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Abstract Poly(3,4-ethylenedioxythiophene):polystyrene sulfonate (PEDOT:PSS), a successfully commercialized polymeric semiconductor material, has potential as a transparent electrode in flexible electronic devices, yet has insufficient conductivity. We present the synthesis, properties, and directed crystallization of the PEDOT:dodecyl sulfate (PEDOT:DS) film. Iron(III) dodecyl sulfate (Fe(DS)3) multi-lamellar vesicles (MLVs), a new growth template, are used to synthesize and direct the growth of the PEDOT:DS film via vapor-phase polymerization of 3,4-ethylenedioxythiophene to form huge PEDOT:DS co-crystal domains within the MLV superstructure. The polycrystalline film has metallic conductivity (avg. ~1.0 × 104 S cm−1), is highly transparent and mechanically durable yet flexible, and suitable for next-generation flexible electronics. These noteworthy properties are conferred by the MLV lamellar superstructure of Fe(DS)3, a selective oxidant and an efficient in situ dopant that enhances the film hydrophobicity and durability. Sophisticated MLV-type oxidants are foreseen to enable the synthesis of more conductive, transparent, robust, flexible, and water-stable polymer electrode materials in future.

Super oil and gas basins provide the energy foundation for social progress and human development. In the context of climate change and carbon peak and carbon neutrality goals, constructing an integrated energy and carbon neutrality system that balances energy production and carbon reduction becomes crucial for the transformation of such basins. Under the framework of a green and intelligent energy system primarily based on “four news”, new energy, new electricity, new energy storage, and new intelligence, integrating a “super energy system” composed of a huge amount of underground resources of coal, oil, gas and heat highly overlapping with abundant wind and solar energy resources above ground, and a regional intelligent energy consumption system with coordinated development and utilization of fossil energy and new energy, with a carbon neutrality system centered around carbon cycling is essential. This paper aims to select the traditional oil and gas basins as “super energy basins” with the conditions to build world-class energy production and demonstration bases for carbon neutrality. The Ordos Basin has unique regional advantages, including abundant fossil fuel and new energy resources, as well as matching CO2 sources and sinks, position it as a carbon neutrality “super energy basin” which explores the path of transformation of traditional oil and gas basins. Under the integrated development concept and mode of “coal + oil + gas + new energy + carbon capture, utilization and storage (CCUS)/carbon capture and storage (CCS)”, the carbon neutrality in super energy basin is basically achieved, which enhance energy supply and contribute to the carbon peak and carbon neutrality goals, establish a modern energy industry and promote regional green and sustainable development. The pioneering construction of the world-class carbon neutrality “super energy system” demonstration basin in China represented by the Ordos Basin will reshape the new concept and new mode of exploration and development of super energy basins, which is of great significance to the global energy revolution under carbon neutrality.

Long non-coding RNA (lncRNA) H19 is an extensively studied lncRNA that is related to numerous pathological changes. Our previous findings have documented that serum lncRNA H19 levels are decreased in patients with chronic kidney disorder and lncRNA H19 reduction is closely correlated with renal tubulointerstitial fibrosis, an essential step in developing end-stage kidney disease. Nonetheless, the precise function and mechanism of lncRNA H19 in renal tubulointerstitial fibrosis are not fully comprehended. The present work utilized a mouse model of unilateral ureteral obstruction (UUO) and transforming growth factor-β1 (TGF-β1)-stimulated HK-2 cells to investigate the possible role and mechanism of lncRNA H19 in renal tubulointerstitial fibrosis were investigated. Levels of lncRNA H19 decreased in kidneys of mice with UUO and HK-2 cells stimulated with TGF-β1. Up-regulation of lncRNA H19 in mouse kidneys remarkably relieved kidney injury, fibrosis and inflammation triggered by UUO. Moreover, the increase of lncRNA H19 in HK-2 cells reduced epithelial-to-mesenchymal transition (EMT) induced by TGF-β1. Notably, up-regulation of lncRNA H19 reduced lipid accumulation and triacylglycerol content in kidneys of mice with UUO and TGF-β1-stimulated HK-2 cells, accompanied by the up-regulation of long-chain acyl-CoA synthetase 1 (ACSL1). lncRNA H19 was identified as a sponge of microRNA-130a-3p, through which lncRNA H19 modulates the expression of ACSL1. The overexpression of microRNA-130a-3p reversed the lncRNA H19-induced increases in the expression of ACSL1. The suppressive effects of lncRNA H19 overexpression on the EMT, inflammation and lipid accumulation in HK-2 cells were diminished by ACSL1 silencing or microRNA-130a-3p overexpression. Overall, the findings showed that lncRNA H19 ameliorated renal tubulointerstitial fibrosis by reducing lipid deposition via modulation of the microRNA-130a-3p/ACSL1 axis.

Tartary buckwheat was used as raw material to extract tartary buckwheat protein, and the enzymatic hydrolysis conditions of tartary buckwheat protein lipid-lowering peptides were screened by single factor and response surface optimization experiments using the inhibition rate of pancreatic lipase as index. The amino acid composition and lipid lowering activity of lipid-lowering peptides were studied. The results showed that the lipid-lowering peptides obtained from tartary buckwheat protein with bromelain had higher inhibitory activity on pancreatic lipase. The optimal enzymatic hydrolysis conditions were hydrolysis time 2.1 h, hydrolysis temperature 62.0 ℃, substrate concentration 3.23%, pH7.0 and enzyme substrate ratio 0.4%. Under these conditions, the inhibitory rate of pancreatic lipase was 81.22%±0.16%. Amino acid analysis showed that essential amino acids, hydrophobic amino acids and acidic amino acids accounted for 27.82%, 32.11%, 35.86%, and the ratio of arginine to lysine was 2.28. The EC50/IC50 values of sodium taurine cholic acid binding rate, cholesterol esterase inhibition rate and pancreatic lipase inhibition rate were 9.136, 3.902 and 0.051 mg/mL, respectively. The results provided a new idea and theoretical basis for the high-value utilization of tartary buckwheat resources and the development of tartary buckwheat protein active peptides.

Background: Over-activated osteoclast (OC) is a major cause of diseases related to bone loss and bone metabolism. Both bone resorption inhibition and apoptosis induction of osteoclast are crucial in treating these diseases. X-linked inhibitor of apoptosis protein (XIAP)-associated factor 1 (XAF1) is an important interferon-stimulated and apoptotic gene. However, how XAF1 regulates bone formation and remodeling is unknown. Methods: We generate global and chimeric Xaf1 knockout mouse models and utilize these models to explore the function and mechanism of XAF1 in regulating bone formation and remodeling in vivo and in vitro. Results: We show that XAF1 depletion enhances osteoclast generation in vitro. XAF1 knockout increases osteoclast number and bone resorption, thereby exacerbating bone loss in both OVX and osteolysis models. Activation of XAF1 with BV6 (a potent XIAP inhibitor) suppresses osteoclast formation. Mechanistically, XAF1 deletion decreases osteoclast apoptosis by facilitating the interaction between XIAP and caspase-3/7. Conclusions: Our data illustrates an essential role of XAF1 in controlling osteoclastogenesis in both osteoporosis and osteolysis mouse models and highlights its underlying mechanism, indicating a potential role in clinical treatment.The translational potential of this article: The translation potential of this article is that we first indicated that osteoclast apoptosis induced by XAF1 contribute to the progression of osteoporosis and osteolysis, which provides a novel strategy in the prevention of osteoporosis and osteolysis.

