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Citrus bacterial canker (CBC) is a serious bacterial disease affecting citrus plantations and the citrus industry all over the world. We have previously shown that an apetala 2/ethylene response factor in Citrus sinensis, CsAP2-09, positively regulated resistance to CBC, although the regulatory mechanisms remained undetermined. Here, we demonstrated that CsAP2-09 positively and sustainably controlled resistance to CBC in three-year transgenic plants. CsAP2-09 was found to be a transcriptional activator, and qRT-PCR and dual luciferase assays showed that it controlled the expression CsGH3.1L. CsAP2-09 bound directly to the promotor of CsGH3.1L, shown by yeast one-hybrid assay, with the binding site confirmed by electrophoretic mobility shift assay. Biochemical assays showed that CsAP2-09 negatively regulated the biosynthesis of indole acetic acid (IAA) and positively regulated that of salicylic acid (SA) and ethylene, verified with transient overexpression of CsGH3.1L. The combination of these results with those of previous reports indicated that SA, ethylene, and IAA can directly regulate CBC resistance. Overall, we revealed a pathway whereby CsAP2-09 conferred CBC resistance by direct binding to the CsGH3.1L promoter, activating its expression and modulating IAA, SA, and ethylene biosynthesis. Our study indicates the potential value of manipulating CsAP2-09 and CsGH3.1L in the breeding of CBC-resistant citrus.

African swine fever virus (ASFV) is an important pathogen that causes a highly contagious and lethal disease in swine, for which neither a vaccine nor treatment is available. The DNA repair enzyme 8-oxoguanine DNA glycosylase 1 (OGG1), which excises the oxidative base lesion 8-oxo-7,8-dihydroguanine (8-oxoG), has been linked to the pathogenesis of different diseases associated with viral infections. However, the role of OGG1-base excision repair (BER) in ASFV infection has been poorly investigated. Our study aimed to characterize the alteration of host reactive oxygen species (ROS) and OGG1 and to analyse the role of OGG1 in ASFV infection. We found that ASFV infection induced high levels and dynamic changes in ROS and 8-oxoG and consistently increased the expression of OGG1. Viral yield, transcription level, and protein synthesis were reduced in ASFV-infected primary alveolar macrophages (PAMs) treated by TH5487 or SU0268 inhibiting OGG1. The expression of BER pathway associated proteins of ASFV was also suppressed in OGG1-inhibited PAMs. Furthermore, OGG1 was found to negatively regulate interferon β (IFN-β) production during ASFV infection and IFN-β could be activated by OGG1 inhibition with TH5487 and SU0268, which blocked OGG1 binding to 8-oxoG. Additionally, the interaction of OGG1 with viral MGF360-14L protein could disturb IFN-β production to further affect ASFV replication. These results suggest that OGG1 plays the crucial role in successful viral infection and OGG1 inhibitors SU0268 or TH5487 could be used as antiviral agents for ASFV infection.

Despite the several researches on the correlates of insight in psychosis, less is known regarding the specificity of disease diagnosis on the relationship between insight and the correlates. The current study sought to explore the effects of insight and disease diagnosis on those in patients with obsessive-compulsive disorder (OCD) and patients with schizo-obsessive disorder (SOD).We evaluated clinical symptoms and neurocognitions among 111 patients (including 41 OCD with good insight, 40 OCD with poor insight, 14 SOD with good insight and 16 SOD with poor insight. Gray matter volume and spontaneous neural activity were also examined by analyzing the voxel-based morphometry and amplitude of low frequency fluctuation (ALFF), respectively.Interactive effects of insight and diagnosis was found on working memory and the gray matter volume in right superior and middle temporal gyrus. Main effect of insight was found on working and visual memory, compulsion and obsession, and ALFF in right middle and superior occipital cortex. Main effect of diagnosis was found on severity of compulsion, relative verbal IQ, executive function, verbal and visual memory, working memory and ALFF in precuneus, medial superior frontal gyrus, anterior cingulate and paracingulate gyri, and inferior parietal, postcentral gyrus, paracentral lobule.As a common feature in mental disorders, insight has its own special influence on neurocognition and possible structural/functional alterations in brain, and the influence is partly dependent of disease diagnosis.

