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Abstract Clear cell renal cell carcinoma (ccRCC) demonstrates enhanced glycolysis, critically contributing to tumor development. Programmed death-ligand 1 (PD-L1) aids tumor cells in evading T-cell-mediated immune surveillance. Yet, the specific mechanism by which glycolysis influences PD-L1 expression in ccRCC is not fully understood. Our research identified that the glycolysis-related gene (GRG) HK3 has a unique correlation with PD-L1 expression. HK3 has been identified as a key regulator of O-GlcNAcylation in ccRCC. O-GlcNAcylation exists on the serine 900 (Ser900) site of EP300 and can enhance its stability and oncogenic activity by preventing ubiquitination. Stably expressed EP300 works together with TFAP2A as a co-transcription factor to promote PD-L1 transcription and as an acetyltransferase to stabilize PD-L1 protein. Furthermore, ccRCC exhibits interactive dynamics with tumor-associated macrophages (TAMs). The uridine 5′-diphospho-N-acetylglucosamine (UDP-GlcNAc), which serves as a critical substrate for the O-GlcNAcylation process, facilitates TAMs polarization. In ccRCC cells, HK3 expression is influenced by IL-10 secreted by M2 TAMs. Our study elucidates that HK3-mediated O-GlcNAcylation of EP300 is involved in tumor immune evasion. This finding suggests potential strategies to enhance the efficacy of immune checkpoint blockade therapy.

Abstract Rate of penetration (ROP) is a key factor in drilling optimization, cost reduction and drilling cycle shortening. Due to the systematicity, complexity and uncertainty of drilling operations, however, it has always been a problem to establish a highly accurate and interpretable ROP prediction model to guide and optimize drilling operations. To solve this problem in the Tarim Basin, this study proposes four categories of hybrid physics-machine learning (ML) methods for modeling. One of which is residual modeling, in which an ML model learns to predict errors or residuals, via a physical model; the second is integrated coupling, in which the output of the physical model is used as an input to the ML model; the third is simple average, in which predictions from both the physical model and the ML model are combined; and the last is bootstrap aggregating (bagging), which follows the idea of ensemble learning to combine different physical models’ advantages. A total of 5655 real data points from the Halahatang oil field were used to test the performance of the various models. The results showed that the residual modeling model, with an R2 of 0.9936, had the best performance, followed by the simple average model and bagging with R2 values of 0.9394 and 0.5998, respectively. From the view of prediction accuracy, and model interpretability, the hybrid physics-ML model with residual modeling is the optimal method for ROP prediction.

UAVs will present significant air traffic in the urban airspace in the future, which brings new challenges to urban air traffic management and control. This paper presents an air route design scheme for multi-rotor UAVs in urban airspace to enable UAV operations at orderly levels. The air routes include legs and intersections, which are the three-dimensional channels of UAV flight. Based on the concept of structured and layered urban airspace, the cylindrical pipeline flight leg is designed, and the operation concept, characteristic parameters and flight procedures of along-road and roundabout intersections are proposed. By defining UAV conflict risk and intersection service level metrics, the operation situation of UAVs is quantitatively evaluated. Taking an urban transportation scenario as a case, the proposed route design scheme is simulated in different scale UAV operating scenarios. The results show that the number of UAVs at the intersection is positively correlated with the conflict probability, the number of crossing routes is negatively correlated with the intersection passing rate, and the UAV arrival rate is positively correlated with the intersection average passing time. The along-road type intersection is suitable for the area with fewer crossing routes and sparse UAVs, while the roundabout type intersection is adapted for the area with more crossing routes and dense UAVs. This research provides a new idea for urban UAV air route design, which is helpful in promoting the standardized management of UAVs and accelerating the integration of UAVs into urban airspace.

