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Abstract Background Bivalves represent a vital economic resource in aquaculture for their high productivity and extensive market demand. Growth is one of the most important and desired aquaculture traits for bivalves, regulated by multiple levels, notably intricate metabolic processes. However, the understanding of the metabolic profiles that influence bivalve growth is limited, particularly from a multi-tissue perspective. Results In this study, metabolic profiles of multiple tissues of Chlamys farreri with different growth performance were systematically investigated by ultraperformance liquid chromatography quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS). Through comparing the metabolic variation between fast-growing (FG) scallops and slow-growing (SG) scallops, 613, 509, 105, and 192 significantly different metabolites (SDMs) were identified in the mantle, gill, adductor muscle, and digestive gland, respectively. Growth-related metabolic pathways including sphingolipid metabolism, fatty acid biosynthesis, and ABC transporter pathway, along with 11 SDMs associated with growth traits were identified in all four tissues, implying they were involved in the growth of multiple tissues in scallops. Tissue-specific metabolic profiling indicated that sulfur-containing amino acid metabolism in the mantle potentially contributed to shell growth, while the gill synergistically participated with the mantle through various metabolic processes, such as tyrosine metabolism, glycine, serine, and threonine metabolism and melanogenesis; energy metabolism was crucial for adductor muscle growth; and nutrients digestion and absorption in the digestive gland were linked to scallop growth. Conclusions Our results represent the first comprehensive analysis of the crucial pathways and metabolites associated with the growth of C. farreri, offering valuable insights for future bivalve aquaculture production.

Abstract Kadsura heteroclita (Roxb) Craib also named Xuetong in Tujia ethnomedicine in China, has been traditionally employed in rheumatoid arthritis (RA) treatment. Our preceding investigations have elucidated that Xuetongsu (XTS), a triterpenoid compound predominant in Xuetong, showed excellent anti-RA-fibroblast-like synoviocytes (RAFLS) proliferation effect. However, XTS belongs to the trace components of the Xuetong plant, which poses certain limitations to the research. In this study, we designed a method that enhanced the extraction yield of XTS and explored the mechanism of its inhibition of RAFLS cell proliferation and migration in the treatment of RA. The results displayed that XTS reduced RAFLS cell proliferation, with an IC50 value of 4.68 ± 0.65 µM. A series of experimental techniques were utilized to show that XTS induce apoptosis in RAFLS cells at concentrations ranging from 4.5 to 18 µM, including wound healing assay, flow cytometry, and western blot analysis. Moreover, XTS at dosages of 0.42–0.84 mg/kg markedly attenuated paw swelling and synovial hyperplasia in arthritic rats, primarily through the inhibition of RAFLS migration and promotion of RAFLS apoptosis via High mobility group box 1 (HMGB-1)/Matrix metalloproteinase-9 (MMP-9)/MMP-13 signaling pathway and Bcl-2/Bax/Caspase-3 signaling pathway, respectively.

Abstract Background Japan implemented strict border control measures and all incoming passengers were subject to entry screening with reverse transcription–polymerase chain reaction or antigen testing. From late 2020, exit screening within 72 h of departure to Japan also became mandatory. In this study, we evaluated the effectiveness of the exit screening policy in Japan by analyzing airport screening data from October 2020 to April 2022. Methods In addition to assessing entry screening data over time of passengers from the United Kingdom, we examined the prevalence of coronavirus disease 2019 (COVID-19) in the United Kingdom based on the Office of National Statistics infection survey. We constructed a statistical model that described entry screening positivity over time using Office of National Statistics prevalence data as the explanatory variable. Ideally, the time-dependent patterns of entry screening and Office of National Statistics prevalence data should resemble each other; however, we found that, sometimes, they were different and regarded the difference to statistically partly reflect the effectiveness of exit screening. Results The average proportion positive in one month before mandatory exit screening was implemented among Japanese passengers was 0.67% (95% confidence interval [CI]: 0.45, 0.98), whereas the proportion positive decreased to 0.49% (95% CI: 0.21, 1.15) in the first month of exit screening. Adjusting for time-dependent prevalence at the origin, we concluded that exit screening contributed to reducing passenger positivity by 59.3% (95% CI: 19.6, 81.3). The overall positivity values among passengers during the Delta and Omicron variant periods were 3.46 times and 1.46 times that during the pre-Delta variant period, respectively. Conclusions We used a simplistic statistical model and empirical data from passengers arriving in Japan from the United Kingdom to support that exit screening helped to reduce the proportion positive by 59%. Although the proportion positive later increased considerably and precluded preventing the introduction of imported cases, submitting a certificate for a negative test result contributed to reducing the positivity among travelers.

The evaluation and matching of CCUS source and sink potential of various geological bodies in Huainan coalfield is of great significance to the engineering popularization of CO2–ECBM technology. In this study, various types of geological bodies, such as deep unworkable coal seam, residual coal body and goaf area, in Huainan coalfield were taken as the research object. Firstly, the evaluation methods of CO2 geologic storage potential of various geologic bodies were discussed. Secondly, the CO2 storage potential of various geologic bodies was analyzed. Then, based on the lowest cost objective function and improved mileage saving method, the source and sink matching research of CO2 geological storage was carried out, and the pipe network design was optimized. Finally, based on the three-step thinking, the design idea of CCS source and sink network planning was proposed. The results show that the total annual CO2 emissions of coal-fired power plants are 58.8 million tons. The total CO2 geological storage potential in deep non-mining coal seam, residual coal and goaf area is 762 million tons, 5.17 million tons and 82.46 million tons, respectively, which can store CO2 for 12.97 years, 0.088 years and 1.40 years, respectively. Within the 10-year cycle, the deep unworkable coal seam can store 587.6 million tons of CO2, and the cumulative planned pipeline is 217.0 960 km with requiring a cumulative capital of 3.73×1010 $. Within the 1.45-year cycle, production mines and closed mines can store 85.2 million tons of CO2, and the cumulative planned pipeline is 464.516 1 km with requiring a cumulative capital of 7.36×109 $. Based on the improved mileage saving method, CCS source and sink matching each geological storage junction saved 266.612 7 km and 1.121×109 $, accounting for 57.40% and 79.95% of the total mileage and total cost of pipeline transportation, respectively. Based on the three-step approach, the whole line of CO2 emission sources and CO2 storage sinks in Huainan coal field can be completed by stages and regions, and all CO2 transportation and geological storage can be realized.

The goal of “double carbon”strategy has put forward new requirements for the transformation and upgrading of the coal industry and the development trend of green and low-carbon. The coal-based energy structure and high intensity coal mining cause solid waste in mining areas to occupy land space, destroy the ecological environment and emit greenhouse gases, which has become one of the prominent problems restricting the green and low-carbon development of the coal industry. Based on the concept of “waste utilization and carbon sequestration, where it comes from”, exploring a new solid waste disposal path of harmless, reduced, resource-based and low carbonization in mining areas, and innovating and developing key technologies that integrate solid waste disposal in mining areas, full utilization of underground space, and CO2 capture, utilization and storage (CCUS), which are urgent demands of green and low carbon development in mining area under the goal of “double carbon”. The research shows that important progress has been made in the resource utilization path and disposal technology of solid waste such as coal gangue, fly ash, furnace bottom slag and coal gasification slag in the underground space filling mining and settlement control, coal mine fire prevention, building materials and agriculture, which provides the basis and insights for the research of solid waste fixed CO2 storage in mining areas. However, it is urgent to strengthen the research on the engineering technology of solid waste CO2 fixed storage in mining area. The solid waste in mining area has great potential and engineering feasibility for fixing and storing CO2. At present, a new technical system of solid waste disposal and coal-based CCUS is being formed in mining area. Solid waste and CO2-based gas-liquid-solid three-phase materials mineralization strengthening, high efficiency mineralization carbon fixation and product control, mineralization carbon fixation filling in underground space and CO2 sealing, the evaluation of CO2 potential and carbon removal in goaf, and the evaluation of CO2 environment and safety in goaf will constitute the core connotation of solid waste disposal - coal-based CCUS-goaf filling technology system. Solid waste disposal in mining area-CCUS based coal-goaf filling technology is the key to realizing the waste free mine circular economy model of “coal production and processing-solid waste disposal in mining area-efficient mineralization carbon sequestration and CO2 storage-underground space filling and utilization-ground subsidence prevention and ecological restoration in mining area” in the future. The research and development of filling and sealing functional materials under the solid waste CO2 base in mining area is an important breakthrough. Moreover, the research and application of integrated technologies such as solid waste disposal in mining areas, coal-based CCUS, goaf filling, underground space utilization, and ecological restoration and protection in mining areas provide a new development idea for the construction of green and low-carbon mines.

