Synthesis, Characterization, and Properties of a Novel Hyperbranched Polymers with Polyacrylamide Side Chains.

A novel hyperbranched polymer with polyacrylamide side chains (HAPAM) was synthesized by aqueous solution polymerization using acrylic acid, acrylamide, 2-acrylamido-2-methyl-1-propanesulfonic acid, hydrophobic monomer of dimethyl octadecyl ammonium chloride, and the homemade skeleton monomer of modified-M2.0 as raw materials and (NH4)2S2O8-NaHSO3 as initiator. The molecular structure, functional groups, and surface morphology of HAPAM were characterized by Fourier transform infrared spectroscopy, nuclear magnetic resonance hydrogen spectroscopy, and scanning electron microscopy. It was found that the performance of HAPAM solution was higher than that of ordinary polyacrylamide solution in terms of thickening ability, shearing resistance, thermal endurance, salt-resistance, resistance-coefficient and residual-resistance-coefficient, ability to reduce interfacial tension between polymer solution and crude oil, and oil-displacement-efficiency. In particular, the enhanced oil recovery of the HAPAM solution was 13.03%, and the improvement of shearing resistance and immunity to chromatographic separation were simultaneously achieved by the HAPAM solution. These results indicate that the successful synthesis of the novel HAPAM opens a promising strategy for developing new high-performance oil-displacing polymers.

Structure-Based Ligand Discovery Targeting the Transmembrane Domain of Frizzled Receptor FZD7.

Despite the essential roles of Frizzled receptors (FZDs) in mediating Wnt signaling in embryonic development and tissue homeostasis, ligands targeting FZDs are rare. A few antibodies and peptide modulators have been developed that mainly bind to the family-conserved extracellular cysteine-rich domain of FZDs, while the canonical binding sites in the transmembrane domain (TMD) are far from sufficiently addressed. Based on the recent structures of FZDs, we explored small-molecule ligand discovery by targeting TMD. From the ChemDiv library with ∼1.6 million compounds, we identified compound F7H as an antagonist of FZD7 with an IC50 at 1.25 ± 0.38 µM. Focusing on this hit, the structural dissection study, together with computing studies such as molecular docking, molecular dynamics simulation, and free energy perturbation calculations, defined the binding pocket with key residue recognition. Our results revealed the structural basis of ligand recognition and demonstrated the feasibility of structure-guided ligand discovery for FZD7-TMD.

Development of Yin-Yang ligand for cannabinoid receptors.

Cannabinoid receptors (CBs), including CB1 and CB2, are the key components of a lipid signaling endocannabinoid system (ECS). Development of synthetic cannabinoids has been attractive to modulate ECS functions. CB1 and CB2 are structurally closely related subtypes but with distinct functions. While most efforts focus on the development of selective ligands for single subtype to circumvent the undesired off-target effect, Yin-Yang ligands with opposite pharmacological activities simultaneously on two subtypes, offer unique therapeutic potential. Herein we report the development of a new Yin-Yang ligand which functions as an antagonist for CB1 and concurrently an agonist for CB2. We found that in the pyrazole-cored scaffold, the arm of N1-phenyl group could be a switch, modification of which yielded various ligands with distinct activities. As such, the ortho-morpholine substitution exerted the desired Yin-Yang bifunctionality which, based on the docking study and molecular dynamic simulation, was proposed to be resulted from the hydrogen bonding with S173 and S285 in CB1 and CB2, respectively. Our results demonstrated the feasibility of structure guided ligand evolution for challenging Yin-Yang ligand.

"Forced Transformation" or "Regulation Capture"-Research on the Interactive Mechanism between Environmental Regulation and Green Transformation of Dairy Farming Subject Production.