Background: In the realm of tumor-targeted therapeutics, Polo-like kinases (PLKs) are a significant group of protein kinases that were found recently as being related to tumors. However, the significance of PLKs in pan-cancer remains systematically studied. Methods and materials: We integrated multi-omics data to comprehensively investigate the expression patterns of the PLK family across various cancer types. Subsequently, study examined the associations between tumor mutation burden (TMB), microsatellite instability (MSI), immune subtype classification, immune infiltration, tumor microenvironment scores, immune checkpoint gene expression, and the PLKs expression profiles within various tumor types. Furthermore, using our mRNA sequencing data (TRUCE01) and four bladder cancer (BLCA) cohorts (GSE111636, GSE176307, and IMvigor210), We examined the correlation between the expression level of PLK and immunotherapy effectiveness. Next, Gene set enrichment analysis (GSEA) was evaluated to find that potentially enriched PLK signaling pathways. Utilizing TIMER 2.0, we conducted an immune infiltration analysis underlying transcriptome expression, copy number variations (CNV), or somatic mutations of PLKs in BLCA. Finally, mRNA expression validation of PLK1/3/4 by real-time PCR within 10 paired BLCA tissues, protein expression verification through the Human Protein Atlas (HPA), and PLK4 in vitro cytological studies have been employed in BLCA. Results: The expression of most of the PLK family members exhibits variation between cancerous tissues and adjacent normal tissues across various cancer species. Furthermore, the expression of PLKs demonstrates a significant association with immunotyping, infiltration of immune cell, tumor mutational burden (TMB), microsatellite instability (MSI), immunological checkpoint gene activity and therapeutic effectiveness in pan-tumor tissues. Additional investigation into the correlation between the PLK family and BLCA has revealed that the expression of the PLK genes holds substantial significance in the biological processes of BLCA. Furthermore, a notable association has been observed between the copy number variation, variant status, and the degree of certain immunological cell infiltration. Of note, the expression validation and in vitro phenotypic experiments have demonstrated that PLK4 has a significant function in promoting the BLCA cell proliferation, migration, and invasion. Conclusion: Collectively, based on various databases, our results highlight the involvement of PLK gene family in the formation of different types of tumors and identify PLK-related genes that may be used for therapy.

With the frequency of extreme rainfall increasing, the risk of waterlogging is significantly exacerbated in subway systems. It is imperative to first identify the rainfall threshold for waterlogging risk for subway stations in order to develop effective waterlogging prevention and control plans. This study focuses on Line 11 of the Beijing Subway, using InfoWorks ICM to construct a model of the research area and simulate waterlogging at various subway stations under different rainfall scenarios. The results indicate that there is a risk of waterlogging at Jinanqiao station, Moshikou station, and Beixinan station on Line 11. The accumulated water may enter the subway station through exits A, B, C, and D of Jinanqiao Station. The inlet sequence of Jinanqiao Station always follows A(B), C, and D, and the difference in waterlogging time for each outlet does not exceed 10 min. We derived the rainfall threshold formula for waterlogging risk at Jinanqiao subway station. Among the three influencing factors of topographic features, step height, and drainage capacity of the pipeline network, step height has a significant effect on increasing the rainfall threshold for waterlogging risk. The conclusions obtained can provide reference for the refined management of waterlogging risks in subway stations.

Background: Danshen Ligustrazine Injection (DSLI), composed of the extract of Salvia miltiorrhiza Bunge and Conioselinum anthriscoides 'Chuanxiong', is commonly used in the clinical treatment of ischemic stroke, which is the most common type of cerebrovascular disease, affected by multiple factors. The brain-gut axis is a new type of influencing factor for ischemic stroke, however, there is a lack of systematic research on the relationship between microbiota and host metabolic phenotype. This study aimed to investigate the host metabolic phenotype-microbiome interface in ischemic stroke and the immunomodulatory effects of DSLI. Methods: In the study, liquid chromatography-mass spectrometry was used to primarily analyze the quality markers (Q-markers) and the polyphenols of DSLI. Based on 16S rRNA gene sequencing and metabolomics, the variations of microbial composition in different groups were characterized. In addition, a network diagram was constructed to reveal the interrelationship between DSLI-regulated gut microbiota changes and DSLI-regulated brain metabolites in MCAO/R rats. The expression of the aryl hydrocarbon receptor (AhR) in the colon and brain by immunofluorescence and suppressors of cytokine signaling 2 (SOCS2) by western blot were further detected. Results: Diminished metabolic diversity and alterations in the tryptophan metabolism pathway were a feature of IS in the study. The results revealed that Clostri_UCG-014 was positively correlated with indoleacrylic acid, indole-3-methylacetate, and Ruminococcaceae was strongly related with L-tryptophan, 3-methylindole, and indole. The results of immunofluorescence showed that the expression of AhR in the colon and brain tissues of rats in the model group was greatly reduced compared with that in the sham-operated group, and was heavily activated with the treatment of DSLI. The levels of aryl hydrocarbon nuclear receptor ARNT2 and SOCS2 were down-regulated in the brains of Model rats, whereas increased by DSLI, further confirming that the brain-gut microbiota-Trp metabolism exists in the pathological changes of stroke and the intervention mechanism of DSLI. Conclusions: The present study findings suggest Clostri_UCG-014, Ruminococcaceae, and Firmicute_RF39 play an important role in improving the regulation of immune function in stroke through tryptophan metabolites by acting on the AhR-SOCS2 axis.