Abstract Arboviruses, transmitted by medical arthropods, pose a serious health threat worldwide. During viral infection, Post Translational Modifications (PTMs) are present on both host and viral proteins, regulating multiple processes of the viral lifecycle. In this study, a mammalian E3 ubiquitin ligase WWP2 (WW domain containing E3 ubiquitin ligase 2) is identified, which interacts with the NS1 protein of Zika virus (ZIKV) and mediates K63 and K48 ubiquitination of Lys 265 and Lys 284, respectively. WWP2‐mediated NS1 ubiquitination leads to NS1 degradation via the ubiquitin‐proteasome pathway, thereby inhibiting ZIKV infection in mammalian hosts. Simultaneously, it is found Su(dx), a protein highly homologous to host WWP2 in mosquitoes, is capable of ubiquitinating NS1 in mosquito cells. Unexpectedly, ubiquitination of NS1 in mosquitoes does not lead to NS1 degradation; instead, it promotes viral infection in mosquitoes. Correspondingly, the NS1 K265R mutant virus is less infectious to mosquitoes than the wild‐type (WT) virus. The above results suggest that the ubiquitination of the NS1 protein confers different adaptations of ZIKV to hosts and vectors, and more importantly, this explains why NS1 K265‐type strains have become predominantly endemic in nature. This study highlights the potential application in antiviral drug and vaccine development by targeting viral proteins' PTMs.

Summary: Here, we present a protocol for small interfering RNA (siRNA)-mediated U1 small nuclear RNA (snRNA) knockdown using fluorinated α-helical polypeptide in macrophages and mouse lungs, providing a dependable approach to silence U1 snRNA in vitro and in vivo. We describe steps for preparing P7F7/siRNA polyplexes and silencing U1 snRNA with P7F7/siRNA polyplexes in macrophages and mouse lungs. Knockdown efficiency is validated through reverse-transcription quantitative real-time PCR analysis. This protocol is applicable for studying the physiological or pathophysiological function of U1 snRNA.For complete details on the use and execution of this protocol, please refer to Zhang et al.1 : Publisher’s note: Undertaking any experimental protocol requires adherence to local institutional guidelines for laboratory safety and ethics.

Background The capacity of high‐density lipoprotein cholesterol (HDL) to acquire free cholesterol (FC) from triglyceride‐rich lipoproteins during lipoprotein lipase–dependent lipolysis in a process of reverse remnant cholesterol transport, has been proposed as a key biological function of HDL particles that underlies the U‐shaped relationship between HDLcholesterol and cardiovascular diseases. Although reverse remnant cholesterol transport has been evaluated in a fasting state, it has never been explored under nonfasting conditions. Methods and Results FC transfer was evaluated in healthy men (n=78) before and throughout the postprandial phase up to 8 hours after consumption of a test meal. Postprandially, the capacity of HDL to acquire FC increased progressively, reaching a maximal mean value of 98.5%±22.5% 6 hours after meal intake (P

Abstract Background Erythroid and myeloid differentiation disorders are commonly occurred in leukemia. Given that the relationship between erythroid and myeloid lineages is still unclear. To find the co-regulators in erythroid and myeloid differentiation might help to find new target for therapy of myeloid leukemia. In hematopoiesis, ALA (alpha lipoic acid) is reported to inhibit neutrophil lineage determination by targeting transcription factor ELK1 in granulocyte-monocyte progenitors via splicing factor SF3B1. However, further exploration is needed to determine whether ELK1 is a common regulatory factor for erythroid and myeloid differentiation. Methods In vitro culture of isolated CD34+, CMPs (common myeloid progenitors) and CD34+ CD371– HSPCs (hematopoietic stem progenitor cells) were performed to assay the differentiation potential of monocytes, neutrophils, and erythrocytes. Overexpression lentivirus of long isoform (L-ELK1) or the short isoform (S-ELK1) of ELK1 transduced CD34+ HSPCs were transplanted into NSG mice to assay the human lymphocyte and myeloid differentiation differences 3 months after transplantation. Knocking down of SRSF11, which was high expressed in CD371+GMPs (granulocyte-monocyte progenitors), upregulated by ALA and binding to ELK1-RNA splicing site, was performed to analyze the function in erythroid differentiation derived from CD34+ CD123mid CD38+ CD371– HPCs (hematopoietic progenitor cells). RNA sequencing of L-ELK1 and S-ELK1 overexpressed CD34+ CD123mid CD38+ CD371– HPCs were performed to assay the signals changed by ELK1. Results Here, we presented new evidence that ALA promoted erythroid differentiation by targeting the transcription factor ELK1 in CD34+ CD371– hematopoietic stem progenitor cells (HSPCs). Overexpression of either the long isoform (L-ELK1) or the short isoform (S-ELK1) of ELK1 inhibited erythroid-cell differentiation, but knockdown of ELK1 did not affect erythroid-cell differentiation. RNAseq analysis of CD34+ CD123mid CD38+ CD371– HPCs showed that L-ELK1 upregulated the expression of genes related to neutrophil activity, phosphorylation, and hypoxia signals, while S-ELK1 mainly regulated hypoxia-related signals. However, most of the genes that were upregulated by L-ELK1 were only moderately upregulated by S-ELK1, which might be due to a lack of serum response factor interaction and regulation domains in S-ELK1 compared to L-ELK1. In summary, the differentiation of neutrophils and erythrocytes might need to rely on the dose of L-ELK1 and S-ELK1 to achieve precise regulation via RNA splicing signals at early lineage commitment. Conclusions ALA and ELK1 are found to regulate both human granulopoiesis and erythropoiesis via RNA spliceosome, and ALA-ELK1 signal might be the target of human leukemia therapy.

Abstract Background Mesenchymal stem/stromal cells (MSCs) are of great therapeutic value due to their role in maintaining the function of hematopoietic stem/progenitor cells (HSPCs). MSCs derived from human pluripotent stem cells represent an ideal alternative because of their unlimited supply. However, the role of MSCs with neural crest origin derived from HPSCs on the maintenance of HSPCs has not been reported. Methods Flow cytometric analysis, RNA sequencing and differentiation ability were applied to detect the characteristics of stromal cells from 3D human brain organoids. Human umbilical cord blood CD34+ (UCB-CD34+) cells were cultured in different coculture conditions composed of stromal cells and umbilical cord MSCs (UC-MSCs) with or without a cytokine cocktail. The hematopoietic stroma capacity of stromal cells was tested in vitro with the LTC-IC assay and in vivo by cotransplantation of cord blood nucleated cells and stroma cells into immunodeficient mice. RNA and proteomic sequencing were used to detect the role of MSCs on HSPCs. Results The stromal cells, derived from both H1-hESCs and human induced pluripotent stem cells forebrain organoids, were capable of differentiating into the classical mesenchymal-derived cells (osteoblasts, chondrocytes, and adipocytes). These cells expressed MSC markers, thus named pluripotent stem cell-derived MSCs (pMSCs). The pMSCs showed neural crest origin with CD271 expression in the early stage. When human UCB-CD34+ HSPCs were cocultured on UC-MSCs or pMSCs, the latter resulted in robust expansion of UCB-CD34+ HSPCs in long-term culture and efficient maintenance of their transplantability. Comparison by RNA sequencing indicated that coculture of human UCB-CD34+ HSPCs with pMSCs provided an improved microenvironment for HSC maintenance. The pMSCs highly expressed the Wnt signaling inhibitors SFRP1 and SFRP2, indicating that they may help to modulate the cell cycle to promote the maintenance of UCB-CD34+ HSPCs by antagonizing Wnt activation. Conclusions A novel method for harvesting MSCs with neural crest origin from 3D human brain organoids under serum-free culture conditions was reported. We demonstrate that the pMSCs support human UCB-HSPC expansion in vitro in a long-term culture and the maintenance of their transplantable ability. RNA and proteomic sequencing indicated that pMSCs provided an improved microenvironment for HSC maintenance via mechanisms involving cell–cell contact and secreted factors and suppression of Wnt signaling. This represents a novel method for large-scale production of MSCs of neural crest origin and provides a potential approach for development of human hematopoietic stromal cell therapy for treatment of dyshematopoiesis.

