PagPXYs improve drought tolerance by regulating reactive oxygen species homeostasis in the cambium of Populus alba × P. glandulosa.

PXY (Phloem intercalated with xylem) is a receptor kinase required for directional cell division during the development of plant vascular tissue. Drought stress usually affects plant stem cell division and differentiation thereby limiting plant growth. However, the role of PXY in cambial activities of woody plants under drought stress is unclear. In this study, we analyzed the biological functions of two PXY genes (PagPXYa and PagPXYb) in poplar growth and development and in response to drought stress in a hybrid poplar (Populus alba × P. glandulosa, '84K'). Expression analysis indicated that PagPXYs, similar to their orthologs PtrPXYs in Populus trichocarpa, are mainly expressed in the stem vascular system, and related to drought. Interestingly, overexpression of PagPXYa and PagPXYb in poplar did not have a significant impact on the growth status of transgenic plants under normal condition. However, when treated with 8 % PEG6000 or 100 mM H2O2, PagPXYa and PagPXYb overexpressing lines consistently exhibited more cambium cell layers, fewer xylem cell layers, and enhanced drought tolerance compared to the non-transgenic control '84K'. In addition, PagPXYs can alleviate the damage caused by H2O2 to the cambium under drought stress, thereby maintaining the cambial division activity of poplar under drought stress, indicating that PagPXYs play an important role in plant resistance to drought stress. This study provides a new insight for further research on the balance of growth and drought tolerance in forest trees.

LncRNA-mediated ceRNA network reveals the mechanism of action of Saorilao-4 decoction against pulmonary fibrosis.

Introduction: Pulmonary fibrosis (PF), a type of interstitial pneumonia with complex etiology and high mortality, is characterized by progressive scarring of the alveolar interstitium and myofibroblastic lesions. In this study, we screened for potential biomarkers in PF and clarified the role of the lncRNA-miRNA-mRNA ceRNA network in the inhibitory effect of SRL-4 on PF. Methods: Healthy male SPF SD rats were randomly divided into three groups, namely, CON, MOD, and SRL-4. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses were performed to determine the biological functions of the target genes. A visualized lncRNA-miRNA-mRNA ceRNA network was constructed using Cytoscape, while key genes in the network were identified using the cytoNCA plugin. Results: Seventy-four differentially expressed lncRNAs and 118 differentially expressed mRNAs were identified. Gene Ontology analysis revealed that the target genes were mainly enriched in the cell membrane and in response to organic substances, while Kyoto Encyclopedia of Genes and Genomes analysis showed that the target genes were mainly enriched in the AMPK, PPAR, and cAMP signaling pathways. We elucidated a ceRNA axis, namely, Plcd3-OT1/rno-miR-150-3p/Fkbp5, with potential implications in PF. Key genes, such as AABR07051308.1-201, F2rl2-OT1, and LINC3337, may be important targets for the treatment of PF, while the AMPK, PPAR, and cAMP signaling pathways are potential key targets and important pathways through which SRL-4 mitigates PF. Conclusion: Our findings suggest that SRL-4 improves PF by regulating the lncRNA-miRNA-mRNA network.

Identification of Central Genes and Regulatory Pathways Associated with Hyperlipidemia in Rats.

Hyperlipidemia is an independent risk factor for cardiovascular and cerebrovascular diseases. The transcriptomic data and the gene regulatory networks of hyperlipidemia are largely unclear. We analyzed the changes in liver gene expression and the serum levels of biochemical indicators in rats with hyperlipidemia induced by high-fat diet (HFD). The body weight, liver weight, and the serum levels of TG, TC, HDL-C, LDL-C, ALT, and AST were significantly higher in the hyperlipidemic rats compared to the healthy controls (P < 0.05). In addition, HFD feeding decreased the antioxidant capacity of the liver tissues and significantly increased the arteriosclerosis index (AI) (P < 0.05). There were 584 differentially expressed genes (DEGs) in the hyperlipidemia model compared to the control, with |log2FC|≥ 1 and P-adjust ≤ 0.05 as the thresholds. GO analysis of the DEGs revealed significant enrichment of 382 biological processes (BP), 18 cellular components (CC), and 40 molecular functions (MF). In addition, pathways related to bile secretion, cholesterol metabolism, and steroid hormone biosynthesis were significantly associated with hyperlipidemia. The key genes potentially involved in the blood lipid changes were Agt, Src, Gnai3, Cyp2c7, Cyp2c11, Cyp2c22, Apoa1, Apoe, and Srebf1. The genes and pathways identified in this study are potential intervention targets for hyperlipidemia and warrant further investigation.

