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Abstract Objectives To investigate the effect of neutral 10-methacryloyloxydecyl dihydrogen phosphate salt (MDP-Na) on the dentin bond strength and remineralization potential of etch-&-rinse adhesive. Methods Two experimental etch-&-rinse adhesives were formulated by incorporating 0 wt% (E0) or 20 wt% (E20) neutral MDP-Na into a basic primer. A commercial adhesive, Adper Single Bond 2 (SB, 3 M ESPE), served as the control. Sixty prepared teeth were randomly allocated into three groups (n = 20) and bonded using either one of the experimental adhesives or SB. Following 24 h of water storage, the bonded specimens were sectioned into resin-dentin sticks, with four resin-dentin sticks obtained from each tooth for microtensile bond strength (MTBS) test. Half of the sticks from each group were immediately subjected to tensile loading using a microtensile tester at a crosshead speed of 1 mm/min, while the other half underwent tensile loading after 6-month incubation in artificial saliva (AS). The degree of conversion (DC) of both the control and experimental adhesives (n = 6 in each group) and the adsorption properties of MDP-Na on the dentin organic matrix (n = 5 in each group) were determined using Fourier-transform infrared spectrometry. Furthermore, the effectiveness of neutral MDP-Na in promoting the mineralization of two-dimensional collagen fibrils and the adhesive-dentin interface was explored using transmission electron microscopy and selected-area electron diffraction. Two- and one-way ANOVA was employed to assess the impact of adhesive type and water storage on dentin bond strength and the DC (α = 0.05). Results The addition of MDP-Na into the primer increased both the short- and long-term MTBS of the experimental adhesives (p = 0.00). No difference was noted in the DC between the control, E0 and E20 groups (p = 0.366). The MDP-Na remained absorbed on the demineralized dentin even after thorough rinsing. The intra- and extra-fibrillar mineralization of the two-dimensional collagen fibril and dentin bond hybrid layer was confirmed by transmission electron microscopy and selected-area electron diffraction when the primer was added with MDP-Na. Conclusions The use of neutral MDP-Na results in high-quality hybrid layer that increase the dentin bond strength of etch-&-rinse adhesive and provides the adhesive with remineralizing capability. This approach may represent a suitable bonding strategy for improving the dentin bond strength and durability of etch-&-rinse adhesive.

Abstract Background The treatment strategy for patients with severe tooth wear associated with Class II Division 2 malocclusion remains a major challenge for dental practitioners. Objectives To systematically review and summarize the literature on treatment strategies, restoration procedures and clinical outcomes for Class II Division 2 malocclusion patients with severe tooth wear. Methods A literature review was conducted using Pubmed, Embase, the Cochrane Library, and Web of Science to identify eligible articles. Publications until October 16th, 2023 were searched independently and cross-checked by two researchers. Results Of 1513 articles screened, 10 reports detailed treatment processes, including six males and four females aged 34–68 years old. Four articles recorded pre-treatment freeway space (FWS) values ranging from 5 to 9 mm. All ten cases had significant occlusal vertical dimension (OVD) loss and the increase in OVD after treatment ranged from 1 to 7 mm. Pre-prosthetic orthodontic treatment was performed in two cases, in one of which only the maxillary region was orthodontically treated. The most common restorations provided were full coverage restorations. In most cases, temporary restorations were applied before the permanent restorations for eight weeks to six months. Four different sequences of final restoration were proposed. Follow-up ranged from four months to six years and included seven patients, one of them showed symptoms of temporomandibular disorder (TMD). Conclusions A multidisciplinary team (MDT) approach to treatment is recommended. Consideration of pre-prosthetic orthodontic treatment is essential. Commonly used cephalometric measurements for anterior teeth include the interincisal angle and collum angle. The increases in OVD ranging from 1 to 7 mm can be effectively accommodated. Temporary restorations are recommended to accommodate the OVD, and the transition periods of 8 weeks to 6 months help the patients adapted well. Four different sequences for final rehabilitation have demonstrated positive clinical outcomes. Full crown restorations have emerged as the preferred choice for the ultimate restoration of these patients.

Abstract Background Anthocyanins are water-soluble flavonoids in plants, which give plants bright colors and are widely used as food coloring agents, nutrients, and cosmetic additives. There are several limitations for traditional techniques of collecting anthocyanins from plant tissues, including species, origin, season, and technology. The benefits of using engineering microbial production of natural products include ease of use, controllability, and high efficiency. Results In this study, ten genes encoding enzymes involved in the anthocyanin biosynthetic pathway were successfully cloned from anthocyanin-rich plant materials blueberry fruit and purple round eggplant rind. The Yeast Fab Assembly technology was utilized to construct the transcriptional units of these genes under different promoters. The transcriptional units of PAL and C4H, 4CL and CHS were fused and inserted into Chr. XVI and IV of yeast strain JDY52 respectively using homologous recombination to gain Strain A. The fragments containing the transcriptional units of CHI and F3H, F3’H and DFR were inserted into Chr. III and XVI to gain Strain B1. Strain B2 has the transcriptional units of ANS and 3GT in Chr. IV. Several anthocyanidins, including cyanidin, peonidin, pelargonidin, petunidin, and malvidin, were detected by LC-MS/MS following the predicted outcomes of the de novo biosynthesis of anthocyanins in S. cerevisiae using a multi-strain co-culture technique. Conclusions We propose a novel concept for advancing the heterologous de novo anthocyanin biosynthetic pathway, as well as fundamental information and a theoretical framework for the ensuing optimization of the microbial synthesis of anthocyanins.

Background: Interdigital tinea pedis is the most common type of foot infection, which is often treated by topical or systemic antifungals. Due to the increase in antifungal resistance, antifungal socks are becoming potential alternatives for the daily management of tinea pedis. Methods: In this study, antifungal fibres were adopted to produce interdigital hygiene socks to split the third and fourth toe seams of the feet. In vitro antifungal activity was first examined to verify the effectiveness of the socks. Preventive efficacy against tinea pedis was then evaluated among healthy participants, followed by therapeutic effect detection in patients diagnosed with tinea pedis by analysing the improvement in total symptom scores (TTS). Results: The interdigital-type hygiene socks exhibited apparent antifungal activities in vitro. An in vivo study demonstrated significant preventive effects against tinea pedis for interdigital socks compared to plain socks (P = 0.011) and a lower TTS than noninterdigital (P = 0.04) or plain socks (P

Abstract The constant emergence of SARS-CoV-2 variants continues to impair the efficacy of existing neutralizing antibodies, especially XBB.1.5 and EG.5, which showed exceptional immune evasion properties. Here, we identify a highly conserved neutralizing epitope targeted by a broad-spectrum neutralizing antibody BA7535, which demonstrates high neutralization potency against not only previous variants, such as Alpha, Beta, Gamma, Delta and Omicron BA.1-BA.5, but also more recently emerged Omicron subvariants, including BF.7, CH.1.1, XBB.1, XBB.1.5, XBB.1.9.1, EG.5. Structural analysis of the Omicron Spike trimer with BA7535-Fab using cryo-EM indicates that BA7535 recognizes a highly conserved cryptic receptor-binding domain (RBD) epitope, avoiding most of the mutational hot spots in RBD. Furthermore, structural simulation based on the interaction of BA7535-Fab/RBD complexes dissects the broadly neutralizing effect of BA7535 against latest variants. Therapeutic and prophylactic treatment with BA7535 alone or in combination with BA7208 protected female mice from the circulating Omicron BA.5 and XBB.1 variant infection, suggesting the highly conserved neutralizing epitope serves as a potential target for developing highly potent therapeutic antibodies and vaccines.