Background: Clear cell renal cell carcinoma (ccRCC) stands as the prevailing variant kidney cancer in humans. Unfortunately, patients with disseminated RCC at diagnosis often have a diminished prognosis. Rapid tumor growth necessitates efficient blood supply for oxygen and nutrients, involving the circulation of blood from vessels to tumor tissues, facilitating tumor cell entry into the extracellular matrix. Vasculogenic mimicry (VM) significantly contributes to tumor growth and metastasis. Within this investigation, we identified vasculogenic mimicry-related genes (VMRGs) by analyzing data from 607 cases of kidney renal clear cell carcinoma (KIRC) in The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO) database (https://www.ncbi.nlm.nih.gov/geo/). These findings offer insights into ccRCC progression and metastasis.Method: We identified VMRGs-related subtypes using consistent clustering methods. The signature of the VMRGs was created using univariate Cox regression and LASSO Cox regression analyses. To evaluate differences in immune cell infiltration, we employed ssGSEA. Afterwards, we created an innovative risk assessment model, known as the VM index, along with a nomogram to forecast the prognosis of ccRCC. Additionally, we verified the expression of an important gene related to VM, peroxiredoxin 2 (PRDX2), in tissue samples. Furthermore, we assessed the sensitivity to drugs in various groups by utilizing the pRRophetic R package.Results: Significant predictors of survival rates in both high- and low-risk groups of KIRC patients were identified as VMRGs. The independent prognostic factors for RCC were confirmed by both univariate and multivariate Cox regression analyses, validating VMRG risk signatures. Differences were observed in drug sensitivity, immune checkpoint expression, and responses to immune therapy between patients classified into high- and low-VMRG-risk groups. Our nomograms consistently demonstrated precise predictive capabilities. Finally, we experimentally verified PRDX2 expression levels and their impact on prognosis.Conclusion: The signature predicts patient prognosis and therapy response, laying the groundwork for future clinical strategies in treating ccRCC patients.

Abstract Anlotinib, as a promising oral small-molecule antitumor drug, its role in glioma has been only reported in a small number of case reports. Therefore, anlotinib has been considered as a promising candidate in glioma. The aim of this study was to investigate the metabolic network of C6 cells after exposure to anlotinib and to identify anti-glioma mechanism from the perspective of metabolic reprogramming. Firstly, CCK8 method was used to evaluate the effects of anlotinib on cell proliferation and apoptosis. Secondly, ultra-high performance liquid chromatography-high resolution mass spectrometry (UHPLC-HRMS)-based metabolomic and lipidomic were developed to characterize the metabolite and lipid changes in cell and cell culture medium (CCM) caused by anlotinib in the treatment of glioma. As a result, anlotinib had concentration-dependent inhibitory effect with the concentration range. In total, twenty-four and twenty-three disturbed metabolites in cell and CCM responsible for the intervention effect of anlotinib were screened and annotated using UHPLC-HRMS. Altogether, seventeen differential lipids in cell were identified between anlotinib exposure and untreated groups. Metabolic pathways, including amino acid metabolism, energy metabolism, ceramide metabolism, and glycerophospholipid metabolism, were modulated by anlotinib in glioma cell. Overall, anlotinib has an effective treatment against the development and progression of glioma, and these remarkable pathways can generate the key molecular events in cells treated with anlotinib. Future research into the mechanisms underlying the metabolic changes is expected to provide new strategies for treating glioma.

