Importantly, the three-pronged NPs inhibit the growth of large tumors without recurrence.

A Biomimic Nanobullet with Ameliorative Inflammatory Microenvironment for Alzheimer's Disease Treatments.

Aß oligomers, formed prior to diagnostic marker-amyloid ß (Aß) plaques, can damage neurons and trigger neuroinflammation, which accelerate the neuronal injury in Alzheimer's disease (AD). Herein, the combination of eliminating the Aß oligomers and alleviating the inflammation is a promising therapeutic strategy for AD. However, the presence of the blood-brain barrier (BBB) and the intrinsic deficiencies of the drugs severely restrict their therapeutic effects. Inspired by the properties of rabies virus, a biomimic nanobullet (PBACR@NRs/SA) targeting neurons has been developed. The biomimic nanobullets possess the BBB penetrating character based on iron oxide nanorods; it can sequentially release rosmarinic acid and small interfering RNA targeting NF-κB triggered by microenvironment, which improve the microenvironment inflammation and realize the cure for AD. Compared with non-biomimic systems, the biomimic nanobullets exhibit a less caveolin-dependent internalization pathway, which reduces ROS production and mitochondrial fission in neurons. Therefore, the biomimic nanobullet is hopeful for the treatment of ADs and provides a promising platform for other brain diseases' treatments.

Stem cell-derived extracellular vesicles in the therapeutic intervention of Alzheimer's Disease, Parkinson's Disease, and stroke.

With the increase in the aging population, the occurrence of neurological disorders is rising. Recently, stem cell therapy has garnered attention due to its convenient sourcing, minimal invasiveness, and capacity for directed differentiation. However, there are some disadvantages, such as poor quality control, safety assessments, and ethical and logistical issues. Consequently, scientists have started to shift their attention from stem cells to extracellular vesicles due to their similar structures and properties. Beyond these parallels, extracellular vesicles can enhance biocompatibility, facilitate easy traversal of barriers, and minimize side effects. Furthermore, stem cell-derived extracellular vesicles can be engineered to load drugs and modify surfaces to enhance treatment outcomes. In this review, we summarize the functions of native stem cell-derived extracellular vesicles, subsequently review the strategies for the engineering of stem cell-derived extracellular vesicles and their applications in Alzheimer's disease, Parkinson's disease, and stroke, and discuss the challenges and solutions associated with the clinical translation of stem cell-derived extracellular vesicles.

Integrated small RNA, transcriptome and physiological approaches provide insight into Taxodium hybrid 'Zhongshanshan' roots in acclimation to prolonged flooding.

Although Taxodium hybrid 'Zhongshanshan' 406 (Taxodium mucronatum Tenore × Taxodium distichum; Taxodium 406) is an extremely flooding-tolerant woody plant, the physiological and molecular mechanisms underlying acclimation of its roots to long-term flooding remain largely unknown. Thus, we exposed saplings of Taxodium 406 to either non-flooding (control) or flooding for 2 months. Flooding resulted in reduced root biomass, which is in line with lower concentrations of citrate, α-ketoglutaric acid, fumaric acid, malic acid and adenosine triphosphate (ATP) in Taxodium 406 roots. Flooding led to elevated activities of pyruvate decarboxylase, alcohol dehydrogenase and lactate dehydrogenase, which is consistent with higher lactate concentration in the roots of Taxodium 406. Flooding brought about stimulated activities of superoxide dismutase and catalase and elevated reduced glutathione (GSH) concentration and GSH/oxidized glutathione, which is in agreement with reduced concentrations of O2- and H2O2 in Taxodium 406 roots. The levels of starch, soluble protein, indole-3-acetic acid, gibberellin A4 and jasmonate were decreased, whereas the concentrations of glucose, total non-structural carbohydrates, most amino acids and 1-aminocyclopropane-1-carboxylate (ACC) were improved in the roots of flooding-treated Taxodium 406. Underlying these changes in growth and physiological characteristics, 12,420 mRNAs and 42 miRNAs were significantly differentially expressed, and 886 miRNA-mRNA pairs were identified in the roots of flooding-exposed Taxodium 406. For instance, 1-aminocyclopropane-1-carboxylate synthase 8 (ACS8) was a target of Th-miR162-3p and 1-aminocyclopropane-1-carboxylate oxidase 4 (ACO4) was a target of Th-miR166i, and the downregulation of Th-miR162-3p and Th-miR166i results in the upregulation of ACS8 and ACO4, probably bringing about higher ACC content in flooding-treated roots. Overall, these results indicate that differentially expressed mRNA and miRNAs are involved in regulating tricarboxylic acid cycle, ATP production, fermentation, and metabolism of carbohydrates, amino acids and phytohormones, as well as reactive oxygen species detoxification of Taxodium 406 roots. These processes play pivotal roles in acclimation to flooding stress. These results will improve our understanding of the molecular and physiological bases underlying woody plant flooding acclimation and provide valuable insights into breeding-flooding tolerant trees.

Quantum critical point of spin-boson model and infrared catastrophe in bosonic bath.

An analytic ground state is proposed for the unbiased spin-boson Hamiltonian, which is non-Gaussian and beyond the Silbey-Harris ground state with lower ground state energy. The infrared catastrophe in Ohmic and sub-Ohmic bosonic bath plays an important role in determining the degeneracy of the ground state. We show that the infrared divergence associated with the displacement of the nonadiabatic modes in bath may be removed from the proposed ground state for the coupling α < αc. Then αc is the quantum critical point of a transition from non-degenerate to degenerate ground state and our calculated αc agrees with previous numerical results.