Abstract The prism-interprisms level of the enamel hierarchical microstructure is the largest degree of structural variation and most sophisticated structural adaptation. We studied the effect of the prism-interprisms three-dimension spatial microstructure on the enamel bond strength. We prepared 11 groups of enamel segments: longitudinally sectioned segments with or without a 45-degree bevel (group = 2), horizontally sectioned segments with or without a 45-degree bevel of three regions (the incisal, middle, and cervical) (group = 6), and tangential (labial) sectioned segments of three regions (the incisal, middle, and cervical) (group = 3). The finished surface of each segment was observed by scanning electric microscopy (SEM) before treatment with four self-etch adhesive systems and applied with four corresponding composite resins. Resin-bonded enamel samples were prepared in beams for microtensile bond strength (MTBS) tests. The results were analyzed with a three-way ANOVA followed by Tukey’s post-hoc HSD multiple comparisons procedure. SEM observations revealed complex arrangements of prisms and interprisms. MTBS measurement showed that the longitudinally sectioned group had the lowest value, without significant differences between the groups with or without 45-degree bevel. Combining SEM observations and MTBS measurements, the prism-interprisms microstructure varied with the incisor regions, and different prism-interprisms microstructures allowed diverse sectioned surfaces, which could affect the enamel bonding.

Abstract Microplastics (MPs) produced by the decomposition of plastics exist persistently, interfering with soil fertility and plant nutrition. Both arbuscular mycorrhizal (AM) fungi and earthworms are beneficial in terrestrial ecosystems, but their interactions under MPs contamination are unclear so far. Here, the influences of inoculating earthworms (Eisenia fetida) on indigenous AM fungi and pepper (Capsicum annuum L.) growth were investigated in a vegetable soil treated with 0.1% low-density polyethylene (LDPE), while the specific interactions of earthworm and AM fungus (Funneliformis caledonium) under LDPE contamination were further resolved in another experiment using sterilized soil. Inoculation of earthworms shifted soil AM fungal community structure, replacing the predominant genus Glomus by Paraglomus, and increased the abundance, diversity (i.e., Shannon) index, and root colonization rate of AM fungi by 108, 34.6 and 45.0%, respectively. Earthworms also significantly decreased soil pH, and significantly increased soil alkaline phosphatase (ALP) activity, shoot biomass and fruit yield of pepper by 394, 82.8 and 188%, respectively. In the sterilized soil, both E. fetida and F. caledonium improved pepper growth, while the latter noticeably increased phosphorus (P) translocation efficiency from root to shoot, and the combination induced the highest soil ALP activity and pepper fruit yield. Furthermore, the significantly interactive effects between earthworm and AM fungus were observed in soil pH and available P concentration, as well as in shoot P concentration and fruit yield of pepper. This study revealed the interaction between earthworms and AM fungi under MPs contamination conditions for the first time, indicating that earthworms could facilitate vegetable growth via enhancing the propagation and P-promoting function of AM fungi in LDPE-contaminated soils. Graphical Abstract

Abstract Background Although human-induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) are a promising cell resource for cardiovascular research, these cells exhibit an immature phenotype that hampers their potential applications. The inwardly rectifying potassium channel Kir2.1, encoded by the KCNJ2 gene, has been thought as an important target for promoting electrical maturation of iPSC-CMs. However, a comprehensive characterization of morphological and functional changes in iPSC-CMs overexpressing KCNJ2 (KCNJ2 OE) is still lacking. Methods iPSC-CMs were generated using a 2D in vitro monolayer differentiation protocol. Human KCNJ2 construct with green fluorescent protein (GFP) tag was created and overexpressed in iPSC-CMs via lentiviral transduction. The mixture of iPSC-CMs and mesenchymal cells was cocultured with decellularized natural heart matrix for generation of 3D human engineered heart tissues (EHTs). Results We showed that mRNA expression level of KCNJ2 in iPSC-CMs was dramatically lower than that in human left ventricular tissues. KCNJ2 OE iPSC-CMs yielded significantly increased protein expression of Kir2.1 and current density of Kir2.1-encoded IK1. The larger IK1 linked to a quiescent phenotype that required pacing to elicit action potentials in KCNJ2 OE iPSC-CMs, which can be reversed by IK1 blocker BaCl2. KCNJ2 OE also led to significantly hyperpolarized maximal diastolic potential (MDP), shortened action potential duration (APD) and increased maximal upstroke velocity. The enhanced electrophysiological maturation in KCNJ2 OE iPSC-CMs was accompanied by improvements in Ca2+ signaling, mitochondrial energy metabolism and transcriptomic profile. Notably, KCNJ2 OE iPSC-CMs exhibited enlarged cell size and more elongated and stretched shape, indicating a morphological phenotype toward structural maturation. Drug testing using hERG blocker E-4031 revealed that a more stable MDP in KCNJ2 OE iPSC-CMs allowed for obtaining significant drug response of APD prolongation in a concentration-dependent manner. Moreover, KCNJ2 OE iPSC-CMs formed more mature human EHTs with better tissue structure and cell junction. Conclusions Overexpression of KCNJ2 can robustly enhance maturation of iPSC-CMs in electrophysiology, Ca2+ signaling, metabolism, transcriptomic profile, cardiomyocyte structure and tissue engineering, thus providing more accurate cellular model for elucidating cellular and molecular mechanisms of cardiovascular diseases, screening drug-induced cardiotoxicity, and developing personalized and precision cardiovascular medicine.

Wound infection is one of the most important factors affecting wound healing, so its effective control is critical to promote the process of wound healing. However, with the increasing prevalence of multi-drug-resistant (MDR) bacterial strains, the prevention and treatment of wound infections are now more challenging, imposing heavy medical and financial burdens on patients. Furthermore, the diminishing effectiveness of conventional antimicrobials and the declining research on new antibiotics necessitate the urgent exploration of alternative treatments for wound infections. Recently, phage therapy has been revitalized as a promising strategy to address the challenges posed by bacterial infections in the era of antibiotic resistance. The use of phage therapy in treating infectious diseases has demonstrated positive results. This review provides an overview of the mechanisms, characteristics, and delivery methods of phage therapy for combating pathogenic bacteria. Then, we focus on the clinical application of various phage therapies in managing refractory wound infections, such as diabetic foot infections, as well as traumatic, surgical, and burn wound infections. Additionally, an analysis of the potential obstacles and challenges of phage therapy in clinical practice is presented, along with corresponding strategies for addressing these issues. This review serves to enhance our understanding of phage therapy and provides innovative avenues for addressing refractory infections in wound healing.

IntroductionMacrophages or T-lymphocytes triggered inflammation and, consequently, activated glial cells may contribute to neuroinflammation and neurotransmitter dysfunction in schizophrenia (SZ), while omega(n)-3 polyunsaturated fatty acids (PUFAs) can attenuate some SZ symptoms through anti-inflammatory effects. However, the correlations between macrophage/T-lymphocyte-produced cytokines and glia phenotypes, between inflammatory status and PUFAs composition, between cytokines and neurotransmitter function, and between n-3 PUFAs and neurotransmitter abnormality in SZ are unclear.MethodsChanges in T-helper (h) patterns, peripheral macrophage/glial markers, PUFAs profile, membrane fluidity, and neurotransmitter functions were evaluated in SZ patients (n = 50) and healthy controls (n = 30) using ELISA, gas chromatography, fluorescence anisotropy techniques, and HPLC, respectively.ResultsCompared to the control, blood lymphocyte proliferation, the concentration of macrophage/microglia phenotype M1 markers, including cytokines IL-1β, TNF-α (Th1) and IL-6 (Th2), and astrocyte phenotype A1 marker S100β was significantly increased, while IL-17 and n-3 PUFAs contents, n-3/n-6 ratio, and membrane fluidity (FLU) were significantly decreased in SZ. Moreover, increased DA and HVA, decreased 5-HT and NE, and their metabolites appeared in SZ. Moreover, negative correlations between IL-6 and A2 marker Brain-Derived Neurotrophic Factor (BDNF) or n-3 PUFAs EPA and between IL-1β and FLU or 5HIAA, while positive correlations between EPA and 5-HIAA and between FLU and DHA were found in SZ.DiscussionThese findings showed (1) no clear Th pattern, but pro-inflammatory-dominant immunity occurred; (2) the pro-inflammatory pattern may result in the activated microglia M1 and astrocyte A1 phenotype; and (3) increased pro-inflammatory cytokines were related to decreased n-3 PUFA and decreased membrane fluidity and dysfunctional neurotransmitter systems in SZ.

