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The study of tradeoffs/synergies among ecosystem services (ESs) is highly significant for land-use planning and regional ecosystem optimization. Land-use change and topographic factors have important implications for ESs. Strengthening the comparative analysis of the capacity of ESs provided by different land-use types in specific regions, studying the topographic gradient effects of ecosystem service trade-offs/synergies with slope changes, and identifying the dominate trade-off/synergy relationship among ESs will help us to carry out ecosystem regulation according to local conditions through land-use layout optimization at a fine scale. Our research site was located in the Dabie Mountains of western Anhui Province, China (DBM), where, based on the InVEST software, R language, self-organizing maps (SOM), and GeoDA, the temporal and spatial variations of five typical ESs, including food supply, soil retention, water yield, carbon storage, and biodiversity maintenance from 2005 to 2020, were analyzed, and spatial distributions of the different ESs clusters were also recognized by using the SOM method. Moreover, the impacts of land-use type and slope on ESs, and the characteristics of trade-offs/synergies among the five ESs, were discussed. Results showed, firstly, that the total values of ESs showed a changing trend of “three increases and two decreases” from 2005 to 2020. Among the ESs, food supply, soil retention and water yield showed upward trends, with annual growth rates of 2.83%, 6.50% and 2.98%, respectively, whereas carbon storage and biodiversity maintenance showed downward trends, with annual decline rates of 0.03% and 0.07%, respectively. Second, the results showed that the Moran’s I index of the total ESs was 0.3995 in 2005 and 0.4305 in 2020, respectively, indicating that they had significant spatial clustering characteristics. The Low-Low clustering regions with reduced changes were mainly in the central and northern parts of the study area, whereas the High-High clustering regions with increased changes were found distributed mainly in the south of the study area. Thirdly, it was found that cropland and woodland were the main contributors to the total amounts of ESs, but the supply capacity of ESs per unit area of woodland was the largest, constituting nearly 1/3 of the total supply capacity of the ESs. Last, the slope effect on trade-offs and synergies was significant between typical ecosystem service pairs in the study area; trade-offs were the main relationships between the pairs of ESs in the study area, which accounted for nearly 60% of all types of trade-offs/synergies during the 15 years. In addition, the spatial distributions of the trade-offs/synergies between ESs pairs were visualized clearly, and the six ES bundles were identified by using the SOM method at the township administrative scale. The identification of ecosystem service bundles is of great significance for the division of ecological functional zones and ecological regulation in the DBM.

Polymer gels are usually used for crystal growth as the recovered crystals have better properties. Fast crystallization under nanoscale confinement holds great benefits, especially in polymer microgels as its tunable microstructures. This study demonstrated that ethyl vanillin can be quickly crystallized from carboxymethyl chitosan/ethyl vanillin co-mixture gels via classical swift cooling method and supersaturation. It found that EVA appeared with bulk filament crystals accelerated by a large quantity of nanoconfinement microregions resulted from space-formatted hydrogen network between EVA and CMCS when their concentration exceeds 1:1.4 and may occasionally arise when the concentration less than 1:0.8. It was observed that EVA crystal growth has two models involving hang-wall growth at the air-liquid interface at the contact line, as well as extrude-bubble growth at any sites on the liquid surface. Further investigations found that EVA crystals can be recovered from as-prepared ion-switchable CMCS gels by 0.1 M hydrochloric acid or acetic acid without defects. Consequently, the proposed method may offer an available scheme for a large-scale preparation of API analogs.

Prevention and control of infections have become a formidable challenge due to the increasing resistance of pathogens to antibiotics. Probiotics have been discovered to have positive effects on the host, and it is well-known that some Lactobacilli are effective in treating and preventing inflammatory and infectious diseases. In this study, we developed an antibacterial formulation consisting of honey and Lactobacillus plantarum (honey–L. plantarum). The optimal formulation of honey (10%) and L. plantarum (1 × 109 CFU/mL) was used to investigate its antimicrobial effect and mechanism in vitro, and its healing effect on wound healing of whole skin infections in rats. Biofilm crystalline violet staining and fluorescent staining results indicated that the honey–L. plantarum formulation prevented the biofilm formation in Staphylococcus aureus and Pseudomonas aeruginosa and increased the number of dead bacteria in the biofilms. Further mechanism studies revealed that the honey–L. plantarum formulation may inhibit biofilm formation by upregulating biofilm-related genes (icaA, icaR, sigB, sarA, and agrA) and downregulating quorum sensing (QS) associated genes (lasI, lasR, rhlI, rhlR, and pqsR). Furthermore, the honey–L. plantarum formulation decreased the number of bacteria in the infected wounds of rats and accelerated the formation of new connective tissue to promote wound healing. Our study suggests that the honey–L. plantarum formulation provides a promising option for the treatment of pathogenic infections and wound healing.