Hypothesis Factor Va (FXa) and Xa (FVa) can assemble on the phosphatidylserine (PS) membrane (of platelet) to form prothrombinase complex and contribute to blood clotting. Very recently, we discovered that Ca-zeolite acts as a type of reinforced activated inorganic platelet to enable assembly of prothrombinase complex and display an unusual zymogen (prothrombin) activation pattern. Inspired but not constrained by nature, it is of great interest to understand how FVa and FXa assembly on the inorganic surface (e.g., zeolites) and perform their biocatalytic function. Experiments Given the important role of FVa C1-C2 domains in the assembly and activity of the prothrombinase complex, in this work, molecular dynamics simulations were performed to investigate the binding details of FVa A3-C1-C2 domains on the PS membranes and Ca2+-LTA-type (CaA) zeolite surface. Findings We found that different from the natural PS membrane, FVa light chain repeatedly exhibits a strong C2 domain anchoring interaction on the CaA zeolite. It mainly arises from the porous surface structure of CaA zeolite and local highly dense solvation water clusters on the CaA zeolite surface restrict the movement of some lysine residues on the C2 domain. The anchoring interaction can be suppressed by reducing the surface negative charge density, so that FVa light chain can change from single-foot (only C2 domain) to double-foot (both C1-C2 domain) adsorption states on the zeolite surface. This double-foot adsorption state is similar to natural PS membrane systems, which may make FVa have higher cofactor activity.

Background: Pyroptosis, gasdermin-mediated programmed cell death, is readily induced in macrophages by activation of the canonical inflammasome (caspase-1) or by intracellular lipopolysaccharide (LPS)-mediated non-canonical inflammasome (caspase-11) activation. However, whether pyroptosis is induced similarly in hepatocytes is still largely controversial but highly relevant to liver pathologies such as alcoholic/nonalcoholic liver disease, drug-induced liver injury, ischemia-reperfusion and liver transplant injury, or organ damage secondary to sepsis. Methods and Results: In this study we found that hepatocytes activate and cleave gasdermin-D (GSDMD) at low levels after treatment with LPS. Overexpression of caspase-1 or caspase-11 p10/p20 activated domains was able to induce typical GSDMD-dependent pyroptosis in hepatocytes both in vitro and in vivo. However, morphologic features of pyroptosis in macrophages (eg, pyroptotic bodies, cell flattening, loss of cell structure) did not occur in pyroptotic hepatocytes, with cell structure remaining relatively intact despite the cell membrane being breached. Our results suggest that hepatocytes activate pyroptosis pathways and cleave GSDMD, but this does not result in cell rupture and confer the same pyroptotic morphologic changes as previously reported in macrophages. This is true even with caspase-1 or caspase-11 artificial overexpression way above levels seen endogenously even after priming or in pathologic conditions. Conclusions: Our novel findings characterize hepatocyte morphology in pyroptosis and suggest alternative use for canonical/non-canonical inflammasome activation/signaling and subsequent GSDMD cleavage because there is no rapid cell death as in macrophages. Improved understanding and recognition of the role of these pathways in hepatocytes may result in novel therapeutics for a range of liver diseases.

This study constructs a multi-player evolutionary game of local governments, tourism enterprises, and residents to analyze the stability strategies of game players in ecotourism protective development. The results show that the evolutionary game system of ecotourism conservation development can form four kinds of stable strategies under different conditions. The marginal influence of restrictive factors on the players’ strategic choice is more significant than that of incentive factors. Government penalties and incentives promote tourism enterprises to choose protective development strategies, and residents to choose supervision strategies. When higher protective development rewards exceed the government’s support capacity, the probability of local governments choosing active supervision strategies will decrease. Tourism enterprises will also reduce the probability of choosing protective development strategies due to the lack of effective supervision. The research results can help decision-makers to formulate ecotourism protection and development policies, and promote the sustainable development of ecotourism.