Sub-Ohmic spin-boson model with off-diagonal coupling: ground state properties.

We have carried out analytical and numerical studies of the spin-boson model in the sub-ohmic regime with the influence of both the diagonal and the off-diagonal coupling accounted for, via the Davydov D1 variational ansatz. While a second-order phase transition is known to be exhibited by this model in the presence of diagonal coupling only, we demonstrate the emergence of a discontinuous first order phase transition upon incorporation of the off-diagonal coupling. A plot of the ground state energy versus magnetization highlights the discontinuous nature of the transition between the isotropic (zero magnetization) state and nematic (finite magnetization) phases. We have also calculated the entanglement entropy and a discontinuity found at a critical coupling strength further supports the discontinuous crossover in the spin-boson model in the presence of off-diagonal coupling. It is further revealed via a canonical transformation approach that for the special case of identical exponents for the spectral densities of the diagonal and the off-diagonal coupling, there exists a continuous crossover from a single localized phase to doubly degenerate localized phase with differing magnetizations.

Grafting Causes Physiological Changes and Promotes Adventitious Root Formation in Rejuvenated Soft Shoots of Taxodium hybrid 'Zhongshanshan'.

Taxodium hybrid 'Zhongshanshan' has been widely used as a timber tree in river network areas and coastal regions and is mainly propagated by cuttings. However, when trees age, their capacity to form adventitious roots becomes weaker. We successfully enhanced the rooting ability of shoots in T. hybrid 'Zhongshanshan 302' by their rejuvenation based on grafting. We recorded temporal variation in endogenous auxin, abscisic acid (ABA), gibberellins (GAs), trans-zeatin-riboside (TZR), soluble sugar and H2O2 after root induction. Auxin, soluble sugars and H2O2 levels were higher in rejuvenated shoots than in mature shoots, whereas the opposite was true for ABA and GAs. Notably, indole-3-acetic acid (IAA) and GA3 presented higher contents with more obvious differences in T. hybrid 'Zhongshanshan 302' rejuvenated shoots vs. mature shoots compared with other kinds of auxin and GAs. The evident improvement in the rooting ability of rejuvenated shoots after grafting likely resulted from the differential regulation of plant hormones, carbohydrates and redox signaling. In addition to the physiological basis of improved rooting ability by grafting, this study provided a theoretical basis for the optimization of subsequent propagation techniques in T. hybrid 'Zhongshanshan' and potentially other Taxodium spp.

Nucleic acid drug vectors for diagnosis and treatment of brain diseases.

Nucleic acid drugs have the advantages of rich target selection, simple in design, good and enduring effect. They have been demonstrated to have irreplaceable superiority in brain disease treatment, while vectors are a decisive factor in therapeutic efficacy. Strict physiological barriers, such as degradation and clearance in circulation, blood-brain barrier, cellular uptake, endosome/lysosome barriers, release, obstruct the delivery of nucleic acid drugs to the brain by the vectors. Nucleic acid drugs against a single target are inefficient in treating brain diseases of complex pathogenesis. Differences between individual patients lead to severe uncertainties in brain disease treatment with nucleic acid drugs. In this Review, we briefly summarize the classification of nucleic acid drugs. Next, we discuss physiological barriers during drug delivery and universal coping strategies and introduce the application methods of these universal strategies to nucleic acid drug vectors. Subsequently, we explore nucleic acid drug-based multidrug regimens for the combination treatment of brain diseases and the construction of the corresponding vectors. In the following, we address the feasibility of patient stratification and personalized therapy through diagnostic information from medical imaging and the manner of introducing contrast agents into vectors. Finally, we take a perspective on the future feasibility and remaining challenges of vector-based integrated diagnosis and gene therapy for brain diseases.

Communication: Engineered tunable decay rate and controllable dissipative dynamics.

We investigate the steering dissipative dynamics of a two-level system (qubit) by means of the modulation of an assisted tunneling degree of freedom which is described by a quantum-oscillator spin-boson model. Our results reveal that the decoherence rate of the qubit can be significantly suppressed and simultaneously its quality factor is enhanced. Moreover, the modulated dynamical susceptibility exhibits a multi-peak feature which is indicative of the underlying structure and measurable in experiment. Our findings demonstrate that the interplay between the combined degrees of freedom and the qubit is crucial for reducing the dissipation of qubit and expanding the coherent regime of quantum operation much large. The strategy might be used to fight against deterioration of quantum coherence in quantum information processing.

Path Planning Algorithm for Multi-Locomotion Robot Based on Multi-Objective Genetic Algorithm with Elitist Strategy.

The multi-locomotion robot (MLR), including bionic insect microrobot, bionic animal robot and so on, should choose different locomotion modes according to the obstacles it faces. However, under different locomotion modes, the power consumption, moving speed, and falling risk of MLR are different, and in most cases, they are mutually exclusive. This paper proposes a path planning algorithm for MLR based on a multi-objective genetic algorithm with elitist strategy (MLRMOEGA), which has four optimization objectives: power consumption, time consumption, path falling risk, and path smoothness. We propose two operators: a map analysis operator and a population diversity expansion operator, to improve the global search ability of the algorithm and solve the problem so that it is easy to fall into the local optimal solution. We conduct simulations on MATLAB, and the results show that the proposed algorithm can effectively optimize the objective function value compared with the traditional genetic algorithm under the equal weight of the four optimization objectives, and, under alternative weights, the proposed algorithm can effectively generate the corresponding path of the decision maker's intention under the weight of preference. Compared with the traditional genetic algorithm, the global search ability is improved effectively.