Reasonable determination of the water pressure on the shaft linings is the key to the optimization design of the vertical shaft of mining. The traditional water pressure calculation model is not suitable for the stratum conditions in western China. A new shaft-surrounding rock seepage model is proposed based on the coordinated seepage conditions of surrounding rock and shaft linings. In the model, the seepage within the shaft depth is assumed happening in a unit thickness confined aquifer. Thereby, the water pressure on the shaft linings is derived by the steady seepage theory, and the water pressure reduction coefficient is defined by normalizing the hydrostatic pressure. The influences of shaft diameter and shaft depth, the permeability coefficient of the surrounding rock, and the seepage flow on the water pressure reduction coefficient are analyzed. After that, the mechanism of reducing water pressure by grouting the surrounding rock is studied by considering the stratum conditions in western China. Finally, a practical equation, which only relating to the depth of the shaft, is fitted on account of the averaged water pressure reduction coefficient from the theoretical model. The effectiveness of the theoretical model and the fitted equation are verified by the measured data and data in the literature.

As the integration of electronic-interfaced devices have increased, microgrid models have become too complex to perform a stability analysis. Thus, an effective model simplification method keeping most dynamics of the system becomes very essential. Singular perturbation is a common way for model simplification. However, its accuracy is insufficient when nonlinear properties dominate. This is caused by the “Quasi-Steady State Assumption” that traditional singular perturbation holds. By assuming that microgrid can only be stabilized when fast variables stop variating, the traditional method ignores some common phenomena before a stabilization occurs, leading to a loss of dynamics. To improve the accuracy, this paper proposes a “second-order singular perturbation”. Here, the traditional “Quasi-Steady State” is updated to a scenario that third-order derivatives of fast variables become zero before the microgrid stabilizes. The updated assumption covers more common phenomena before a stabilization occurs. This leads to a more precise simplification. Simulation results indicate that the proposed method outperforms traditional singular perturbation in accuracy.

Abstract Background The growth and development of insects is strictly dependent on the precise regulation of chitin synthase (CHS), which is absent in vertebrates and plants. Therefore, CHS represents an attractive target for insecticides. At present, the research on the CHS gene in mosquitoes, especially its biological functions, remains limited. Results The full-length cDNA of the chitin synthase B gene in Culex pipiens pallens (CpCHSB) was prepared and consists of 5158 nucleotides with an open reading frame (ORF) of 4722 nucleotides encoding a protein of 1573 amino acid residues. Among different tissues, CpCHSB gene is mainly expressed in the midgut tissue with the highest expression in adult mosquitoes. Knockdown of CpCHSB in the larval stage significantly lowered the chitin content (16.5%) decreased body size (reduced by 25.6% in the larval stage and by 25.6% in the adult stage), and diminished reproduction (20%). Injecting siCHSB into adult mosquito mainly decreased reproduction (27%). Conclusions CpCHSB plays essential roles in growth and development, by severely reducing larval chitin content, midgut permeability, and reducing the number of female mosquito offspring. These results indicate that CHSB may serve as a potential novel target for exploring biosafe insecticides.

Abstract Background Acute fibrinous and organizing pneumonia (AFOP) is a very rare form of acute or subacute lung injury, which is characterized by patches of “fibrin balls” distributed within the alveoli. Given the lack of typical clinical manifestations, AFOP is often misdiagnosed as pneumonia, tuberculosis, etc. Definitive diagnosis is obtained from a lung biopsy. Corticosteroids are usually effective. Case presentation We report two cases of patients with histopathological manifestations of AFOP, which were significantly improved after corticosteroid therapy. Previous reports of the clinical and pathological characteristics of AFOP were reviewed to improve clinicians’ understanding of this disease. Conclusions Early identification and diagnosis are very important for AFOP treatment. The prognosis is acceptable after timely and effective treatment.