Exploring the inherent mechanism of residents' participation behavior in neighborhood regeneration projects: an empirical study using an extended IMB model in China.

Introduction: Resident participation has gained increasing prominence and significance in the pursuit of sustainable neighborhoods regeneration. However, the current state of resident participation practices remains beset by several challenges, which present formidable impediments to the initiation and execution of neighborhood regeneration initiatives. This study aims to investigate the underlying mechanisms of residents' participation behavior to enhance resident participation in neighborhood regeneration projects. Methods: The present study employs the extended Information-Motivation-Behavioral (IMB) model to examine the determinants and mechanisms influencing residents' willingness and participation in neighborhood regeneration projects, with a specific focus on the Chinese context. Drawing upon data from 477 meticulously validated questionnaires administered to residents, the study applies structural equation modeling (SEM) to unravel the intrinsic dynamics of residents' participation behavior. Results: The empirical findings of this research reveal that information, motivation, and the perceived local government support all exert a significant impact on residents' participation willingness. Notably, motivation emerges as the most influential factor. Discussion: This study uncovers a direct influence of local government organizations on both residents' willingness and their actual participation, suggesting that government organizations can spearhead innovative strategies to bolster residents' willingness and furnish avenues for translating willingness into tangible participation. The outcomes of this study furnish an indispensable theoretical framework and offer policy recommendations that hold paramount importance for the deployment of novel interventions geared toward stimulating active involvement of residents in neighborhood regeneration.

Caveolin-mediated cytosolic delivery of spike nanoparticle enhances antitumor immunity of neoantigen vaccine for hepatocellular carcinoma.

Rationale: Although neoantigen-based cancer vaccines have shown promise in various solid tumors, limited immune responses and clinical outcomes have been reported in patients with advanced disease. Cytosolic transport of neoantigen and adjuvant is required for the activation of intracellular Toll-like receptors (TLRs) and cross-presentation to prime neoantigen-specific CD8+T cells but remains a significant challenge. Methods: In this study, we aimed to develop a virus-like silicon vaccine (V-scVLPs) with a unique spike topological structure, capable of efficiently co-delivering a hepatocellular carcinoma (HCC)-specific neoantigen and a TLR9 agonist to dendritic cells (DCs) to induce a robust CD8+T cell response to prevent orthotopic tumor growth. We evaluated the antitumor efficacy of V-scVLPs by examining tumor growth and survival time in animal models, as well as analyzing tumor-infiltrating CD8+T cells and cytokine responses in the tumor microenvironment (TME). To evaluate the synergistic efficacy of V-scVLPs in combination with α-TIM-3 in HCC, we used an orthotopic HCC mouse model, a lung metastasis model, and a tumor rechallenge model after hepatectomy. Results: We found that V-scVLPs can efficiently co-deliver the hepatocellular carcinoma (HCC)-specific neoantigen and the TLR9 agonist to DCs via caveolin-mediated endocytosis. This advanced delivery strategy results in efficient lymph node draining of V-scVLPs to activate lymphoid DC maturation for promoting robust CD8+T cells and central memory T cells responses, which effectively prevents orthotopic HCC tumor growth. However, in the established orthotopic liver tumor models, the inhibitory receptor of TIM-3 was significantly upregulated in tumor-infiltrating CD8+T cells after immunization with V-scVLPs. Blocking the TIM-3 signaling further restored the antitumor activity of V-scVLPs-induced CD8+T cells, reduced the proportion of regulatory T cells, and increased the levels of cytokines to alter the tumor microenvironment to efficiently suppress established orthotopic HCC tumor growth, and inhibit lung metastasis as well as recurrence after hepatectomy. Conclusion: Overall, the developed novel spike nanoparticles with efficient neoantigen and adjuvant intracellular delivery capability holds great promise for future clinical translation to improve HCC immunotherapy.

