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Studies have shown that acupuncture is very effective in treating chronic stress depression. However, little is known about the therapeutic mechanism of electro-acupuncture. Metabolomics, on the other hand, is a technology that determines the metabolic changes of organisms caused by various interventions as a whole and is related to the overall effect of electro-acupuncture (EA). 1HNMR, serum sample analysis, and histopathology and molecular biology analysis were used to evaluate the effects of EA. The results show that electro-acupuncture points can regulate the heat pain threshold of chronic stress model rats and change the morphology of adrenal cortex cells Structure, and regulate the contents of corticotropin-releasing hormone, Corticosterone (CORT), glucose, alanine and valine in the samples. These findings help to clarify the therapeutic mechanism of electro-acupuncture on heterologous chronic stress model rats. The effect of electro-acupuncture on improving chronic stress is likely to be achieved by regulating glucose metabolism, which can provide a reference for clinical acupuncture treatment of chronic stress depression.

Kucha (Camellia sinensis) is a kind of unique wild tea resources in southwest China, containing sizeable amounts of theacrine (1,3,7,9-tetramethyluric acid) and having a special bitter taste both in fresh leaves and made tea. Theacrine has good healthy function locally. But the molecular mechanism of theacrine metabolism in Kucha was still unclear. In order to illuminate the biosynthesis and catabolism of theacrine in Kucha plants, three tea cultivars, C. sinensis ‘Shangyou Zhongye’ (SY) with low-theacrine, ‘Niedu Kucha 2’ (ND2) with middle-theacrine and, ‘Niedu Kucha 3’ (ND3) with high-theacrine, were used for our research. Purine alkaloid analysis and transcriptome of those samples were performed by High Performance Liquid Chromatography (HPLC) and RNA-Seq, respectively. The related gene expression levels of purine alkaloid were correlated with the content of purine alkaloid, and the results of quantitative real-time (qRT) PCR were also confirmed the reliability of transcriptome. Based on the data, we found that theacrine biosynthesis is a relatively complex process, N-methyltransferase (NMT) encoded by TEA024443 may catalyze the methylation at 9-N position in Kucha plant. Our finding will assist to reveal the molecular mechanism of theacrine biosynthesis, and be applied to selection and breeding of Kucha tea cultivars in the future.

We provide a unified and exact framework for the variance-based uncertainty relations. This unified framework not only recovers some well-known previous uncertainty relations, but also fixes the deficiencies of them. Utilizing the unified framework, we can construct the new uncertainty relations in both product and sum form for two and more incompatible observables with any tightness we require. Moreover, one can even construct uncertainty equalities to exactly express the uncertainty relation by the unified framework, and the framework is therefore exact in describing the uncertainty relation. Some applications have been provided to illustrate the importance of this unified and exact framework. Also, we show that the contradiction between uncertainty relation and non-Hermitian operator, i.e., most of uncertainty relations will be violated when applied to non-Hermitian operators, can be fixed by this unified and exact framework.

Some studies have proved that both acupuncture and moxibustion are very effective for the treatment of CAG. However, little is known about therapeutic mechanism of electro-acupuncture and moxibustion on CAG as well as the difference between them. On the other hand, metabolomics is a ‘top-down’ approach to understand metabolic changes of organisms caused by disease or interventions in holistic context, which consists with the holistic thinking of electro-acupuncture and moxibustion treatment. In this study, the difference of therapeutic mechanism between electro-acupuncture and moxibustion on CAG rats was investigated by a 1H NMR-based metabolomics analysis of multiple biological samples (serum, stomach, cerebral cortex and medulla) coupled with pathological examination and molecular biological assay. For all sample types, both electro-acupuncture and moxibustion intervention showed beneficial effects by restoring many CAG-induced metabolic changes involved in membrane metabolism, energy metabolism and function of neurotransmitters. Notably, the moxibustion played an important role in CAG treatment mainly by regulating energy metabolism in serum, while main acting site of electro-acupuncture treatment was nervous system in stomach and brain. These findings are helpful to facilitate the therapeutic mechanism elucidating of electro-acupuncture and moxibustion on CAG rats. Metabolomics is promising in mechanisms study for traditional Chinese medicine (TCM).