Based on seismic, drilling, and source rock analysis data, the petroleum geological characteristics and future exploration direction of the oil-rich sags in the Central and West African Rift System (CWARS) are discussed. The study shows that the Central African Rift System mainly develops high-quality lacustrine source rocks in the Lower Cretaceous, and the West African Rift System mainly develops high-quality lacustrine organic matter-rich marine source rocks in the Upper Cretaceous, and the two types of source rocks provide a material basis for the enrichment of oil and gas in the CWARS. Multiple sets of reservoir rocks including fractured basement and three sets of regional cap rocks in the Lower Cretaceous, the Upper Cretaceous, and the Paleogene are developed in the CWARS. Since the Late Mesozoic, due to the geodynamic factors including the dextral strike-slip movement of the Central African Shear Zone, the basins in different directions of the CWARS differ in terms of rifting stages, intervals of regional cap rocks, trap types and accumulation models. The NE–SW trending basins have mainly preserved one stage of rifting in the Early Cretaceous, with regional cap rocks developed in the Lower Cretaceous strata, forming traps of reverse anticlines, flower-shaped structures and basement buried hill, and two types of hydrocarbon accumulation models of “source and reservoir in the same formation, and accumulation inside source rocks” and “up-source and down-reservoir, and accumulation below source rocks”. The NW–SE basins are characterized by multiple rifting stages superimposition, with the development of regional cap rocks in the Upper Cretaceous and Paleogene, forming traps of draping anticlines, faulted anticlines, antithetic fault blocks and the accumulation model of “down-source and up-reservoir, and accumulation above source rocks”. The combination of reservoir and cap rocks inside source rocks of basins with multiple superimposed rifting stages, as well as the lithologic reservoirs and the shale oil inside source rocks of strong inversion basins are important fields for future exploration in basins of the CWARS.

The effects of microencapsulated eutectic phase change materials (MEPCMs) on the viscosity-temperature relationship, viscoelasticity, creep recovery, and low-temperature properties of base asphalt and SBS asphalt were investigated using dynamic shear rheometer (DSR) and bending beam rheometer (BBR). The results revealed that the incorporation of microcapsules led to a reduction in the complex modulus and viscosity of the asphalt. Notably, at a concentration of 13 wt%, microcapsules disrupted the linear viscoelastic behavior of the asphalt and compromised its phase uniformity. However, the addition of microcapsules improved the low-temperature rheological properties of the asphalt. Specifically, the S and m-values of the asphalt decreased and increased, respectively, with increasing microcapsule content. Moreover, SBS asphalt exhibited less susceptibility to the effects of microcapsules compared to base asphalt, owing to its superior performance across a wide range of temperatures. This characteristic renders SBS asphalt more compatible with MPCMs for practical applications.

Canopy height serves as an important dynamic indicator of crop growth in the decision-making process of field management. Compared with other commonly used canopy height measurement techniques, ultrasonic sensors are inexpensive and can be exposed in fields for long periods of time to obtain easy-to-process data. However, the acoustic wave characteristics and crop canopy structure affect the measurement accuracy. To improve the ultrasonic sensor measurement accuracy, a four-year (2018−2021) field experiment was conducted on maize and wheat, and a measurement platform was developed. A series of single-factor experiments were conducted to investigate the significant factors affecting measurements, including the observation angle (0−60°), observation height (0.5−2.5 m), observation period (8:00−18:00), platform moving speed with respect to the crop (0−2.0 m min−1), planting density (0.2−1 time of standard planting density), and growth stage (maize from three−leaf to harvest period and wheat from regreening to maturity period). The results indicated that both the observation angle and planting density significantly affected the results of ultrasonic measurements (p-value< 0.05), whereas the effects of other factors on measurement accuracy were negligible (p-value > 0.05). Moreover, a double-input factor calibration model was constructed to assess canopy height under different years by utilizing the normalized difference vegetation index and ultrasonic measurements. The model was developed by employing the least-squares method, and ultrasonic measurement accuracy was significantly improved when integrating the measured value of canopy heights and the normalized difference vegetation index (NDVI). The maize measurement accuracy had a root mean squared error (RMSE) ranging from 81.4 mm to 93.6 mm, while the wheat measurement accuracy had an RMSE from 37.1 mm to 47.2 mm. The research results effectively combine stable and low-cost commercial sensors with ground-based agricultural machinery platforms, enabling efficient and non-destructive acquisition of crop height information.

To study the optimal enzymatic hydrolysis conditions and uric acid-lowering activity of lipid-lowering peptides from quinoa protein, this study used quinoa as raw material to extract protein, and used pancreatic lipase inhibition rate as the activity index. The enzymatic hydrolysis process of lipid-lowering peptides was optimized by single factor experiment and response surface analysis. The pancreatic lipase inhibitory activity, sodium taurocholate binding activity, cholesterol esterase inhibitory activity, xanthine oxidase inhibitory activity and amino acid composition of quinoa protein peptides were analyzed and characterized. The results showed that the optimal enzymatic hydrolysis conditions of lipid-lowering peptides from quinoa were as follows: pH1.6, enzymatic hydrolysis temperature 42.9 ℃, substrate concentration 3.03%, enzymatic hydrolysis time 1 h and enzyme to substrate ratio 0.2%. The theoretical value of inhibition rate of pancreatic lipase was 90.43%, and the actual value was 90.93%±0.10%. The optimal enzymatic hydrolysates showed excellent effect of lowering lipid in vitro. The IC50 of pancreatic lipase inhibition rate and cholesterol esterase inhibition rate were 7.49 μg/mL and 4.73 mg/mL, respectively. Meanwhile, the EC50 of taurocholic sodium binding rate was 0.53 mg/mL. In addition, the optimal enzymatic hydrolysates showed good xanthine oxidase inhibition effect (IC50=5.97 mg/mL), indicating that it had the uric acid-lowering effect in vitro. Amino acid analysis showed that quinoa protein peptides were rich in essential amino acids (34.23%), and the percentage of hydrophobic amino acid and acidic amino acid were 34.11% and 31.66%, respectively. The quinoa protein peptides had high lipid-lowering and uric acid-lowering activities in vitro, which provided a theoretical basis for the high-value application of quinoa protein peptides.

Transition metal supported N-doped carbon (M-N-C) catalysts for oxygen reduction reaction (ORR) are viewed as the promising candidate to replace Pt-group metal (PGM) for proton exchange membrane fuel cells (PEMFCs). However, the stability of M-N-C is extremely challenging due to the demetalation, H2O2 attack, etc. in the strongly oxidative conditions of PEMFCs. In this study, we demonstrate the universal effect of Zn on promoting the stability of atomically dispersed M-Nx/C (M = Co, Fe, Mn) catalysts and the enhancement mechanism is unveiled for the first time. The best-performing dual-metal-site Zn-Co-N-C catalyst exhibits a high half-wave potential (E1/2) value of 0.81 V vs. reversible hydrogen electrode (RHE) in acid and outstanding durability with no activity decay after 15,000 accelerated degradation test (ADT) cycles at 60 °C, surpassing most reported Co-based PGM-free catalysts in acid media. For comparison, the Co-N-C in the absence of Zn suffers from a rapid degradation after ADT due to the demetalation and higher H2O2 yield. X-ray adsorption spectroscopy (XAS) and density functional theory (DFT) calculations suggest the more negative formation energy (by 1.2 eV) and increased charge transfer of Zn-Co dual-site structure compared to Co-N-C could strength the Co-N bonds against the demetalation and the optimized d-band center accounts for the improved ORR kinetics.

In scenarios such as nearshore and inland waterways, the ship spots in a marine radar are easily confused with reefs and shorelines, leading to difficulties in ship identification. In such settings, the conventional ARPA method based on fractal detection and filter tracking performs relatively poorly. To accurately identify radar targets in such scenarios, a novel algorithm, namely YOSMR, based on the deep convolutional network, is proposed. The YOSMR uses the MobileNetV3(Large) network to extract ship imaging data of diverse depths and acquire feature data of various ships. Meanwhile, taking into account the issue of feature suppression for small-scale targets in algorithms composed of deep convolutional networks, the feature fusion module known as PANet has been subject to a lightweight reconstruction leveraging depthwise separable convolutions to enhance the extraction of salient features for small-scale ships while reducing model parameters and computational complexity to mitigate overfitting problems. To enhance the scale invariance of convolutional features, the feature extraction backbone is followed by an SPP module, which employs a design of four max-pooling constructs to preserve the prominent ship features within the feature representations. In the prediction head, the Cluster-NMS method and α-DIoU function are used to optimize non-maximum suppression (NMS) and positioning loss of prediction boxes, improving the accuracy and convergence speed of the algorithm. The experiments showed that the recall, accuracy, and precision of YOSMR reached 0.9308, 0.9204, and 0.9215, respectively. The identification efficacy of this algorithm exceeds that of various YOLO algorithms and other lightweight algorithms. In addition, the parameter size and calculational consumption were controlled to only 12.4 M and 8.63 G, respectively, exhibiting an 80.18% and 86.9% decrease compared to the standard YOLO model. As a result, the YOSMR displays a substantial advantage in terms of convolutional computation. Hence, the algorithm achieves an accurate identification of ships with different trail features and various scenes in marine radar images, especially in different interference and extreme scenarios, showing good robustness and applicability.

