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Abstract RNA methylation is an important regulatory process to determine immune cell function but how it affects the anti-tumor activity of CD8 T cells is not fully understood. Here we show that the N 6-methyladenosine (m6A) RNA reader YTHDF2 is highly expressed in early effector or effector-like CD8 T cells. We find that YTHDF2 facilitates nascent RNA synthesis, and m6A recognition is fundamental for this distinctively nuclear function of the protein, which also reinforces its autoregulation at the RNA level. Loss of YTHDF2 in T cells exacerbates tumor progression and confers unresponsiveness to PD-1 blockade in mice and in humans. In addition to initiating RNA decay that is necessary for mitochondrial fitness, YTHDF2 orchestrates chromatin changes that promote T cell polyfunctionality. YTHDF2 interacts with IKZF1/3, which is important for sustained transcription of their target genes. Accordingly, immunotherapy-induced efficacy could be largely restored in YTHDF2-deficient T cells through combinational use of IKZF1/3 inhibitor lenalidomide in a mouse model. Thus, YTHDF2 coordinates epi-transcriptional and transcriptional networks to potentiate T cell immunity, which could inform therapeutic intervention.

Abstract Background Oral squamous cell carcinoma (OSCC) remains a major death cause in head and neck cancers, but the exact pathogenesis mechanisms of OSCC are largely unclear. Results Saliva derived from OSCC patients but not healthy controls (HCs) significantly promotes OSCC development and progression in rat models, and metabolomic analyses reveal saliva of OSCC patients but not HCs and OSCC tissues but not adjacent non-tumor tissues contain higher levels of kynurenic acid (KYNA). Furthermore, large amounts of Streptococcus mutans (S. mutans) colonize in OSCC tumor tissues, and such intratumoral S. mutans mediates KYNA overproductions via utilizing its protein antigen c (PAc). KYNA shifts the cellular types in the tumor microenvironment (TME) of OSCC and predominantly expedites the expansions of S100a8highS100a9high neutrophils to produce more interleukin 1β (IL-1β), which further expands neutrophils and induces CD8 + T cell exhaustion in TME and therefore promotes OSCC. Also, KYNA compromises the therapeutic effects of programmed cell death ligand 1 (PD-L1) and IL-1β blockades in oral carcinogenesis model. Moreover, KYNA-mediated immunosuppressive program and aryl hydrocarbon receptor (AHR) expression correlate with impaired anti-tumor immunity and poorer survival of OSCC patients. Conclusions Thus, aberration of oral microbiota and intratumoral colonization of specific oral bacterium such as S. mutans may increase the production of onco-metabolites, exacerbate the oral mucosal carcinogenesis, reprogram a highly immunosuppressive TME, and promote OSCC, highlighting the potential of interfering with oral microbiota and microbial metabolism for OSCC preventions and therapeutics. Video Abstract

Real-time monitoring of key quality variables is essential and crucial for stable and safe operations of wastewater treatment plants (WWTPs). Next generation reservoir computing (NG-RC) has recently garnered significant attention in quality prediction, such as COD and BOD, as an effective alternative to traditional reservoir computing (RC), then is able to act as a data-driven soft sensor to twin a hardware sensor for quality variable measurements. Unlike RC, NG-RC does not require random sampling matrices to define the weights of recurrent neural networks and has fewer hyperparameters. However, NG-RC is usually used online but trained offline, thus leading to model degradation under dynamic scenarios. This paper proposes a sparse online NG-RC approach to meet the real-time requirements of WWTPs and mitigate the impact of measurement noise on the model. First, inspired by the Woodbury matrix identity, an incremental strategy is designed, using sequentially arriving data blocks to learn the output weights of NG-RC online. Then, an ensemble sparse strategy is combined to alleviate overfitting issues of the prediction model. Moreover, a soft sensor based on the ensemble sparse online NG-RC is developed to perform real-time prediction of quality indicators in wastewater treatment processes. Finally, two datasets from actual WWTPs are used to validate the effectiveness of the proposed model.