Herba Gynostemma (Jiaogulan) is an herbaceous plant of the genus Gynostemma in the family Cucurbitaceae. Gynostemma longipes has lipid-lowering activity, thus, it is used as a medicinal material. However, its medicinal using parts have been recorded as whole plants or aerial parts in different provincial quality standards; therefore, it is necessary to conduct a comprehensive compositional analysis of the different parts of G. longipes (rhizomes, stems, and leaves) used in traditional medicine. In this study, offline two-dimensional liquid chromatography-ion mobility-quadrupole time-of-flight mass spectrometry (2D-LC/IM-QTOF-MS) was used to analyze the different parts of G. longipes obtained from Shaanxi province, China. By combining the retention times, mass fragments, collision cross-section values, reference standards, and information concerning literature compounds, 396 components were identified from the three parts of the plant, including 94 groups of isomers, and 217 components were identified or tentatively identified as new compounds. In the rhizomes, leaves, and stems, 240, 220, and 168 compounds, respectively, were identified. Differential analysis of the compounds in the rhizomes and aerial parts was also carried out, and 36 differential components were identified, of which 32 had higher contents in the rhizomes. Therefore, these findings indicate that the number of chemical components and the content of major differential components are higher in the rhizomes than the leaves and stems of G. longipes from the Maobaling Planting Base in Pingli county, Shaanxi province. Thus, the rhizomes of G. longipes are also an important part for medicinal use. These results will contribute to the establishment of quality control methods for G. longipes.

Abstract Background The treatment and management of patients suffering from hypophosphatemic rickets (HR) remain a major challenge for dental practitioners and affected patients. Objectives To report a case of HR presenting with specific dental findings and to review the dental manifestations and treatment of HR patients. Methods Case: A 32-year-old male presented with multiple dental abscesses and short stature. A thorough history was taken followed by clinical oral examination, and relevant radiological investigation was done. Literature research: In 2020, electronic literature searches were carried out in PubMed and complemented by a careful assessment of the reference lists of the identified relevant papers. Articles and reports fulfilled the inclusion criteria: indexed reviews, case series and case reports in English and restricted to human studies were considered. Results The intraoral examination revealed multiple dental abscesses and general periodontal disease; the radiographic examination showed poorly defined lamina dura, large pulp chambers and periapical lesions. Based on the contents of the 43 articles identified in the search, the current knowledge of dental manifestations, treatment and management of HR was summarized. Conclusions As HR is a multisystem disease, multidisciplinary care is needed. By summarizing current evidences, we proposed an evidence-based dental management and provided recommendations on diagnosis and treatment of the disease. It is of profound clinical significance to acquire knowledge of the dental manifestations and provide optimal treatment options for patients.

Objective: To determine the extent to which Lycium barbarum polysaccharide (LBP) improves 60Co γ-ray radiation-induced brain injury (RIBI) by regulating the gut microbiota. Methods: The RIBI model of mice was established with the appropriate dose of 60Co γ-ray to identify the changes in the body weight, behaviors, gut microbiota, and inflammatory reactions of mice. Mice were randomly divided into healthy, RIBI model, and LBP groups. The related inflammatory cytokines were determined using an enzyme linked immunosorbent assay kit. Then, 16S rRNA sequencings of feces were carried out to evaluate the differences in intestinal flora. Results: Compared with the spontaneous activity and exploratory spirit of the healthy group, those traits in the RIBI model mice in the open field significantly decreased, the freezing time in the elevated plus maze (EPM) significantly increased, and the number of times the mice discriminated the novel object was significantly lower. Hematoxylin-eosin slides showed that the main histopathological changes of RIBI occurred in the hippocampus. In addition, the diversity and relative abundances ratio of the gut bacterial phylum, order, family, and genus in the model group varied widely. Changes in Bacteroidetes, Firmicutes, and Proteobacteria were the most obvious after head radiation exposure. In comparison, LBP could accelerate the recovery of weight loss in RIBI mice. The frequency that mice entered the center of the open field, facing the open arm in the EPM, and the number of times they discriminated the novel object were significantly increased with LBP administration. LBP could also reduce the levels of inflammatory factor caused by RIBI. LBP increased the diversity and abundance of gut microbiota in RIBI model mice. In addition, LBP increased the relative abundance of Bacteroidetes but decreased the levels of Firmicutes and Proteobacteria for irradiated mice. Conclusion: LBP can improve depression and tension by regulating the composition of gut microbiota, including lowering the relative abundance of Clostridia and Burkholderiales and raising that of Lactobacillales. Thus, LBP provides a new strategy for improving the protective effects of RIBI.

Abstract SARS-CoV-2 Omicron subvariants have demonstrated extensive evasion from monoclonal antibodies (mAbs) developed for clinical use, which raises an urgent need to develop new broad-spectrum mAbs. Here, we report the isolation and analysis of two anti-RBD neutralizing antibodies BA7208 and BA7125 from mice engineered to produce human antibodies. While BA7125 showed broadly neutralizing activity against all variants except the Omicron sublineages, BA7208 was potently neutralizing against all tested SARS-CoV-2 variants (including Omicron BA.1–BA.5) except Mu. By combining BA7208 and BA7125 through the knobs-into-holes technology, we generated a biparatopic antibody BA7208/7125 that was able to neutralize all tested circulating SARS-CoV-2 variants. Cryo-electron microscopy structure of these broad-spectrum antibodies in complex with trimeric Delta and Omicron spike indicated that the contact residues are highly conserved and had minimal interactions with mutational residues in RBD of current variants. In addition, we showed that administration of BA7208/7125 via the intraperitoneal, intranasal, or aerosol inhalation route showed potent therapeutic efficacy against Omicron BA.1 and BA.2 in hACE2-transgenic and wild-type mice and, separately, effective prophylaxis. BA7208/7125 thus has the potential to be an effective candidate as an intervention against COVID-19.

Measurement(s) seed plants on taxonomy, geography and ecology Technology Type(s) literature search, data extraction and structure Sample Characteristic - Organism Spermatophyta Sample Characteristic - Environment mountain range Sample Characteristic - Location Qinling Mountains • Daba Mountains

Based on the aircraft measurements on 28 February 2021, combined with ERA5 reanalysis data and sounding data, the weather background and the characteristics of cloud structure of a severe icing case on the aircraft are analyzed. The severe icing process is induced by the joint influence of high-level trough, low-level shear line, low-level jet and cold front. The ERA5 reanalysis data show that the maximum value area of supercooled water is mainly distributed at the height of 700 hPa to 600 hPa on the warm side of the front area and the ambient temperature is -4 to -12℃, accompanied by an upward movement of -0.2 to -0.8 Pa·s-1. The sounding data show that the cloud system is distributed in multiple layers. There is a deep dry layer between the upper ice crystal cloud and the lower supercooled water cloud. The temperature in the aircraft detection area is -9 to -3℃ and the dew-point spread is 0℃, which are favorable for icing. During the icing process, the air temperature is -8 to -5℃. Aircraft measurements show that there is abundant supercooled water in clouds. The average liquid water content by cloud particles probe is 0.35 g·m-3, and the maximum value is 0.7 g·m-3. The average liquid water content by total water content measurement probes is 0.5 g·m-3, the maximum value is 0.85 g·m-3, and for 11 minutes the liquid water content is larger than 0.45 g·m-3. The average median volume diameter of cloud particles is 20.3 μm, and the number concentration of cloud particles is 149.3 cm-3 on average. The number concentration of cloud particles tends to increase from low level to high level and vice versa for the median volume diameter of cloud particles. Finally, the conditions with different icing intensity that the King-air 350 aircraft may encounte during weather modification work in the cloud are discussed. The calculation shows that the King-air 350 aircraft carries out observation research or weather modification tasks when the liquid water content in the cloud is higher than 0.04 g·m-3, 0.15 g·m-3 and 0.45 g·m-3, it may encounter light, moderate, and severe icing, under certain conditions.