Litsea pungens Hemsl., a type of deciduous or evergreen small tree or shrub, has significant value in fragrance, flavoring, and medicinal applications. However, the industry faces challenges such as low product technological content, limited processing models, and insufficient utilization in high-value processing. This article systematically reviews the volatile aroma compounds found in Litsea pungens Hemsl., including sesquiterpenes, limonene, citral, and linalool, as well as non-volatile constituents such as alkaloids, fatty acids, resin, and amides. It also explores its biological activities, which include antimicrobial, antioxidant, anti-inflammatory, and anti-arthritic properties. The article elucidates the sensory similarities between Litsea pungens Hemsl. and Sichuan pepper or black pepper, identifying amide compounds and eugenol as the chemical constituents responsible for the pungent sensation. It reviews research progress in its applications such as food quality preservation, salt reduction in dishes, enhancement of tobacco flavor, weed and pest control, and auxiliary dental treatments. Therefore, strengthening fundamental research on Litsea pungens Hemsl. and expediting the translation of related scientific achievements carry significant practical implications for advancing the industry chain and augmenting economic benefits.

Abstract Background Tumor-associated macrophages (TAMs) constitute a substantial part of human hepatocellular carcinoma (HCC). The present study was devised to explore TAM diversity and their roles in HCC progression. Methods Through the integration of multiple 10 × single-cell transcriptomic data derived from HCC samples and the use of consensus nonnegative matrix factorization (an unsupervised clustering algorithm), TAM molecular subtypes and expression programs were evaluated in detail. The roles played by these TAM subtypes in HCC were further probed through pseudotime, enrichment, and intercellular communication analyses. Lastly, vitro experiments were performed to validate the relationship between CD63, which is an inflammatory TAM expression program marker, and tumor cell lines. Results We found that the inflammatory expression program in TAMs had a more obvious interaction with HCC cells, and CD63, as a marker gene of the inflammatory expression program, was associated with poor prognosis of HCC patients. Both bulk RNA-seq and vitro experiments confirmed that higher TAM CD63 expression was associated with the growth of HCC cells as well as their epithelial-mesenchymal transition, metastasis, invasion, and the reprogramming of lipid metabolism. Conclusions These analyses revealed that the TAM inflammatory expression program in HCC is closely associated with malignant tumor cells, with the hub gene CD63 thus representing an ideal target for therapeutic intervention in this cancer type.

Abstract Background Elevated interstitial fluid pressure within tumors, resulting from impaired lymphatic drainage, constitutes a critical barrier to effective drug penetration and therapeutic outcomes. Results In this study, based on the photosynthetic characteristics of algae, an active drug carrier (CP@ICG) derived from Chlorella pyrenoidosa (CP) was designed and constructed. Leveraging the hypoxia tropism and phototropism exhibited by CP, we achieved targeted transport of the carrier to tumor sites. Additionally, dual near-infrared (NIR) irradiation at the tumor site facilitated photosynthesis in CP, enabling the breakdown of excessive intratumoral interstitial fluid by generating oxygen from water decomposition. This process effectively reduced the interstitial pressure, thereby promoting enhanced perfusion of blood into the tumor, significantly improving deep-seated penetration of chemotherapeutic agents, and alleviating tumor hypoxia. Conclusions CP@ICG demonstrated a combined effect of photothermal/photodynamic/starvation therapy, exhibiting excellent in vitro/in vivo anti-tumor efficacy and favorable biocompatibility. This work provides a scientific foundation for the application of microbial-enhanced intratumoral drug delivery and tumor therapy. Graphical Abstract

Abstract Background The Japanese government has instituted border control measures against COVID-19, including entry and exit screening of people arriving from overseas. We sought to evaluate the effectiveness of the exit screening policy in Japan in reducing the risk of importing COVID-19 cases among travelers from Asian and Pacific countries. Methods The study period was stratified based on the timing of exit screening: (i) the control period (the pre-exit screening period from 25 October 2020 to 16 January 2021), (ii) the time period with the Alpha variant from 17 January to 10 April 2021, and (iii) the time period with the Delta variant from 2 May to 2 October 2021. Incidence data in the countries of origin were used to adjust for the risk of infection among travelers. The positivity rate of entry screening in Japan was compared among the three different study periods, adjusting for the risk of infection in the country of origin. Results The adjusted relative risk of positivity was greatly reduced and substantially below the value of 1 during the Alpha variant period compared with the control period. Although the relative risks increased when comparing the Delta variant period against control, the estimate remained below 1, except for among travelers from India and Myanmar. The relative risk reduction was greatest in high-income countries, with estimates of 100% and 96% risk reduction during the Alpha and Delta variant periods, respectively, followed by upper-middle-income countries with estimates of 90% and 76%, respectively. Conclusions Even in the presence of the Alpha and Delta variants, exit screening clearly reduced the risk of infection among travelers arriving from Asian and Pacific nations. As the testing relies on the country of origin, the effectiveness varied greatly by the socioeconomic income status and epidemiological situation of those countries. Test standardization and quality assurance may be required in low- and middle-income countries.

Conversational agents (CAs) primarily adopt knowledge scaffolding (KS) or emotional scaffolding (ES) to intervene in learners’ knowledge gain and emotional experience in online learning. However, the ill-defined design for KS and ES, as well as insufficient understanding of their interactive effects on learning outcomes, have hindered the advancement of CAs in theory and practice. This study proposed systematic KS and ES design principles based on Zone of Proximal Development and growth mindset theories. We investigated their individual and combined impacts on knowledge gain and emotional experience. A quasi-experiment was conducted with 128 undergraduate students divided into four groups, corresponding to four distinct CAs: a non-scaffolding control group (CG), ES, KS, and Knowledge and Emotional Scaffolding (K&ES) CA. The results showed that K&ES-based CA had a significant impact on knowledge gain and emotional experience, with both being slightly improved compared to CG. Besides, KS-based CA had a positive effect on knowledge gain and emotional experience, while ES-based CA only slightly improved emotional experience compared to CG. The results validated the effectiveness of the proposed ES and KS design principles. The fine-grained analysis revealed a significant correlation between the achievement positive emotion and knowledge transfer, highlighting the importance of integrating KS and ES. In conclusion, this study offers valuable theoretical, methodological, and empirical insights for utilizing CAs to optimize online learning experiences.

In the context of the “dual carbon” (carbon peak and carbon neutrality) strategy, the carbon capture, utilization, and storage (CCUS) is one of the key technologies for achieving large-scale low-carbon utilization of fossil energy. In recent years, the CCUS has shown a trend of scaling and clustering development. The scientific and reasonable source-sink matching for the CCUS is an important basis for the site selection of the CCUS cluster deployment projects, and can establish some efficient pipe networks and reduce the emission reduction costs of CCUS. Ningxia is an important guarantee base for the strategic layout of national energy security, facing an enormous pressure of CO2 emission reduction due to its obvious characteristics of coal-oriented energy structure and industrial structure. In view of the source-sink matching problem of CCUS cluster deployment in Ningxia, the characteristics of industrial carbon emission sources and geological carbon sink potential in Ningxia were investigated and evaluated, and the CCSU source-sink matching model was constructed. Then, based on a full consideration of source and sink properties, costs of capture, transport, and storage, transportation distance. regional geographical conditions, land use types, population density, etc. the source-sink matching optimization and application scheme in Ningxia were obtained using the improved mileage saving method and the lowest cost path optimization method based on GIS (geographic information system), combining ArcGIS platform and optimization solution software. Finally, the suggestions for the CCUS cluster deployment in Ningxia were presented. The results show that as of 2021, Ningxia has 107 industrial carbon emission sources, with a total carbon emission of 226 million tonnes per year, mainly from the chemical industry (including self-owned power plants) and the power industry. The main geological bodies for storage in Ningxia include deep saltwater layers, deep non-exploitable coal seams, and oil and gas reservoirs. The theoretical geological storage capacity of CO2 is 15.155 billion tonnes, with the deep saltwater layer having the greatest storage potential. The CCUS source-sink matching in Ningxia is well. In the case of direct connection of sources and sinks, the total cost of CCUS cluster deployment (30 years planning period) of large industrial carbon emission source with annual emission of over 100 000 tonnes in Ningxia is about 2.45 trillion yuan, mainly from capture costs, which accounting for 83.65%. The unit emission reduction cost of CCUS is 402.32 yuan/t, and a total of 2 459 km of CO2 transportation pipelines need to be constructed. The improved mileage saving method and the lowest cost path optimization method based on GIS can significantly reduce the total cost of CCUS cluster deployment after optimization, the unit emission reduction cost of CCUS is reduced to 381.76 yuan/t, and the pipeline construction mileage reduced by 938 km. Ningxia should focus on its “two high” (high energy consumption, high emissions) industries, such as power industry and chemical industry. The application of CCUS technology in the northern and eastern regions, should be in advance to create five characteristic CCUS clusters, including Ningdong energy chemical industry base, Yinchuan-Wuzhong, Shizuishan, Zhongwei, and Guyuan. Then, the engineered full flowsheet technology of CCUS technology model is established with Ningxia’s characteristics.