Abstract Epstein‒Barr virus (EBV)-associated gastric cancer (GC) manifests an intriguing immunotherapy response. However, the cellular basis for EBV-imprinted tumour immunity and on-treatment response remains undefined. This study aimed to finely characterize the dynamic tumour immune contexture of human EBV (+) GC treated with immunochemotherapy by longitudinal scRNA-seq and paired scTCR/BCR-seq. EBV (+) GC exhibits an inflamed-immune phenotype with increased T-cell and B-cell infiltration. Immunochemotherapy triggers clonal revival and reinvigoration of effector T cells which step to determine treatment response. Typically, an antigen-specific ISG-15+CD8+ T-cell population is highly enriched in EBV (+) GC patients, which represents a transitory exhaustion state. Importantly, baseline intratumoural ISG-15+CD8+ T cells predict immunotherapy responsiveness among GC patients. Re-emerged clonotypes of pre-existing ISG-15+CD8+ T cells could be found after treatment, which gives rise to a CXCL13-expressing effector population in responsive EBV (+) tumours. However, LAG-3 retention may render the ISG-15+CD8+ T cells into a terminal exhaustion state in non-responsive EBV (+) tumours. In accordance, anti-LAG-3 therapy could effectively reduce tumour burden in refractory EBV (+) GC patients. Our results delineate a distinct implication of EBV-imprinted on-treatment T-cell immunity in GC, which could be leveraged to optimize the rational design of precision immunotherapy.

We present a two-stage scheduling approach including proactive and reactive scheduling to solve the ground resource scheduling problem with uncertain arrival time. In the first stage, an integer programming model is constructed to minimize the delay and transfer costs. After solving this model, we obtain a baseline scheduling plan that considers the service arrival time uncertainty. In the second stage, the feasibility of the subsequent benchmark plan is evaluated based on the current state of the services and resources. The reactive scheduling model is enabled when trigger conditions are met. Moreover, an improved adaptive large neighborhood search is designed to solve the proactive scheduling model effectively. Real data from an international airport in South China is used as a test case to compare different scheduling strategies. The results show that it is difficult to handle the uncertainty of the problem with the benchmark plan that simply considered buffer time. Compared with rolling time-domain scheduling, the average transfer cost of the scheduling strategy proposed in this paper increased slightly, but the average service delay cost can be reduced significantly. Algorithm-wise, instances of different scales are designed to verify the effectiveness of the improved adaptive large neighborhood search algorithm. The efficiency of the algorithm scheme is better than that of the Gurobi solver scheme in medium to large-scale problems. Therefore, the forward and reactive strategies can better handle the uncertainty of airport ground protection services as they can simultaneously guide the allocation and utilization of airport ground protection resources.

ABSTRACTMagnitude and diversity of gut microbiota and metabolic systems are critical in shaping human health and diseases, but it remains largely unclear how complex metabolites may selectively regulate gut microbiota and determine health and diseases. Here, we show that failures or compromised effects of anti-TNF-α therapy in inflammatory bowel diseases (IBD) patients were correlated with intestinal dysbacteriosis with more pro-inflammatory bacteria, extensive unresolved inflammation, failed mucosal repairment, and aberrant lipid metabolism, particularly lower levels of palmitoleic acid (POA). Dietary POA repaired gut mucosal barriers, reduced inflammatory cell infiltrations and expressions of TNF-α and IL-6, and improved efficacy of anti-TNF-α therapy in both acute and chronic IBD mouse models. Ex vivo treatment with POA in cultured inflamed colon tissues derived from Crohn’s disease (CD) patients reduced pro-inflammatory signaling/cytokines and conferred appreciable tissue repairment. Mechanistically, POA significantly upregulated the transcriptional signatures of cell division and biosynthetic process of Akkermansia muciniphila, selectively increased the growth and abundance of Akkermansia muciniphila in gut microbiota, and further reprogrammed the composition and structures of gut microbiota. Oral transfer of such POA-reprogrammed, but not control, gut microbiota induced better protection against colitis in anti-TNF-α mAb-treated recipient mice, and co-administration of POA with Akkermansia muciniphila showed significant synergistic protections against colitis in mice. Collectively, this work not only reveals the critical importance of POA as a polyfunctional molecular force to shape the magnitude and diversity of gut microbiota and therefore promote the intestinal homeostasis, but also implicates a new potential therapeutic strategy against intestinal or abenteric inflammatory diseases.