Histamine receptor antagonists, which can bind to specific histamine receptors on target cells, exhibit substantial therapeutic efficacy in managing a variety of histamine-mediated disorders. Notably, histamine H1 and H2 receptor antagonists have been extensively investigated and universally acknowledged as recommended treatment agents for numerous allergic diseases and acid-related disorders, respectively. Historically, the combination of H1 and H2 receptor antagonists has been considered a classic treatment strategy, demonstrating relatively superior efficacy compared with single-drug therapies in the treatment of diverse histamine-mediated diseases. The latest emerging studies have additionally suggested the underlying roles of histamine and H1R and H2R in the development of anxiety disorders, arthritic diseases, and postexercise hypotension. Nevertheless, there is still a lack of systematic reviews on the clinical efficacy of combination therapy, greatly limiting our understanding of its clinical application. Here, we present a comprehensive overview of the current knowledge and perspectives regarding the combination of H1 and H2 histamine receptor antagonists in various histamine-mediated disorders. Furthermore, we critically analyze the adverse effects and limitations associated with combination therapy while suggesting potential solutions. Our review can offer a systematic summary and promising insights into the in-depth and effective application of the combination of H1 and H2 receptor antagonists.

In order to provide the basic data of lithology modeling with high resolution in the early stage of coal precise mining geological guarantee, this paper established the p-wave impedance model of wedge-shaped coal seam according to the thickness and storage conditions of coal measure strata based on geostatistical inversion theory. The influence of different probability density functions and transverse range parameters on thickness inversion of coal seam are analyzed through multiple inversion experiments. The effect of inversion under different amount and location constraints is further discussed. Experimental results show that geostatistical inversion parameters have a great influence on the inversion results. Reasonable probability density function, lateral range and constrained well selection can improve the accuracy of inversion. Results shows that geostatistical inversion can predict about 1 m thin coal seam, and the error range between the inversion coal seam thickness and the logging data is 1.82 % ~12.24 %. It is therefore feasible to predict the thickness of thin coal seam, and can provide valuable modeling data for the early lithologic geological modeling of "transparent mine".

IntroductionFine roots are the critical functional organs of plants to absorb water and nutrients from the soil environment, while the relation between fine root morphological characteristics and yield & quality has received less attention for medicinal plants.MethodsTherefore, we investigated the relationship between fine root morphological characteristics and biomass & gypenosides content. We explored the primary environmental drivers of fine root indicators for Gynostemma longipes from three provenances cultivated at two altitude habitats.ResultsAt the end of the growing season, compared with the low-altitude habitat, the underground biomass of G. longipes in the high-altitude habitat increased significantly by 200%~290% for all three provenances. The response of gypenosides content to different altitude habitats varied with provenance and plant organs. The biomass of G. longipes strongly depended on the fine root characteristic indicators (P < 0.001), fine root length density, and fine root surface area. Our results also showed that the harvest yield of G. longipes could be effectively increased by promoting the growth of fine roots per unit leaf weight (P < 0.001, R2 = 0.63). Both fine root length density and fine root surface area had strong positive correlations with soil nutrient factors (R2 > 0.55) and a strong negative correlation with soil pH (R2 > 0.48). In a word, the growth of G. longipes is strongly controlled by the fine root morphological characteristics through the response of fine roots to soil nutrient factors and pH.DiscussionOur findings will help to deepen the understanding of the root ecophysiological basis driven by soil factors for the growth and secondary metabolites formation of G. longipes and other medicinal plants under changing habitat conditions. In future research, we should investigate how environmental factors drive plant morphological characteristics (e.g., fine roots) to affect the growth & quality of medicinal plants over a longer time scale.

The Hedgehog (Hh) signaling pathway is pervasively involved in human malignancies, making it an effective target for cancer treatment for decades. In addition to its direct role in regulating cancer cell attributes, recent work indicates that it has an immunoregulatory effect on tumor microenvironments. An integrated understanding of these actions of Hh signaling pathway in tumor cells and tumor microenvironments will pave the way for novel tumor treatments and further advances in anti-tumor immunotherapy. In this review, we discuss the most recent research about Hh signaling pathway transduction, with a particular emphasis on its role in modulating tumor immune/stroma cell phenotype and function, such as macrophage polarity, T cell response, and fibroblast activation, as well as their mutual interactions between tumor cells and nonneoplastic cells. We also summarize the recent advances in the development of Hh pathway inhibitors and nanoparticle formulation for Hh pathway modulation. We suggest that targeting Hh signaling effects on both tumor cells and tumor immune microenvironments could be more synergistic for cancer treatment.

Prefabricated slab has been widely used in the global construction industry due to energy saving, environmental protection, and good economic advantages. In this paper, a new type of fully prefabricated staggered flip-down slab without cast-in-situ operation has been proposed. First, the experiments were carried out on the new slab. The structural performance of the new slab was compared with the cast-in-situ slabs and composite slabs of the same specification. The experimental results showed that the ultimate bearing capacity of the new slab meets the requirements for practical utilization. On this basis, an additional CFRP sheet could be pasted on the bottom initial seam between prefabricated slabs to enhance the integrity and prevent cracks. Then, the whole loading process of the slab was simulated, and the results were consistent with the experimental results. Finally, through experiments and parametric analysis, recommendations for improvement were put forward to enhance the mechanical properties of this kind of slab.

Abstract Backgrounds To compare the irrigation efficiency with different needle working length and different root canal curvature based on a real unshaped root canal using computational fluid dynamics (CFD) method. Methods Images of the root canal of the maxillary first molar after being prepared to .04/15 were scanned using micro-CT, and then imported into the software for three-dimensional reconstruction. A palatal root canal with a curvature of 23.4° was selected as the experiment canal. The needle working length of the 30-G flat needle was 4.75 mm, 5 mm, 5.25 mm and 5.5 mm short of apical foramen respectively, the flow pattern, irrigation velocity, shear stress were compared. The modified curved canals with a curvature of 0°, 5°, 10°, 20° and 30°were reconstructed via software. The flat needle was replaced at the optical inserted depth, and key parameters of irrigation efficiency were analyzed. Results Decreased needle working length had a positive impact on irrigation efficiency. With the optimal needle working length, the replacement of the apical irrigation fluid, the effective velocity, and wall shear stress were significantly improved in more severely curved root canals. With the same needle working depth and analogous canal curvature, irrigation efficiency is higher in real canal than that of modified canal. Conclusions Short needle working depth, large curvature and the anomalous inner wall of canals help to improve irrigation efficiency.

Abstract Myocardial regeneration has been considered a promising option for the treatment of adult myocardial injuries. Previously, a chick early amniotic fluid (ceAF) preparation was shown to contain growth-related factors that promoted embryonic growth and cellular proliferation, though the nature of the components within ceAF were not fully defined. Here we tested whether this ceAF preparation is similarly effective in the promotion of myocardial regeneration, which could provide an alternative therapeutic for intervening myocardial injury. In this study, a myocardial ischemic injury model was established in adult mice and pigs by multiple research entities, and we were able to show that ceAF can efficiently rescue damaged cardiac tissues and markedly improve cardiac function in both experimental models through intravenous administration. ceAF administration increased cell proliferation and improved angiogenesis, likely via down-regulation of Hippo-YAP signaling. Our data suggest that ceAF administration can effectively rescue ischemic heart injury, providing the key functional information for the further development of ceAF for use in attenuating myocardial injury.