The Xinjiang Uygur Autonomous Region has presented the expected resource conditions and work foundations for a large-scale coalbed methane (CBM) exploration and development, which shows that its CBM resources below the depth of 2000 m are 7.5 trillion m3, 450 CBM wells have been constructed, and the annual gas production has approached to 80 million m3. Xinjiang has put forward the goal of the annual CBM production of 2.5 billion m3 in 2025. Therefore, the large-scale and efficient development of CBM in Xinjiang has become an urgent and significant demand. In this paper, the main research progresses of Xinjiang CBM made in five key technical fields have been systematically summarized, including the CBM enrichment model and area optimization technology, the prediction and detection technology for sweet spot distribution, the technological strategy of the accelerated rolling development and rapid increase of reserves and productions, the geological adaptation technology system, and the cooperative exploration and development of CBM with coal, oil and gas. Then, the potential breakthrough directions have been analyzed and proposed. Research has shown that the coal reservoirs in Xinjiang show the unique geological characteristics of CBM, including widely developed multi-thick coal seams, low rank coal development, the frequent occurrence of steep coal seams, the significant deformation and structural control of coal bodies, complex hydrologic and outcrop conditions, and the gas-bearing and physical properties with three “low” (low gas content, methane concentration, and gas saturation) and five “high” (high gas intensity, porosity, stress change, reservoir pressure change, and permeability change). The Xinjiang CBM has multiple genetic types and enrichment models, including biogenic mechanism, thermogenic mechanism, and biogenic-thermogenic composite genetic mechanism, etc., and their corresponding enrichment models. Biogenic gas reservoirs or biogenic gas contribute widely. The distribution and occurrence patterns of CBM in Xinjiang show some significant differences between foreland basin and intermountain basin. Therefore, the first breakthrough direction is to innovate and form the scientific evaluation based on the principle of “two separation” (low-rank and middle- and high-rank; shallow and deep coal) and “two combination” (geological and engineering evaluation; multivariate data) and the precise target optimization technology based on “machine learning + three-dimensional geological modeling”. The sweet spot of deep CBM/CMG (coal measure gas) in Xinjiang is mainly the uplift of the depression in the basin, the depression of the uplift in the basin, and the slope around the basin margin. The potential well location is the structurally high position, and the potential reservoir is the fissure-developed primary structure coal seam or pore and fissure-developed coal bearing sand conglomerate reservoir. Then, the second breakthrough direction is the sweet spot prediction and exploration technology for deep CBM/CMG based on “new method of geophysics, rock physics and rock mechanics stratigraphy” and “new concept of geological and engineering sweet spot”. The basic principles of the accelerated rolling development are low-risk, short-cycle, high-efficiency, and multi-batch project deployment. The technical strategies of the rapid increase of CBM reserves and productions in the middle and shallow coal seams include the new well layout and construction in the new optimized block and the old well reconstruction for the increase of CBM production in the mature block. While this strategy for the deep coal seam is to give priority to deployment and development in the sweet spot in the deep but gentle slope in the large basin and the uplift in the basin. Then, the third breakthrough direction is the engineering deployment methods and technical strategies for the scientific accelerated rolling development, and efficient and rapid increase of the gas reserves and productions. The important progresses have been made in the engineering technologies of Xinjiang CBM, such as the differential optimization and deployment of the well type and pattern, the drilling and cementing with a low reservoir damage, the high reliability logging and well testing, the efficient staged fracturing with the multi-well types, and the drainage control with the low casing pressure and controlled pressure. The fourth breakthrough direction is to develop and construct a geological adaptability technology system for a large-scale and efficient exploration and development of CBM in Xinjiang. For the middle and shallow CBM and coal cooperative exploration and development, the gas extraction followed by coal mining, the co-extraction of CBM and coal, and the co-extraction of CBM and in-situ oil-rich coal should be conducted. For the deep CBM, oil, and gas cooperative exploration and development, the development of coal measure superimposed gas reservoir, the co-exploration and co-extraction of CBM and CMG, and the exploration and development of the whole petroleum system in coal-bearing sequence should be conducted. These cooperative exploration and development of deep CBM, oil, and gas is the fifth breakthrough direction, whose developments have been considered and explored. The results of this study are expected to provide the technical support and engineering decision reference for a large-scale and efficient exploration and development of CBM in Xinjiang.

This study explores the cavitation suppression mechanisms of biomimetic hydrofoils inspired by whale flipper tubercles, focusing on viscous oil flow around hydrofoils. A novel test system for viscous oil cavitation was developed, featuring a high-speed camera to capture transient cavitation phenomena. The study compared the cavitation behaviour of the flow around a basic blade (Base-blade) with that around a biomimetic blade (Bio-blade) designed with leading-edge tubercles. The visualization results demonstrated that the biomimetic structure significantly reduced the degree and unsteadiness of cavitation. The study also employed a three-dimensional CFD model using the Stress-Blended Eddy Simulation (SBES) method and the Zwart-Gerber-Belamri (ZGB) cavitation mass transfer model to reveal the flow mechanism. The Bio-blade reduced the vapour volume fraction by 9.67%, decreased the drag coefficient (Cd) by 9.36%, and minimized the lift fluctuations compared to the Base-blade. The biomimetic design reduces the transient shedding cavitation scale, effectively suppressing severe cavitation events. The Bio-blade inhibited the formation of leading-edge separation vortices and reduced the scale of U-shaped vortices that enhance cavitation evolution. In summary, this study provides a comprehensive analysis of the cavitation suppression mechanisms of biomimetic hydrofoils in high-viscosity fluids, offering valuable insights for future research and engineering applications.

Addressing the dual environmental challenges of dredged sludge disposal and the repurposing of industrial by-products, this study pioneers the application of Calcium Carbide Residue (CCR)-based materials for stabilizing dredged sludge in road subgrade construction. The proliferation of dredged sludge, characterized by high moisture content and pollutants, presents a significant environmental hazard, while CCR, a by-product of acetylene production, poses disposal and pollution challenges. This research endeavors to mitigate these issues by exploring the stabilization potential of CCR when mixed with dredged sludge, aiming to enhance the mechanical properties of materials used in road subgrade construction. Through comprehensive laboratory testing, including unconfined compressive strength assessments, scanning electron microscope analyses, and X-ray diffraction examinations, the study reveals the intricate physicochemical interactions between CCR and sludge. These interactions lead to notable improvements in material strength and moisture reduction, substantiating the efficacy of CCR-based binders in sludge stabilization. The CCR-based binder can make the strength of the stabilized sludge reach 215.4kPa and the water content drop to 32 %. Field tests conducted to assess real-world applicability confirm the laboratory results, demonstrating the treated material's suitability for road construction as per secondary road design criteria and its environmental safety. The research highlights the environmental and engineering benefits of using CCR-based materials for sludge stabilization, offering a sustainable solution to the challenges of dredged sludge management and industrial waste utilization. The findings represent a step forward in waste-to-resource conversion, promoting environmental sustainability in civil engineering practices.

Abstract Intrinsic plasticity, a fundamental process enabling neurons to modify their intrinsic properties, plays a crucial role in shaping neuronal input‐output function and is implicated in various neurological and psychiatric disorders. Despite its importance, the underlying molecular mechanisms of intrinsic plasticity remain poorly understood. In this study, a new ubiquitin ligase adaptor, protein tyrosine phosphatase receptor type N (PTPRN), is identified as a regulator of intrinsic neuronal excitability in the context of temporal lobe epilepsy. PTPRN recruits the NEDD4 Like E3 Ubiquitin Protein Ligase (NEDD4L) to NaV1.2 sodium channels, facilitating NEDD4L‐mediated ubiquitination, and endocytosis of NaV1.2. Knockout of PTPRN in hippocampal granule cells leads to augmented NaV1.2‐mediated sodium currents and higher intrinsic excitability, resulting in increased seizure susceptibility in transgenic mice. Conversely, adeno‐associated virus‐mediated delivery of PTPRN in the dentate gyrus region decreases intrinsic excitability and reduces seizure susceptibility. Moreover, the present findings indicate that PTPRN exerts a selective modulation effect on voltage‐gated sodium channels. Collectively, PTPRN plays a significant role in regulating intrinsic excitability and seizure susceptibility, suggesting a potential strategy for precise modulation of NaV1.2 channels' function.

BackgroundDue to the low incidence of malignant tracheoesophageal fistula and the paucity of relevant clinical studies, the benefits of stent implantation have not been well documented. It remains unclear which factors may affect fistula closure.MethodsBetween January 2015 and January 2021, 344 patients who were diagnosed with malignant tracheoesophageal fistula at Zhongda Hospital, Southeast University, were retrospectively enrolled. Demographic and clinical data were collected. Risk factors for fistula closure identified by univariate analysis were further analyzed using multivariable logistic regression.ResultsA total of 288 patients were analyzed in this study, of which 94 were treated conservatively, 170 were treated with an esophageal stent, and 24 were treated with a tracheal stent. Among them, the delta Karnofsky’s performance status score values (after 2 weeks/before treatment [p = 0.0028], after 1 month/before treatment [p = 0.0103]) were significantly different between conservative and stent treatment. There was a significant reduction of pneumonia incidence in the stenting group (33.53%) compared to the conservative treatment group (77.05%) after one month (p

Abstract CRISPR/Cas12a‐based combinational screening has shown remarkable potential for identifying genetic interactions. Here, we describe an innovative method for combinational genetic screening with rapid construction of a dual‐CRISPR RNA (crRNA) library using gene splicing through overlap extension PCR (SOE PCR) and the adoption of CeCas12a, which we previously identified with strict PAM recognition and low off‐targeting to guarantee fidelity and efficiency. The custom‐pooled SOE crRNA array (SOCA) library for double‐knockout screening could be conveniently constructed in the laboratory for widespread use, and the CeCas12a‐mediated high‐fidelity screen displayed good performance even under a negative selection screen. By designing a SOCA dual‐crRNA library that covered most of the kinase and metabolism‐associated gene targets of FDA‐approved drugs implicated in hepatocellular carcinoma (HCC) tumourigenesis, novel cross‐talk between the two gene sets was negatively selected to inhibit HCC cell growth in vitro and in vivo and was validated using virtual double‐knockdown screening based on TCGA databases. Thus, this rapid, efficient and high‐fidelity double‐knockout screening system is promising for systemically identifying potential genetic interactions between multiple gene sets or combinations of FDA‐ approved drugs for clinical translational medicine in the future.