The use of a surfactant solution during oil and gas field development might improve the recovery rate of oil reservoirs. However, the serious emulsification of the produced liquid will bring challenges to the subsequent treatment process and storage and transportation. It is urgent to understand the coalescence mechanism of crude oil under the action of surfactant solution. This research investigates the coalescence mechanism of numerous oil droplets under liquid flow perturbation. The model was established to study the coalescence process of multiple oil droplets. The effects of the number of oil droplets under homogeneous conditions, the size of oil droplets, and the distance between oil droplets under non-homogeneous conditions on the coalescence process were analyzed. Meanwhile, the change rules of the completion time of oil droplet coalescence were drawn. The results show that the smaller the size of individual oil droplets under non-homogeneous conditions, the longer the coalescence completion time is, and when the size of individual oil droplets reaches the nanometer scale, the time for coalescence of oil droplets is dramatically prolonged. Compared to static circumstances, the time it takes for oil droplets to coalesce is somewhat shorter under gravity. In the fluid flow process, in the laminar flow zone, the coalescence time of oil droplets decreases with the increase of the liquid flow rate. However, in the turbulent flow zone, the coalescence time of oil droplets increases with the increase in the liquid flow rate. The coalescence time is in the range of 600~1000 ms in the flow rate of 0.05~0.2 m/s. In the presence of surfactants, the oil content in the emulsion system increases under the influence of pumping flow. The change in oil content rate with various surfactants is less impacted by flow rate, owing to the stable emulsion structure created by the extracted fluid within the reservoir. The study findings presented in this research provide technical assistance for effective crude oil storage and transportation.

A proposed method for analyzing the effectiveness of rainwater storage tanks (RWSTs) based on various enabling rule scenarios has been proposed to address the issue of incomplete strategies and measures for controlling excessive rainwater runoff. Three enabling rules for RWSTs have been proposed, as follows: enabling rule I, which involves activation upon rainfall; enabling rule II, which requires the rainfall intensity to reach a predetermined threshold; and enabling rule III, which necessitates the cumulative rainfall to reach a set threshold. In order to assess the effectiveness of these enabling rules when reducing the total volume of rainwater outflow (TVRO), peak flow rate (PFR), and peak flow velocity (PFV), a comparative analysis was conducted to determine which enabling rule yielded the most optimal control effect. The findings indicate that the enabling rule I is responsible for determining the optimal unit catchment’s rainfall capture volume (UCRCV), which is measured at 300 m3·ha−1. Additionally, the control effect of the TVRO of the RWSTs remains largely unaffected by the peak proportion coefficient. Enabling rule II establishes the optimal activation threshold at a rainfall intensity of 1 mm·min−1; under this enabling rule, RWSTs demonstrate the most effective control over PFR and PFV. Enabling rule III enables the determination of the optimal activation threshold, which is set at a cumulative rainfall of 20 mm; under this enabling rule, the implementation of the RWST technique yields the most effective control over the TVRO. Consequently, the optimal rainwater runoff reduction plan for the study area has been successfully determined, providing valuable guidance for the implementation of scientific and reasonable optimal runoff management.

ABSTRACTSolid-state recycling of used aluminum alloy beverage cans was accomplished by thermomechanical consolidation of the sheet fragments produced by shredding the cans. Different samples were obtained using two thermomechanical consolidation routes, one involving direct hot extrusion of a sheet fragment compact and the other involving upset hot-forging of a sheet fragment compact followed by hot extrusion of the forged ingot. The microstructures and mechanical properties of the samples were investigated. It was found that the samples contained less pores and exhibited better mechanical properties with a higher extrusion temperature and involving upset forging than with only hot extrusion, the highest tensile strength is 209.5 MPa and the largest elongation to fracture is 29.1%. The surface layers of the samples exhibited a clearly higher strength and tensile ductility than the interior. They also showed significantly different fracture behaviors, with the former being like fully ductile fracture and the latter involving delamination of the sheet fragments, suggesting that the bonding between the fragments is significantly stronger in the surface layer, possibly due to a higher amount of plastic deformation in it. Overall, the best quality solid state recycled material has tensile properties comparable with those of wrought aluminum alloy with the same composition.