Abstract Background Statins have long been extensively prescribed as effective lipid-lowering agents, but statins have also been recognized as novel immunomodulators in recent years. This study was designed to investigate the immunomodulatory effects of atorvastatin on lupus-prone MRL/lpr mice. Methods A total of 30 8-week-old female MRL/lpr mice were randomly divided into three groups and orally administered vehicle, atorvastatin orhydroxychloroquine sulfate for 11 weeks. In vivo, the effects of atorvastatin on the survival rate, renal function and spleen index in MRL/lpr mice were examined. Ex vivo, splenic B-cell proliferation was assessed by a Cell Counting Kit-8. Results Oral atorvastatin failed to prolong survival time, or reduce the levels of proteinuria, or serum anti-dsDNA antibody and complement proteins (C3, C4). Histologically, no significant improvement by atorvastatin was observed in the pathological manifestations of renal damage, while hydroxychloroquine sulfate significantly improved glomerular injury. Ex vivo, atorvastatin suppressed the proliferation of splenic B lymphocytes. Conclusion Oral atorvastatin monotherapy had no therapeutic effects on MRL/lpr mice, whereas atorvastatin inhibited splenic B-cell proliferation in vitro, suggesting that atorvastatin has a potential therapeutic effect on systemic lupus erythematosus.

Abstract Background We aimed to compare the oncological outcomes between the oblique occlusion technique and the traditional technique for robot-assisted radical nephrectomy (RARN) with inferior vena cava (IVC) thrombectomy, and to explore the safety and effectiveness of the oblique occlusion technique. Methods Overall, 21 patients with renal cell carcinoma (RCC) and IVC tumor thrombus (TT) were admitted to our hospital from August 2019 to June 2020. All the patients underwent RARN with IVC thrombectomy, of which the IVC oblique occlusion technique was used in 11 patients and traditional occlusion technique was used in 10 patients. The oblique occlusion technique refers to oblique blocking from the upper corner of the right renal vein to the lower corner of the left renal vein using a vessel tourniquet or a vessel clamp (left RCC with IVCTT as an example). Results Compared with patients in the traditional group, those in the oblique group had lower serum creatinine at follow-up (3 month) (95 ± 21.1 vs. 131 ± 30.7 μmol/L, P = 0.03). There was no significant difference in operation time [149 (IQR 143–245) min vs. 148 (IQR 108–261) min, p = 0.86], IVC clamping time [18 (IQR 12–20) min vs. 20 (IQR 14–23) min, p = 0.41], and estimated intraoperative blood loss [300 (IQR 100–800) mL vs. 500 (IQR 175–738) mL, p = 0.51] between both groups. During a 16-month (range, 15–23 months) follow-up period, two cases progressed in the oblique group and three cases progressed in the traditional group. Conclusions The modified IVC oblique occlusion technique procedure is relatively safe and effective in RARN with IVC thrombectomy. The IVC oblique occlusion technique may play a role in the protection of renal function.

ABSTRACTAs the first version of synthetic hydrogel, poly(2-hydroxyethyl methacrylate) hydrogels have found broad applications. However, their poor mechanical performances have been long-standing hurdles for practical deployments. Herein, we report on strengthening the poly(2-hydroxyethyl methacrylate) hydrogels with biochar nanoparticles and hydrophobic aggregations, which are induced by solvent exchange and reinforced by freeze-thaw. Both the vast anchoring points on the multifunctional surfaces of the biochar nanoparticles and the aggregates formed between poly(2-hydroxyethyl methacrylate) chains engender strong and dissipative physical crosslinks. The resulting hydrogels exhibit marked mechanical properties, encompassing high stretchability ~7, high fracture toughness ~1360 J m−2, high elastic modulus ~180 kPa, low friction coefficient ~0.2, self-recovery, and non-swellability. Furthermore, we demonstrate the versatility of the proposed strategy by using water/ionic liquid binary solvent as the solvent system, Laponite as the nano-reinforcement, and dry-anneal as the hydrophobic aggregation enhancer to synthesize mechanically robust hydrogels. Poly(2-hydroxyethyl methacrylate) hydrogels of superior mechanical properties are expected to enable previously inaccessible applications in biomedicine and engineering.