IntroductionSleep loss and sleep deprivation (SD) cause deleterious influences on health, cognition, mood and behaviour. Nevertheless, insufficient sleep and SD are prevalent across many industries and occur in various emergencies. The deleterious consequences of SD have yet to be fully elucidated. This study aimed to assess the extensive influences of SD on physiology, vigilance, and plasma biochemical variables.MethodsSeventeen volunteers were recruited to participate in a 32.5-h SD experiment. Multiple physiological and cognitive variables, including tympanic temperature, blood oxygen saturation (SaO2), and vigilance were recorded. Urinal/salivary samples were collected and subjected to cortisol or cortisone analysis, and plasma samples were subjected to transcriptomic analysis of circular RNA (circRNA) expression using microarray. Plasma neurotransmitters were measured by targeted metabolic analysis, and the levels of inflammatory factors were assessed by antibody microarray.ResultsThe volunteers showed significantly increased sleepiness and decreased vigilance during SD, and the changes in circadian rhythm and plasma biochemistry were observed. The plasma calcium (p = 0.0007) was induced by SD, while ischaemia-modified albumin (IMA, p = 0.0030) and total bile acid (TBA, p = 0.0157) decreased. Differentially expressed circRNAs in plasma were identified, which are involved in multiple signaling pathways including neuronal regulation and immunity. Accordingly, SD induced a decrease in 3-hydroxybutyric acid (3OBH, p = 0.0002) and an increase in thyroxine (T4, p

Summary: The presence of antibiotic persisters is one of the leading causes of recurrent and chronic diseases. One challenge in mechanistic research on persisters is the enrichment of pure persisters. In this work, we validated a proposed method to isolate persisters with notorious Staphylococcus aureus cultures. With this, we analyzed the proteome profile of pure persisters and revealed the distinct mechanisms associated with vancomycin and enrofloxacin induced persisters. Furthermore, morphological and metabolic characterizations were performed, indicating further differences between these two persister populations. Finally, we assessed the effect of ATP repression, protein synthesis inhibition, and reactive oxygen species (ROS) level on persister formation. In conclusion, this work provides a comprehensive understanding of S. aureus vancomycin and enrofloxacin induced persisters, facilitating a better mechanistic understanding of persisters and the development of effective strategies to combat them.

Abstract Rheumatoid arthritis (RA) is a chronic autoimmune inflammatory disease characterized by inflammation of the synovial tissue and joint bone destruction, often leading to significant disability. The main pathological manifestation of joint deformity in RA patients is bone destruction, which occurs due to the differentiation and proliferation of osteoclasts. The transcription factor nuclear factor-activated T cell 1 (NFATc1) plays a crucial role in this process. The regulation of NFATc1 in osteoclast differentiation is influenced by three main factors. Firstly, NFATc1 is activated through the upstream nuclear factor kappa-B ligand (RANKL)/RANK signaling pathway. Secondly, the Ca2+-related co-stimulatory signaling pathway amplifies NFATc1 activity. Finally, negative regulation of NFATc1 occurs through the action of cytokines such as B-cell Lymphoma 6 (Bcl-6), interferon regulatory factor 8 (IRF8), MAF basic leucine zipper transcription factor B (MafB), and LIM homeobox 2 (Lhx2). These three phases collectively govern NFATc1 transcription and subsequently affect the expression of downstream target genes including TRAF6 and NF-κB. Ultimately, this intricate regulatory network mediates osteoclast differentiation, fusion, and the degradation of both organic and inorganic components of the bone matrix. This review provides a comprehensive summary of recent advances in understanding the mechanism of NFATc1 in the context of RA-related bone destruction and discusses potential therapeutic agents that target NFATc1, with the aim of offering valuable insights for future research in the field of RA. To assess their potential as therapeutic agents for RA, we conducted a drug-like analysis of potential drugs with precise structures.

This paper proposes a radar signal transceiver framework that combines single-bit sampling and time division multiplexing receivers to satisfy the application requirements of low-cost lightweight radars. Firstly, this paper explains the advantages of saving the number of receivers by introducing the working principle of the framework. From the perspective of radar resource allocation, the importance of single-bit sampling in this framework was analyzed; additionally, the proposed framework can achieve better performance than a classical linear frequency modulation continuous wave radar using time and space exchange. Subsequently, the formulas for range, velocity and angle measurement were derived, along with the Cramér-Rao bound for estimating target parameters. Accordingly, the performance advantages of the proposed framework were verified, and the signal-to-noise ratio conditions for its stable operation were determined. Finally, this paper verifies the accuracy of the target acquisition principle of the proposed framework and the reliability of the performance analysis by using a velocity dimensional pairing algorithm based on single-bit two-dimensional multiple signal classification.

Abstract Background A major epidemic of COVID-19 caused by the Delta variant (B.1.617.2) occurred in India from March to July 2021, resulting in 19 million documented cases. Given the limited healthcare and testing capacities, the actual number of infections is likely to have been greater than reported, and several modelling studies and excess mortality research indicate that this epidemic involved substantial morbidity and mortality. Methods To estimate the incidence during this epidemic, we used border entry screening data in Japan to estimate the daily incidence and cumulative incidence of COVID-19 infection in India. Analysing the results of mandatory testing among non-Japanese passengers entering Japan from India, we calculated the prevalence and then backcalculated the incidence in India from February 28 to July 3, 2021. Results The estimated number of infections ranged from 448 to 576 million people, indicating that 31.8% (95% confidence interval (CI): 26.1, 37.7) – 40.9% (95% CI: 33.5, 48.4) of the population in India had experienced COVID-19 infection from February 28 to July 3, 2021. In addition to obtaining cumulative incidence that was consistent with published estimates, we showed that the actual incidence of COVID-19 infection during the 2021 epidemic in India was approximately 30 times greater than that based on documented cases, giving a crude infection fatality risk of 0.47%. Adjusting for test-negative certificate before departure, the quality control of which was partly questionable, the cumulative incidence can potentially be up to 2.3–2.6 times greater than abovementioned estimates. Conclusions Our estimate of approximately 32–41% cumulative infection risk from February 28 to July 3, 2021 is roughly consistent with other published estimates, and they can potentially be greater, given an exit screening before departure. The present study results suggest the potential utility of border entry screening data to backcalculate the incidence in countries with limited surveillance capacity owing to a major surge in infections.

Glioma is a kind of brain disease with high incidence, high recurrence rate, high mortality, and low cure rate. To obtain accurate diagnosis results of brain glioma, doctors need to manually compare the imaging results of different modalities many times, which will increase the diagnosis time and reduce the diagnostic efficiency. Image fusion technology has been widely used in recent years to obtain information on multimodal medical images. This paper proposes a novel image fusion framework, target information enhanced image fusion network (TIEF), using cross-modal learning and information enhancement techniques. The framework consists of a multi-sequence feature extraction block, a feature selection block, and a fusion block. The multi-sequence feature extraction block consists of multiple sobel dense conv leaky ReLu block (SDCL-block). SDCL-block mainly realizes the extraction of edge features, shallow features, and deep features. The feature selection block identifies the feature channels with rich texture information and strong discrimination ability through the effective combination of global information entropy criterion and feature jump connection. The feature fusion block mainly comprises multi-head and spatial attention mechanisms, which can realize the fusion of intra-modality and inter-modality features. On this basis, considering the influence of tumor spatial location and structure information on the fusion results, a loss function is designed, which is a weighted combination of texture loss, structure loss, and saliency loss so that texture information from multimodal magnetic resonance imaging (MMRI) and saliency information from different anatomical structures of the brain can be fused at the same time to improve the expression ability of features. In this paper, the TIEF algorithm is trained and validated on the MMRI and (Single-Photon Emission Computed Tomography-MRI) SPECT-MRI datasets of glioma and generalized on the (Computed Tomography-MRI) CT-MRI dataset of meningioma to verify the performance of the TIEF algorithm. In the image fusion task, quantitative results showed that TIEF exhibited optimal or suboptimal performance in information entropy, spatial frequency, and average gradient metrics. Qualitative results indicate that the fused images can highlight tumor and edematous features. A downstream image segmentation task was used for evaluation to further verify TIEF’s effectiveness. TIEF achieved the best results in both (Dice similarity coefficient) Dice and (Hausdorff distance 95%) HD95 segmentation metrics. In the generalization task, quantitative results indicated that TIEF obtained more information in the meningioma dataset. In conclusion, TIEF can effectively achieve cross-domain information acquisition and fusion and has robustness and generalization ability.