Molecular insights into the inhibition mechanism of harringtonine against essential proteins associated with SARS-CoV-2 entry.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has recently posed a serious threat to global public health. Harringtonine (HT), as a small-molecule antagonist, has antiviral activity against a variety of viruses. There is evidence that HT can inhibit the SARS-CoV-2 entry into host cells by blocking the Spike protein and transmembrane protease serine 2 (TMPRSS2). However, the molecular mechanism underlying the inhibition effect of HT is largely elusive. Here, docking and all-atom molecular dynamics simulations were used to investigate the mechanism of HT against the receptor binding domain (RBD) of Spike, TMPRSS2, as well as the complex of RBD and angiotensin-converting enzyme 2 complex (RBD-ACE2). The results reveal that HT binds to all proteins primarily through hydrogen bond and hydrophobic interactions. Binding with HT influences the structural stability and dynamic motility processes of each protein. The interactions of HT with residues N33, H34 and K353 of ACE2, and residue K417 and Y453 of RBD contribute to disrupting the binding affinity between RBD and ACE2, which may hinder the virus entry into host cells. Our research provides molecular insights into the inhibition mechanism of HT against SARS-CoV-2 associated proteins, which will help for the novel antiviral drugs development.

Pheromone effect of estradiol regulates the conjugative transfer of pCF10 carrying antibiotic resistance genes.

Horizontal gene transfer (HGT) mediated by conjugative plasmids greatly contributes to bacteria evolution and the transmission of antibiotic resistance genes (ARGs). In addition to the selective pressure imposed by extensive antibiotic use, environmental chemical pollutants facilitate the dissemination of antibiotic resistance, consequently posing a serious threat to the ecological environment. Presently, the majority of studies focus on the effects of environmental compounds on R plasmid-mediated conjugation transfer, and pheromone-inducible conjugation has largely been neglected. In this study, we explored the pheromone effect and potential molecular mechanisms of estradiol in promoting the conjugative transfer of pCF10 plasmid in Enterococcus faecalis. Environmentally relevant concentrations of estradiol significantly increased the conjugative transfer of pCF10 with a maximum frequency of 3.2 × 10-2, up to 3.5-fold change compared to that of control. Exposure to estradiol induced the activation of pheromone signaling cascade by increasing the expression of ccfA. Furthermore, estradiol might directly bind to the pheromone receptor PrgZ and promote pCF10 induction and finally enhance the conjugative transfer of pCF10. These findings cast valuable insights on the roles of estradiol and its homolog in increasing antibiotic resistance and the potential ecological risk.

Modeling residents' multidimensional social capital in China's neighborhood renewal projects: SEM and MIMIC approaches.

Neighborhood renewal is now an important approach to sustainable urban development in China. However, neighborhood renewal projects are often beset with social problems such as noncooperation from residents, which can be attributed to diverse interests and complex relationships among residents. However, there is little research on resident relations in China and intra-resident conflict. Based on social capital, this study provided a better understanding of resident relationships in neighborhood renewal in China. To this end, we developed a theoretical framework of residents' multidimensional social capital (structural, relational, and cognitive). Then, a survey was conducted to collect data from 590 residents across China who were experiencing or had experienced neighborhood renewal. Structural equation modeling (SEM) and multiple indicators multiple causes (MIMIC) modeling were used. The results revealed positive effects of structural social capital on relational and cognitive social capital, and the mediation role of relational social capital was demonstrated. We also tested the effects of differences in sociodemographic characteristics. Our findings verify the explanatory power of social capital regarding residents' complex relationships in neighborhood renewal in China. Implications for theory and policy are discussed. This study helps to improve our understanding of residents' social systems in neighborhood renewal and provides theoretical support for formulating neighborhood renewal policies in China and abroad.