Abstract Subseasonal droughts including flash droughts have occurred frequently in recent years, which are accompanied by heatwaves or wildfires that raise a wide concern on environmental risk. However, the changing characteristics of subseasonal drought propagation, and the possible climate and environmental drivers remain unknown. This study quantifies the propagation characteristics from meteorological drought to soil drought using a Copula‐based Bayesian framework, and shows that higher propagation risks mainly occur in more humid regions with denser vegetation cover. Trends in drought propagation risk vary regionally, with a global increase of 2%/decade (p 71% of the global vegetated lands, with mean contribution rates of 39.5% and 36.5% respectively. Other climatic factors including vapor pressure deficit and precipitation also paly critical roles, which closely correlate with temperature and vegetation. These findings highlight the importance of vegetation greening on subseasonal drought propagation dynamics.

Long non-coding RNAs (lncRNAs) are well known for their oncogenic or anti-oncogenic roles in cancer development. AGAP2-AS1, a new lncRNA, has been extensively demonstrated as an oncogenic lncRNA in various cancers. Abundant experimental results have proved the aberrantly high level of AGAP2-AS1 in a great number of malignancies, such as glioma, colorectal, lung, ovarian, prostate, breast, cholangiocarcinoma, bladder, colon and pancreatic cancers. Importantly, the biological functions of AGAP2-AS1 have been extensively demonstrated. It could promote the proliferation, migration and invasion of cancer cells. Simultaneously, the clinical significances of AGAP2-AS1 were also illustrated. AGAP2-AS1 was exceptionally overexpressed in various cancer tissues. Clinical studies disclosed that the abnormal overexpression of AGAP2-AS1 was tightly connected with overall survival (OS), lymph nodes metastasis (LNM), clinical stage, tumor infiltration, high histological grade (HG), serous subtype and PFI times. However, to date, the biological actions and clinical significances of AGAP2-AS1 have not been systematically reviewed in human cancers. In the present review, the authors overviewed the biological actions, potential mechanisms and clinical features of AGAP2-AS1 according to the previous studies. In summary, AGAP2-AS1, as a vital oncogenic gene, is a promising biomarker and potential target for carcinoma prognosis and therapy.

Geothermal wells often suffer from production difficulties such as disappointing injectivity/productivity right from the start or declining injectivity/productivity during long-term operation, Acid fracturing, as a soft stimulation technology, is becoming the preferred technology to stimulate the carbonate geothermal reservoir of low permeability in large depth. The basic mechanism of acid fracturing is to inject acid into the carbonate geothermal reservoir through geothermal wells, and then the matrix porosity and fracture apertures can be significantly improved through acid corrosion. Since the acid fracturing technology in geothermal reservoirs is mainly based on the experiences obtained from oil and gas fields, a complete technical system has not yet been established. To be specific, its design method and field implementation process lack theoretical guidance. In this paper, two correction coefficients are proposed to describe the acid etching induced changes in fracture normal stiffness and the maximum closure, based on which a nonlinear fracture constitutive model considering the coupled mechanical-chemical mediations on fracture apertures is developed. The developed nonlinear fracture constitutive model is incorporated into the theoretical framework of coupled thermal-hydraulic-mechanical-chemical processes in fractured rock mass, and a numerical modeling method suitable for acid fracturing in deep carbonate geothermal reservoir is developed. Based on the field test of acid fracturing in the geothermal well D22 in Xiong’an New Area, Hebei, China, the accuracy of the developed modeling method is verified, and the influences of human-controlled parameters including perforation position, acid concentration (mass fraction) and injection rate on the stimulation efficiency of acid fracturing is investigated though sensitivity analysis. The results show that acid fracturing mainly occurs within the fractures with high initial apertures in the carbonate geothermal reservoir of low permeability in large depth. The acid-etched fractures gradually propagated into the surrounding reservoir rocks with high permeability, and a stimulated network is formed after acid fracturing. Stimulation efficiency of acid fracturing is dependent on not only the increase in fracture apertures induced by acid etching and hydraulic pressure, but also the closure path of fractures after stimulation. The closer the perforation position is to the reservoir rocks with high permeability, the better stimulation efficiency of acid fracturing. The high acid concentration and injection rate are helpful to stimulate long fractures, by which the reservoir rocks with high permeability may be connected, and thus the better stimulation efficiency of acid fracturing is obtained.

The essence of energy system transition is the “energy revolution”. The development of the “resource-dominated” energy system with fossil energy as the mainstay has promoted human progress, but it has also triggered energy crisis and ecological environment crisis, which is not compatible with the new demands of the new round of scientific and technological revolution, industrial transformation, and sustainable human development. It is in urgent need to research and develop a new-type energy system in the context of carbon neutrality. In the framework of “technique-dominated” new green and intelligent energy system with “three new” of new energy, new power and new energy storage as the mainstay, the “super energy basin” concepts with the Ordos Basin, NW China as a representative will reshape the concept and model of future energy exploration and development. In view of the “six inequalities” in global energy and the resource conditions of “abundant coal, insufficient oil and gas and infinite new energy” in China, it is suggested to deeply boost “China energy revolution”, sticking to the six principles of independent energy production, green energy supply, secure energy reserve, efficient energy consumption, intelligent energy management, economical energy cost; enhance “energy scientific and technological innovation” by implementing technique-dominated “four major science and technology innovation projects”, namely, clean coal project, oil production stabilization and gas production increasing project, new energy acceleration project, and green-intelligent energy project; implement “energy transition” by accelerating the green-dominated “four-modernization development”, namely, fossil energy cleaning, large-scale new energy, coordinated centralized energy distribution, intelligent multi-energy management, so as to promote the exchange of “two 80%s” in China's energy structure and construct the new green and intelligent energy system.

The monotone variational inequalities are being widely used as mathematical tools for studying optimal control problems and convex programming. In this paper, we propose a new prediction-correction method for monotone variational inequalities with linear constraints. The method consists of two procedures. The first procedure (prediction) utilizes projections to generate a predictor. The second procedure (correction) produces the new iteration via some minor computations. The main advantage of the method is that its main computational effort only depends on evaluating the resolvent mapping of the monotone operator, and its primal and dual step sizes can be enlarged. We prove the global convergence of the method. Numerical results are provided to demonstrate the efficiency of the method.

Abstract Open-loop borehole heat exchanger (OBHE) is a single well geothermal heat exchanger with an open-loop structure that can realize the geothermal energy extraction without mining the geothermal water. In this paper, a sandbox experiment is designed to simulate the convective heat transfer process in the reservoir area of OBHE. The mechanism of convective heat transfer in the reservoir area is studied, and the key factors that affect the convection heat transfer intensity are analyzed. The results show that the convection heat transfer of OBHE in the reservoir area is affected by both the driving effect of fluid flow inside the screen tube and the buoyancy effect. In the forward flow mode, the two effects have the opposite direction. While in the backward mode, the two effects have the same direction. The backward flow mode is more conducive to convective heat transfer. In addition, many factors influencing significantly the convective heat transfer of OBHE include inlet temperature, inlet flow rate, reservoir temperature, fluid flow direction and inner tube diameter.