Broken soft and low permeability (BSLP) coal reservoirs are widely distributed in China. However, due to its soft and broken structure and low permeability, the conventional vertical/horizontal well direct fracturing technology is not ideal for the enhancement of BSLP coal seams and the surface development of coalbed methane (CBM). The efficient development of CBM in BSLP coal reservoirs has been an important technical bottleneck restricting the large-scale development of CBM industry and the efficient treatment of coal mine gas control in China. Based on the systematic analysis of the characteristics of BSLP coal reservoirs and the problems existing in the surface development of CBM, the current technological progress in the enhancement of BSLP coal reservoirs and surface development of CBM were reviewed by taking horizontal well as the base well type and focusing on three different technical directions: indirect fracturing, stress relief and consolidation before fracturing. The CBM development technologies of indirect fracturing, including roof indirect fracturing, gangue indirect fracturing and hard coal stratification indirect fracturing were summarized. The stress release CBM development technologies using different stress release methods, such as hydraulic jet cavitation, gas dynamic cavitation, mechanical + hydraulic + induced instability coupling cavitation and hydraulic slit, were reviewed. Furthermore, the CBM development technology of first consolidation and then fracturing of BSLP coal reservoirs induced by microorganisms was also summarized. The exploration of indirect fracturing technology has accumulated a lot of engineering practice, and has achieved a good effect on enhancing the BSLP coal reservoirs in areas with suitable geological conditions. The exploration of new technology for enhancing BSLP coal reservoir represented by stress release has also made great progress, and has entered the stage of engineering tests and verification. According to the characteristics of BSLP coal reservoir and the new development principle, the horizontal well stress release technology has greater potential for reservoir reconstruction and better effect for CBM development. Based on the horizontal well stress release method, the development trend of BSLP coal reservoir enhancement and surface CBM development technology was forecasted in three aspects: expanding the stress release range, improving the development effect of CBM and achieving the co-production of coal and CBM. It is expected to provide reference for improving the stimulation effect of BSLP coal reservoir and increasing the production of CBM well in China.

This study evaluates petrophysical properties (especially porosity, permeability, tortuosity, and diffusivity) of representative geological rocks in the context of injectivity, storage space, and caprock integrity for effective utilization and long-term storage of carbon dioxide. A total of 10 geological rocks were selected as representative storage media for consideration as saline aquifers & depleted oil and gas reservoirs (sandstones and carbonates), basalts, and cap rocks, as well as utilization in organic-rich shale and coal seams. An integrated suite of laboratory tests, including liquid immersion porosimetry, gas expansion porosimetry, grain size distribution, mercury intrusion porosimetry, and gas diffusion, were performed on these various rock samples. The results exhibit a disparity of petrophysical properties among two broad groups of rocks: rocks selected for possible storage of CO2have porosities of ∼10-25%, permeabilities of ∼10−16-10−13m2, μm-sized pore-throat size distribution, and mostly good pore connectivity; in contrast, the potential caprocks have porosities of ∼0.5-5%, permeabilities of ∼10−20-10−18m2, pore throat sizes of

Cordyceps primarily consists of ascomycetes, a parasitic fungus that infects insects and arthropods. Recently, Cordyceps has been shown to manifest a diverse range of pharmacological activities, rendering it applicable for the treatment and mitigation of various diseases, such as diabetes, acute liver injury, and colitis. Many active constituents have been identified from Cordyceps sinensis, including cordycepin, adenosine, sterols, and polysaccharides. Polysaccharides constitute a primary active component of Cordyceps, exhibiting immunomodulatory effects. We searched the Web of Science database with the keywords of cordyceps, polysaccharide, and immune modulation; collected related studies from 2004 to 2024; and eliminated articles with low influence and workload. A review of the research advancements regarding the immunomodulatory effects of Cordyceps polysaccharides was conducted with the aim of furnishing valuable reference information. Research indicates that polysaccharides exhibiting immunomodulatory activity are predominantly sourced from Cordyceps sinensis and Cordyceps militaris. Immunological experimental results demonstrate that Cordyceps polysaccharides can augment the activities of macrophages, lymphocytes, and dendritic cells while fostering the expression of immune-active substances such as cytokines and chemokines. Furthermore, animal experiments have substantiated the immunomodulatory effects of Cordyceps polysaccharides. These effects encompass ameliorating immune suppression induced by drugs or radiation, enhancing immune organ indices, elevating the expression of immunoreactive substances, and mitigating immune evasion prompted by tumors. In conclusion, Cordyceps polysaccharides exhibit significant immunomodulatory activity and merit further investigation.

The geochemical processes of groundwater in arid regions are generally influenced by both natural hydrological processes and human activities. However, impacts of water-rock interactions on groundwater recharge via hydrological processes, controlled by both intermittent river water flow and groundwater withdrawals, is still poorly understood. In this study, 327 groundwater chemistry datasets collected from the upper, middle (including Gobi and riparian zones), and lower regions of the Ejina Delta in Northwest China from 2001 to 2023 were analyzed. Our results revealed that the total dissolved solids (TDS) concentration of groundwater in Ejina Delta ranged from approximately 881.5 ± 331.6 mg/L in the upper regions to 1,953.6 ± 1,208.5 mg/L in the lower regions, with an increasing trend observed. Ecological water conveyance (EWC), recharging aquifer through intermittent river water flow, resulted in a decrease in TDS concentrations from 2001 to 2023 mainly in the upper region. While irrigation notably affected groundwater chemistry in the lower region, resulting in a substantial increase in groundwater salinity. Groundwater chemistry in the Middle Gobi region remained relatively stable over the study period. Generally, the hydrochemical composition shifted from the Na-Mg-SO4-HCO3 and Na-Mg-Ca-SO4-HCO3 types in the upper region to Na-Mg-SO4-HCO3 and Na-Mg-SO4-Cl types in the lower region, with Na-SO4-Cl predominant in the Middle Gobi. These shifts were likely be attributed to the interplay of water-rock interactions, coupled with evaporation-crystallization processes. Inverse modeling using PHREEQC revealed that in the upper-middle region, primary water-rock interactions involved calcite dissolution and the precipitation of dolomite, gypsum, halite, and sylvite salts, as well as cation exchange reactions (2NaX+Ca2+→CaX2+2Na+). In contrast, the hydrogeological system in the middle-lower region exhibited an opposite pattern of water-rock interactions. Overall, ecological water conveyance partially facilitated water-rock interactions during lateral groundwater flow, while irrigation disrupted the natural hydrogeochemical equilibrium, involving halite dissolution and opposite cation exchange reactions compared to other regions.

Extrachromosomal DNA (ecDNA) is a self-replicating circular DNA originating from the chromosomal genome and exists outside the chromosome. It contains specific gene sequences and non-coding regions that regulate transcription. Recent studies have demonstrated that ecDNA is present in various malignant tumors. Malignant tumor development and poor prognosis may depend on ecDNA's distinctive ring structure, which assists in amplifying oncogenes. During cell division, an uneven distribution of ecDNA significantly enhances tumor cells' heterogeneity, allowing tumor cells to adapt to changes in the tumor microenvironment and making them more resistant to treatments. The application of ecDNA as a cancer biomarker and therapeutic target holds great potential. This article examines the latest advancements in this area and discusses the potential clinical applications of ecDNA.

Abstract Background Obesity, characterized by excessive white adipose tissue expansion, is associated with several metabolic complications. Identifying new adipogenesis regulators may lead to effective therapies for obesity-induced metabolic disorders. Results Here, we identified the growth arrest and DNA damage-inducible A (GADD45A), a stress-inducible histone-folding protein, as a novel regulator of subcutaneous adipose metabolism. We found that GADD45A expression was positively correlated with subcutaneous fat deposition and obesity in humans and fatty animals. In vitro, the gain or loss function of GADD45A promoted or inhibited subcutaneous adipogenic differentiation and lipid accumulation, respectively. Using a Gadd45a -/- mouse model, we showed that compared to wild-type (WT) mice, knockout (KO) mice exhibited subcutaneous fat browning and resistance to high-fat diet (HFD)-induced obesity. GADD45A deletion also upregulated the expression of mitochondria-related genes. Importantly, we further revealed that the interaction of GADD45A with Stat1 prevented phosphorylation of Stat1, resulting in the impaired expression of Lkb1, thereby regulating subcutaneous adipogenesis and lipid metabolism. Conclusions Overall, our results reveal the critical regulatory roles of GADD45A in subcutaneous fat deposition and lipid metabolism. We demonstrate that GADD45A deficiency induces the inguinal white adipose tissue (iWAT) browning and protects mice against HFD-induced obesity. Our findings provide new potential targets for combating obesity-related metabolic diseases and improving human health.