Accounting Conformational Dynamics into Structural Modeling Reflected by Cryo-EM with Deep Learning.

With the continuous development of structural biology, the requirement for accurate threedimensional structures during functional modulation of biological macromolecules is increasing. Therefore, determining the dynamic structures of bio-macromolecular at high resolution has been a highpriority task. With the development of cryo-electron microscopy (cryo-EM) techniques, the flexible structures of biomacromolecules at the atomic resolution level grow rapidly. Nevertheless, it is difficult for cryo-EM to produce high-resolution dynamic structures without a great deal of manpower and time. Fortunately, deep learning, belonging to the domain of artificial intelligence, speeds up and simplifies this workflow for handling the high-throughput cryo-EM data. Here, we generalized and summarized some software packages and referred algorithms of deep learning with remarkable effects on cryo-EM data processing, including Warp, user-free preprocessing routines, TranSPHIRE, PARSED, Topaz, crYOLO, and self-supervised workflow, and pointed out the strategies to improve the resolution and efficiency of three-dimensional reconstruction. We hope it will shed some light on the bio-macromolecular dynamic structure modeling with the deep learning algorithms.

Docosahexaenoic acid inhibits pheromone-responsive-plasmid-mediated conjugative transfer of antibiotic resistance genes in Enterococcus faecalis.

The rapid spread of antibiotic-resistance genes (ARGs) in Enterococcus faecalis (E. faecalis) poses a great challenge to human health and ecological and environmental safety. Therefore, it is important to control the spread of ARGs. In this study, we observed that the addition of 5 µg/mL docosahexaenoic acid (DHA) reduced the conjugative transfer of pCF10 plasmid by more than 95% in E. faecalis. DHA disturbed the pheromone transport by inhibiting the mRNA levels of the prgZ gene, causing the iCF10 pheromone to accumulate in the donor bacteria and bond to the PrgX receptor to form an inhibitory phase, which resulted in the down-regulation of the expression of genes related to conjugative transfer, inhibiting biofilm formation, reducing bacterial adhesion and thus inhibiting conjugative transfer. Collectively, DHA exhibited an admirable inhibitory effect on the transfer of ARGs in E. faecalis. This study provided a technical option to control the transfer of ARGs.

Bisphenols Promote the Pheromone-Responsive Plasmid-Mediated Conjugative Transfer of Antibiotic Resistance Genes in Enterococcus faecalis.

The enrichment and spread of antibiotic resistance genes (ARGs) induced by environmental chemical pollution further exacerbated the threat to human health and ecological safety. Several compounds are known to induce R plasmid-mediated conjugation through inducing reactive oxygen species (ROS), increasing cell membrane permeability, enhancing regulatory genes expression, and so forth. Up to now, there has been no substantial breakthrough in the studies of models and related mechanisms. Here, we established a new conjugation model using pheromone-responsive plasmid pCF10 and confirmed that five kinds of bisphenols (BPs) at environmentally relevant concentrations could significantly promote the conjugation of ARGs mediated by plasmid pCF10 in E. faecalis by up to 4.5-fold compared with untreated cells. Using qPCR, gene knockout and UHPLC, we explored the mechanisms behind this phenomenon using bisphenol A (BPA) as a model of BPs and demonstrated that BPA could upregulate the expression of pheromone, promote bacterial aggregation, and even directly activate conjugation as a pheromone instead of producing ROS and enhancing cell membrane permeability. Interestingly, the result of mathematical analysis showed that the pheromone effect of most BPs is more potent than that of synthetic pheromone cCF10. These findings provide new insight into the environmental behavior and biological effect of BPs and provided new method and theory to study on enrichment and spread of ARGs induced by environmental chemical pollution.