Background: This study constructs a molecular subtype and prognostic model of bladder cancer (BLCA) through endoplasmic reticulum stress (ERS) related genes, thus helping to clinically guide accurate treatment and prognostic assessment.Methods: The Bladder Cancer (BLCA) gene expression data was downloaded from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) database. We clustered by ERS-related genes which obtained through GeneCards database, results in the establishment of a new molecular typing of bladder cancer. Further, we explored the characteristics of each typology in terms of immune microenvironment, mutations, and drug screening. By analyzing the ERS-related genes with univariate Cox, LASSO and multivariate Cox analyses, we also developed the four-gene signature, while validating the prognostic effect of the model in GSE32894 and GSE13507 cohorts. Finally, we evaluated the prognostic value of the clinical data in the high and low ERS score groups and constructed a prognostic score line graph by Nomogram.Results: We constructed four molecular subtypes (C1- C4) of bladder cancer, in which patients with C2 had a poor prognosis and those with C3 had a better prognosis. The C2 had a high degree of TP53 mutation, significant immune cell infiltration and high immune score. In contrast, C3 had a high degree of FGFR3 mutation, insignificant immune cell infiltration, and reduced immune checkpoint expression. After that, we built ERS-related risk signature to calculate ERS score, including ATP2A3, STIM2, VWF and P4HB. In the GSE32894 and GSE13507, the signature also had good predictive value for prognosis. In addition, ERS scores were shown to correlate well with various clinical features. Finally, we correlated the ERS clusters and ERS score. Patients with high ERS score were more likely to have the C2 phenotype, while patients with low ERS score were C3.Conclusion: In summary, we identified four novel molecular subtypes of BLCA by ERS-related genes which could provide some new insights into precision medicine. Prognostic models constructed from ERS-related genes can be used to predict clinical outcomes. Our study contributes to the study of personalized treatment and mechanisms of BLCA.

Mailuoshutong pill (MLSTP) is a traditional Chinese medicine compound preparation used for the treatment of thromboangiitis obliterans. However, component responsible for those effects are not yet identified, nor with their accurate contents and in-vivo movement, which means the quality markers of MLSTP are still unknown. The aim of this study was to discovery quality markers of MLSTP by developing a new multi-dimensional network strategy based on “Content-Pharmacokinetics-Pharmacology”. 40 analytes were determined by UHPLC-MS/MS in 8 min and the average contents in 11 batches of commercial MLSTP samples were used as the content dimension, the pharmacokinetics and pharmacology dimension were evaluated by five variables based on ADME Prediction and Prediction of Activity Spectra. Each dimension of the characteristic network was quantified by multivariate statistical analysis, and a three-dimensional network was constructed. Finally, Liquiritin, Calycosin-7-glucoside and Albiflorin with larger regression area were preferred as quality markers of MLSTP, which had satisfactory comprehensive properties of content, pharmacokinetic properties and pharmacological activity. In summary, the potential quality markers of MLSTP were identified by multi-dimensional characteristic network of content, pharmacokinetics and pharmacology. Also, the new strategy established in this work provided a valuable perspective for the selection of quality control indicators from compound formula.

Water is the most critical resource that affects the stability of ecosystems and socio-economic development in arid and semi-arid regions. The rational development and utilization of water resources in Yinchuan Plain play a vital role in supporting and leading its ecological environment protection and high-quality agricultural development. Irrigation water from the Yellow River and groundwater are the main water resources of Yinchuan Plain. To understand the ecological impact of the Yellow River irrigation, the research analyzed the interaction between surface water and shallow groundwater using isotope hydrochemical method. The results show that both surface water and shallow groundwater are neutral and alkaline, the hydraulic relationships among the water bodies are strong. The correlation between 17O-excess and δ18O depends on the proportions of precipitation recharge and the intensity of evaporation. The chemical characteristics of water are controlled by evaporation, irrigation activities and water–rock interactions. Hydrochemical characteristics indicate that Yellow River irrigation has little impact on the Yellow River, but it has caused a rise in the groundwater level, intensified evaporation, and aggravated soil salinization. Isotopes indicate that Water-Saving Transformation Project has brought about a new ecological problem-lake shrinkage while reducing salinization. Therefore, we propose to moderately increase the amount of water diversion to flush the groundwater ions and extract the groundwater for human activities during the irrigation period to reduce salinization and water resource shortage. Salinization should be considered in relation to sustainable agricultural development and ecological environment health in Yinchuan Plain as well as other similar arid regions.