The development of ice-and-snow tourism (IST) has great potential for poverty alleviation and is of great significance for promoting the sustainable development of alpine areas. However, little attention has been given to evaluating the suitability and potential of ice-and-snow tourism in poverty-stricken areas. Taking 832 poverty-stricken counties in China as samples, this study proposed an integrity suitability index (ISI) based on natural and socioeconomic factors to evaluate the suitability and potential of developing ice-and-snow tourism in poverty-stricken counties. The results showed that there are significant differences between the spatial distributions of the suitability of glacier- and ski-related tourism. The former is mainly distributed in the Qinghai‒Tibet Plateau, while the latter is distributed in low-altitude mountainous areas. Additionally, 36.0% of the total number of poverty-stricken counties have the potential to match medium-to high-level ISIs of ice-and-snow tourism, of which 2.5%, 32.9% and 0.2% are suitable for glacier excursions, ski sports and both, respectively. Furthermore, climate change and environmental protection are the main constraints on the development of ice-and-snow tourism and corresponding development strategies are proposed. This study can provide references for scientific planning and policy making regarding the sustainable development in poverty-stricken areas.

Immunotherapies based on immune checkpoint-blocking antibodies have been considered the most attractive cancer treatments in recent years. However, the systemic administration of immune checkpoint-blocking antibodies is limited by low response rates and high risk of inducing immune-related adverse events (irAEs), which might be overcome by the tumor-targeted delivery of these antibodies. To achieve tumor-targeted delivery, immune checkpoint-blocking antibodies are usually modified with tumor-homing ligands through difficult genetic fusion or chemical conjugation. As most immune checkpoint-blocking antibodies are immunoglobin G (IgG) antibodies, we hypothesize that these IgG antibodies might be noncovalently modified with a tumor-homing ligand fused to an IgG-binding domain (IgBD). To test this hypothesis, the tumor-homing ZPDGFRβ affibody, which targets platelet-derived growth factor receptor β (PDGFRβ), was fused to the Fab-selective IgBD in a trimeric format. After mixing ZPDGFRβ fused to the IgBD with immune checkpoint-blocking IgG against programmed death-ligand 1 (αPD-L1), a novel homogenous complex was formed, indicating that αPD-L1 had been successfully modified with ZPDGFRβ fused to the IgBD. ZPDGFRβ-modified αPD-L1 bound to both PDGFRβ and PD-L1, thus leading to greater tumor uptake and antitumor effects in mice bearing PDGFRβ+PD-L1+ tumor grafts. In addition, due to the broad spectrum of IgBD for IgG, immune checkpoint-blocking IgG antibodies against cytotoxic T-lymphocyte-associated protein 4 (αCTLA-4) and signal regulatory protein alpha (αSIRPα) were also modified with ZPDGFRβ fused to the IgBD. These results demonstrated that a tumor-homing ligand fused to the IgBD might be developed as a versatile platform for the modification of immune checkpoint-blocking IgG antibodies to achieve tumor-targeted delivery.

Considering that the particular geometric shape of a quasi-rectangular shield, the grout flowing law and its motion process are more complicated than those of a conventional circular shield. To interpret the grouting mechanical behavior in the special-shape shield tail void, the filling and diffusion mechanism of synchronous grouting was analysed. The grout flowing is separated into two independent motion processes, which contains a circumferential filling and a longitudinal diffusion. The theoretical model of the grout pressure spatial distribution was derived based on the principle of fluid mechanics. Then, the pressure distributions in the two directions were obtained using a case study and compared with the field measured data to verify the validation of the model. Although the overall spatial pattern of grout pressure distribution on the tunnel profile show a change trend dominated by the self-weight effect mostly, its local fluctuation characteristics is very abnormal relative to that of a circular shield tunnel. Moreover, the important factors in the model were analysed, including the grout material parameters, the grouting construction parameters, and some geometry parameters. The results show that the pressure loss along this way is positively correlated with the grout flow velocity and is sensitive to the shear yield stress of the grout. The pressure loss along the circumferential direction is the most sensitive to the thickness of the ring cake, and the value range suitable for the model should be 0.02–0.03 m. The pressure loss along the longitudinal diffusion direction is the most sensitive to the size of the tail void. The research results can provide a theoretical basis for the control of special-shape shield construction.