The aircraft ferry service is an important link in the transfer of travelers between the remote parking stand and the terminal. By analyzing the process of inbound and outbound ferry service, the relationship between the in-place time of each ferry on the same flight is clarified. A ferry service splitting method considering the difference in in-place time is proposed. Based on this, a dynamic programming scheduling model for ferries is innovatively developed. Considering the impact of flight arrival and departure uncertainty on the in-place time of ferry service, the model is transformed into a dynamic programming stochastic model with opportunity constraints. The optimization objective of this model is to minimize the number of ferries used. To describe the model more easily, a sample average approximation technique is introduced to transform the stochastic model into a deterministic model with confidence. A genetic algorithm based on Monte Carlo random sampling is designed to solve the model. The experimental results based on the actual operation data of an airport in South China show that the dynamic splitting method considering the difference in the in-place time of the ferry can improve the resource utilization efficiency; the scheduling scheme based on the dynamic planning stochastic model has better robustness.

In this paper, we propose a deterministic shift design model with task-based demand and give the corresponding stochastic version with a probability constraint such that the shift plan designed is staffed with the workforce with a certain probability of performing all given tasks. Since we currently find no suitable methods for solving this stochastic model from the literature related to solving stochastic shift design models, we developed a single-stage heuristic method based on statistics, whose main idea is to reduce the occurrence of manpower shortage by prolonging the resource occupation time of a task, but this leads to a serious waste of resources, which is common in solving resource allocation problems with uncertain durations. To reduce the cost of wastage, we also propose a two-stage heuristic approach that is a two-stage heuristic with an evolutionary strategy. The two heuristics show their effectiveness in solving the proposed stochastic model in numerical experiments, and the two-stage heuristic significantly outperforms the one-stage heuristic in cost optimization and solution time stability.

Cyclic neutropenia (CyN) is a rare, ELANE-related neutropenia. Oral manifestations are among the initial signs of CyN and an important reason that leads patients to seek professional help. This case report describes a 12-year-old girl with recurrent oral ulcers, severe chronic periodontitis, and pathological tooth migration as the initial and main clinical symptoms of CyN. Two novel mutations in ELANE, c.180T>G (p.I60M) and c.182C>G (p.A61G) associated with CyN were observed. Bioinformatics research indicated lower stability and impaired molecular linkages of the mutant neutrophil elastase (NE) encoded by ELANE. However, the enzyme affinity to the classic substrate Suc–Ala–Ala–Ala–pNA was not substantially changed, suggesting that the impaired integrity and stability of the mutant NE, rather than catalytic deficiency, might be the pathogenic mechanism of ELANE mutation-induced neutropenia. The patient was prescribed scaling and root planing (SRP) and monthly periodontal maintenance without systemic management. Although the routine periodontal treatment was occasionally interrupted by the 2019 coronavirus pandemic, her periodontal devastation remained well-remitted in the 5-year follow-up assessment. The results of this study confirmed the importance of plaque control and proper diagnosis in the periodontal management of such patients and provide better clinical references. In addition, the novel mutations identified in this study expand the spectrum of known ELANE mutations in CyN and further contribute to knowledge regarding its pathogenic mechanism.