Optical illusion refers to the phenomenon in which the scene observed by the human eye is not completely consistent with the objectively presented scene. Optical illusions in stomatology, as well as their clinical application, are demonstrated in this paper in terms of shade, shape and aesthetic design. Shade is not only affected by the optical illusions with which it is associated, such as color metamerism, color constancy and the Chevreul illusion, but also influenced by the surroundings. It is suggested that the surrounding lighting during veneering should be the same as that during color matching in the clinic. As indicated by the Poggendorf illusion and the Leaning Tower illusion, the practice should be conducted and checked from multiple perspectives to compensate for the limitation of human eyes, such as intraoral scanning. Other digital technologies, including digital facial scanning and cephalometric measurement, could be used to reduce the subjective influence of observation. In terms of esthetic design, the interaction of the part and the whole, suggested by Ebbinghaus illusion, should be considered: an individual harmony smile should be designed considering the characteristics of the personality and the features of the face, lips, teeth and gingiva of the patient. Furthermore, personal information, such as gender and age, should be taken into consideration in beautification presentation. Further research should be focused on the influence of optical illusions in stomatology in more details. More communication among doctors, technicians and patients is needed. Clinicians should be aware of the impact of optical illusions to reduce subjective bias in clinical standardized operations and further take advantage of optical illusions to create beautification presentations of dental restorations and smiles.

In this paper, we consider the Cauchy problem for a family of evolution-parabolic coupled systems, which are related to the classical thermoelastic plate equations containing non-local operators. By using diagonalization procedure and WKB analysis, we derive representation of solutions in the phase space. Then, sharp decay properties in a framework of $ L^p-L^q $ are investigated via these representations. Particularly, some thresholds for the regularity-loss type decay properties are found.

Abstract Two typical classes of cyclones originating from the tropics (ToCs) and extratropics (EoCs) with distinct preconditions, and passing the Kuroshio Extension (KE) region in cold season in the North Pacific are detected and tracked based on high‐resolution atmospheric simulations with and without mesoscale sea surface temperature (SST) forcing. A comparison between ToC‐to‐mesoscale SST and EoC‐to‐mesoscale SST responses indicates that the different cyclone development and the environmental water vapor restoration in the KE are primarily attributed to different ToC and EOC's preconditions. The higher initial intensity of ToCs leads to stronger atmospheric response to mesoscale SSTs and extended cyclone growth whilst the colder and drier precondition of EoCs induces stronger water vapor restoration in the KE after EoCs passing‐by. It is further demonstrated that the water vapor restoration is dominated by moisture convergence. The study provides new insights into the physical understanding of mesoscale SSTs' influence on cyclogenesis in the midlatitudes.

The rhizoma of Polygonatum odoratum (PO) is used to treat yin injuries of the lung and stomach in traditional Chinese medicine. The chemical constituents of this herb are steroidal saponins, homoisoflavanones, and alkaloids. Xiangyuzhu (XPO) and Guanyuzhu (GPO) are available in the market as two specifications of the commodity. Nonetheless, systematic research on the identification and comparison of chemical constituents of these two commercial specifications is yet lacking. Herein, an integrated method combing ultra-high-performance liquid chromatography-quadruple time-of-flight mass spectrometry (UHPLC-Q-TOF/MS) with ultra-high-performance liquid chromatography-charged aerosol detection (UHPLC-CAD) was employed for the comprehensively qualitative and quantitative analyses of PO. A total of 62 compounds were identified by UHPLC-Q-TOF/MS, among which 13 potential chemical markers were screened out to distinguish two commercial specifications. Subsequently, the absolute determination method for polygodoraside G, polygonatumoside F, and timosaponin H1 was established and validated by UHPLC-CAD. The contents of the three compounds were 13.33–236.24 μg/g, 50.55–545.04 μg/g, and 13.34–407.83 μg/g, respectively. Furthermore, the ratio of timosaponin H1/polygodoraside G could be applied to differentiate the two specifications. Samples with a ratio 5 are considered GPO. Therefore, the above results provide a valuable means for the quality control of PO.

Objective To systematically evaluate the disinfection efficacy of the two most frequently used disinfectants, sodium hypochlorite and glutaraldehyde, and their effects on the surface properties of four different dental impression materials. Methods A systematic literature search was performed in four databases until May 1st, 2022 to select the studies which evaluated disinfection efficacy of disinfectants or surface properties of dental impressions after chemical disinfection. Main results A total of 50 studies were included through electronic database searches. Of these studies, 13 studies evaluated disinfection efficacy of two disinfectants, and 39 studies evaluated their effects on the surface properties of dental impressions. A 10-minute disinfection with 0.5–1% sodium hypochlorite or 2% glutaraldehyde was effective to inactivate oral flora and common oral pathogenic bacteria. With regard to surface properties, chemical disinfection within 30 min could not alter the dimensional stability, detail reproduction and wettability of alginate and polyether impressions. However, the wettability of addition silicone impressions and the dimensional stability of condensation silicone impressions were adversely affected after chemical disinfection, while other surface properties of these two dental impressions were out of significant influence. Conclusions Alginate impressions are strongly recommended to be disinfected with 0.5% sodium hypochlorite using spray disinfection method for 10 min. Meanwhile, elastomeric impressions are strongly recommended to be disinfected with 0.5% sodium hypochlorite or 2% glutaraldehyde using immersion disinfection method for 10 min, however, polyether impression should be disinfected with 2% glutaraldehyde.

BackgroundClinical prevalence of major depression is higher in women than men, while the psychoneuroimmunological mechanisms underlying the differences between the two sexes are not fully understood.MethodsThe present study explored sex differences in the behaviors and depressive pathological mechanisms induced by chronic unpredictable mild stress (CUMS). Depression- and anxiety-like behaviors were assessed by the sucrose preference test (SPT), force swimming test (FST), open field test (OFT), and elevated plus-maze (EPM). The enzyme-linked immunosorbent assay (ELISA) was used to measure cytokine concentrations, high-performance liquid chromatography (HPLC) was used to measure monoamine neurotransmitters and metabolite contents, and real-time quantitative PCR (qPCR) and western blotting (WB) were used to measure glial parameters in the hippocampus.ResultsUnder control conditions, female rats exhibited shorter immobility times in the FST, lower interferon (IFN)-γ, and interleukin (IL)-4 levels in the hippocampus, lower norepinephrine (NE) and homovanillic acid (HVA), and higher p75 and glial-derived neurotrophic factor (GDNF) expression than male rats. CUMS markedly reduced rat body weight gain, sucrose preference, locomotor activity, number of entries into the central zone and rearing in the OFT, as well as the number of entries into and time spent in open arms of the EPM; however, CUMS increased the immobility times of the rats of both sexes in the FST. Interestingly, more pronounced changes in sucrose preference and locomotor activity were observed in female rats than in males. Consistently, CUMS-increased glucocorticoid concentration, M1 microglial marker CD11b, and peripheral IL-1β and IL-4, while decreased hippocampal IL-10, serotonin (5-HT), dopamine metabolite 3,4-dihydroxyphenylacetic acid (DOPAC), and norepinephrine metabolite 3-methoxy-4-hydroxyphenylglycol (MHPG) were more significant in females than in males.ConclusionThese data revealed possible mechanisms by which females suffer more depression than males at least in a stressful environment.