Under the situation of an increasing resource and environment shortage, the green transformation of dairy farming subject production driven by environmental regulation is the concentrated embodiment of a "promising government" to solve the problem of breeding environmental pollution. Due to the shortcomings of environmental regulation itself and the undefined connotation of the green transformation of dairy farming subject production, the interactive relationship between the two remains unclear at present. Based on defining the concept of green transformation of dairy farming subject production, this paper aims to analyze the interactive mechanism between the environmental regulation and green transformation of dairy farming main production, build a dynamic game model between the environmental regulators and dairy farming subject, and introduce the constraints and benefits of a reputation mechanism on the behavior in the model to explore whether environmental regulation can drive the green transformation of dairy farming subject production. The results showed that the green transformation of dairy farming subject production followed the "subject substitution view" and emphasized "source reduction, process control and terminal treatment". Strictly designed environmental regulations could effectively drive the green transformation of dairy farming subject production, but it was inevitable that the environmental regulators were vulnerable to the rent-seeking behavior of dairy farming subjects, which was "regulation capture". The introduction of the reputation mechanism has greatly improved the rent-seeking behavior of dairy farming subjects and the probability that environmental regulators have "regulation capture", indirectly forcing dairy farming subjects to participate in the green transformation of production. The greater the punishment for dairy farming subjects who do not participate in the green transformation of production was, the more they can be forced to participate in the green transformation of production. At the same time, it also reduces the risk of damage to the credibility of the government. Based on the studies above, this paper also further discussed the shortcomings of environmental regulation itself, including the "re exit and light implementation" of the environmental regulation policy, "decentralization and light inspection" of the environmental regulation subject, "result and light process" of the environmental regulation mode, and "formal regulation and light informal regulation" of the environmental regulation form, which provides a scientific reference for the formulation of the environmental regulation policy of livestock and poultry breeding in the future. Compared with previous studies, this paper is innovative in two aspects: first, it defines the conceptual connotation of a green transformation of dairy farming subject production, and second, it systematically discusses the interaction mechanism between the environmental regulation and green transformation of dairy farming subject production. This paper provides a scientific reference for the development of future environmental regulation policies for livestock and poultry farming.

Can Information Intervention Enhance Consumers' Purchase Intentions of Organic Agricultural Products? A Choice Experiment Based on Organic Milk.

Despite the current rapid growth of organic agriculture, the problem of low demand for organic agricultural products persists in China, and the consumption space warrants improvement. Exploring consumers' preferences for organic agricultural products and increasing their purchase intentions are of utmost significance to promote organic agricultural production. Thus, this study takes organic milk, which accounts for 58% of China's organic processed agricultural products in sales, as the research object, and uses a choice experiment to investigate the influence of consumers on the purchase intention of organic milk under the intervention of environmental protection information and quality and safety information. The main research results revealed that both environmental protection information and quality and safety information have significantly increased consumers' willingness to purchase and that quality and safety information has increased more than environmental protection information.

Structure-Activity Relationship Studies of Hydantoin-Cored Ligands for Smoothened Receptor.

An underside binding site was recently identified in the transmembrane domain of smoothened receptor (SMO). Herein, we report efforts in the exploration of new insights into the interactions between the ligand and SMO. The hydantoin core in the middle of the parent compound was found to be highly conservative in chirality, ring size, and substituents. On each benzene at two ends, a plethora of variations, particularly halogen substitutions, were introduced and investigated. Analysis of the structure-activity relationship revealed miscellaneous halogen effects. The ligands with double halogen substituents exhibit remarkably enhanced potency, providing promising candidates that potentially overcome the common drug resistance and useful heavy-atom labeled chemical tools for co-crystallization studies of SMO.

Preparation and use of nanogels as carriers of drugs.

Nanogels have high tunability and stability while being able to sense and respond to external stimuli by showing changes in the gel volume, water content, colloidal stability, mechanical strength, and other physical/chemical properties. In this article, advances in the preparation of nanogels will be reviewed. The application potential of nanogels in drug delivery will also be highlighted. It is the objective of this article to present a snapshot of the recent knowledge of nanogel preparation and application for future research in drug delivery.

Long Noncoding RNA Expression Profiles of Periodontal Ligament Stem Cells from the Periodontitis Microenvironment in Response to Static Mechanical Strain.