Background Continuous renal replacement therapy (CRRT) is commonly employed for rhabdomyolysis (RM) patients. However, the optimal initiation timing of CRRT and prognostic factors were not well evaluated for patients with RM. We aimed to investigate the efficacy of CRRT timing on mortality and the risk factors for death in RM patients who received CRRT.Methods RM patients who received CRRT between 1 May 2010 and 31 May 2021 in our center were retrospectively included. Univariate and multivariate logistic analyses were performed to identify the risk factors for primary outcome (90-day mortality).Results A total of 134 patients were included in our study. The 90-day mortality rate was 38.06%. The median time from CRRT initiation to peak CK occurrence was 4.8 h (IQR −16, 14), 67 patients received CRRT before 4.8 h after peak CK occurrence (early CRRT), and 67 patients received CRRT beyond 4.8 h after peak CK occurrence (late CRRT). Multivariate logistic regression analysis showed that the time from CRRT initiation to the peak CK (per 1 h, OR 1.026, 95% CI 1.004–1.049, p = 0.023), late CRRT (OR 3.082, 95% CI 1.072–8.859, p = 0.037), elevated serum cardiac troponin I (cTnI) (per 1 ng/mL, OR 1.218, 95% CI 1.011–1.468, p = 0.038), older age (per 1 year, OR 1.042, 95% CI 1.003–1.081, p = 0.032), and need of mechanical ventilation support (OR 4.632, 95% CI 1.292–16.61, p = 0.019) were independent risk factors for 90-day mortality.Conclusions Earlier CRRT initiation before 4.8 h after peak CK occurrence was associated with lower 90-day patient mortality.

Abstract This paper focuses on how to obtain globally optimal multisensor data association results under the condition that the number of targets is unknown. This problem is likely to occur in scenarios where the sensors’ fields of view (FoVs) are limited. The authors proved that, ideally, the cost of the association result is a convex function of the assumed target number and with the minimal value only if the target number is correctly assumed. Based on this, a multiple hypothesis S‐dimensional assignment (MHSDA) algorithm is proposed, which replaces the traditional irrevocable onetime assumption with a multiple hypothesis approach to counteract the effect of target number uncertainty. Furthermore, a hybrid implementation architecture based on Union Find plus MHSDA is proposed to ensure the real‐time performance. The proposed algorithm requires neither prior knowledge on the number of targets nor on the FoVs of sensors and is applicable to target dense scenarios. Simulation results under different FoV, target number and measurement noise configurations demonstrate the effectiveness of the proposed algorithm.

Geothermal energy, as a clean and renewable resource distributed worldwide, has received extensive focus in recent years. With the improvement in drilling and logging technology, the depth of geothermal exploration has gradually increased. Carbonate reservoirs are presently the main layer for geothermal development and use in China that have the characteristics of wide distribution, large reserves, and easy reinjection. The current use is limited to the strong karst development zone, approximately 200 m at the top of the reservoirs. Because of the low permeability and strong heterogeneity, the deep carbonate geothermal reservoirs cannot be commercially developed. This study aims to solve the key technical problems of efficiently developing deep carbonate geothermal reservoirs with extreme thickness. The target section was selected by analyzing comprehensive logging and fracture imaging logging data. An innovative simulation technology combining hydraulic jetting and acid fracturing is developed, which has the characteristics of fixed-point fracturing, effective sealing, strong penetration, and a large stimulation range. A production enhancement test was conducted for carbonate geothermal wells in the following order: comprehensive logging, imaging logging, casing cementing, perforation, pumping test, small pressure test, hydraulic injection acid fracturing, pumping test (after fracturing), and other construction processes. Comprehensive logging is an effective means to interpret the macroscopic pore and permeability properties of a reservoir and can be used to initially select the target geothermal reservoir. Fracture imaging logging can provide a more intuitive understanding of fracture development and distribution characteristics. The results show that the fracture density of geothermal well D22 does not decrease substantially with increasing depth, and the fracture width tends to decrease with depth clearly. The experimental geothermal well D22, which has the largest thickness of carbonate geothermal reservoir exposed in the Xiong'an New Area, was selected to perform a pilot field test of stimulation. The results show that the water inflow of the target section at 3024–3174 m increased from 4.72 m3·h−1 before stimulation to 44.10 m3·h−1 after stimulation, increasing by 8.3-fold. The unit water inflow increased from 0.024 m3·(h·m)−1 before stimulation to 0.745 m3·(h·m)−1 after stimulation, increasing by 30-fold. The reservoir permeability coefficient increased from 4.4×10−3 m·d−1 to 146.3×10−3 m·d−1. The wellhead water temperature increased from 60.0 °C before stimulation to 66.5 °C after stimulation. Therefore, the development potential of deep and thick carbonate geothermal reservoirs can be substantially improved through the developed stimulation. This research can provide technical support for the large-scale development of geothermal resources in China.

ObjectiveTo meet the requirements of remotely controlling ship in curved, narrow and crowded inland waterways, this paper proposes an approach that consists of CNN-based algorithms and knowledge based models under ship-shore cooperation conditions. MethodOn the basis of analyzing the characteristics of ship-shore cooperation, the proposed approach realizes autonomous perception of the environment with visual simulation at the core and navigation decision-making control based on deep reinforcement learning, and finally constructs an artificial intelligence system composed of image deep learning processing, navigation situation cognition, route steady-state control and other functions. Remote control and short-time autonomous navigation of operating ships are realized under inland waterway conditions, and remote control of container ships and ferries is carried out. ResultsThe proposed approach is capable of replacing manual work by remote orders or independent decision-making, as well as realizing independent obstacle avoidance, with a consistent deviation of less than 20 meters. ConclusionsThe developed prototype system carries out the remote control operation demonstration of the above ship types in such waterways as the Changhu Canal Shenzhou line and the Yangtze River, proving that a complete set of algorithms with a CNN and reinforcement learning at the core can independently extract key navigation information, construct obstacle avoidance and control awareness, and lay the foundation for inland river intelligent navigation systems.

In high-traffic harbor waters, marine radar frequently encounters signal interference stemming from various obstructive elements, thereby presenting formidable obstacles in the precise identification of ships. To achieve precise pixel-level ship identification in the complex environments, a customized neural network-based ship segmentation algorithm named MrisNet is proposed. MrisNet employs a lightweight and efficient FasterYOLO network to extract features from radar images at different levels, capturing fine-grained edge information and deep semantic features of ship pixels. To address the limitation of deep features in the backbone network lacking detailed shape and structured information, an adaptive attention mechanism is introduced after the FasterYOLO network to enhance crucial ship features. To fully utilize the multi-dimensional feature outputs, MrisNet incorporates a Transformer structure to reconstruct the PANet feature fusion network, allowing for the fusion of contextual information and capturing more essential ship information and semantic correlations. In the prediction stage, MrisNet optimizes the target position loss using the EIoU function, enabling the algorithm to adapt to ship position deviations and size variations, thereby improving segmentation accuracy and convergence speed. Experimental results demonstrate MrisNet achieves high recall and precision rates of 94.8% and 95.2%, respectively, in ship instance segmentation, outperforming various YOLO and other single-stage algorithms. Moreover, MrisNet has a model parameter size of 13.8M and real-time computational cost of 23.5G, demonstrating notable advantages in terms of convolutional efficiency. In conclusion, MrisNet accurately segments ships with different spot features and under diverse environmental conditions in marine radar images. It exhibits outstanding performance, particularly in extreme scenarios and challenging interference conditions, showcasing robustness and applicability.