Bioretention facilities reduce stormwater runoff and pollutants, but there is a concern that plants in bioretention facilities may absorb heavy metal pollutants from stormwater runoff, which might impair the growth of the plant species. To investigate this issue, stormwater runoff containing various amounts of Pb and Cd heavy metals was used as the irrigation water in a bioretention facility. The low concentrations of Pb and Cd were 0.08 and 0.04 mg/L, and the high values were 0.68 and 0.32 mg/L. The plant heavy metal content and physiological indicators were measured. The indicators were chlorophyll content (CC), net photosynthetic rate (NPR), and transpiration rate (TR). The results showed that the changes in plant chlorophyll content (CC) were highly correlated with changes in the plants’ Pb. Low concentrations of Pb and Cd slightly inhibited the Ginkgo biloba L. and Ligustrum × vicaryi NPRs, the effect was more obvious at high concentrations and the Ligustrum × vicaryi’s NPR decreased from the initial 8.97 μmol CO2/(m2s) to 5.77 μmol CO2/(m2s) under high concentration conditions. Pb and Cd increased the Ginkgo biloba L. and Ligustrum × vicaryi’s TRs, and the effect at low Pb and Cd concentrations was more significant. Under low concentrations of Pb and Cd stress, the Ginkgo biloba L.’s TRs reached 0.63 mmol H2O/(m2s), Ligustrum × vicaryi’s TRs reached 1.30 mmol H2O/(m2s). The TRs of the two plants in the experimental groups remained high throughout the experiment, and there was no significant inhibition. The study found that Pb and Cd in stormwater runoff did affect the physiological function of species to some extent. Different plant species behaved differently in bioretention facilities, but the stormwater runoff did not lead to the death of species. Our study may provide a better understanding of the development of typical plant species in bioretention facilities.

The speed increase in high-speed trains is a critical procedure in the promotion of high-speed railway technology. As an indispensable and complex structure of high-speed trains, the pantograph’s aerodynamic drag and noise is a significant limitation in the speed increase process of high-speed trains. In the present study, the hybrid method of large eddy simulation (LES) and Ffowcs Williams-Hawkings (FW-H) acoustic analogy is applied to analyze the aerodynamic and aeroacoustic performances of pantograph installed in different ways, i.e., sinking platform and fairing. The results of simulation show that the application of pantograph fairing can reduce the aerodynamic drag greatly. In addition, compared with the pantographs installed alone on the train roof, the installation of the sinking platform brings about 2 dBA reduction in sound pressure level (SPL). Meanwhile, the utilization of the pantograph fairing mainly decreases the noise in the frequency band above 1000 Hz and the largest SPL reduction is up to 3 dBA among the monitoring points. Further analysis shows that the influence of different diversion strategies on the spectral characteristics actually attenuates the dominant frequency of the panhead. In the horizontal plane, the noise directivity of the pantograph installed with a fairing is similar to the pantograph installed alone on the train roof.

Based on the existing research results, a theoretical fracture model of strata under the compound impact of static and harmonic dynamic load is improved, and the fracture characteristic parameters (stress intensity factor, T-stress, and fracture initiation angle) under the two far-field stress are determined according to the crack dip angle. Additionally, the effects of harmonic dynamic load on the distribution of the stress field and the fracture characteristic (the crack initiation angle, the fracture degree, the number of fracture units, and the fracture area) are further calculated and discussed by theoretical model solution, extended finite element simulation, and the secondary development of the simulation module, respectively. The research results show that the far-field stress, stress intensity factor, and T-stress vary in harmonic form with time under the compound impact of static and harmonic dynamic loads. The frequency of dynamic load affects the number of reciprocal fluctuations of stress intensity factor and T-stress as well as the crack initiation time, but has less influence on the crack initiation angle and fracture degree. While the amplitude of dynamic load affects the stress intensity factor, the extreme value of T-stress and fracture characteristics of the crack. This study has theoretical guiding significance for parameters’ optimization and realization of resonance impact drilling technology.