ObjectiveTo develop a neoantigen-targeted personalized cancer treatment for non-small cell lung cancer (NSCLC), neoantigens were obtained from collected human lung cancer samples, and the utility of neoantigen and neoantigen-reactive T cells (NRTs) was assessed.MethodsTumor specimens from three patients with NSCLC were obtained and analyzed by whole-exome sequencing, and neoantigens were predicted accordingly. Dendritic cells and T lymphocytes were isolated, NRTs were elicited and IFN-γ ELISPOT tests were conducted. HLA-A2.1/Kb transgenic mice were immunized with peptides from HLA-A*02:01+patient with high immunogenicity, and NRTs were subjected to IFN-γ, IL-2 and TNF-α ELISPOT as well as time-resolved fluorescence assay for cytotoxicity assays to verify the immunogenicity in vitro. The HLA-A*02:01+lung cancer cell line was transfected with minigene and inoculated into the flanks of C57BL/6nu/nu mice and the NRTs induced by the immunogenic polypeptides from autologous HLA-A2.1/Kb transgenic mice were adoptively transfused to verify their immunogenicity in vivo.ResultsMultiple putative mutation-associated neoantigens with strong affinity for HLA were selected from each patient. Immunogenic neoantigen were identified in all three NSCLC patients, the potency of ACAD8-T105I, BCAR1-G23V and PLCG1-M425L as effective neoantigen to active T cells in suppressing tumor growth was further proven both in vitro and in vivo using HLA-A2.1/Kb transgenic mice and tumor-bearing mouse models.ConclusionNeoantigens with strong immunogenicity can be screened from NSCLC patients through the whole-exome sequencing of patient specimens and machine-learning-based neoantigen predictions. NRTs shown efficient antitumor responses in transgenic mice and tumor-bearing mouse models. Our results indicate that the development of neoantigen-based personalized immunotherapies in NSCLC is possible.PrecisNeoantigens with strong immunogenicity were screened from NSCLC patients. This research provides evidence suggesting that neoantigen-based therapy might serve as feasible treatment for NSCLC.

Abstract Background Understanding how organisms adapt to high-elevation environments at a genome scale provides novel insights into the process of adaptive evolution. Previous studies have mainly focused on endothermic organisms, while poikilothermic species may have evolved different mechanisms to cope with high-elevation environments. In this context, we sequenced transcriptomes of a pair of closely related anuran species, Rana chensinensis and R. kukunoris, which inhabit respective low- and high-elevation habitats. By comparing the two transcriptomes, we identified candidate genes that may be involved in high-elevation adaption in poikilothermic species. Results Over 66 million sequence reads from each transcriptome were generated. A total of 41,858 and 39,293 transcripts for each species were obtained by de novo assembly. By comparing the orthologous transcripts, we identified 125 protein-coding genes that have likely experienced strong positive selection (Ka/Ks>1). In addition, 335 genes that may bear a signature of positive selection (1≥Ka/Ks>0.5) were also recognized. By considering their functions, fourteen candidate genes were determined to be likely involved in high-elevation adaptation, including two CYP genes, USP-1, and several others. Conclusions We identified a set of candidate genes that may have promoted adaptation of R. kukunoris to its high-elevation environment. These include several genes that have previously been associated with oxygen binding, response to UV radiation, and repair of free radical injury. Detailed molecular, physiological, and phenotypic studies are required to better understand the roles of these genes in improving the performance of R. kukunoris in a high-elevation environment. We have evidence for both convergent and divergent evolution between endothermic and poikilothemic species, but additional research across a wide range of organisms will be necessary to comprehend the complexity of high-elevation adaptation.

Segment uplift is a frequent problem during the construction of shield tunnels. The phenomenon of segment uplift in Xuzhou Metro Line 1 is investigated. The segment uplift magnitude in the shale layer is quite smaller than that in the clay layer. A tunnel segment uplift calculation model based on the Pasternak foundation beam model is proposed, which considers the hardening process of the grouted body with time. The finite difference method is adopted to calculate the magnitude of segment uplift during different tunnel construction stages, and a numerical solution of segment uplift on the longitudinal direction is obtained. The applicability of the numerical solution is studied by comparing with the field test results and parametric analyses are also performed to investigate the effects of different factors on segment uplifting. The results show that the coefficient of subgrade modulus, shear stiffness of the shear layer, and grout pressure all influence the segment uplifting of the tunnel. The influence of the coefficient of subgrade modulus and grout pressure on segment uplift is more significant.