Tuberculosis (TB) induced by Mycobacterium tuberculosis (M. tuberculosis) infection remains a global most deadly infectious disease. While development of more effective TB vaccines and therapeutics relies on identifications of true biomarkers designating an immune protection against M. tuberculosis infection, exact protective immune components against M. tuberculosis infection remain largely unidentified. We previously found that severe TB induced remarkable up-regulation of interferon regulatory factor 7 (IRF7) and IRF7-related gene signatures, implicating that some unknown downstream molecules in IRF7 signaling cascades may determine the M. tuberculosis infection outcomes and serve as a protective immune component against M. tuberculosis infection. Indeed, here, we observe that genetic ablation of IRF7 leads to more severe lung pathology, increased M. tuberculosis burdens, impaired differentiation of effector/memory T subsets, and extensively elevated expression of pro-inflammatory cytokines in lungs. Importantly, IRF7 is vital for sustaining expression of PD-1/PD-L1 and PD-1/PD-L1-modulated miRNA-31. Moreover, interventions of miRNA-31 expressions via administration of miRNA-31 agomir reduces lung pathology and bacilli burdens via inducing up-regulation of gene sets involved in biological processes of defense response or cellular and chemical homeostasis in lungs. Thus, this study uncovers previously unrecognized importance and mechanisms of IRF7-mediated miRNA-31 as a protective immune component against M. tuberculosis infection.

Sedum alfredii Hance is a perennial herb native to China that can particularly be found in regions with abandoned Pb/Zn mines. It is a Cd/Zn hyperaccumulator that is highly tolerant to Pb, Cu, Ni, and Mn, showing potential for phytoremediation of soils contaminated with multiple heavy metals. A better understanding of how this species responds to different heavy metals would advance the phytoremediation efficiency. In this study, transcriptomic regulation of S. alfredii roots after Cd, Zn, Pb, and Cu exposure was analyzed to explore the candidate genes involved in multi-heavy metal tolerance. Although Zn and Cd, Pb and Cu had similar distribution patterns in S. alfredii, distinct expression patterns were exhibited among these four metal treatments, especially about half of the differentially expressed genes were upregulated under Cu treatment, suggesting that it utilizes distinctive and flexible strategies to cope with specific metal stress. Most unigenes regulated by Cu were enriched in catalytic activity, whereas the majority of unigenes regulated by Pb had unknown functions, implying that S. alfredii may have a unique strategy coping with Pb stress different from previous cognition. The unigenes that were co-regulated by multiple heavy metals exhibited functions of antioxidant substances, antioxidant enzymes, transporters, transcription factors, and cell wall components. These metal-induced responses at the transcriptional level in S. alfredii were highly consistent with those at the physiological level. Some of these genes have been confirmed to be related to heavy metal absorption and detoxification, and some were found to be related to heavy metal tolerance for the first time in this study, like Metacaspase-1 and EDR6. These results provide a theoretical basis for the use of genetic engineering technology to modify plants by enhancing multi-metal tolerance to promote phytoremediation efficiency.

Citrus are one of the most important fruit crops in the world, and the citrus hybrid cv. Beni-Madonna (BM) is widely cultivated in Xiangshan County in China because of its profitability. However, due to the lack of technical guidance and management, nutritional unbalances of trees occur frequently and are a major constraint for fruit quality and yield. In this study, the soil and fruit nutritional status of 62 citrus orchards in three diverse landforms (mountain, flat, and coastal saline–alkali land) located in Xiangshan County has been investigated. Higher pH, calcium, and magnesium content but lower soil organic matter, nitrogen, iron, and boron content were observed in orchards of the coastal saline–alkali land compared with the mountain and flat lands. Compared to Citrus x unshiu, another major hybrid citrus cultivar in Xiangshan county, the Fe deficiency in fruits of BM in coastal saline–alkali lands was more severe, leading to chlorosis symptoms. In addition, long-term cultivation under plastic housing increased soil salinization and affected the absorption of Fe and other nutrients by BM. In conclusion, organic fertilizers, acidic fertilizers, and micronutrient fertilizers should be applied in citrus orchards located in coastal saline–alkali lands. Especially, BM orchards should be supplemented with iron fertilizer and not rely excessively on protection with plastic films.