During the period of orthodontic tooth movement, periodontal ligament stem cells (PDLSCs) play an important role in transducing mechanical stimulation and tissue remodeling. However, our previous studies verified that the periodontitis microenvironment causes damage to the biological functions of PDLSCs and abnormal mechanical sensitivity. Long noncoding RNAs (lncRNAs) participate in the inflammatory pathogenesis and development of many diseases. Whether lncRNAs are abnormally expressed in PDLSCs obtained from periodontal tissues of periodontitis patients (PPDLSCs) and whether putative lncRNAs participate in the mechanotransductive process in PDLSCs remain poorly understood. First, we subjected PDLSCs obtained from healthy periodontal tissues (HPDLSCs) and PPDLSCs to static mechanical strain (SMS) with 12% elongation at 0.1 Hz frequency using an FX-4000T system and screened overall lncRNA profiles in both cell types by microarray. Among lncRNAs with a fold change (FC) > 20.0, 27 lncRNAs were upregulated in strained HPDLSCs, and 16 lncRNAs (9 upregulated and 7 downregulated) were detected in strained PPDLSCs. For mRNAs with FC > 20.0, we detected 25 upregulated mRNAs and one downregulated mRNA in strained HPDLSCs and 7 upregulated and 5 downregulated mRNAs in strained PPDLSCs. Further enrichment analysis showed that, unlike HPDLSCs with annotations principally involving transduction-associated signaling pathways, dysregulated mRNAs in PPDLSCs are mainly responsible for pathological conditions. Moreover, coexpressed lncRNA-mRNA networks confirmed the pathological state and exacerbated inflammatory conditions in strained PPDLSCs. Taken together, when compared with strained HPDLSCs, various lncRNAs and mRNAs were dysregulated in PPDLSCs under mechanical forces, implicating the response of lncRNAs in PPDLSCs to mechanical stress. Moreover, we provide potential lncRNA targets, which may contribute to future intervention strategies for orthodontic treatment in periodontitis patients.

Boosting Li3V2(PO4)3 cathode stability using a concentrated aqueous electrolyte for high-voltage zinc batteries.

We demonstrate that the capacity decay and voltage drop issues of the Li3V2(PO4)3 cathode are significantly addressed by using a concentrated aqueous electrolyte based on Zn and Li salts. The resultant aqueous Zn//Li3V2(PO4)3 battery achieves a high output voltage of 1.75 V and a long lifespan with 82.3% capacity retention over 2000 cycles. Joint structural and spectroscopic characterizations reveal that this battery operates through Li+ (de)intercalation into the cathode along with Zn2+ plating/stripping at the anode.

Analysis of the postharvest storage characteristics of the new red-fleshed apple cultivar 'meihong'.

This study examined the effects of postharvest storage conditions on the fruit quality of a new red-fleshed apple cultivar ('Meihong'). Mature 'Meihong' and 'Golden delicious' apples were exposed to room temperature, low temperature, and low temperature and 1-MCP, after which several fruit characteristics were evaluated (i.e., firmness, ethylene release rate, relative content of aroma components, phenolic compounds and antioxidant capacity, fruit softening-related enzyme activities, and related gene expression). Both 'Meihong' and 'Golden delicious' were ACS1-1/-2 heterozygotes, but the ethylene release rate in 'Meihong' fruits was lower than that in 'Golden delicious' fruits during storage. Therefore, 'Meihong' fruits are more conducive to storage. The low temperature storage with and without 1-MCP delayed fruit softening, decreased the ethylene release rate and ester aroma component content, and maintained total flavonoid and anthocyanin contents. Therefore, storage at low temperatures with 1-MCP or other preservatives may be useful for maintaining the 'Meihong' fruit quality.

A coarse-to-fine registration method for three-dimensional MR images.

Three-dimensional (3D) multimodal magnetic resonance (MR) image registration aims to align similar things in different MR images spatially. Such a technology is useful in auxiliary disease diagnosis and surgical treatment. However, inconsistent intensity correspondence and large initial displacement contribute to the difficulty in registering multimodal MR volumes. A coarse-to-fine method is proposed in this study for pairwise 3D MR image rigid registration. Firstly, the proposed method extracts image feature points to form unregistered point sets and performs coarse registration based on point set registration to reduce the initial displacements of offset images effectively. Then, this method calculates a grey histogram based on voxels in the adaptive region of interest and further improves registration accuracy by maximizing mutual information of coarse-registered images. Some representative registration methods are compared on the basis of three MR image datasets to evaluate the performance of the proposed method. Experimental results show that the proposed method improved more in registration success rate and accuracy compared with conventional registration methods, especially when initial displacements are large.