White- and brown-rot fungal decay via distinct pathways imparts characteristic molecular imprints on decomposing wood. However, the effect that a specific wood-rotting type of fungus has on proximal soil organic matter (SOM) accumulation remains unexplored. We investigated the potential influence of white- and brown-rot fungi-decayed Abies nephrolepis logs on forest SOM stocks (i.e., soil total carbon (C) and nitrogen (N)) and the concentrations of amino sugars (microbial necromass) at different depths and horizontal distances from decaying woody debris. The brown-rot fungal wood decay resulted in higher concentrations of soil C and N and a greater increase in microbial necromass (i.e., 1.3- to 1.7-fold greater) than the white-rot fungal wood decay. The white-rot sets were accompanied by significant differences in the proportions of the bacterial residue index (muramic acid%) with soil depth; however, the brown-rot-associated soils showed complementary shifts, primarily in fungal necromass, across horizontal distances. Soil C and N concentrations were significantly correlated with fungal rather than bacterial necromass in the brown-rot systems. Our findings confirmed that the brown-rot fungi-dominated degradation of lignocellulosic residues resulted in a greater SOM buildup than the white-rot fungi-dominated degradation.

Plasma dipeptidyl-peptidase-4 activity (DPP4a) is inversely associated with left ventricular function in patients with heart failure (HF) or diabetes. However, the association between DPP4a and left ventricular function in ST-segment elevation myocardial infarction (STEMI) patients has not been reported. We studied this association in 584 consecutive STEMI patients at a tertiary referral center from July 2014 to October 2015. DPP4a and plasma N-terminal prohormone of B-type natriuretic peptide (NT-proBNP) levels were quantified by enzymatic assays. The median serum NT-proBNP levels were highest in patients of the lowest tertile (T1) of DPP4a compared with that of the highest tertile (T3) (p = 0.028). The STEMI patients in T1 exhibited lower left ventricular systolic function (T1 vs. T3: left ventricular ejection fraction (LVEF): 50.13 ± 9.12 vs. 52.85 ± 6.82%, p = 0.001). Multivariate logistic-regression analyses (adjusted for confounding variables) showed that a 1 U/L increase in DPP4a was associated with a decreased incidence of left ventricular systolic dysfunction (LVSD) (adjusted odds ratio: 0.90; 95% CI: 0.87–0.94; p

The demagnetization progress of various hard/soft multilayers with perpendicular crystalline anisotropy has been studied by a micromagnetic model, incorporating the effect of the interface anisotropy, which is evident on the nucleation field when the soft layer thickness is small. Both microscopic and macroscopic hysteresis loops as well as angular distributions for the magnetizations in the thickness direction have been calculated, taking into account of realistic values of the interface anisotropy. The formula for the nucleation field has been derived analytically, where the nucleation field increases linearly with the interface anisotropy for a wide thickness region. While the nucleation field could change by more than 90% due to the influence of the interface anisotropy, the interface anisotropy has no effect on the pinning field or the coercivity, but it has some slight influence on the angular distributions. On the other hand, positive interface anisotropy enhances the remanence and the energy products, whereas negative interface anisotropy deteriorates both of them. Comparison with the experimental data justifies our calculation, indicating that negative interface anisotropy should be avoided in the experiment.

Lysine succinylation is a novel dynamic and evolutionarily conserved post-translational modification (PTM) that regulates various biological processes. ‘Anji Baicha’ is an albino tea variety that exhibits temperature-based variability of leaf colour and amino acid concentrations. However, the mechanism underlying albinism in ‘Anji Baicha’ has not been investigated at the level of succinylation. Here, we identify 3530 lysine succinylation sites mapped to 2132 proteins in ‘Anji Baicha’, representing the first extensive data on the lysine succinylome in the tea plant. Eleven conserved succinylation motifs were enriched among the identified succinylated peptides. The protein-protein interaction maps were visualized using Cytoscape software. Comparison across three typical developmental stages of ‘Anji Baicha’ revealed that proteins exhibiting differential succinylation levels were primarily involved in photosynthesis, carbon fixation, biosynthesis of amino acids and porphyrin and chlorophyll metabolism, suggesting that these succinylated proteins are involved in ‘Anji Baicha’ leaf colour variability. These results not only deepen our understanding of the mechanism underlying ‘Anji Baicha’ albinism and the regulatory role of succinylation in the tea plant but also provide new insight into molecular breeding for leaf colour variety.