Fabrication of heterojunction with specialized geometry shape could improve the photodegradation efficiency of catalysts more efficiently based on the synergistic effect of components. Herein, the BiVO4/ZnCr-LDH type-II heterojunction was successfully synthesized by the growth of two-dimensional (2D) ZnCr-LDH on 2D BiVO4, forming a unique three-dimensional (3D) hierarchical structure. The 3D hierarchical BiVO4/ZnCr-LDH type-II heterojunction with intimate 2D/2D heterointerfaces enlarges the interfacial contact areas and shortens the transfer distance of carriers simultaneously, which could promote the separation and transfer of photoinduced carriers and prolong the lifetime of carriers. Additionally, the 3D structure could enhance the photon utilization efficiency caused by the multiple reflections of incident light, and provide more active sites to promote the adsorption of pollutants. Therefore, the visible light catalytic performance of the optimal heterostructure for the removal of tetracycline hydrochloride is 3.47 times and 22.43 times higher than that of BiVO4 and ZnCr-LDH, respectively. Superoxide radical (·O2−) is confirmed as the primary active species, whereas hole (h+) is the secondary active species in the photodegradation process. This work provides a facile strategy to enhance the visible light catalytic behavior of BiVO4 through the fabrication of 3D hierarchical architecture heterojunction for the removal of organic pollutant.

IntroductionRadix Notoginseng, one of the most famous Chinese traditional medicines, is the dried root of Panax notoginseng (Araliaceae). Stems and leaves of P. notoginseng (SLPN) are rich in secondary metabolites and nutrients, and authorized as a food resource, however, its utilization needs further research.MethodsA SLPN-instant beverage was manufactured from SLPN through optimization by response surface design with 21-fold of 48.50% ethanol for 39 h, and this extraction was repeated twice; the extraction solution was concentrated to 1/3 volume using a vacuum rotatory evaporator at 45°C, and then spray dried at 110°C. Nutritional components including 14 amino acids, ten mineral elements, 15 vitamins were detected in the SLPN-instant beverage; forty-three triterpenoid saponins, e.g., ginsenoside La, ginsenoside Rb3, notoginsenoside R1, and two flavonoid glycosides, as well as dencichine were identified by UPLC-MS.ResultsThe extraction rate of SLPN-instant beverage was 37.89 ± 0.02%. The majority nutrients were Gly (2.10 ± 0.63 mg/g), His (1.23 ± 0.07 mg/g), α-VE (18.89 ± 1.87 μg/g), β-VE (17.53 ± 1.98 μg/g), potassium (49.26 ± 2.70 mg/g), calcium (6.73 ± 0.27 mg/g). The total saponin of the SLPN-instant beverage was 403.05 ± 34.98 mg/g, majority was notoginsenoside Fd and with contents of 227 ± 2.02 mg/g. In addition, catechin and γ-aminobutyric acid were detected with levels of 24.57 ± 0.21 mg/g and 7.50 ± 1.85 mg/g, respectively. The SLPN-instant beverage showed good antioxidant activities with half maximal inhibitory concentration (IC50) for scavenging hydroxyl (OH–) radicals, superoxide anion (O2–) radicals, 1,1-diphenyl-2-picrylhydrazyl (DPPH) radicals and 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonate) (ABTS+) radicals were 0.1954, 0.2314, 0.4083, and 0.3874 mg/mL, respectively.ConclusionWe optimized an analytical method for in depth analysis of the newly authorized food resource SLPN. Together, an instant beverage with antioxidant activity, rich in nutrients and secondary metabolites, was manufactured from SLPN, which may improve the utilization of SLPN.

Abstract Demineralization of hard tooth tissues leads to dental caries, which cause health problems and economic burdens throughout the world. A biomimetic mineralization strategy is expected to reverse early dental caries. Commercially available anti-carious mineralizing products lead to inconclusive clinical results because they cannot continuously replenish the required calcium and phosphate resources. Herein, we prepared a mineralizing film consisting of hydroxypropylmethylcellulose (HPMC) and polyaspartic acid-stabilized amorphous calcium phosphate (PAsp-ACP) nanoparticles. HPMC which contains multiple hydroxyl groups is a film-forming material that can be desiccated to form a dry film. In a moist environment, this film gradually changes into a gel. HPMC was used as the carrier of PAsp-ACP nanoparticles to deliver biomimetic mineralization. Our results indicated that the hydroxyl and methoxyl groups of HPMC could assist the stability of PAsp-ACP nanoparticles and maintain their biomimetic mineralization activity. The results further demonstrated that the bioinspired mineralizing film induced the early mineralization of demineralized dentin after 24 h with increasing mineralization of the whole demineralized dentin (3–4 µm) after 72–96 h. Furthermore, these results were achieved without any cytotoxicity or mucosa irritation. Therefore, this mineralizing film shows promise for use in preventive dentistry due to its efficient mineralization capability. Graphical Abstract

Spatial decay estimates for the Fochheimer fluid interfacing with a Darcy flow in a semi-infinite pipe was studied. The exponential decay result can be obtained by integrating a first-order differential inequality. The result can be seen as the usage of Saint-Venant's principle for the interfacing fluids.

Myocardial infarction (MI) is the major cause of mortality around the world. We recently demonstrated that chick early amniotic fluid (ceAF) can effectively rescue ischemic heart injury, indicating that it has a therapeutic function in MI. However, its functional components and the underlying mechanisms remain to be clarified. Here, we demonstrated that a fraction of ceAF, peak 8 (P8), had a protective effect on acute MI. P8 significantly decreased cardiomyocyte cross-sectional areas and cardiomyocyte apoptosis in MI mice. Using a human embryonic stem cell-derived cardiomyocyte model, which was subjected to hypoxia and reoxygenation, mimicking MI state, we found that P8 treatment reduced apoptosis and reversed myocardial contractility. Mechanistically, P8 improved cardiac function by inhibiting NF-κB signaling and downregulating inflammatory cytokine expression. Using mass spectrometry, we identified that guanosine and deoxynucleoside were the main functional components of P8 that suppressed the inflammatory response in human embryonic stem cell-derived cardiomyocytes. Collectively, our data suggest that specific components from ceAF are promising therapeutic agents for ischemic heart injury and could be a potential supplement to current medications for MI.

Phytochemical investigation was carried out for the flowers of Epimedium acuminatum Franchet. by first conducting LC-MS analysis, leading to the identification of 32 compounds. Furthermore, guided by LC-MS profiling, three new 8-prenylated quercetin glycosides (3′-hydroxylikarisoside C, 3′-hydroxylepimedoside E, 3′-hydroxyldiphylloside B), one new anthocyanin (delphinidin-3-O-p-coumaroyl-sophoroside) and six known compounds were isolated from the flowers of E. acuminatum for the first time, and their structures were characterized based on spectroscopic methods including 1D and 2D NMR, and HRESIMS. Combining our discoveries and literature survey, a revised classification of Epimedium flavonols was proposed as Type A (8-prenylated kaempferol based), which was further subdivided into subtype icaritin and subtype demethylicaritin, and Type B (8-prenylated quercetin based), which was further subdivided into subtype 3′-hydroxylicaritin and subtype 3′-hydroxyldemethylicaritin. The structure-activity relationship (SAR) study was carried out by comparing testosterone production-promoting activities of all the new compounds along with nine related Epimedium flavonols, revealing that the new 8-prenylated quercetin glycosides (subtype 3′-hydroxyldemethylicaritin in Type B) exhibited lower testosterone production-promoting activities in rat primary Leydig cells than Epimedium flavonols of subtype demethylicaritin in Type A, but possessed higher activities than the Epimedium flavonols of subtype icaritin in Type A. These results suggested that either methylation at C-4′ position or hydroxylation at C-3′ position of ring B could significantly reduce the testosterone production-promoting activities of Epimedium flavonols.