Involvement of astrocytes activation in orofacial hyperalgesia induced by experimental tooth movement.

OBJECTIVE: The study aimed to investigate the involvement of astrocytes in the medullary dorsal horn (MDH) in the orofacial hyperalgesia induced by experimental tooth movement (ETM) and related mechanism. MATERIALS AND METHODS: Experimental tooth movement was produced with nickel-titanium alloy closed-coil spring fixed between the left maxillary first molar and the left upper incisor. Fluorocitrate was administrated through medullary subarachnoid at 3 days after ETM. Pressure pain threshold (PPT) in masseter cutaneous area was measured. The expression of glial fibrillary acidic protein (GFAP) and c-Fos in MDH was measured using immunofluoroscence staining. The expression of interleukin-1ß (IL-1ß) and phosphorylated N-methyl-D-aspartic acid (NMDA) receptor subunit NR1 (p-NR1) was measured with Western blotting. RESULTS: Experimental tooth movement-induced orofacial hyperalgesia from 1 to 9 days as the PPT was significantly reduced (P < .05). Immunofluoroscence staining showed that the expression of c-Fos in MDH was dramatically upregulated at 1 day and 3 days after ETM, while GFAP expression with both immunofluoroscence staining and Western blotting was significantly enhanced at 3 days and 7 days after ETM. Western blotting analysis indicated that the expression of IL-1ß and p-NR1 in MDH was significantly enhanced at 3 days after ETM. Furthermore, we found that fluorocitrate administration at 3 days after ETM could markedly suppress the expression of c-Fos, GFAP, IL-1ß and p-NR1 and attenuate the reduction of PPT induced by ETM. CONCLUSION: Astrocyte activation in MDH is involved in the mechanical hyperalgesia, and the subsequent upregulated IL-1ß and overexpression of p-NR1 may participate in this process.

Emerging impact of the long noncoding RNA MIR22HG on proliferation and apoptosis in multiple human cancers.

An increasing number of studies have shown that long noncoding RNAs (lncRNAs) play important roles in diverse cellular processes, including proliferation, apoptosis, migration, invasion, chromatin remodeling, metabolism and immune escape. Clinically, the expression of MIR22HG is increased in many human tumors (colorectal cancer, gastric cancer, hepatocellular carcinoma, lung cancer, and thyroid carcinoma), while in others (esophageal adenocarcinoma and glioblastoma), it is significantly decreased. Moreover, MIR22HG has been reported to function as a competitive endogenous RNA (ceRNA), be involved in signaling pathways, interact with proteins and interplay with miRNAs as a host gene to participate in tumorigenesis and tumor progression. In this review, we describe the biological functions of MIR22HG, reveal its underlying mechanisms for cancer regulation, and highlight the potential role of MIR22HG as a novel cancer prognostic biomarker and therapeutic target that can increase the efficacy of immunotherapy and targeted therapy for cancer treatment.

A four-year prospective study of self-assembling nano-modified dental implants in patients with type 2 diabetes mellitus.

BACKGROUND/PURPOSE: Dental implantation has become an efficient and important method of replacing lost teeth. However, the success rate of dental-implant treatment in diabetics is higher than patients without diabetes. The aim of this study was to prospectively evaluate long-term marginal bone loss (MBL) and the stability of a self-assembling nano-modified implant in patients with type 2 diabetes mellitus compared with a conventional implant. MATERIALS AND METHODS: Twenty-five patients with type 2 diabetes were recruited for this study. Through a random selection process, one site in each patient received a conventional implant and the other site received a nano-modified implant. The implant stability quotient was measured using resonance frequency analysis (RFA), and MBL was measured using panoramic radiography from uncovering to four-year follow-up. RESULTS: No significant difference in implant stability quotient was found between the two groups (P > 0.05), except for the time at implant insertion (P < 0.05). MBL in the nano-modified implant group exhibited a decreasing change compared with the conventional implant group, between the uncovering and the loading stage (P < 0.05), while there was no significant difference in other stages (P > 0.05). CONCLUSION: There was potentially increased implant stability and diminished MBL around the self-assembling nano-modified implant in the uncovering-loading stage of early osseointegration in patients with type 2 diabetes.