This study aimed to investigate application of Onodera prognostic nutrition index (OPNI) and neutrophil-to-lymphocyte ratio (NLR) in evaluating risk of postoperative complications in Crohn’s disease (CD). Clinical data of 108 postoperative CD patients in 9 years were respectively reviewed. OPNI and NLR were within 1 week preoperatively. Average OPNI was 38.8 ± 8.2 and significantly lower in patients with: CD type B3; lymphopenia; decreased haemoglobin, prealbumin, and albumin; and daily enteral nutrition

ADIPOQ gene polymorphisms have been indicated to be associated with hypertension; however, published studies have reported inconsistent results. Eligible studies were retrieved by searching the PubMed, Embase and China National Knowledge Infrastructure databases. The case group consisted of patients with hypertension, and the control group consisted of subjects with normal blood pressure. Based on eleven published articles, involving 4837 cases and 5618 controls, the pooled results from rs2241766 polymorphism showed increased risk in the allelic model (G VS T: OR = 1.16, 95%CI = 1.06–1.27), recessive model (GG VS GT + TT: OR = 1.34, 95%CI = 1.10–1.63), dominant model (GG + GT VS TT: OR = 1.15, 95%CI = 1.02–1.30) and homozygote model (GG VS TT: OR = 1.38, 95%CI = 1.21–1.69). In addition, rs266729 polymorphism showed increased risk for hypertension in the recessive model (GG VS GC + CC: OR = 1.43, 95%CI = 1.02–2.01). In the Caucasian subgroup, rs1501299 polymorphism showed decreased risk of hypertension in the allelic model (T VS G: OR = 0.75, 95%CI = 0.58–0.97), dominant model (TT + TG VS GG: OR = 0.83, 95%CI = 0.71–0.98) and heterozygote model (TG VS GG: OR = 0.82, 95%CI = 0.68–0.99). The rs2241766 polymorphism was associated with a significant increase in hypertension risk based on our analysis. Moreover, an increased risk of rs266729 in hypertension patients was also detected. Our meta-analysis suggests that the rs1501299 polymorphism may play a protective role in hypertension in Caucasian subgroup; however, this finding requires further study.

Realgar (As4S4) has been demonstrated to be effective for the treatment of acute myeloid leukemia (AML); it has the advantages of no drug resistance and oral administration. Nevertheless, its poor solubility has been an obstacle to its bioavailability, requiring high-dose administration over a long period. We investigated whether crushing realgar crystals to the nanoscale and encapsulating the particles in a water-soluble polymer in one step using hot-melt extrusion would increase the bioavailability of As4S4. Raw As4S4 (r-As4S4) and water-soluble polymer were processed via co-rotating twin screw extrusion. The resulting product (e-As4S4) was characterized by SEM, XRD, and DLS. The cytotoxicity and therapeutic effects of e-As4S4 were evaluated in vivo and in vitro. The results show that e-As4S4 dissolved rapidly in water, forming a stable colloid solution. The average size of e-As4S4 particles was 680 nm, which was reduced by more than 40-fold compared with that of r-As4S4. The bioavailability of e-As4S4 was up to 12.6-fold higher than that of r-As4S4, and it inhibited the proliferation of HL-60 cells much more effectively than did r-As4S4, inducing apoptosis and significantly reducing the infiltration of HL-60 cells into the bone marrow, spleen, and liver. This in turn prolonged the survival of AML mice.

Understanding the role of surface decoration of nanoparticles in protein adsorption and cellular uptake is of great importance in biomedicine. Here, by using dissipative particle dynamics simulations, we take two typical coating polymers (i.e., hydrophilic and zwitterionic polymers) as an example and systematically investigate their effect on cellular delivery of hydrophobic and charged nanoparticles (in the presence of serum protein). Our results show that though two types of polymers are charge-neutral and can both reduce the protein adsorption, there exist some differences between their ability of protein resistance, especially in the case of positively charged nanoparticles. Besides, it is found that the coating polymers may also greatly decrease the cellular uptake efficiency of nanoparticles. Nevertheless and importantly, since the zwitterionic polymers may become positively charged under low pH environments, the nanoparticle can attach onto cell membrane more firmly than that coated with hydrophilic polymers, which can further enhance the active targeting of nanoparticles. Finally, we also provide the design maps for surface decoration to achieve efficient cellular delivery. These results can help better understand how to keep the balance between protein resistance and cell targeting, which may give some useful guidelines on optimal design of future nanomaterials in drug delivery.