The incidence of cerebral ischemic stroke characterized by high mortality is increasing every year. Danshen Chuanxiongqin Injection (DSCXQ), a traditional Chinese medicine (TCM) preparation, is often applied to treat cerebral apoplexy and its related sequelae. However, there is a lack of systematic research on how DSCXQ mediates its protective effects against cerebral ischemia stroke. Metabolomic analysis based on UHPLC-Q-Orbitrap HRMS was employed to explore the potential mechanisms of DSCXQ on ischemic stroke induced by transient middle cerebral artery occlusion (MCAO). Pattern analysis and metabolomic profiling, combined by multivariate analysis disclosed that 55 differential metabolites were identified between Sham group and Model group, involving sphingolipid metabolism, glycerophospholipid metabolism, phenylalanine, tyrosine and tryptophan biosynthesis, primary bile acid biosynthesis, pantothenate and CoA synthesis and valine, leucine and isoleucine biosynthesis pathways. DSCXQ could reverse brain metabolic deviations in stroke by significantly upregulating the levels of L-tryptophan, Lyso (18:0/0:0), LPC (18:2), Indole-3-methyl acetate, and downregulating the levels of sphinganine 1-phosphate, L-threonic acid, glutaconic acid and N6,N6,N6-Trimethyl-L-lysine. In our study, we focused on the neuroprotective effects of DSCXQ against neuroinflammatory responses and neuronal apoptosis on a stroke model based on sphingolipid metabolism. The expressions of Sphk1, S1PR1, CD62P, Bcl-2, Bax, and cleaved Caspase-3 in brain tissue were evaluated. The neurological deficit, cerebral infarct size and behavioral abnormality were estimated. Results showed that DSCXQ intervention significantly reduced cerebral infarct size, ameliorated behavioral abnormality, inhibited the expression of Sphk1, S1PR1, CD62P, Bax, Cleaved Caspase-3, while increased the level of Bcl-2, and prevented neuronal apoptosis. The limitations are that our study mainly focused on the verification of sphingolipid metabolism pathway in stroke, and while other metabolic pathways left unverified. Our study indicates that SphK1-SIP axis may potentiate neuroinflammatory responses and mediate brain damage through neuronal apoptosis, and DSCXQ could suppress the activity of SphK1-SIP axis to protect brain tissue in cerebral ischemia. In conclusion, this study facilitates our understanding of metabolic changes in ischemia stroke and the underlying mechanisms related to the clinical application of DSCXQ.

The reservoir architecture analysis of braided rivers, especially falling-silt seam forms, has played a key role in predicting remaining oil distributions. However, no studies have used architecture analyses that document braided river outcrops and researched the tapping of the few remaining oil distributions based on outcrops in the Songliao basin, northeast China. In this paper, the architecture characteristics and remaining oil distribution of braided river reservoirs are studied using a combination of an outcrop, modern deposition and subsurface well data. The new 8–13 m thick Lower Cretaceous Quantou Formation outcrop of the Songliao basin is a braided fluvial succession arranged in one large fining-upward cycle. Eight facies (Gt, St, Sm, Sh, Sp, Sw, Fl and Fm), four architecture elements (CH, DA, LV, and FF), and three orders of bounding surfaces (third-, fourth-, and fifth-order) are recognized. A new distribution pattern of falling-silt seams and a braided river architecture model are presented according to the analysis of the outcrop. In the mid-channel bar, the falling-silt seams thin from the mid-bar to the bar tail following the flow direction. Each falling-silt seam is oriented tangentially to the basal surface of the mid-channel bar, and the upper falling-silt seam extends farther than the lower one. In a Daqing Oilfield exploitation block in the Songliao basin, while channels and bars are the main reservoir units, they have different remaining oil distribution patterns. For bars, water injection wells located at the mid-bar, zonal injection technology, the drilling of horizontal wells, and proper well patterns are proposed. Fourth-order bounding surfaces, single braided channels, stacking patterns, and the lateral blocking of levees and floodplains are the key factors affecting the remaining oil distribution in channels.