In order to determine the optimal extraction process, and antioxidant and antibacterial activities of anthocyanins from Perilla friesians leaf, in this study, Perilla friesians leaf was used as raw material. Response surface method was used to optimize the optimal process conditions of ultrasonic-assisted extraction of anthocyanins from Perilla friesians leaf, and liquid mass combined technology was used to conduct qualitative and quantitative analysis of anthocyanins and anthocyanins in the extracts. The antioxidant activity and antibacterial activity of the extracts were studied. The results showed that the optimum conditions were as follows: The ratio of material to liquid was 1:20 g/mL, the ultrasonic temperature was 47 ℃, the ultrasonic time was 57 min, and ethanol concentration was 62%, and the maximum extraction rate was 7.18±0.32 mg/g DW under these conditions. The extract was mainly composed of cyanidin, delphinidin 3-O-glucoside, and cyanidin 3-O-glucoside. The extract showed significant scavenging activity on DPPH and ABTS+ free radicals, and the IC50 values were 0.49 and 0.32 mg/mL, respectively. The lowest inhibitory concentration against Staphylococcus aureus was 160 mg/mL. This study provides a theoretical basis for the extraction and application of anthocyanins from Perilla friesians leaf.

Abstract We published a paper in BMC Bioinformatics comprehensively evaluating the performance of structural variation (SV) calling with long-read SV detection methods based on simulated error-prone long-read data under various sequencing settings. Recently, C.Y.T. et al. wrote a correspondence claiming that the performance of NanoVar was underestimated in our benchmarking and listed some errors in our previous manuscripts. To clarify these matters, we reproduced our previous benchmarking results and carried out a series of parallel experiments on both the newly generated simulated datasets and the ones provided by C.Y.T. et al. The robust benchmark results indicate that NanoVar has unstable performance on simulated data produced from different versions of VISOR, while other tools do not exhibit this phenomenon. Furthermore, the errors proposed by C.Y.T. et al. were due to them using another version of VISOR and Sniffles, which caused many changes in usage and results compared to the versions applied in our previous work. We hope that this commentary proves the validity of our previous publication, clarifies and eliminates the misunderstanding about the commands and results in our benchmarking. Furthermore, we welcome more experts and scholars in the scientific community to pay attention to our research and help us better optimize these valuable works.

Milk thermal treatment, such as pasteurization, high-temperature short-time processing, and the emerging ultra-short-time processing (

With escalating human activities and the substantial emissions of greenhouse gases, global warming intensifies. This phenomenon has led to increased occurrences of various extreme hydrological events, precipitating significant changes in lakes and rivers across the Qinghai Tibet Plateau. Therefore, accurate information extraction about and delineation of water bodies are crucial for lake monitoring. This paper proposes a methodology based on the Normalized Difference Water Index (NDWI) and Gumbel distribution to determine optimal segmentation thresholds. Focusing on Qinghai Lake, this study utilizes multispectral characteristics from the US Landsat satellite for analysis. Comparative assessments with seven alternative methods are conducted to evaluate accuracy. Employing the proposed approach, information about water bodies in Qinghai Lake is extracted over 38 years, from 1986 to 2023, revealing trends in area variation. Analysis indicates a rising trend in Qinghai Lake’s area following a turning point in 2004. To investigate this phenomenon, Pearson correlation analysis of temperature and precipitation over the past 38 years is used and unveils the fact that slight precipitation impacts on area and that there is a positive correlation between temperature and area. In conclusion, this study employs remote sensing data and statistical analysis to comprehensively investigate mechanisms driving changes in Qinghai Lake’s water surface area, providing insights into ecological shifts in lake systems against the backdrop of global warming, thereby offering valuable references for understanding and addressing these changes.

The scientific understanding of the fluid flow and mass transfer mechanism in pores and fractures of coal seam are the fundamental strategy to achieve the efficient production of coalbed methane (CBM). During CBM development, the occurrence, migration, and production characteristics of coalbed water not only determine the drainage and depressurization effect of CBM well, but also significantly affect the desorption, migration, and production process of CH4, which is crucial to the efficient drainage and production control of CBM well. Taking the Fanzhuang block in the southern Qinshui Basin as an example, based on the occurrence form, production process, and flow form of coalbed water, the research on the mechanism of phase change and mass transfer process of coalbed water has been carried out. The threshold pore diameter of phase change and the mass transfer process of coalbed water in anthracite reservoir under the engineering background have been quantified, and its engineering implications for CBM production have been discussed. The results show that the occurrence state of coalbed water can be changed dynamically, and the fluid pressure difference is the main mechanism of its dynamic change. In the single-phase flow stage of water, the migration of movable water is mainly affected by the surface tension. Under the engineering background, the migration and production of movable water in pores and fractures with macropore (pore diameter > 50 nm) is the precondition of the overall release of coal seam pressure, and lays the foundation for a high and stable production of CBM well. In the gas-water two-phase flow stage, the transformation of bound water (capillary water) to movable water is greatly affected by the wettability of coal, and the interface property and interaction between gas and water. The pressure condition requirements of the transformation of bound water (capillary water) to movable water increase due to the capillary effect. In the bubbly flow and plug flow stage, CH4 desorption promotes the transformation of bound water (capillary water) to movable water in some pores and fractures with mesopore (2−50 nm) scale, which determines the overall release of coal seam pressure. This also indicates that after the CBM well has casing pressure, the overall release of the coal seam pressure is the result of the joint action of the gas and water, and the slow transition from the water production stage to the depressurization and gas production stage is necessary for the high production of the CBM well. The continuous casing pressure holding may lead to early formation of slug flow in pores and fractures with mesopore scale, which is not conducive to the high and stable production of CBM well. Moreover, with the decrease of coal seam pressure, the liquid water in pores and fractures with the equivalent pore size > 40 nm can be vaporized and separated to the gaseous free water, which forms competitive adsorption/desorption with the adsorbed CH4. However the water in pores and fractures with the equivalent pore size < 40 nm is preserve with liquid or transported by wetting migration, and has little influence on the transformation of bound water (capillary water) to movable water in the gas-water two-phase flow stage.

Large-scale cluster deployment is the development direction of the CCUS (Carbon Capture, Utilization and Storage) technology and the national major demand of fossil energy low-carbon utilization. The synergistic relationship and mechanism between CO2 geological storage potential and energy resources are the theoretical basis of the CCUS large-scale cluster deployment. In this study, the major progress in the fields of CO2 geological storage potential and its evaluation methods, the CCUS source-sink matching and pipe network design model, the synergistic relationship between CO2 geological storage potential and energy resources, and the technical basis and mode of the CCUS cluster deployment are systematically reviewed. The research ideas on the theoretical methodology of synergy between CO2 geological storage potential and energy resources in China are discussed and envisioned. The main conclusions of the research are as follows. The CO2 geological storage potential restricts the development potential and application scale of the CCUS technology. The evaluation method system of CO2 geological storage potential is preliminarily established, which is composed of suitability evaluation method, storage capacity evaluation method, and storage site selection method. However, the evaluation method system of CO2 geological storage potential urgently needs to be improved and developed in future research. Source-sink matching is the important direct basis for the CO2 transportation pipeline network design and the CCUS large-scale cluster deployment. The improvement and establishment of the optimization model between the CCUS source-sink matching and the CCUS cluster pipe network model is the key technology for the CCUS source-sink matching, and the transformation from single-stage static planning model to multi-stage dynamic planning model is the development direction. The synergy between CO2 geological storage potential and energy resources constitutes the constraint condition of the CCUS technology. The synergy between the CCUS technology and new energy technology, e.g., renewable energy, hydrogen energy, energy storage, etc. will be expected to form a new path, new mode, and new direction to achieve energy system decarbonization. The synergistic relationships between CO2 geological storage potential and biomass and water resources restrict the large-scale deployment area of the CCUS technology and the application potential of the BECCS (Bioenergy with Carbon Capture and Storage) technology. Therefore, the research on the optimization model of energy and resources system based on the CCUS source-sink matching model will be a new technical requirement. The CO2 geological storage potential, energy-system constrained CCUS source-sink matching optimization scheme, and full flowsheet CCUS technology constitute the key technical basis for the CCUS cluster deployment. The CCUS cluster deployment mode of onshore storage with near-source transportation should be the priority development direction in China. The CCUS cluster deployment mode of onshore storage and offshore storage with remote-source transmission also have development prospects in Yangtze River Delta and Great Bay Area.