Understanding the variation patterns of mountain plant species diversity is becoming increasingly important in forest ecosystem management and protection. However, the research on plant species diversity has mainly focused on changes in whole plant species. Therefore, an in-depth study of the change mode of plant species via different classification methods and its impact on the overall change in plant diversity is very important for forestland restoration and biodiversity protection. In this study, the Qinling-Daba Mountains, a major feature of China's north–south transitional zone, were selected as the study area. Based on the floristic data of 58 nature reserves in the Qinling-Daba Mountains and its adjacent areas, the north–south change patterns of plant orders, families, genera and species diversity were first analyzed. Second, plant species were divided into different groups according to taxonomic group (orders, families and genera), life form (trees, shrubs and herbs) and endemism (species endemic and nonendemic to China). The change patterns of each group in the north–south direction were analyzed. Finally, the effects of different groups on the north–south change patterns of whole species are discussed. The species diversity of orders, genera and species exhibited a typical latitudinal gradient pattern, specifically, it gradually decreases from south to north, but the species diversity is relatively scattered. According to the north–south variation in species diversity in each order, families and genus, 5% of the orders, 2% of the families and 6% of the genera were positively correlated with latitude, and the rest were negatively correlated or uncorrelated. According to the north–south variation patterns of different life forms, the diversity of trees and shrubs showed a bimodal Gaussian distribution with latitude. According to the north–south variation patterns of plant endemism, the diversity of endemic species showed a Gaussian distribution with latitude, but the diversity of nonendemic species was negatively correlated with latitude. The dispersion of whole species diversity is caused by species in a few orders, families and genera, trees and shrubs, and endemic species. They may be more strongly affected by the vertical zonality of the mountains, which is inconsistent with the typical latitude gradient model. Our research will provide a basis for forestland management, nature reserve establishment and biodiversity conservation.

How to detect grain moisture content storage inefficiently, non-destructively, and quickly is a critical task in the storage process of the modern grain industry. The influence of media with different moisture content on the propagation and attenuation of electromagnetic wave energy is the premise and basis for applying electromagnetic wave technology in detecting grain moisture content. To explore the applicability of electromagnetic wave technology in detecting grain moisture content, we used ground penetrating radar (GPR) technology and auto regressive and moving average (ARMA) power spectrum analysis method to detect and study the moisture content of the typical national grain depots and local grain depots. The results show that GPR technology could realize the moisture content of stored grains and solve the problems of detection distance, non-destructive, and detection dead ends. Compared with the actual test data, the correlation is above 90%, the error can be controlled within 0.5%, and the measurement accuracy is higher, within ±0.3%. The continuous distribution profile of stored grain moisture content was obtained using the ARMA method. The moisture content distribution range of the rice barn was 10-14%, showing the regularity of the moisture content distribution in the middle layer > upper-middle layer > lower-middle layer > bottom layer > grain surface layer. It indicates that the GPR technology has particular advantages in food safety detection and provides data support for real-time detection of food storage safety.

The altitude of alpine timberline elevation has been considered to correlate with certain climatic factors. Many related isotherms (e.g., warmest month 10 °C isotherm) have been proposed to explain the altitudinal distribution of alpine timberline at the global scale. However, any climatic index actually has a wide range at the alpine timberline position worldwide. The altitudinal position of the alpine timberline is related to far more than just one climatic factor. Therefore, we developed a multivariable model for timberline elevation variability by collecting data from 473 timberline sites on the Eurasian continent. We analyzed 12 climatic variables that potentially account for timberline variation. Principal component and regression analyses were used to mine four climatic variables. The mean temperature of the warmest month (MTWM), mean temperature of the coldest month (MTCM), climatic continentality (K), and annual precipitation (AP) explained 95% of the variability of timberline elevation. MTWM, MTCM, K, and AP contributed 18%, 41.28%, 34.9%, and 5.82%, respectively, to the altitudinal distribution of alpine timberline on the whole continent; 20%, 44%, 28.86%, and 7.14% in the eastern continent; and 17.71%, 39.79%, 40.21%, and 2.29% in the western continent. We showed that MTWM, MTCM, K, and AP are deterministic factors for the altitudinal distribution of alpine timberline in the Eurasian continent. MTCM and K contributed to explaining the altitudinal distribution of timberline both in the entire, eastern, and western parts of the Eurasian continent. Our research highlights the significance of MTCM for the altitudinal distribution of timberline.

The epidermis, the outmost layer of the skin, is a stratified squamous epithelium that protects the body from the external world. The epidermis and its appendages need constantly renew themselves and replace the damaged tissues caused by environmental assaults. The mechanistic target of rapamycin (mTOR) signaling is a central controller of cell growth and metabolism that plays a critical role in development, homeostasis and diseases. Recent findings suggest that mTOR signaling is activated in a spatiotemporal and context-dependent manner in the epidermis, coordinating diverse skin homeostatic processes. Dysregulation of mTOR signaling underlies the pathogenesis of skin diseases, including psoriasis and skin cancer. In this review, we discuss the role of epidermal mTOR signaling activity and function in skin, with a focus on skin barrier formation, hair regeneration, wound repair, as well as skin pathological disorders. We propose that fine-tuned control of mTOR signaling is essential for epidermal structural and functional integrity.

Song et al describe and identify monoclonal antibodies that target the SARSCoV-2 Spike protein, including CA521FALA, which demonstrated neutralising potential in vivo and in vitro. They performed structural analysis, which revealed that CA521FALA recognizes an epitope overlapping with angiotensin converting enzyme 2 (ACE2)-binding sites in SARS-CoV-2 Spike protein therefore making it a promising therapeutic antibody.

Abstract Double-network (DN) hydrogels, consisting of two contrasting and interpenetrating polymer networks, are considered as perhaps the toughest soft-wet materials. Current knowledge of DN gels from synthesis methods to toughening mechanisms almost exclusively comes from chemically-linked DN hydrogels by experiments. Molecular modeling and simulations of inhomogeneous DN structure in hydrogels have proved to be extremely challenging. Herein, we developed a new multiscale simulation platform to computationally investigate the early fracture of physically-chemically linked agar/polyacrylamide (agar/PAM) DN hydrogels at a long timescale. A “random walk reactive polymerization” (RWRP) was developed to mimic a radical polymerization process, which enables to construct a physically-chemically linked agar/PAM DN hydrogel from monomers, while conventional and steered MD simulations were conducted to examine the structural-dependent energy dissipation and fracture behaviors at the relax and deformation states. Collective simulation results revealed that energy dissipation of agar/PAM hydrogels was attributed to a combination of the pulling out of agar chains from the DNs, the disruption of massive hydrogen bonds between and within DN structures, and the strong association of water molecules with both networks, thus explaining a different mechanical enhancement of agar/PAM hydrogels. This computational work provided atomic details of network structure, dynamics, solvation, and interactions of a hybrid DN hydrogel, and a different structural-dependent energy dissipation mode and fracture behavior of a hybrid DN hydrogel, which help to design tough hydrogels with new network structures and efficient energy dissipation modes. Additionally, the RWRP algorithm can be generally applied to construct the radical polymerization-produced hydrogels, elastomers, and polymers.