Melting is considered to be one of the most fundamental problems in physical science. Generally, dimensionality plays an important role in melting. In three-dimension, it’s well known that a crystal melts directly into a liquid via a first-order transition. In two-dimension (2D), however, the melting process has been widely debated whether it is a first-order transition or a two-step transition with an intermediate hexatic phase. Experimentally 2D melting has been intensively studied in equilibrium systems such as molecular and colloidal crystals, but rarely been explored in non-equilibrium system such as granular materials. In this paper, we experimentally studied the 2D melting in a driven granular model system at single particle level using video recording and particle tracking techniques. Measurements of orientational/translational correlation functions show evidences that the melting is a two-step transition. A novel concept of orientational/translational susceptibilities enable us to clearly resolve the intermediate hexatic phase. Our results are in excellent agreement with the two-step melting scenario predicted by KTHNY theory and demonstrate that the KTHNY melting scenario can be extended to non-equilibrium systems.

Quaternary climatic cycles have influenced marine organisms’ spatial distribution and population dynamics. This study aimed to elucidate the evolutionary influences of contemporary and glacial physical barriers on the population structure, demography and colonization history of the mudskipper (Periophthalmus modestus) based on a mitochondrial gene segment (ND5) from 131 individual fish sampled in the northwestern Pacific Ocean. The current Kuroshio Current and the glacial exposure of the Taiwan Strait appeared to have restricted migration among the South China Sea, coastal East China and Japan. However, genetic homogeneity (Nm>1) also suggested contemporary larval transportation by sea circulation between the East China Sea and the South China Sea or historical dispersal along the glacial exposed shoreline among China, Japan and the Ryukyu Islands. Evolutionary signals of the strengthened East Asian Summer Monsoon in the mid-Pleistocene and regional difference in intertidal primary productions were indicated by a late-Pleistocene population expansion of P. modestus with a higher effective population size in the South China Sea than in the East China Sea. Furthermore, a potential colonization origin from the South China Sea was consistently inferred by different clues, including the populations’ coalescence times, the ancestral haplotype distribution, the number of private haplotypes and species/genetic diversity.

Orientation controllable DNA biosensors hold great application potentials in recognizing small molecules and detecting DNA hybridization. Though electric field is usually used to control the orientation of DNA molecules, it is also of great importance and significance to seek for other triggered methods to control the DNA orientation. Here, we design a new strategy for controlling DNA orientation in biosensors. The main idea is to copolymerize DNA molecules with responsive polymers that can show swelling/deswelling transitions due to the change of external stimuli and then graft the copolymers onto an uncharged substrate. In order to highlight the responsive characteristic, we take thermo-responsive polymers as an example and reveal multi-responsive behavior and the underlying molecular mechanism of the DNA orientation by combining dissipative particle dynamics simulation and molecular theory. Since swelling/deswelling transitions can be also realized by using other stimuli-responsive (like pH and light) polymers, the present strategy is universal, which can enrich the methods of controlling DNA orientation and may assist with the design of the next generation of biosensors.

A putative etiological association exists between noise exposure and Alzheimer’s disease (AD). Amyloid-β (Aβ) pathology is thought to be one of the primary initiating factors in AD. It has been further suggested that subsequent dysregulation of Aβ may play a mechanistic role in the AD-like pathophysiology associated with noise exposure. Here, we used ELISA, immunoblotting, cytokine arrays and RT-PCR, to examine both hippocampal Aβ pathology and neuroinflammation in rats at different time points after noise exposure. We found that chronic noise exposure significantly accelerated the progressive overproduction of Aβ, which persisted for 7 to 14 days after the cessation of exposure. This effect was accompanied by up-regulated expression of amyloid precursor protein (APP) and its cleavage enzymes, β- and γ-secretases. Cytokine analysis revealed that chronic noise exposure increased levels of tumor necrosis factor-α and the receptor for advanced glycation end products, while decreasing the expression of activin A and platelet-derived growth factor- AA. Furthermore, we found persistent elevations of glial fibrillary acidic protein and ionized calcium-binding adapter molecule 1 expression that closely corresponded to the noise-induced increases in Aβ and neuroinflammation. These studies suggest that lifelong environmental noise exposure may have cumulative effects on the onset and development of AD.