Background Clinical studies have suggested that there is a significant correlation between left ventricular (LV) false tendon and premature ventricular complexes (PVCs). Objective This study aimed to investigate the electrophysiological characteristics and the outcome of radiofrequency catheter ablation (RFCA) for this category of PVCs. Methods From a total of 2284 patients with idiopathic PVCs who underwent catheter ablation at 6 institutions in China, intracardiac echocardiography (ICE) was used during the procedure in 346 cases; 10 patients (2.9%) with PVCs associated with false tendon were retrospectively reviewed and enrolled in the present study. Activation mapping and pace mapping were performed to localize the origin of PVCs. ICE was used in all patients. If the false tendon was directly visualized and identified, we attempted to identify the distinct relationship with the PVC origin. Results The PVCs were successfully eliminated by ablation in all patients. The target sites were confirmed to be related to false tendon. The origin of PVCs was located at the attachment of the false tendon to the papillary muscle, LV septum, or LV apex. At the target site, high-frequency Purkinje potentials were observed preceding local ventricular activation in 7 patients. Conclusion LV false tendon can be associated with PVCs, which can be cured by RFCA. An ICE-guided electroanatomical approach should be considered to improve the safety and feasibility of this procedure.

Intra-arterial infusion chemotherapy (IAIC), using immunomodulatory cisplatin, is a novel treatment for bladder cancer (BC) that allows the delivery of specific drugs to the local malignant lesion. To explore the immunomodulatory effect of cisplatin during IAIC, we detected the proportion of immunosuppressed cells in BC tissue from eight BC patients, with the reduction of myeloid-derived suppressor cells (MDSCs), more specifically fibrocytic-MDSCs (f-MDSCs). Further, we demonstrated that cisplatin inhibits their proliferation and immunosuppressive activity. f-MDSCs promote tumor proliferation and metastasis in the BC immune environment. Then, we analyzed the genetic differences detected in samples before and after chemotherapy and found that granulocyte colony-stimulating factors (G-CSF) decreased after IAIC. Furthermore, G-CSF methylation decreased following treatment with cisplatin. Specifically, treatment with cisplatin decreased the methylase (METTL3) levels in BC cells, which is important for G-CSF production. Collectively, cisplatin decreased the number of f-MDSCs during IAIC, by blocking G-CSF methylation via targeting METTL3.

Selective coupling of methyl radicals to produce C2 species (C2H4 and C2H6) is a key challenge for oxidative coupling of methane (OCM). In traditional OCM reaction systems, homogeneous transformation of methyl radicals in O2-containing gases are uncontrollable, resulting in limited C2 selectivity and yield. Herein, we demonstrate that methyl radicals generated by La2O3 at low reaction temperature can selectively couple on the surface of 5 wt% Na2WO4/SiO2. The controllable surface coupling against overoxidation barely changes the activity of La2O3 but boosts the C2 selectivity by three times and achieves a C2 yield as high as 10.9% at bed temperature of only 570 °C. Structure-property studies suggest that Na2WO4 nanoclusters are the active sites for methyl radical coupling. The strong CH3· affinity of these sites can even endow some methane combustion catalysts with OCM activity. The findings of the surface coupling of methyl radicals open a new direction to develop OCM catalyst. The bifunctional OCM catalyst system, which composes of a methane activation center and a CH3· coupling center, may deliver promising OCM performance at reaction temperatures below the ignition temperature of C2H6 and C2H4 (~600 °C) and is therefore more controllable, safer, and certainly more attractive as an actual process.

Based on density functional theory (DFT) and transition state theory, the effect of alkali metal Na on the formation mechanism and path of NH3 and HCN during coal pyrolysis was studied at the M06-2X/6-311G(d) level. The seven membered ring containing pyridine was selected as the coal model, and the adsorption structure of Na on the coal surface was used as the coal model containing Na. The results show that the presence of Na significantly strengthens the bonding between N and C atoms in pyridine ring, which makes the stripping of N atom from benzene ring requires higher activation energy, thus inhibiting the formation of HCN. However, Na can improve the surface activity of coal, and the energy barrier of NH3 formation rate determination step in the presence of Na is 271.35 kJ/mol lower than that in the absence of Na, which significantly promotes the formation of NH3.