The Influence Mechanism of Reputation Information on the Formation of Safety Trust in Chinese Infant Milk Powder.

Infant milk powder has always been one of the food categories most sensitive to safety reputation information. The safety reputation of Chinese infant milk powder has been seriously damaged due to the occurrence of safety accidents and the resulting consumers' still-unrestored confidence is an important factor which restricts the dairy industry revitalization. Therefore, this paper analyzes the impact of reputation information on the formation of safety trust in Chinese infant milk powder, taking reputation information transmission as the starting point and consumer psychological perception as the researching perspective. A questionnaire survey was conducted and 685 valid questionnaires were collected. The structural equation model is adopted to verify the theoretical model and corresponding research hypothesis that reputation information affects the safety trust of Chinese infant milk powder. The reputation information transmitted between relatives and friends has a stronger effect on the formation of safety trust in Chinese infant milk powder than the media. The degree of media pursuit of "news effect" and negative word-of-mouth have a significant negative impact on the formation of safety trust in Chinese infant milk powder, while reputation quality, positive word-of-mouth and relationship strength have a significant positive impact on that. The quality of word-of-mouth perceived by consumers from highly involvement group, rational group, urban group and high-educated group has a stronger influence on the formation of safety trust. The degree of media pursuit of "news effect", positive word-of-mouth, negative word-of-mouth and relationship strength perceived by consumers from low involvement group, emotional group, rural group and low-educated group have stronger influence on the formation of safety trust.

Periostin Mediates Oestrogen-Induced Osteogenic Differentiation of Bone Marrow Stromal Cells in Ovariectomised Rats.

Osteoporosis is a metabolic disease that results in the progressive loss of bone mass, which, in postmenopausal women, is related to oestrogen deficiency. Periostin (POSTN) plays a key role in the early stages of bone formation. However, whether POSTN participates in oestradiol regulation of osteogenic differentiation of bone marrow stromal cells (BMSCs) from ovariectomised (OVX) rats remains unclear. In vivo, using microcomputed tomography (micro-CT), immunohistochemistry, and dynamic analysis of femurs, we found that 17ß-E2 promotes bone formation and POSTN expression at the endosteal surface. In vitro, 17ß-E2 upregulated POSTN expression in OVX-BMSCs. POSTN overexpression activated the Wnt/ß-catenin signalling pathway and enhanced osteogenic differentiation of OVX-BMSCs. Furthermore, knockdown of Postn blocks the involvement of 17ß-E2 in the osteogenic differentiation of OVX-BMSCs. Collectively, our study indicated the role of POSTN in the osteogenesis and stemness of OVX-BMSCs and proves that 17ß-E2 reduces osteoporosis and promotes osteogenesis through the POSTN-Wnt/ß-catenin pathway. POSTN could, therefore, be a novel target gene for anti-osteoporosis therapies.

miR-138 Increases Depressive-Like Behaviors by Targeting SIRT1 in Hippocampus.

BACKGROUND: Major depressive disorder (MDD) is a serious and common mood disorder with unknown etiology. Emerging evidence has demonstrated the critical roles of SIRT1 and microRNAs (miRNAs) in the progression of MDD. However, the underlying molecular mechanisms remain to be fully understood. METHODS: In the present study, the expression level of miR-138 and SIRT1 were analyzed by RT-PCR or Western blotting in a chronic unpredictable mild stress (CUMS) model. The depressive-like behaviors were analyzed by forced swimming test (FST) and sucrose preference test (SPT) in mice injected with miR-138 and SIRT1 overexpression lentivirus. The luciferase reporter assay was used to assess the direct regulation of miR-138 on SIRT1 expression. RESULTS: The upregulation of miR-138 was found in the hippocampus of the CUMS mice and correlated with decreased SIRT1 expression. C57BL/6J mice treated with SIRT1- and miR-138-expressing (miR-138) lentivirus showed increased depressive-like behaviors. In contrast, SIRT1 or si-miR-138 lentivirus treated C57BL/6J mice showed decreased depressive-like behaviors. Moreover, the Sirt1/PGC-1α/FNDC5/BDNF pathway was downregulated following miR-138 overexpression and increased upon miR-138 knockdown in hippocampus in CUMS mice and cultured primary neuronal cells. Mechanistically, luciferase reporter assay demonstrated that SIRT1 gene was a downstream transcriptional target of miR-138. CONCLUSION: Our data demonstrated the regulation role of miR-138 on SIRT1 gene expression, miR-138 increased depressive-like behaviors by regulating SIRT1 expression in hippocampus.