CO2 geological sequestration-enhanced coalbed methane (CO2-ECBM) strengthens the development of coalbed methane (CBM) and realizes the stimulation of coalbed methane wells. At the same time, CO2 is stored in deep coal seams. This technology has some great development prospects. Relying on the demonstration project, numerical simulation based on geological modeling is still an important path for its technological development. Based on the analysis of the characteristics for the corner grid geological model and the geological modeling ability of COMSOL Multiphysics, a geological model that can clearly display the three-dimensional spatial morphology and heterogeneity distribution of gas content, adsorption time, porosity, permeability, elastic modulus and Poisson’s ratio of the No. 3 coal in the Shizhuang South Block of Qinshui Basin was established in COMSOL Multiphysics using the split-reconstruction method. On this basis, the numerical simulation of CO2-ECBM for controlling gas injection pressure was carried out in combination with the adsorption-hydraulic-thermal-mechanical-chemical (AHTMC) multi-field coupling mathematical model, and the impact of CO2 injection pressure on CH4 stimulation, CO2 storage and the geochemical environment of coal reservoir were analyzed. Moreover, two kinds of shut-in modes, namely, simultaneous shut-in and sequential shut-in, and four CO2-ECBM engineering objectives, namely, time saving, CH4 stimulation, CO2 storage and comprehensive consideration of the three, were proposed. In addition, the CO2 injection pressures were optimized according to the two shut-in modes with the four objectives. The results show that: ① Under the limit of 15-year and the injection pressure of 5.50−9.50 MPa for the CO2-ECBM project, with the increase of CO2 injection pressure, the CH4 production rate of CBM wells and the CO2 storage capacity of coal reservoir increase, with the maximum of 14.39% and 8.31×107 m3 respectively, the area of coal reservoir containing acid fissure water expands. The CO2 storage rate decreases due to the large output of CO2 from CBM wells with the increase of gas injection pressure, but remains above 95%. ② The heterogeneity of coal reservoirs has a great impact on the production of CBM wells. The higher the CH4 content and the greater the porosity and permeability of the coal reservoirs around the CBM wells, the more significant the CH4 stimulation effect. The stronger the CO2 adsorption capacity of the coal reservoirs surrounding CBM wells, the lower their CO2 production rate. ③ Under the simultaneous and sequential shut-in, CO2 injection pressure has a significant impact on the CO2 concentration and CH4 production rate of gas produced by well group, and the CH4 recovery of coal reservoir decreases with the increase of injection pressure at the end of CO2-ECBM project with 33.28% and 41.63% for 3.50 MPa, 18.90% and 28.03% for 6.50 MPa and 12.81% and 23.01% for 9.50 MPa, respectively. ④ The optimal injection pressure of CO2 for the engineering objectives of time saving, CH4 stimulation, CO2 storage and comprehensive consideration of above three are 8.05, 3.50, 6.35 and 6.25 MPa for the simultaneous shut-in, respectively, and 9.50, 9.50, 3.50 and 9.50 MPa for the sequential shut-in, respectively. ⑤ Compared with simultaneous shut-in, the sequential shut-in can achieve better CH4 stimulation and CO2 storage effects by extending the engineering time when using the optimal CO2 injection pressure.

Abstract Pork is the most consumed meat in the world, and its quality is associated with human health. Intramuscular fat (IMF) deposition (also called marbling) is a key factor positively correlated with various quality traits and lipo-nutritional values of meat. However, the cell dynamics and transcriptional programs underlying lipid deposition in highly marbled meat are still unclear. Here, we used Laiwu pigs with high (HLW) or low (LLW) IMF contents to explore the cellular and transcriptional mechanisms underlying lipid deposition in highly-marbled pork by single-nucleus RNA sequencing (snRNA-seq) and bulk RNA sequencing. The HLW group had higher IMF contents but less drip loss than the LLW group. Lipidomics results revelled the changes of overall lipid classes composition (e.g., glycerolipids including triglycerides, diglycerides, and monoglycerides; sphingolipids including ceramides and monohexose ceramide significantly increased) between HLW and LLW groups. SnRNA-seq revealed nine distinct cell clusters, and the HLW group had a higher percentage of adipocytes (1.40% vs. 0.17%) than the LLW group. We identified 3 subpopulations of adipocytes, including PDE4D+/PDE7B+ (in HLW and LLW), DGAT2+/SCD+ (mostly in HLW) and FABP5+/SIAH1+ cells (mostly in HLW). Moreover, we showed that fibro/adipogenic progenitors could differentiate into IMF cells and contribute to 43.35% of adipocytes in mice. In addition, RNA-seq revealed different genes involved in lipid metabolism and fatty acid elongation. Our study provides new insights into the cellular and molecular signatures of marbling formation; such knowledge may facilitate the development of new strategies to increase IMF deposition and the lipo-nutritional quality of high marbled pork.

Taraxacum kok-saghyz (TKS) latex is a natural latex produced from its root, and its extraction optimization process is mainly studied in the present paper. The composition of fresh roots of TKS was quantitatively analyzed, and the results showed that the moisture content of the fresh root was approximately 70 %, and the rubber content averaged to 6 % (dry weight ratio). An optimal process route for extracting the TKS latex was finally determined, making the extraction efficiency reach about 80 %, and a new latex extraction process was established and optimized and named “the process of Buffer Extraction TKS Latex (BETL)”. Hevea latex, extracted TKS latex and TKS latex collected directly from the broken roots were compared for study. The results showed that, like Hevea latex, the appearance of TKS latex was milky white; and after centrifugation, both showed four layers from top to bottom: rubber particles, Frey-Wyssling particles, C-serum and lutoids. The results of the composition analysis showed that the concentration of TKS latex ranged from 54.54 % to 68.25 %, which is close to that of concentrated Hevea latex; the moisture content of TKS latex was between 31.75 % and 45.46 %. The protein content of TKS latex was 13.51 mg/mL, which was lower than that of Hevea latex at the same rubber hydrocarbon concentration. The molecular structures and properties of Hevea latex, the extracted TKS latex, and the collected TKS latex were characterized by FTIR, 13C NMR, GPC, TG, SEM and LPSA, and the results showed that the main components and structure of the three latexes were similar, which are all cis-1,4-polyisoprene, and include the proteins and lipids. The distributions molecular weights of the three latexes all showed a bimodal distribution, but the molecular weight of the latex collected from TKS was lower, which indicates the larger molecules were difficult to flow outside the root automatically. The Hevea latex and TKS latex rubber particles were both core-shell structure and the size distribution were bimodal, which was consistent with the GPC analysis results.

Objectives To explore the association between non-high-density lipoprotein (non-HDL) and mortality risk, both short-term and long-term, in Chinese people.Design A prospective cohort study.Setting The National Basic Public Health Service (BPHS) in China.Participants Including 621 164 elderly individuals around Hunan Province who underwent healthcare management receiving check-ups in China BPHS from 2010 to 2020. Exclusion criteria: (1) missing information on gender; (2) missing records of lipid screening; (3) missing information on key covariates; and (4) missing records of comorbidities (cardiovascular disease, hypertension, diabetes, cancer.)Primary and secondary outcome measures The study’s primary endpoint was all-cause and cause-specific mortality, sourced from Hunan’s CDC(Center for Disease Control and Prevention)-operated National Mortality Surveillance System, tracking participants until 24 February 2021.Results 26 758 (4.3%) deaths were recorded, with a median follow-up of 0.83 years. Association between non-HDL and mortality was non-linear after multivariable adjustment, with the optimum concentration (OC) being 3.29 and 4.85 mmol/L. Compared with OC, the risk increased by 1.12-fold for non-HDL

Abstract The development of real-time and accurate visual stress detection is crucial for the field of building engineering. Herein, a new strategy is explored for the development of novel cementitious materials by hierarchical aggregation smart luminescent material and resin-based material. The cementitious material with such layered structure is inherently capable of visualization of stress monitoring and recording by converting the stress to visible light. The specimen fabricated by the novel cementitious material could repetitively emit green visible light under excitation of a mechanical pulse for 10 cycles, suggesting that the cementitious material shows highly reproducible performance. Moreover, the numerical simulations and analysis for the models of stress indicate that the luminescent time is synchronous with the stress and the emission intensity is proportional to the value of stress. To the best of our knowledge, this is the first study that the cementitious material realizes visible stress monitoring and recording, which supplies new insights for exploring modern multi-functional building materials.

During the hydraulic fracturing of coalbed methane (CBM) well, the deposition of coal fines in propped fractures and the migration of coal fines in cleats will damage the permeabilities of propped fractures and cleats, consequently affecting the hydraulic fracturing and the subsequent drainage of CBM well. For the purpose of dredging propped fractures and avoiding the clogging of cleats effectively, a novel method for the control of coal fines in propped fractures and cleats during hydraulic fracturing was proposed by optimizing the salinity of fracturing fluid. With the salinity decreasing stepwise, the experiments on the migration of coal fines in propped fractures and cleats were conducted on quartz sand-packed columns and anthracite coal plugs, respectively, to investigate the response characteristics of the migration of coal fines to the change of salinity. Additionally, the migration of coal fines was simulated by using the extended DLVO method, to elucidate the influence mechanisms of salinity on the migration of coal fines. On this basis, the optimal salinity range that takes into account the control of coal fines in propped fractures and cleats was explored. The results indicated that there existed a critical salt concentration (CSC) for the migration of coal fines in both propped fractures and cleats. When the salinity was lower than the CSC, the permeability of propped fractures abruptly increased while that of cleats decreased sharply, accompanied by a large amount of coal fines produced. The value of the CSC for the migration of coal fines in propped fractures was higher than that in cleats, which can be attributed to the fact that the surface electronegativity of proppants was stronger than that of cleats, while the hydrophobicity was weaker than that of cleats. With the gradual decrease of salinity, the electric double layer (EDL) repulsive force between coal fines and channel increased continuously. When the salinity decreased to the CSC, the EDL repulsion started to be greater than the sum of Lifshitz-van der Waals attraction and Lewis acid-base attraction, resulting in the migration of coal fines. Both the values of the predicted CSCs for the migration of coal fines in propped fractures and cleats were consistent with experimental data, indicating the effectiveness of the model. During hydraulic fracturing, the salinity of fracturing fluid can be designed between the CSCs for the migration of coal fines in propped fractures and cleats. In that case, the production of coal fines in propped fractures is promoted while the migration of coal fines is inhibited in cleats, so as to achieve the dual purposes of coal fines control in propped fractures and cleats.