The development of Qingzang national park cluster is part of China’s efforts to establish a major ecological civilization project in the Qingzang Plateau, in line with global sustainable development goals. Based on preliminary scientific investigation and research in the Qingzang Plateau, the construction of the park cluster will include 21 national parks. To mitigate the conflict between conservation of the national park cluster and the development of local communities, this study proposes an analysis framework to identify the spatial coupling features between the national park cluster and sustainable development of communities. Four elements were selected to construct the analysis framework, including natural conditions, geographic location, cultural background, and national policies. This framework was applied to the 457 township communities within the 21 national parks. Results show the weak influence of the construction of the national park cluster for approximately 304 township communities, without significant spatial coupling traits, while the remaining 153 communities demonstrated significant spatial coupling features. These latter townships had developed four types of spatial coupling with national parks, including eco-migrants, transportation hubs, characteristic cultures, and border development, which account for 17.4%, 35.3%, 19.8%, and 27.5% of the 153 townships respectively. A composite type with more than one spatial coupling feature was also found for 14 communities within the 153 townships. This provides a reference for policy making towards four major types of interactive modes between townships and the national park construction for the sustainable development of Qingzang Plateau.

Formaldehyde (HCHO) plays an important role in atmospheric ozone (O

The Qinghai-Tibet Plateau (QTP) is a region with unique and distinctive natural landscapes and cultural characteristics and presents a useful case to improve understanding of sustainable development for regions with extreme environments and unique social backgrounds. Research has been conducted for small-scale regions, however there has been insufficient exploration of the problems and countermeasures for sustainable development in Tibet. This study analyzes different functional zones (urbanized zones, agricultural zones, pastoral zones and ecological security zones) of the QTP. Then it develops a sustainable livelihood index (SLI) based on the sustainable livelihood analysis framework resulting in three main findings. First, sustainable livelihoods vary greatly across functional zones. The SLI for farmers and herdsmen in the urbanized zones is the highest, with a value of 3.57, followed by the agricultural zones of 3.07. In comparison, the SLI values in the ecological security zones and pastoral zones are 2.92 and 2.85, respectively, indicating that the two zones present challenges for sustainable development in the QTP. Second, all counties had few natural, social or physical assets, indicating the need to expand assets to achieve sustainable livelihoods. Finally, urbanized and agricultural counties had more robust livelihood strategies than ecological and pastoral counties. In light of these results, strategic options have been formulated to promote sustainable development. These options include: accelerating construction of the third pole national park group; establishing a pattern of green mining; promoting the biological resources industry; and initiating a carbon trading market in the QTP.

Herein, a bottom-down design is presented to successfully fabricate ZIF-derived Co3O4, grown in situ on a one-dimensional (1D) α-MnO2 material, denoted as α-MnO2@Co3O4. The synergistic effect derived from the coupled interface constructed between α-MnO2 and Co3O4 is responsible for the enhanced catalytic activity. The resultant α-MnO2@Co3O4 catalyst exhibits excellent catalytic activity at a T90% (temperature required to achieve a toluene conversion of 90%) of approximately 229 oC, which is 47 and 28 °C lower than those of the pure α-MnO2 nanowire and Co3O4-b obtained via pyrolysis of ZIF-67, respectively. This activity is attributed to the increase in the number of surface-adsorbed oxygen species, which accelerate the oxygen mobility and enhance the redox pairs of Mn4+/Mn3+ and Co2+/Co3+. Moreover, the result of in situ diffuse reflectance infrared Fourier transform spectroscopy suggests that the gaseous oxygen could be more easily activated to adsorbed oxygen species on the surface of α-MnO2@Co3O4 than on that of α-MnO2. The catalytic reaction route of toluene oxidation over the α-MnO2@Co3O4 catalyst is as follows: toluene → benzoate species → alkanes containing oxygen functional group → CO2 and H2O. In addition, the α-MnO2@Co3O4 catalyst shows excellent stability and good water resistance for toluene oxidation. Furthermore, the preparation method can be extended to other 1D MnO2 materials. A new strategy for the development of high-performance catalysts of practical significance is provided.