Physical penetration of lipid bilayer membranes presents an alternative pathway for cellular delivery of nanoparticles (NPs) besides endocytosis. NPs delivered through this pathway could reach the cytoplasm, thereby opening the possibility of organelle-specific targeting. Herein we perform dissipative particle dynamics simulations to elucidate the transmembrane penetration mechanisms of multiple NPs. Our simulations demonstrate that NPs’ translocation proceeds in a cooperative manner, where the interplay of the quantity and surface chemistry of the NPs regulates the translocation efficiency. For NPs with hydrophilic surfaces, the increase of particle quantity facilitates penetration, while for NPs with partly or totally hydrophobic surfaces, the opposite highly possibly holds. Moreover, a set of interesting cooperative ways, such as aggregation, aggregation-dispersion and aggregation-dispersion-reaggregation of the NPs, are observed during the penetration process. We find that the penetration behaviors of multiple NPs are mostly dominated by the changes of the NP-membrane force components in the membrane plane direction, in addition to that in the penetration direction, suggesting a different interaction mechanism between the multiple NPs and the membrane compared with the one-NP case. These results provide a fundamental understanding in the underlying mechanisms of cooperative penetration of NPs and shed light on the NP-based drug and gene delivery.

High density DNA brush is not only used to model cellular crowding, but also has a wide application in DNA-functionalized materials. Experiments have shown complicated cooperative hybridization/melting phenomena in these systems, raising the question that how molecular crowding influences DNA hybridization. In this work, a theoretical modeling including all possible inter and intramolecular interactions, as well as molecular details for different species, is proposed. We find that molecular crowding can lead to two distinct cooperative behaviours: negatively cooperative hybridization marked by a broader transition width and positively cooperative hybridization with a sharper transition, well reconciling the experimental findings. Moreover, a phase transition as a result of positive cooperativity is also found. Our study provides new insights in crowding and compartmentation in cell and has the potential value in controlling surface morphologies of DNA functionalized nano-particles.

The solution viscosity near an interface, which affects the solution behavior and the molecular dynamics in the solution, differs from the bulk. This paper measured the effective viscosity of a dilute poly (ethylene glycol) (PEG) solution adjacent to a Au electrode using the quartz crystal microbalance with dissipation (QCM-D) technique. We evidenced that the effect of an adsorbed PEG layer can be ignored and calculated the zero shear rate effective viscosity to remove attenuation of high shear frequency oscillations. By increasing the overtone n from 3 to 13, the thickness of the sensed polymer solution decreased from ~70 to 30 nm. The zero shear rate effective viscosity of the polymer solution and longest relaxation time of PEG chains within it decrease with increasing solution thickness. The change trends are independent of the relation between the apparent viscosity and shear frequency and the values of the involved parameter, suggesting that the polymer solution and polymer chains closer to a solid substrate have a greater effective viscosity and slower relaxation mode, respectively. This method can study the effect of an interface presence on behavior and phenomena relating to the effective viscosity of polymer solutions, including the dynamics of discrete polymer chains.

The major challenge in cancer therapy is to efficiently translocate drug molecules into cancer tumors without doing any damage to healthy tissues. Since there exist pH gradients between tumor and normal tissues, pH-sensitive materials may have great potential to overcome such challenge. Here, we report one new type of pH-responsive drug delivery system where pH-sensitive polymers are introduced to control the cellular uptake of nanoparticles under different pH environments through dissipative particle dynamics simulations. Interestingly, the behavior of cellular uptake of nanoparticles here exhibits “smart” pH-responsive properties: for lower and higher pH, the nanoparticles can be taken up by cell membranes, while for pH in middle range, the endocytosis is blocked. Further, it is found that receptor-ligand interactions as well as surface charge property of nanoparticles and membranes can also have important impacts on the endocytosis. The present study may give some significant insights into future stimulus-responsive medical materials design.