This study investigated the potential financial benefits that private forest famers can derive when participating in a larch carbon sink plantation project in the northwestern Chinese province of Gansu. A decision matrix was developed to help forest farmers justify participation in forest carbon sink projects relative to the traditional land-use goal of timber production under various carbon trading prices, site conditions, and contract terms. The results showed that when the carbon trading price is at the theoretically optimal carbon price (CNY 110/tCO2e, equivalent to USD 17/tCO2e), Chinese business entities are willing to pay for forest carbon credits under the current global carbon emissions level, and forest farmers who participate in a 25-year forest carbon sink plantation project on high-productivity sites would generate the greatest financial benefit compared with the net income from pure timber production forests. Thus, the government does not need to provide a carbon sink subsidy for participating tree farmers. However, at the current average carbon trading price (CNY 19.8/tCO2e or USD 3/tCO2e) in the domestic market, a minimum additional subsidy of CNY 735/ha (USD 113/ha) is required upfront to motivate forest farmers to convert timber production forests into carbon sink forests. The results of this study can help policymakers and forest managers formulate optimal eco-compensation strategies for enrollment in forest-based carbon sequestration programs.

FANCD2 and FANCI are essential components of the Fanconi anaemia DNA damage repair pathway. Here the authors present the cryo-EM structure of the FANCD2-FANCI complex, providing insight into how the complex is recruited to stalled replication forks.

Xuebijing (XBJ) injection is an ethnomedicinal formula that has been widely used in the therapy of sepsis in China. However, the underlying theraputic mechanisms remain uninvestigated. In this research, a metabolomic method based on UHPLC-Q-Orbitrap HRMS was applied to make a holistic evaluation of XBJ on septic rats which were induced by the classical cecal ligation and puncture (CLP) operation. The plasma metabolic changes were profiled and evaluated by multivariate analytical (MVA) methods. In the results, a total of 41 differential metabolites were identified between CLP-operated group and sham-operated group, which were mainly involved in amino acid metabolism and lipid metabolism. After pathway analysis, it was finally discovered that the majority of the influenced metabolic pathways caused by sepsis mainly involved in energy metabolism, oxidative stress, and inflammation metabolism. When intervened by XBJ injection, 32 of the 41 disordered metabolites had been adjusted in reverse, which suggested that XBJ could mediate the abnormal metabolic pathways synergistically. In conclusion, the present study systematically investigated the efficacy and its underlying therapeutic mechanisms of XBJ on sepsis, while offering a new insight for the subsequent relevant exploration of other Chinese medicine at the same time.

Total organic carbon (TOC) content in lake sediments is typically used for the reconstruction of paleoenvironments. It remains uncertain, however, whether these sediment variables in lakes supplied by groundwater in the hinterland of the Badain Jaran Desert are applicable. Moreover, it is still uncertain whether the TOC content in these lakes can be used as a proxy to identify past climatic change and environmental evolution studies. In this study, the spatial distributions of the TOC contents and C/N ratios were analyzed for 109 surface sediment samples collected from five lakes without runoff recharge. The results revealed that the TOC content of the lake surface sediments was extremely low (0.03% - 1.01%) and consisted of both allochthonous organic matter carried by wind, as well as autochthonous organic matter generated in the lakes. Within a lake, spatial differences in the amount of TOC found in surface sediments may be caused by several processes including bathymetry topography and wind-induced wave activity. In addition, wind-induced wave activity produces a higher TOC content, which is more pronounced in larger lakes (>0.21 km2) with longer fetches. By contrast, in smaller lakes, organic matter accumulates in the deeper waters, but can be affected by many factors. It is therefore necessary to consider lake area when applying the TOC content of lake sediments for the reconstruction of a paleolake evolution. Furthermore, because the TOC content of lake sediments in hyper-arid regions is extremely low, and the organic matter may have a multiple and varied sources, a single proxy (TOC) cannot be used to reconstruct lake evolution.