XPro1595 ameliorates bone cancer pain in rats via inhibiting p38-mediated glial cell activation and neuroinflammation in the spinal dorsal horn.

Bone cancer pain (BCP) profoundly compromises the life quality of patients with bone metastases. Severe side effects of the drugs which were widely used and effective in the various stages of this condition results in a huge challenge for BCP treatment. Here, we investigated the antinociceptive effects of XPro1595, a soluble tumor necrosis factor (solTNF) inhibitor with considerable immunoregulatory efficacy, on BCP, as well as the underlying mechanisms within the spinal dorsal horn (SDH). Walker 256 mammary gland carcinoma cells were intratibially inoculated to induce BCP. Intrathecal administration of XPro1595 alleviated bone cancer-induced chronic pain in a dose-dependent manner, with an ED50 of 9.69 mg/kg. Bone cancer resulted in the activation of astrocytes and microglia in the SDH through the upregulation of mitogen-activated protein kinase (MAPK) pathways, which was accompanied by an over-expression of pro-inflammatory cytokines, including TNF-α, IL-1ß, and IL-6. XPro1595suppressed bone cancer-evoked glial activation and the consequent neuroinflammation. These inhibitory effects of XPro1595 were, at least partially, mediated by a reduction in the phosphorylation of p38 MAPK in spinal glial cells. In conclusion, inhibition of spinal glia by XPro1595 may have utility in the treatment of bone cancer-induced neuroinflammation, and our results further implicate XPro1595 as a new promising therapeutic agent for BCP.

Typical pharmaceutical molecule removal behavior from water by positively and negatively charged composite hollow fiber nanofiltration membranes.

The rejection behaviors of two different charged composite hollow fiber nanofiltration (NF) membranes for six pharmaceutical molecules, primidone, carbamazepine, sulfamethoxazole, atenolol, sulfadimidine and norfloxacin, were characterized in this study. The saturation adsorption behaviors of the different pharmaceutical molecules on each membrane surface were studied and found to be related to the molecular weight, charge and hydrophilicity of the pharmaceutical molecules. After the pharmaceutical molecules reached adsorption equilibrium, the rejection rates of different NF membranes were characterized. The rejection rates of primidone, carbamazepine, sulfamethoxazole, atenolol, sulfadimidine and norfloxacin by the PEI-NF membrane were 85.6%, 91.8%, 79.9%, 98.1%, 93.3%, and 97.1%, respectively. Meanwhile, the rejection rates of the pharmaceutical molecules by the PIP-NF membrane were 82.2%, 85.4%, 91.5%, 79.1%, 87% and 93.3%, respectively. The influence of feed concentration, operation pressure, temperature, pH and ionic strength on the rejection behaviors of the different charged NF membranes were also studied.

Employing shells to eliminate concentration quenching in photonic upconversion nanostructure.

It is generally accepted that a lanthanide ions based upconversion material follows an activator low doping strategy (normally <3 mol%), because of the restriction of the harmful concentration quenching effect. Here, we demonstrate that this limitation can be broken in nanostructures. Simply by using an inert shell coating strategy, the concentration quenching effect for the activator (Er3+) could be eliminated and highly efficient upconversion luminescence realized in the activator fully doped nanostructure, e.g. NaErF4@NaYF4. More importantly, this novel nanostructure achieves some long-cherished desires, such as multiple-band co-excitation (∼800 nm, ∼980 nm and ∼1530 nm) and monochromic red emission. Proof-of-concept experiments are presented of the potential benefit of this structure in solar cells and anti-counterfeiting. This nanostructure offers new possibilities in realizing high upconversion emission and novel functionalities of lanthanide based nanomaterials.