Abstract Paroxysmal dyskinesias are a group of neurological diseases characterized by intermittent episodes of involuntary movements with different causes. Paroxysmal kinesigenic dyskinesia (PKD) is the most common type of paroxysmal dyskinesia and can be divided into primary and secondary types based on the etiology. Clinically, PKD is characterized by recurrent and transient attacks of involuntary movements precipitated by a sudden voluntary action. The major cause of primary PKD is genetic abnormalities, and the inheritance pattern of PKD is mainly autosomal-dominant with incomplete penetrance. The proline-rich transmembrane protein 2 (PRRT2) was the first identified causative gene of PKD, accounting for the majority of PKD cases worldwide. An increasing number of studies has revealed the clinical and genetic characteristics, as well as the underlying mechanisms of PKD. By seeking the views of domestic experts, we propose an expert consensus regarding the diagnosis and treatment of PKD to help establish standardized clinical evaluation and therapies for PKD. In this consensus, we review the clinical manifestations, etiology, clinical diagnostic criteria and therapeutic recommendations for PKD, and results of genetic analyses in PKD patients performed in domestic hospitals.

Based on the logistics performance index proposed by the World Bank, this study uses the entropy method to construct the green logistics performance index and empirically analyzes the impact of the green logistics performance of Regional Comprehensive Economic Partnership (RCEP) countries on China’s export trade using the expanded trade gravity model. The results show that the green logistics performance of RCEP countries can significantly promote China’s export trade to RCEP countries, and various measures to improve green logistics performance have different impacts on China’s export trade. The order of influence degree is the efficiency of a customs clearance procedure, the convenience of arranging freight with a competitive price, the timeliness of cargo transportation, the ability and quality of logistics service, and the intensity of CO2 and N2O emission. To promote China’s export trade, we should give full play to the functions of the customs of various countries and improve the efficiency of regulatory procedures. The regression results reveal that GLPI has a significant and positive impact on export trade RCEP countries, as indicated by the coefficient value of 2.887 at a 1% level of significance. The component factors of GLPI also positively and significantly influence the export trade, but carbon emissions and nitrogen emissions proved to be negative. This study establish with RCEP countries, promote the layout of logistics transport routes among RCEP members, and enhance the popularity of green logistics services; Give full play to the positive role of regional economic organizations and mechanisms, and promote green logistics cooperation between RCEP member countries with high and low GLPI; Through logistics planning, logistics policy and advanced low-carbon logistics technology, promote sustainable development of green logistics.

Dynamic emissive materials in aqueous media have received much attention owing to their ease of preparation, tunable luminescence and environmental friendliness. However, hydrophobic fluorophores usually suffer from aggregation-caused quenching in water. In this work, we constructed an artificial light-harvesting system by using a non-covalent aggregation-induced emission dimer as antenna and energy donor. The dimer is quadruple hydrogen bonded from a ureidopyrimidinone derivative (M) containing a tetraphenylethylene group. The dispersed nano-assemblies based on the dimer in aqueous media were fabricated with the help of surfactant. By loading a hydrophobic acceptor molecule DBT into the nano-assemblies, man-made light-harvesting nanoparticles were fabricated, showing considerable energy transfer efficiency and a relatively high antenna effect. Additionally, the fluorescence color of the system can be gradually tuned by varying the content of the acceptors. This study provides a general way for the construction of an aqueous light-harvesting system based on a supramolecular dimer, which is important for potential application in luminescent materials.

Mesenchymal stem cells (MSCs) secrete cytokines in a paracrine or autocrine manner to regulate immune response and tissue regeneration. Our previous research revealed that MSCs use the complex of Fas/Fas-associated phosphatase-1 (Fap-1)/caveolin-1 (Cav-1) mediated exocytotic process to regulate cytokine and small extracellular vesicles (EVs) secretion, which contributes to accelerated wound healing. However, the detailed underlying mechanism of cytokine secretion controlled by Cav-1 remains to be explored. We show that Gingiva-derived MSCs (GMSCs) could secrete more C-X-C motif chemokine ligand 10 (CXCL10) but showed lower phospho-Cav-1 (p-Cav-1) expression than skin-derived MSCs (SMSCs). Moreover, dephosphorylation of Cav-1 by a Src kinase inhibitor PP2 significantly enhances CXCL10 secretion, while activating phosphorylation of Cav-1 by H2O2 restraints CXCL10 secretion in GMSCs. We also found that Fas and Fap-1 contribute to the dephosphorylation of Cav-1 to elevate CXCL10 secretion. Tumor necrosis factor-α serves as an activator to up-regulate Fas, Fap-1, and down-regulate p-Cav-1 expression to promote CXCL10 release. Furthermore, local applying p-Cav-1 inhibitor PP2 could accelerate wound healing, reduce the expression of α-smooth muscle actin and increase cleaved-caspase 3 expression. These results indicated that dephosphorylation of Cav-1 could inhibit fibrosis during wound healing. The present study establishes a previously unknown role of p-Cav-1 in controlling cytokine release of MSC and may present a potential therapeutic approach for promoting scarless wound healing.