Background and aims The assessment of visceral adiposity is of great significance for the prevention of hyperuricemia (HUA), especially in non-obese individuals. The metabolic score for visceral fat (METS-VF) is a newly proposed surrogate of visceral obesity. We aimed to evaluate the longitudinal associations of METS-VF with the risk of HUA in non-obese adults. Methods and results A total of 16,058 non-obese adults without HUA were included for this retrospective cohort analyses. The crude incidence rate of HUA in non-obese women and men were 20.9 and 69.6 per 1000 person-years, respectively. The Cox proportional hazards model indicated that METS-VF was significantly associated with the risk of HUA in both genders. Whereas, METS-VF only had the highest HR in women, but not in men. Conclusions METS-VF, a novel surrogate of visceral adiposity combined biochemical and anthropometric parameters, age, and gender, could be a useful tool for the hierarchical prevention and management of HUA among non-obese women.

Here, we demonstrate a photochemical strategy to site-specifically deposit Pd atoms on Au nanoparticles. The high-sensitivity low-energy ion scattering spectra combined with the X-ray photoelectron spectra reveal that the surface electronic structure of Pd can be continuously regulated by tailoring the Pd-to-Au molar ratio and the location of Pd atoms in AuPd nanoparticles. It is revealed that electron-rich Pd atoms are considerably more active than the net Pd atoms in aerobic alcohol oxidation. Remarkably, the catalyst with the most electron-rich Pd sites (binding energy downshift: 1.0 eV) exhibits an extremely high turnover frequency (˜500000 h−1 vs 12000 h−1 for that with net Pd atoms) for solvent-free selective oxidation of benzyl alcohol, which is, to the best of our knowledge, the highest value ever reported. Kinetic studies reveal that electron-rich Pd atoms can accelerate the oxidation of benzyl alcohol by facilitating C-H cleavage, as indicated by the significant reduction in the activation energy as compared to net Pd atoms.

Maternal smoking during pregnancy and lactation is associated with increased fat mass in the offspring, but the mechanism by which this occurs is not fully understood. Our study focused on the relationships among maternal nicotine exposure, adipose angiogenesis and adipose tissue function in female offspring. Pregnant rats were randomly assigned to nicotine or control groups. Microvascular density, lipid metabolism and α7nAChR-Egr1-FGF2 signaling pathway genes/proteins were tested in 4-, 12- and 26-week female offspring. In vitro, nicotine concentration- and time-response experiments were conducted in 3T3-L1. Lipid metabolism and α7nAChR-Egr1-FGF2 signaling pathway genes/proteins were tested. The conditioned media of differentiated 3T3-L1 treated with nicotine were used to observe tube formation in human umbilical vein endothelial cells (HUVECs). Nicotine-exposed females presented higher adipose microvascular density. The gene expression of α7nAChR, Egr1 and FGF2 was significantly increased in gonadal white adipose tissue (gWAT) and inguinal subcutaneous WAT (igSWAT) of nicotine-exposed females at 4 weeks of age. The protein expression of α7nAChR, Egr1 and FGF2 was increased in gWAT and igSWAT of nicotine-exposed females at 4 weeks of age, and increased in gWAT at 26 weeks. In vitro, nicotine increased the expression of lipid metabolism and α7nAChR-Egr1-FGF2 signaling pathway genes/proteins in a concentration- and time-dependent manner. In the tube formation experiment, adipocytes affected by nicotine promoted HUVEC angiogenesis. Therefore, maternal nicotine exposure promoted the early angiogenesis of adipose tissue via the α7nAChR-Egr1-FGF2 signaling pathway, and this angiogenesis mechanism was associated with increased adipogenesis in adipose tissue of female offspring.