Abstract To explore the applicability of multi-arterial phase imaging technique in gadoxetate disodium-enhanced MRI. We studied 140 consecutive patients with suspected liver lesions who underwent gadoxetate disodium-enhanced MRI before surgery. All patients were randomized into three groups: group A (n = 50) was examined with VIBE-based single-artery phase imaging, group B (n = 44) with StarVIBE, and group C (n = 46) with CAIPIRINHA-Dixon-TWIST-VIBE (CDT-VIBE)-based multi-artery phase imaging. We evaluated the display rate of late arterial images and image quality in arterial phase images. We performed a study of 140 consecutive patients suspected with liver lesions who received gadoxetate disodium-enhanced MRI examination before surgery. All patients were randomly divided into three groups: group A (n = 50) was examined with single arterial phase imaging based on VIBE, group B (n = 44) was based on StarVIBE and group C (n = 46) was analyzed with multi-arterial phase imaging based on CAIPIRINHA-Dixon-TWIST-VIBE (CDT-VIBE). We evaluated the display rate of late arterial images and the image quality of dynamically enhanced images. Both radiologists had an almost perfect agreement (Kappa value > 0.8) in the assessment of late arterial and image quality. For late arterial acquisition, group C was superior to groups A and B (x 2 = 18.940, P

Given the cumbersome determination method of the Soil Water Characteristic Curve (SWCC), the collapsible loess (silty clay loam) in Lanzhou was taken as the research object to explore a symmetrical prediction method for SWCC in a low suction section on the inflection point, and to determine the optimal suction section and the inflection point. The results showed that in the range of 0–7,000 cm suction, the spatial variation coefficient (CV) of soil saturation of each bulk density increased with the increase of suction. Soil saturation showed weak spatial variability when suction

Highlights 1. Diacerein/rhein as NLRP3 blockers used in treating osteoarthritis clinically. 2. RFAs including rhein/diacerein are main components of Rhubarb contained in yinchenhao decoction. 3. RFAs inhibited the transcription and assembly of NLRP3 inflammasome. 4. RFAs, Rhubarb and yinchenhao decoction improved NAFLD probably by inhibiting NLRP3 inflammasome. 5. RFAs are the potential NLRP3 inflammasome blockers for treating NAFLD clinically.

Abstract Many methods are used to locate preoperative small pulmonary nodules. However, deficiencies of complications and success rates exist. We introduce a novel magnetic gel for small pulmonary nodules localization in rabbit model, and furtherly evaluate its safety and feasibility. Rabbits were used as the experimental objects. A magnetic gel was used as a tracer magnet, mixed as sodium alginate-Fe3O4 magnetic fluid and calcium gluconate solution. In short-term localization, a coaxial double-cavity puncture needle was applied to inject the gel into the lung after thoracotomy, and a pursuit magnet made of Nd-Fe-B permanent magnetic materials was used to attract the gel representing location of the nodule. In long-term localization, the gel was injected under X-ray guidance. Imaging changes to the lung were observed under X-ray daily. Thoracotomy was performed to excise tissue containing the gel, and hematoxylin–eosin staining was used to observe the tissue on postoperative days 1, 3, 5, and 7. Observe tissues morphology of heart, liver, spleen, and kidney in the same way. The gel was formed after injection and drew lung tissue to form a protrusion from the lung surface under the applied magnetic field. No complication was observed. The shape and position of the gel had not changed when viewed under X-ray. Pathological analysis showed the gel had a clear boundary without diffusion of magnetic fluid. All tissues retained good histologic morphology and no magnetic fluid was observed. Our study preliminarily suggested that the technique using sodium alginate-Fe3O4 magnetic gel to locate small pulmonary nodules with guidance of X-ray, and to search for them under an applied magnetic field during the operation is safe and feasible.

Abstract A well-documented finding is that explicitly using jumps cannot efficiently enhance the predictability of crude oil price volatility. To address this issue, we find a phenomenon, “momentum of jumps” (MoJ), that the predictive ability of the jump component is persistent when forecasting the oil futures market volatility. Specifically, we propose a strategy that allows the predictive model to switch between a benchmark model without jumps and an alternative model with a jump component according to their recent past forecasting performance. The volatility data are based on the intraday prices of West Texas Intermediate. Our results indicate that this simple strategy significantly outperforms the individual models and a series of competing strategies such as forecast combinations and shrinkage methods. A mean–variance investor who targets a constant Sharpe ratio can realize the highest economic gains using the MoJ-based volatility forecasts. Our findings survive a wide variety of robustness tests, including different jump measures, alternative volatility measures, various financial markets, and extensive model specifications.

Abstract Past ground surface temperature (GST), one of the important aspects of paleoclimate reconstructions, can be inverted from borehole temperature measurements. Here, we report continuous 6,100‐m temperature logs in the International Continental Scientific Drilling Program SK‐2e. We inverted the past GST changes from upper borehole temperature logging (

Abstract Yangtze River basin (YZB) experienced record‐breaking heat in the summer of 2022. Here, we focused on daytime‐nighttime compound heat waves, and used the magnitude index that considers both duration and intensity to investigate the risk of the 2022 extreme heat. The magnitude of heatwaves in 2022 was much larger than the historical average level, which was estimated as a 1‐in‐64‐year event over 1979–2014 climate. Without mitigation efforts (SSP585), the record‐breaking heat would emerge as normal during 2050s, and would affect ∼70% of land and projected population in the basin before global mean temperature change reaches 3°C. Such an emergence could be progressively delayed and impacts could be reduced under lower warming levels. The affected area would be 60% lesser at 2°C warming, and the emergence could be avoided by limiting warming to 1.5°C. Our results call for urgent mitigation efforts for reducing the risk of compound heat extremes.

Lung cancer has high morbidity and mortality rates worldwide, and NSCLC accounts for 85% of all lung cancer cases. Despite the development of targeted therapies and immunotherapy, many NSCLC patients do not effectively respond to treatment, and new treatment strategies are urgently needed. Aberrant activation of the FGFR signaling pathway is closely related to the initiation and progression of tumors. AZD4547, which is a selective inhibitor of FGFR 1-3, can suppress the growth of tumor cells with deregulated FGFR expression in vivo and in vitro. However, further exploration is needed to determine whether AZD4547 can play an antiproliferative role in tumor cells without deregulated FGFR expression. We investigated the antiproliferative effect of AZD4547 on NSCLC cells without deregulated FGFR expression. In vivo and in vitro experiments showed that AZD4547 exerted a weak antiproliferative effect on NSCLC cells without deregulated FGFR expression, but it significantly enhanced the sensitivity of NSCLC cells to nab-paclitaxel. We found that AZD4547 combined with nab-paclitaxel suppressed the phosphorylation of the MAPK signaling pathway, led to cell cycle arrest in the G2/M phase, promoted apoptosis, and inhibited cell proliferation more substantially than nab-paclitaxel alone. These findings provide insight into the rational use of FGFR inhibitors and personalized treatment of NSCLC patients.

Energy is the basis of human development and the impetus of society progress. There are three sources of energy: energy of celestial body outside the Earth, the Earth energy and energy of interaction between the Earth and other celestial bodies. Meanwhile, there are three scales of co-evolution: the evolution of the Sun-Earth-Moon system on an ultra-long time scale has provided energy sources and extra-terrestrial environmental conditions for the formation of the Earth system; the evolution of the Earth system on a long time scale has provided the material preconditions such as energy resources and suitable sphere environment for life birth and the human development; on a short time scale, the development of human civilization makes the human circle break through the Earth system, expanding the extraterrestrial civilization. With the co-evolution, there are three processes in the carbon cycle: inorganic carbon cycle, short-term organic carbon cycle and long-term organic carbon cycle, which records human immoderate utilization of fossil energy and global sphere reforming activities, breaking the natural balance and closed-loop path of the carbon cycle of the Earth, causing the increase of greenhouse gases and global climate change, affecting human happiness and development. The energy transition is inevitable, and carbon neutrality must be realized. Building the green energy community is a fundamental measure to create the new energy system under carbon neutrality target. China is speeding up its energy revolution and developing a powerful energy nation. It is necessary to secure the cornerstone of the supply of fossil energy and forge a strong growing pole for green and sustainable development of new energy. China energy production and consumption structure will make a revolutionary transformation from the type of fossil energy domination to the type of new energy domination, depending on a high-level self-reliance of science and technology and a high-quality green energy system of cleaning, low-carbon, safety, efficiency and independence. Energy development has three major trends: low-carbon fossil energy, large-scale new energy and intelligent energy system, relying on the green innovation, contributing the green energy and constructing the green homeland.