Grouting reinforcement is an effective method for controlling the stability of engineering rock mass. The mechanism is mainly to inject or infiltrate the grout into the fracture of rock mass to form a grouting entity, and strengthen the stability of rock mass and the ability to resist failures. In order to realize the calculation of the whole process of grouting diffusion and consolidation in broken surrounding rock, a diffusion-consolidation mechanism of grouting based on discrete element method was proposed. Also, the model checking and example analysis were carried out, and the results show that: ① In the full-length grouting of single fracture scenario, the shear peak strength of the post-fractured rock mass is higher than that of the non-grouting fracture, which depends on the frictional resistance generated by the solidification and cohesion of the slurry. ② In the point grouting simulation experiment, as the grouting pressure increases, the grout continues to diffuse. Therefore, the pre-peak shear yielding and post-peak phases of the rock mass are strengthened. ③ For the engineering-scale simulation test, as the grouting pressure increases, the diffusion radius increases in two stages. When the grout expands to the high-stress area, it needs to overcome a greater compressive stress to achieve flow. After reaching a relative higher grouting pressure, the diffusion area of adjacent boreholes is superimposed to form a grouting whole body that surrounds the roadway. When the solidification bond strength of the grout is low, the failure of contact is still the main controlling factor to determine the failure and instability of the roadway.

Abstract Background Cell division cycle‐associated 8 (CDCA8) is involved in numerous signaling networks, and it serves a crucial modulatory function in multiple malignant tumors. However, its significance in prognosis and immune infiltration in hepatocellular carcinoma (HCC) remains unclear. Materials and methods Herein, we examined the CDCA8 levels in tumor tissues, as well as its associated signaling pathways and correlation with immune infiltration. Additionally, we further clarified the prognostic significance of CDCA8 among HCC patients. HCC patient information was recruited from The Cancer Genome Atlas (TCGA). Using bioinformatics, the following parameters were analyzed among HCC patients: CDCA8 expression, enrichment analysis, immune infiltration, and prognosis analysis. Moreover, we employed in vitro investigations, such as, qRT‐PCR, immunohistochemistry (IHC), and cell functional experiments to validate our results. Results Elevated CDCA8 expression in HCC patients was markedly associated with T stage, pathological status (PS), tumor status (TS), histologic grade (HG), and AFP. Elevated CDCA8 expression HCC patients exhibited reduced overall survival (OS) (p

This study was conducted to investigate the effects of fermented mixed feed (FMF) on growth performance, carcass traits, meat quality, muscle amino acid and fatty acid composition and mRNA expression levels of genes related to lipid metabolism in finishing pigs. In the present study, 144 finishing pigs (Duroc × Berkshire × Jiaxing Black) were randomly allocated to 3 dietary treatments with 4 replicate pens per group and 12 pigs per pen. The dietary treatments included a basal diet (CON), a basal diet + 5% FMF and a basal diet + 10% FMF. The experiment lasted 38 d after 4 d of acclimation. The results showed that 5% and 10% FMF significantly increased the average daily gain (ADG) of the females but not the males (P

The dynamic behaviors of articulated buses during braking and steering processes are exceedingly complex due to the transmission of various forces and torques by the articulated device. The coupling of forces between the front and rear carriages often renders the bus prone to yaw instability under extreme operating conditions. In this paper, according to the characteristics of the structure and parameter matching of an electrically driven articulated bus, a dynamic model of longitudinal and transverse coupling applied on an articulated bus is established, and the influence of the articulated structure on the yaw stability of the drive vehicle is analyzed. Combined with the relationship between the driving motor, the hinge device, and the vehicle motion, a cruise simulation model of the bus is developed, enabling a comparative analysis and verification of vehicle stability under typical road conditions. The results offer a theoretical foundation for the design and control of highly reliable articulated buses.

Despite being a major cyanide species in the process water, it is unclear how iron cyanide influences pyritic gold ore flotation as well as how lead ions influence pyritic gold ore flotation in the presence of iron cyanide. This study aims at revealing the interaction of Fe(CN)63− and lead ions in pyrite flotation to investigate the strong depressing effect of Fe(CN)63− on pyritic gold ore flotation and the significant activating effect of lead ions on pyritic gold ore flotation in the presence of Fe(CN)63− using flotation, zeta potential measurement and surface analysis methods. The flotation results showed that upon 5 × 10−5 mol/L Fe(CN)63− addition, pyrite recovery drastically decreased from about 51.3% to 8.6%, while the subsequent addition of 9.5 × 10−4 mol/L lead ions significantly activated pyrite with the recovery increasing from 8.6% to 91%, which demonstrated that Fe(CN)63− strongly depressed pyrite flotation, while lead ions completely activated pyrite in the presence of Fe(CN)63−. Zeta potential measurement, surface analysis using Cryogenic X-ray photoelectron spectroscopy (Cryo-XPS) and electrochemical impedance spectroscopy (EIS) revealed that Fe(CN)63− depression was attributed to the chemical adsorption of Fe(CN)63− on iron sites of pyrite as Prussian Blue (Fe[Fe(CN)6]); however, this hydrophilic layer could be covered totally by lead ions which adsorbed on as lead hydroxide/oxide through electrostatic interactions, which resulted in the significant activation effect of lead ions. The results from this study will lead to improved flotation of gold associated with pyrite in gold flotation plants.

Carotenoids are essential nutrients for humans and animals, and carotenoid coloration represents an important meat quality parameter for many farmed animals. Increasingly, studies have demonstrated that vertebrate carotenoid cleavage oxygenases (CCOs) are essential enzymes in carotenoid metabolism and are therefore potential candidate genes for improving carotenoid deposition. However, our understanding of carotenoid bioavailability and CCOs functions in invertebrates, particularly marine species, is currently quite limited. We previously identified that a CCO homolog, PyBCO-like 1, was the causal gene for carotenoid coloration in the ‘Haida golden scallop’, a variety of Yesso scallop (Patinopecten yessoensis) characterized by carotenoid enrichment. Here, we found that another CCO-encoding gene named PyBCO2 (β-carotene oxygenase 2) was widely expressed in P. yessoensis organs/tissues, with the highest expression in striated muscle. Inhibiting BCO2 expression in P. yessoensis through RNA interference led to increased carotenoid (pectenolone and pectenoxanthin) deposition in the striated muscle, and the color of the striated muscle changed from white to light orange. Our results indicate that PyBCO2 might be a candidate gene used for improving carotenoid content in normal Yesso scallops, and also in ‘Haida golden scallops’.

Mobile robot olfaction of toxic and hazardous odor sources is of great significance in anti-terrorism, disaster prevention, and control scenarios. Aiming at the problems of low search efficiency and easily falling into a local optimum of the current odor source localization strategies, the paper proposes the adaptive space-aware Infotaxis II algorithm. To improve the tracking efficiency of robots, a new reward function is designed by considering the space information and emphasizing the exploration behavior of robots. Considering the enhancement in exploratory behavior, an adaptive navigation-updated mechanism is proposed to adjust the movement range of robots in real time through information entropy to avoid an excessive exploration behavior during the search process, which may lead the robot to fall into a local optimum. Subsequently, an improved adaptive cosine salp swarm algorithm is applied to confirm the optimal information adaptive parameter. Comparative simulation experiments between ASAInfotaxis II and the classical search strategies are carried out in 2D and 3D scenarios regarding the search efficiency and search behavior, which show that ASAInfotaxis II is competent to improve the search efficiency to a larger extent and achieves a better balance between exploration and exploitation behaviors.

As an important component of coal structure, the macropores have a great influence on CBM recovery. In this paper, the macropores characteristic of two coal samples collected from 3# coal seam in the south of Qinshui Basin, China was analyzed on the basic of mercury intrusion porosimetry, and a fully coupled triple-porosity/double permeability mathematical model for CBM recovery was established according to the physical structure of coal and the non-Darcy flow of methane in macropores. Then, the various factors affecting the macropores permeability were discussed and the influence of size distribution and connectivity of macropores on CBM recovery was investigated. The following conclusions have been drawn from these efforts: (1) in 3# coal seam of the south of Qinshui Basin, the macropores have an extremely heterogeneous pore size distribution with the high variation, and their connectivity is not good because they are mainly composed of the conical and cylindrical pores with one dead end and the open pores, the structure characteristics of macropores are not conducive to CBM recovery; (2) the fully coupled triple-porosity/double permeability mathematical model containing the non-Darcy flow of methane in the macropores includes the methane occurrence-migration field, hydraulic field, thermal field and stress field as well as the complex intercoupling between them, and the model was verified by the fitting of methane production history, with an average error of 3.24%; (3) the macropores permeability is closely related to the Knudsen number controlled by methane pressure and temperature in macropores and the intrinsic permeability which is an internal attribute of macropores affected by size distribution and connectivity of pore; (4) the pressure drop of reservoir plays a major role in the macropores permeability, which promotes the increase of macropores permeability with time, and the high intrinsic permeability of macropores corresponding to the good pore size distribution and connectivity is more conducive to the improvement of fracture permeability and methane production rate of coal reservoir during CBM recovery. It is recommended that coal seams including the macropores with uniform size distribution and good connectivity should be preferentially used for the development of CBM.