The microparameter calibration of the particle flow parallel bond model (PBM) is mostly based on a uniaxial compression test. The microparameters calibrated only by uniaxial compression tests cannot be directly used to study the mechanical properties of rocks with surrounding pressure conditions. To analyze the relationship between the macroparameters and microparameters in the model and select appropriate particle flow model parameters, this study conducted a particle flow numerical simulation experiment based on the basic test principles of the uniaxial compression, Brazilian splitting, and triaxial compression tests. An orthogonal experimental design was performed for the calibration of the microparameters of the particle flow PBM, and multifactor analysis of variance was used to screen out the factors that have a considerable influence on the experimental indicators. Regression analysis was performed on the significant influencing factors and test indicators, and the corresponding linear and nonlinear relationships between the macroparameters and microparameters were obtained. Lastly, the microparameters of the model were determined in accordance with the macroparameters of the mechanical test of the Barun open-pit mine dolomite, and a numerical simulation test was conducted. Simulation test results were consistent with the actual test results, thus providing a basis for a subsequent numerical simulation study on the mechanical properties of dolomite.

Calculation of the electrostatic double layer force (EDL force) between clay particles is relevant as it is closely related to important macroscopic mechanical behaviors of clays. The popular method to calculate the EDL force is to integrate the electric potential and Maxwell stress along the boundary enclosing a simply connected domain within which a clay particle resides. The EDL force has also been calculated by the integration of the electrostatic force density over the preceding domain. However, the subtle relation of the EDL forces calculated by the different existing methods has not yet been investigated. By means of theoretical analysis and finite element simulation, it was shown that the force calculated by the integration of Maxwell stress along the complete boundary enclosing a multiply connected domain in which the clay particle is excluded, and that along the partial boundary enclosing the preceding simply connected domain represents the electrical attractive force and osmotic repulsive force, respectively, while the integration of the potential along both the same complete and partial boundary denotes the osmotic force. Numerical results showed that the calculated EDL force deviates from its actual value significantly with the decrease in distance between the chosen integral boundary and particle surface, and the deviation varies with surface potential and angle between particles. Moreover, the recommended minimum distance was proposed to be 10 times the thickness of the particle based on the present simulation results.

Dehydration-responsive element-binding (DREB) transcription factors regulate diverse processes during plant development. Here, a 2-year field study was conducted to assess the potential effects of DREB-genetically modified maize (GM1) on arthropod species and ecological communities. Arthropod abundance, diversity, and community composition in GM1 and its non-transformed counterpart maize variety, Chang 7-2, were compared using whole plant inspection, pitfall trap, and suction sampler methods. Based on Shannon–Wiener diversity, Simpson’s diversity, Pielou’s indexes, number of species, and total number of individuals, GM1 had a negligible effect on arthropod abundance and diversity. Redundancy analysis indicated that the composition of arthropod community was not associated with maize type in the three investigation methods, while it exhibited significant correlation with year and sampling time in whole plant inspection and suction sample methods, and distinctly correlated with sampling time in the pitfall trap method. Nonmetric multidimensional scaling analysis of variable factors in the three investigation methods showed that sampling time, rather than maize type or year, was closely related to the composition of arthropod community in the field. Our results provide direct evidence to support that DREB-GM maize had negligible effects on arthropods in the Jilin Province under natural conditions.

Abstract Background Epithelial-to-mesenchymal transition (EMT) plays an important role in the progression of renal interstitial fibrosis, which finally leads to renal failure. Oleanolic acid (OA), an activator of NF-E2-related factor 2 (Nrf2), is reported to attenuate renal fibrosis in mice with unilateral ureteral obstruction. However, the role of OA in the regulation of EMT and the underlying mechanisms remain to be investigated. This study aimed to evaluate the effects of OA on EMT of renal proximal tubular epithelial cell line (NRK-52E) induced by TGF-β1, and to elucidate its underlying mechanism. Methods Cells were incubated with TGF-β1 in the presence or absence of OA. The epithelial marker E-cadherin, the mesenchymal markers, α-smooth muscle actin (α-SMA), fibronectin, Nrf2, klotho, the signal transducer (p-Smad2/3), EMT initiator (Snail), and ILK were assayed by western blotting. Results Our results showed that the NRK-52E cells incubated with TGF-β1 induced EMT with transition to the spindle-like morphology, down-regulated the expression of E-cadherin but up-regulated the expression of α-SMA and fibronectin. However, the treatment with OA reversed all EMT markers in a dose-dependent manner. OA also restored the expression of Nrf2 and klotho, decreased the phosphorylation of Smad2/3, ILK, and Snail in cells which was initiated by TGF-β1. Conclusion OA can attenuate TGF-β1 mediate EMT in renal tubular epithelial cells and may be a promising therapeutic agent in the treatment of renal fibrosis.