Guanzhong Basin is a typical medium-low temperature geothermal field mainly controlled by geo-pressure in the west of China. The characteristics of hydrogen and oxygen isotopes were used to analyze the flow and storage modes of geothermal resources in the basin. In this paper, the basin was divided into six geotectonic units, where a total of 121 samples were collected from geothermal wells and surface water bodies for the analysis of hydrogen-oxygen isotopes. Analytical results show that the isotopic signatures of hydrogen and oxygen throughout Guanzhong Basin reveal a trend of gradual increase from the basin edge areas to the basin center. In terms of recharge systems, the area in the south edge belongs to the geothermal system of Qinling Mountain piedmont, while to the north of Weihe fault is the geothermal system of North mountain piedmont, where the atmospheric temperature is about 0.2℃-1.8℃ in the recharge areas. The main factors that affect the geothermal water δ18O drifting include the depth of geothermal reservoir and temperature of geothermal reservoir, lithological characteristics, water-rock interaction, geothermal reservoir environment and residence time. The δ18O-δD relation shows that the main source is the meteoric water, together with some sedimentary water, but there are no deep magmatic water and mantle water which recharge the geothermal water in the basin. Through examining the distribution pattern of hydrogen-oxygen isotopic signatures, the groundwater circulation model of this basin can be divided into open circulation type, semi-open type, closed type and sedimentary type. This provides some important information for rational exploitation of the geothermal resources.

Summary: Highway constructions on the Qinghai-Tibet Plateau (QTP) face great challenges induced by the unique local environmental, geological, and engineering conditions. The large area of permafrost, great temperature variability, strong UV rays, and complex geological conditions are the major factors that adversely influence the long-term performance of pavement systems. Since 1960s, Chinese engineers and researchers have started conducting research on the QTP to enhance the performance and durability of pavement systems. The present paper provide a comprehensive review of challenge, research and practice of highway constructions on the QTP including the special environmental and geological conditions, history of highway constructions on the QTP, major challenges and the state-of-the-art technology of subgrade constructions on permafrost, developments of the pavement structures and materials, performance prediction and maintenance methods of pavement surfaces, and applications of the research achievements on the first expressway on the QTP (i.e., Gongyu Expressway). Based on the comprehensive literature review, it can be found that (1) frost heave and thaw weakening induced subgrade disease and longitudinal cracks on the pavement surface are complex coupled water-thermal-load problems. Engineering solutions are focusing on active cooling and thermal insulation methods, which can help to reduce temperature variations in the subgrade and thus improving its stability, (2) the harsh environmental and construction conditions may reduce the early strength and induce premature damage of cement-treated base materials. Some field validations showed that geocell-reinforced or asphalt-treated flexible base materials can provide better long-term performance, (3) the large temperature variability and strong UV rays can significantly accelerate aging of asphalt binders and greatly reduce the service life of asphalt mixtures. Various binder modification methods were developed for improving their viscoelasticity and enhance the low-temperature cracking resistance of pavement surface materials but are still lack of field validation data and comparisons of their life cycle costs. Therefore, it is recommended that a demonstration research project build test sections to examine a range of pavement structures and materials, and compare their long-term performance and life cycle costs, which can serve as important reference for future highway constructions on the QTP.

With the application of the advanced measurement infrastructure in power grids, data driven electricity theft detection methods become the primary stream for pinpointing electricity thieves. However, owing to anomaly submergence, which shows that the usage patterns of electricity thieves may not always deviate from those of normal users, the performance of the existing usage-pattern-based method could be affected. In addition, the detection results of some unsupervised learning algorithm models are abnormal degrees rather than “0-1” to ascertain whether electricity theft has occurred. The detection with fixed threshold value may lead to deviation and would not be sufficiently flexible to handle the detection for different scenes and users. To address these issues, this study proposes a new electricity theft detection method based on load shape dictionary of users. A corresponding strategy for tunable threshold is proposed to optimize the detection effect of electricity theft, and the efficacy and applicability of the proposed adaptive electricity theft detection method were verified from numerical experiments.

Frequent outbreaks of emerging and re-emerging pathogenic viruses have become one of the major challenges for global public health [...]

Objective: Temporomandibular joint (TMJ) osteoarthritis (OA) is a type of TMJ disorders with clinical symptoms of pain, movement limitation, cartilage degeneration and joint dysfunction. This review article is aiming to summarize recent findings on signaling pathways involved in TMJ OA development and progression. Methods: Most recent findings in TMJ OA studies have been reviewed and cited. Results: TMJ OA is caused by inflammation, abnormal mechanical loading and genetic abnormalities. The molecular mechanisms related to TMJ OA have been determined using different genetic mouse models. Recent studies demonstrated that several signaling pathways are involved in TMJ OA pathology, including Wnt/β-catenin, TGF-β and BMP, Indian Hedgehog, FGF, NF-κB, and Notch pathways, which are summarized in this review article. Alterations of these signaling pathways lead to the pathological changes in TMJ tissues, affecting cartilage matrix degradation, catabolic metabolism and chondrocyte apoptosis. Conclusion: Multiple signaling pathways were involved in the pathological process of TMJ OA. New therapeutic strategies, such as stem cell application, gene editing and other techniques may be utilized for TMJ OA treatment. The translational potential of this article: TMJ OA is a most important subtype of TMJ disorders and may lead to substantial joint pain, dysfunction, dental malocclusion, and reduced health-related quality of life. This review article summarized current findings of signaling pathways involved in TMJ OA, including Wnt/β-catenin, TGF-β and BMP, Indian Hedgehog, FGF, NF-κB, and Notch pathways, to better understand the pathological mechanisms of TMJ OA and define the molecular targets for TMJ OA treatment.

Abstract Deficiency of P18 can significantly improve the self-renewal potential of hematopoietic stem cells (HSC) and the success of long-term engraftment. However, the effects of P18 overexpression, which is involved in the inhibitory effects of RUNX1b at the early stage of hematopoiesis, have not been examined in detail. In this study, we established inducible P18/hESC lines and monitored the effects of P18 overexpression on hematopoietic differentiation. Induction of P18 from day 0 (D0) dramatically decreased production of CD34highCD43− cells and derivative populations, but not that of CD34lowCD43− cells, changed the cell cycle status and apoptosis of KDR+ cells and downregulated the key hematopoietic genes at D4, which might cause the severe blockage of hematopoietic differentiation at the early stage. By contrast, induction of P18 from D10 dramatically increased production of classic hematopoietic populations and changed the cell cycle status and apoptosis of CD45+ cells at D14. These effects can be counteracted by inhibition of TGF-β or NF-κB signaling respectively. This is the first evidence that P18 promotes hematopoiesis, a rare property among cyclin-dependent kinase inhibitors (CKIs).

Global climate change caused by geological processes is one of the main causes of the 5 global mass extinctions in geological history. Human industrialization activities have caused serious damage to the ecosystem, the greenhouse effect of atmospheric CO2 has intensified, and the living environment is facing threats and challenges. Carbon neutrality is the active action and common goal of mankind in the face of the climate change crisis, therefore, probing into its theoretical and technological connotation, scientific and technological innovation system has far-reaching significance and broad prospects. Studies indicate that (1) Carbon neutrality reflects the theoretical connotations of “energy science” and “carbon neutrality science”, including technical connotations of carbon emission reduction, zero carbon emission, negative carbon emission, and carbon trading. (2) Carbon neutrality spawns new industries such as carbon industry centering on CO2 capture, utilization, and storage (CCUS, or CO2 capture and storage CCS), and hydrogen industry centering on green hydrogen. “Gray carbon” and “black carbon” are the two application attributes of CO2. “Carbon+”, “Carbon−”, and “Carbon=” are three carbon-neutral products and technologies. (3) China faces three major challenges in achieving the goal of carbon neutrality: first, energy transition is large in scale and the cycle is short; Second, there are many problems in the process of energy transition, such as security uncertainties, economic utilization, and unpredictable disruptive technologies; Third, after transition, we may face new key techno-logical “bottlenecks” and “broken chain” of key mineral resources. (4) Based on current knowledge to predict the top 10 disruptive technologies and industries in the energy field: underground coal gasification, in-situ conversion process of medium and low-mature shale oil, CCUS/CCS, hydrogen energy and fuel cells, bio-photovoltaic power generation, space-based solar power generation, optical storage smart micro-grid, super energy storage, controllable nuclear fusion, wisdom energy Internet. Five strategic projects will be implemented, including energy conservation and efficiency improvement, carbon reduction and sequestration, scientific and technological innovation, emergency reserve and policy support. (5) In the future, different types of energy will have different orientations. Coal will play the role of ensuring the national energy strategy “reserve” and “guarantee the bottom line”. Petroleum will play the role of ensuring national energy security “urgent need” and the “cornerstone” of raw materials in people's livelihood. Natural gas will play the role in ensuring national energy “safety” and “best partner” of new energy. New energy will play the role in ensuring the “replacement” and “main force” of the national energy strategy. (6) Carbon neutrality is a major practice of the green industrial revolution, carbon reduction energy revolution, and ecological technology revolution, which will bring new and profound changes to human society, the environment and the economy. (7) Carbon neutrality needs to follow the four principles of “disruptive breakthroughs in technology, guarantee of energy security, realization of economic feasibility, and controllable social stability”. We should rely on technological innovation and management changes to ensure the realization of national energy “independence” and carbon neutrality goal, and make China's contribution to the construction of a livable earth, green development, and ecological civilization.