CO2-Containing Reservoir Evaluation Based on the Joint Inversion of Nuclear Logs and Resistivity Logs: A Case Study of Ultrahigh-Temperature and High-Pressure Gas Reservoirs in the Yinggehai Basin, China.

Due to the unique characteristics of reservoirs in the Yinggehai Basin in the South China Sea, such as high temperature and high pressure (HPHT), low porosity, low permeability, complex pore structure, and high lime content, the log responses of these reservoirs have very complex characteristics, which makes it difficult to evaluate reservoir parameters accurately. In addition, most reservoirs in Ledong Block of the Yinggehai Basin in the South China Sea contain CO2, posing great difficulties for subsequent exploration and development. Accurate evaluation of CO2 layers is of paramount importance for the development of oil and gas fields. In this study, we used a method for the joint inversion of multiple well logs to evaluate the reservoirs and determine CO2 saturation level and other formation parameters. We optimized the joint inversion model based on the characteristics of the reservoirs in the Yinggehai Basin and adjusted the forward simulation model to consider the effects of high temperature and high pressure on gas density. In view of high lime content in the formations in this area, we adjusted the resistivity forward simulation model to consider the effect of lime content. The inversion results show that the values of porosity, permeability, and water saturation level obtained through inversion are largely consistent with the core data. The CO2 saturation level determined through joint inversion is 22%, which represents a deviation of less than 10% from the drilling system testing (DST) result, indicating that the joint inversion method is accurate. The error in the water saturation level determined through the joint inversion method is smaller than that in the calculated results from conventional multimineral inversion models. We performed forward simulation of the results calculated with the joint inversion method and compared the results of forward simulation with actual log curves. For the sandstone interval, the results of forward simulation are largely consistent with the actual log curves, indicating that the joint inversion method is accurate. In summary, the method presented in this paper can accurately determine reservoir parameters and provide strong support for the exploration and development of oil and gas fields in the Yinggehai Basin in the South China Sea.

Molecular Dynamics Study on Mechanical Properties of Nanopolycrystalline Cu-Sn Alloy.

Molecular dynamics simulation is one kinds of important methods to research the nanocrystalline materials which is difficult to be studied through experimental characterization. In order to study the effects of Sn content and strain rate on the mechanical properties of nanopolycrystalline Cu-Sn alloy, the tensile simulation of nanopolycrystalline Cu-Sn alloy was carried out by molecular dynamics in the present study. The results demonstrate that the addition of Sn reduces the ductility of Cu-Sn alloy. However, the elastic modulus and tensile strength of Cu-Sn alloy are improved with increasing the Sn content initially, but they will be reduced when the Sn content exceeds 4% and 8%, respectively. Then, strain rate ranges from 1 × 109 s-1 to 5 × 109 s-1 were applied to the Cu-7Sn alloy, the results show that the strain rate influence elastic modulus of nanopolycrystalline Cu-7Sn alloy weakly, but the tensile strength and ductility enhance obviously with increasing the strain rate. Finally, the microstructure evolution of nanopolycrystalline Cu-Sn alloy during the whole tensile process was studied. It is found that the dislocation density in the Cu-Sn alloy reduces with increasing the Sn content. However, high strain rate leads to stacking faults more easily to generate and high dislocation density in the Cu-7Sn alloy.

Thermal Neutron Cross Section Logging based on compensated neutron logging.

In this paper, the compensated neutron logging is transformed into the Thermal Neutron Cross Section Logging (TNXS) to improve the application effect. Because the compensated neutron logging measures the neutron count, TNXS cannot be directly measured by the compensated neutron logging tool. Moreover, the thermal neutron ratio cannot be directly converted into the TNXS due to the influence of lithology and fluid. The ratio of thermal neutron count is related not only to the formation hydrogen index, but also to the formation density and the formation capture cross section. The density and the capture cross section of formations can be used to reduce the influence of lithology and fluid. Therefore, the thermal neutron counting ratio can be converted into the TNXS by density and the capture cross section of formations. The accuracy of the porosity calculated by the TNXS is studied based on the Monte Carlo method. The results show that the thermal neutron counting ratio can be accurately converted to the TNXS by density and the capture cross section of formations. The porosity calculated by TNXS is closer to the formation porosity than that calculated by the compensated neutron logging, especially in gas-bearing formations and complex lithologic formations.