Abstract Background Genome-wide association studies have established clusterin (CLU) as a genetic modifier for late-onset Alzheimer’s disease (AD). Both protective and risk alleles have been identified which may be associated with its expression levels. However, the physiological function of clusterin in the central nervous system remains largely unknown. Methods We examined Clu expression in mouse brains by immunohistochemistry and high-resolution imaging. We performed electrophysiological recordings and morphological analysis of dendritic spines in wild-type and Clu knockout mice. We tested synaptic function of astrocytic Clu using neuron-glia co-cultures and by AAV-mediated astroglial Clu expression in vivo. Finally, we investigated the role of astrocytic Clu on synaptic properties and amyloid pathology in 5xFAD transgenic mouse model of AD. Results We show that astrocyte secreted Clu co-localizes with presynaptic puncta of excitatory neurons. Loss of Clu led to impaired presynaptic function and reduced spine density in vivo. Neurons co-cultured with Clu-overexpressing astrocytes or treated with conditioned media from HEK293 cells transfected with Clu displayed enhanced excitatory neurotransmission. AAV-mediated astroglial Clu expression promoted excitatory neurotransmission in wild-type mice and rescued synaptic deficits in Clu knockout mice. Overexpression of Clu in the astrocytes of 5xFAD mice led to reduced Aβ pathology and fully rescued the synaptic deficits. Conclusion We identify Clu as an astrocyte-derived synaptogenic and anti-amyloid factor; the combination of these activities may influence the progression of late-onset AD.

Objective: To study the preventive effect of Timosaponin BII (T-BII) -loaded temperature/ion-sensitive nasal in situ hydrogels (ISGs) on Alzheimer's disease (AD), its preparation technology, characteristics and in vivo effects were evaluated. Methods: The morphological and rheological properties were evaluated. The preventive effects of T-BII ISG on scopolamine-induced AD in mice were determined with the index of muscarinicreceptor 1 (M1) expression and pathological changes. Results: Results revealed that T-BII ISG significantly increased the content of M1 choline receptors in the hippocampus of mice and ameliorated the damage incurred to the hippocampal cornu ammonis 1 (CA1) area. Conclusion: T-BII ISGs is a reasonable and convenient method of exerting an obvious preventive effect on mice with AD induced by scopolamine. This, thereby, lays forth a new treatment option for preventing AD.

In order to meet the needs of the intelligent management of modern commercial buildings,with the Internet of things (IoT) and edge computing technology,the intelligent building management system (IBMS) was developed based on ubiquitous building IoT by using the self-developed IoT gateway.The ubiquitous IoT eliminated the boundaries between the traditional building automation and information automation systems.The edge computing technology was used in the integrated management system to enhance the on-site decision-making ability and response speed of IBMS.The architecture of the integrated management system and the implementation of edge computing were discussed.The application of the system in the Shenzhen Dashi intelligent building shows the feasibility and effectiveness of the intelligent integrated management system based on ubiquitous building IoT.

The Qinling-Daba Mountains (QBM), which are a major feature of China's north–south transitional zone, play important roles in the geographical and ecological patterns of China. The spatiotemporal changes in winter evergreen vegetation in the QBM are closely related to the protection of vegetation in China and have profound impacts on the sustainable development of vegetation in North and South China. This study aimed to introduce geographical distribution measurement methods into vegetation cover research by geographically characterizing evergreen vegetation, temperature, and precipitation. We used gravity centre analysis and standard deviation ellipse (SDE) methods to statistically analyse the concentration tendency, principal orientation, dispersion trend, and distribution differences of the winter normalized difference vegetation index (WNDVI), average temperature in winter (WAT), and accumulated precipitation in winter (WAP) in 1986–1990, 1991–1995, 1996–2000, 2001–2005, 2006–2010, and 2011–2015. The results show that (1) the gravity centres of the WNDVI and WAT in the QBM moved northwards, indicating that winter temperature is the main factor driving the northwards movement of evergreen vegetation in the QBM. (2) The angle between the development orientations of the WNDVI and the WAT remained basically stable, at close to horizontal, indicating that the development orientation of evergreen vegetation is mainly affected by winter temperature in the QBM. (3) The spatial differentiation coefficient between the WNDVI and the WAP decreased from 0.21 to 0.07; thus, the spatial distribution difference between evergreen vegetation and winter precipitation decreased gradually. These results confirm that in the QBM, winter temperature is the main factor affecting the overall evolution and development orientation of winter evergreen vegetation and that winter precipitation is the main factor affecting the internal distribution pattern of winter evergreen vegetation. The results of this study have reference value for evaluating the spatial distribution of evergreen vegetation development and resource management in the QBM.

Abstract Background Radix Paeoniae Alba (RPA) and other natural medicines have remarkable curative effects and are widely used in traditional Chinese Medicine (TCM). However, due to their multi-component and multi-target characteristics, it is difficult to study the detailed pharmacological mechanisms for those natural medicines in vivo. Therefore, their real effects on organisms is still uncertain. Methods RPA was selected as research object, the present study was designed to study the complex mechanisms of RPA in vivo by integrating and interpreting the transcriptomic based RNA-seq and metabolomic based NMR spectrum after RPA administration in mice. A variety of dimension-reduction algorithms and classifier models were applied to the processing of high-throughput data. Results Among serum metabolites, the contents of PC and glucose were significantly increased, while the contents of various amino acids, lipids and their metabolites were significantly decreased in mice after RPA administration. Based on the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) databases, differential analysis showed that the liver was the site where RPA exerted a significant effect, which confirmed the rationality of “meridian tropism” in the theory in TCM. In addition, RPA played a role in lipid metabolism by regulating genes encoding enzymes of the glycerolipid metabolism pathway, such as 1-acyl-sn-glycerol-3-phosphate acyltransferase (Agpat), phosphatidate phosphatase (Lpin), phospholipid phosphatase (Plpp) and endothelial lipase (Lipg). We also found that RPA regulates several substance addiction pathways in the brain, such as the cocaine addiction pathway, and the related targets were predicted based on the sequencing data from pathological model in the GEO database. The overall effective pattern of RPA was intuitively presented with a multidimensional radar map through a self-designed model which found that liver and brain were mainly regulated by RPA compared with the traditional meridian tropism theory. Conclusions Overall this study expanded the potential application of RPA and provided possible targets and directions for further mechanism study, meanwhile, it also established a multi-dimensional evaluation model to represent the overall effective pattern of TCM for the first time. In the future, such study based on the high-throughput data sets can be used to interpret the theory of TCM and to provide a valuable research model and clinical medication reference for the TCM researchers and doctors.

Abstract In this paper, we study the blow-up phenomenon for a general nonlinear nonlocal porous medium equation in a bounded convex domain ( Ω ∈ R n , n ≥ 3 ) $(\varOmega\in \mathbb{R}^{n}, n\geq 3)$ with smooth boundary. Using the technique of a differential inequality and a Sobolev inequality, we derive the lower bound for the blow-up time under the nonlinear boundary condition if blow-up does really occur.

The regulation of water and fertilizer for alfalfa growth is not precise enough because the regulation strategy cannot track alfalfa growth dynamically. In this paper, we propose a precision regulation model of water and fertilizer for alfalfa based on agriculture cyber-physical system (ACPS) for irrigation and fertilizer management in alfalfa (PRMWFA-ACPS). The proposed PRMWFA-ACPS is a comprehensive model that includes the biophysical submodel, the computation submodel of water and fertilizer regulation, and the interaction of the submodels for both. The proposed model interacts with the alfalfa growth and its physical environment along with the irrigation strategy to improve the precise regulation of water and fertilizer. To verify the performance of the proposed model, we develop a simulation platform for PRMWFA-ACPS based on Ptolemy. Through physical experiments performed in the field at the Ningxia irrigation area of the Yellow River over three years (2016-2018), we verified and analyzed PRMWFA-ACPS by comparing the simulated and measured values, such as the growth period, leaf area index, soil water content and alfalfa yield. The experimental results show that the mean relative error of the growth period simulated by the model is between 1.9% and 6.8%, the mean relative error of the leaf area index simulated by the model is between 2.1% and 9.8%, the mean relative error of the soil water content simulated by the model is between 4.3% and 12.8%, and the mean relative error of the yield simulated by the model is between 1.2% and 14.3%. These findings indicate that PRMWFA-ACPS has promising applicability to the Ningxia irrigation area of the Yellow River and improves the accurate regulation of water and fertilizer application to alfalfa in a complex physical environment.