Traditional computational fluid dynamics (CFD) techniques deduce the dynamic variations in flow fields by using finite elements or finite differences to solve partial differential equations. CFD usually involves several tens of thousands of grid nodes, which entail long computation times and significant computational resources. Fluid data are usually irregular data, and there will be turbulence in the flow field where the physical quantities between adjacent grid nodes are extremely nonequilibrium. We use a graph attention neural network to build a fluid simulation model (GAFM). GAFM assigns weights to adjacent node-pairs through a graph attention mechanism. In this way, it is not only possible to directly calculate the fluid data but also to adjust for nonequilibrium in vortices, especially turbulent flows. The GAFM deductively predicts the dynamic variations in flow fields by using spatiotemporally continuous sample data. A validation of the proposed GAFM against the two-dimensional (2D) flow around a cylinder confirms its high prediction accuracy. In addition, the GAFM achieves faster computation speeds than traditional CFD solvers by two to three orders of magnitude. The GAFM provides a new idea for the rapid optimization and design of fluid mechanics models and the real-time control of intelligent fluid mechanisms.

Bladder cancer (BC) is the most common malignancy of the urinary system. Pyroptosis is a host programmed cell death. However, the effects of pyroptosis-related lncRNAs (PRLs) on BC have not yet been completely elucidated. In this study, a prognostic PRLs model and two ceRNA networks were established using sufficient bioinformatics analysis and preliminary RT-qPCR validation in vitro. 6 PRLs were identified to construct a prognostic model. Then, the prognostic model risk score was verified to be an effective independent factor (Training cohort: Univariate analysis: HR = 1.786, 95% Cl = 1.416-2.252, p < 0.001; multivariate analysis: HR = 1.664, 95% Cl = 1.308-2.116, p < 0.001; testing cohort: Univariate analysis: HR = 1.268, 95% Cl = 1.144-1.405, p < 0.001; multivariate analysis: HR = 1.141, 95% Cl = 1.018-1.280, p = 0.024). Moreover, ROC and nomogram were performed to assess the accuracy of this signature (1-year-AUC = 0.764, 3-years-AUC = 0.769, 5-years-AUC = 0.738). Consequently, we evaluated the survival curves of these 6 lncRNAs using Kaplan–Meier survival analysis, demonstrating that MAFG-DT was risk lncRNA, while OCIAD1-AS1, SLC25A25-AS1, SNHG18, PSMB8-AS1 and TRM31-AS1 were protective lncRNAs. We found a strong correlation between PRLs and tumor immune microenvironment by Pearson’s correlation analysis. As for sensitivity of anti-tumor drugs, the high-risk group was more sensitive to Sorafenib, Bicalutamide and Cisplatin, while the low-risk group was more sensitive to AKT.inhibitor.VIII, Salubrinal and Lenalidomide, etc. Meanwhile, we identified lncRNA OCIAD1-AS1/miR-141-3p/GPM6B and lncRNA OCIAD1-AS1/miR-200a-3p/AKAP11 regulatory axes, which may play a potential role in the progression of BC.

Regulatory B cells have important roles in inflammation and autoimmune diseases. A newly discovered subpopulation of B cells with a CD19hiFcγRIIbhi phenotype inhibits the proliferation of CD4+ T cells by secreting interleukin (IL)-10. The expansion of CD19hiFcγRIIbhi B cells in mouse spleen can be induced by lipopolysaccharide (LPS) or CpG oligodeoxynucleotide stimulation. However, the mechanism of CD19hiFcγRIIbhi B cell expansion and its role in inflammatory diseases are unclear. Here, we report that, under inflammatory conditions, the proliferation and immunosuppressive function of CD19hiFcγRIIbhi B cells were decreased in high mobility group box1 (HMGB1) C106A mutant mice, compared with wild-type mice. The HMGB1 (C106A) mutation in B cells reduced STAT3 phosphorylation, restricting the expansion and suppressive function of CD19hiFcγRIIbhi B cells. Compared with CD19hiFcγRIIbhi B cells from wild-type mice, CD19hiFcγRIIbhi B cells from Hmgb1(C106A) mice significantly reduced the survival of mice with sepsis. Recombinant HMGB1 promoted the expansion of IL-10-producing CD19hiFcγRIIbhi B cells among LPS-activated B cells in vitro. Furthermore, the percentage of CD19hiFcγRIIbhi regulatory B cells in the peripheral blood was increased in patients with sepsis, compared with healthy controls. These findings implicate the role of HMGB1 in the expansion and immunosuppressive function of CD19hiFcγRIIbhi B cells.

Granulocyte-monocyte progenitors (GMPs) differentiate into both neutrophils and monocytes. Recently, uni-potential neutrophil progenitors have been identified both in mice and humans using an array of surface markers. However, how human GMPs commit to neutrophil progenitors and the regulatory mechanisms of fate determination remain incompletely understood. In the present study, we established a human neutrophil deficiency model using the small molecule alpha-lipoic acid. Using this neutrophil deficiency model, we determined that the neutrophil progenitor commitment process from CD371+ CD115– GMPs defined by CD34 and CD15 and discovered that critical signals generated by RNA splicing and rRNA biogenesis regulate the process of early commitment for human early neutrophil progenitors derived from CD371+ CD115– GMPs. These processes were elucidated by single-cell RNA sequencing both in vitro and in vivo derived cells. Sequentially, we identified that the transcription factor ELK1 is essential for human neutrophil lineage commitment using the alpha-lipoic acid (ALA)-inducing neutrophil deficiency model. Finally, we also revealed differential roles for long-ELK1 and short-ELK1, balanced by SF3B1, in the commitment process of neutrophil progenitors. Taken together, we discovered a novel function of ALA in regulating neutrophil lineage specification and identified that the SF3B1-ELK axis regulates the commitment of human neutrophil progenitors from CD371+ CD115– GMPs.

Background: To determine the safety and efficacy of corticosteroids (CS) combined with cyclophosphamide (CTX), compared with CS combined with mycophenolate mofetil (MMF) for IgA nephropathy (IgAN) patients with stage 3 and 4 CKD and proteinuria ≥1.0 g/24 h in a 10-year real-world study.Methods: We recruited 296 IgAN patients with renal insufficiency and proteinuria ≥1.0 g/24 h who received uncontrolled supportive care (USC) (n = 44), CS + CTX therapy (n = 164) and CS + MMF therapy (n = 88) in Xijing Hospital from July 2008 to December 2019. The combined event was defined as a ≥50% decrease in eGFR, ESRD, or death.Results: The median of the follow-up period was 39.3 months. One hundred and twenty-five patients experienced the combined event, 65.9, 37.8, and 38.6% in the USC, CS + CTX, and CS + MMF group, respectively. In multivariate Cox regression analyses, CS combined with CTX (HR = 0.457, 95% CI 0.238-0.878, p = 0.019) significantly reduced the incidence of the combined event, whereas CS + MMF (HR = 0.523, 95% CI 0.246-1.109, p = 0.091) did not reduce the risk of the combined event, compared with USC. The incidence of pneumonia and death due to infection in the CS + MMF group was higher than other two groups.Conclusion: Compared with USC and CS + MMF therapy, CS + CTX therapy was more safety and possibly more effective. The results need to be further confirmed by large randomized controlled studies.