In-situ photopolymerized polyhedral oligomeric silsesquioxane-derived monolithic capillary columns with quinidine functionality for enantioseparation by nano-liquid chromatography.

The successful fabrication of monolithic capillary columns for enantiomer separations was achieved within vinylized fused silica capillaries via fast "one-pot" photo-initiated free radical polymerization reaction. A mixture consisting of polyhedral oligomeric silsesquioxane, O-[2-(methacryloyloxy)ethylcarbamoyl]-10,11-dihydroquinidine was copolymerized in the presence of n-butanol, ethylene glycol and photo-initiator 2,2-dimethoxy-2-phenylacetophenone. The morphology of the resultant polymeric hybrid inorganic-organic material and its permeability as well as porosity can be controlled by adjusting the composition of the monomers and binary porogenic solvent. The chromatographic characteristics of the columns have been investigated. Separation factors of N-acetyl-phenylalanine (Ac-Phe) and dichlorprop dropped with decrease of chiral functional monomer. Permeability was better when the macroporogen ethyleneglycol was present at higher concentrations during the polymerization. In general, the chiral compounds were well separated (dichlorprop: α = 1.53, Rs up to 4.14; Ac-Phe: α = 1.36, Rs up to 2.69) by nano-HPLC with an optimized enantioselective monolithic capillary column which can be prepared within a few minutes.

Research on spectral processing methods of the carbon/oxygen spectral logging in sandstone.

The inelastic spectrum-based carbon/oxygen spectral logging has been widely applied in the interpretation of residual oil saturation. The effects of traditional spectral processing methods for obtaining inelastic spectrum are influenced by salinity (including pore fluid salinity and borehole fluid salinity), clay content, porosity, etc. The interpretation accuracy thereof needs to be improved. In this paper, we proposed a new method for obtaining inelastic spectrum. To validate the new method and compare it with the traditional methods, the numerical simulation method (Monte Carlo) is used to simulate different formation models. The result shows that in addition to sandstone formation with clay, the new method improves the interpretation accuracy of oil saturation.

In-situ photopolymerized C4-functionalized organosilicon monoliths for reversed-phase protein separation in nano-liquid chromatography.

In this study, polyhedral oligomeric silsesquioxane (POSS)-based capillary monoliths with short alkyl chain ligand in the form of butyl (C4) were synthesized via two different polymerization routes, namely UV-initiated free radical copolymerization of methacrylate-derivatized POSS (POSS-MA) with butylmethacrylate (BMA) and UV-initiated thiol-methacrylate copolymerization of POSS-MA with butanethiol (BT). An organosilicon monolith with a pore size distribution lying on both mesoporous and macroporous scales, a lower mean pore size and a higher specific surface area was obtained with UV-initiated thiol-methacrylate polymerization. Both monoliths were then comparatively evaluated for gradient separation of proteins under reversed phase conditions in nano-liquid chromatography. The chromatographic performance was defined in terms of peak-resolution and peak capacity. Four carbon (C4) functionalized-poly(POSS-MA) monolith produced by UV-initiated thiol-methacrylate polymerization exhibited better separation performance with higher peak resolutions and peak capacities. Both, the morphological characterization of monoliths and the results of gradient separation of proteins showed that thiol-methacrylate polymerization was more suitable for the synthesis of C4 functionalized organosilicon based stationary phases for reversed-phase protein separation. The monolith prepared by thiol-methacrylate polymerization was also successfully applied for impurity analysis of two important hormones, namely insulin and genotropin. A comparison with a commercial poly(styrene-co-divinylbenzene) monolith documented the good chromatographic performance of the new BT-attached poly(POSS-MA) monolith.