Proppant placement in hydraulic fractures is crucial for avoiding fracture closure and maintaining a high conductivity pathway for oil and gas flow from the reservoir. The curving fracture is the primary fracture form in formation and affects proppant–fluid flow. This work experimentally examines proppant transport and placement in narrow curving channels. Four dimensionless numbers, including the bending angle, distance ratio, Reynolds number, and Shields number, are used to analyze particle placement in curving fractures. The results indicate that non-uniform proppant placement occurs in curving fractures due to the flow direction change and induces an irregular proppant dune. The dune height and covered area are lower than that in the straight fracture. The curving pathway hinders proppant distribution and leads to a dune closer to the inlet. When the distance increases between the inlet and curving section, a large depleted zone in the curving section will be formed and hinder oil and gas flowback. The covered area has negative linear correlations with the Reynolds number and Shields numbers. Four dimensionless parameters are used to develop a model to quantitatively predict the covered area of particle dune in curving fractures.

To explore the methodology for improving ultralow permeability reservoir recovery, cores of ultralow permeability reservoirs in China’s Ordos Basin were selected to study the dynamic imbibition micromechanism of crude oil in nanopore throat through core-flooding laboratory experiment and nuclear magnetic resonance (NMR) observation. In the meantime, the microimbibition characteristics and dynamic discharge of oil between matrix and fracture in partially closed boundary reservoirs were simulated to utmostly reflect the actual reservoir conditions. Our findings suggest that dynamic imbibition between fracture and matrix serves the core technology for improving the recovery of ultralow permeability reservoirs, while the main factors affecting dynamic imbibition efficiency include wettability, permeability, injection rate, fracture, water huff and puff cycles, and soaking time. Wettability, in particular, weighs the most, and imbibition can take place either on water-wet rocks or transformed oil-wet rocks with an imbibition agent added in during the waterflooding process. Meanwhile, the higher the permeability is in place, the greater the dynamic imbibition recovery might achieve. The experiments indicate that the dynamic imbibition recovery of a fractured core is 16.26% higher than that of a nonfractured core. Additionally, fractures can not only enhance imbibition recovery but also accelerate the occurrence of dynamic imbibition. The optimal water injection rate of dynamic imbibition is 0.1 mL/min; the reasonable huff and puff cycle of the ultralow permeability reservoirs tends to be two to three cycles; the optimal soaking time of ultralow permeability reservoir is speculated to be 30 days. Finally, the field practice shows that after Stimulated Reservoir Volume (SRV) and dynamic imbibition in 5 horizontal wells in An83 oilfield, there is a remarkable drop in water cut and a noticeable rise in oil production. This research underpins the significance of a dynamic imbibition effect in the development of ultralow permeability oilfield.

With the development of computer hardware and software, digital art is a new discipline. It uses computers and digital technology as tools to perform artistic expression. It can be expanded to various binary numerical codes with computers as the center and can also be refined to various categories of creation with computers. The research scope is set in the field of digital art, and all kinds of accidental factors of digital art creation based on the machine learning algorithm are mined and analyzed for feature correlation. Based on the hidden association relationship of massive data, the study focuses on the implicit association mining of digital art features of data for the recommendation algorithm. The classification and continuous data feature attributes are introduced and discretized, and the binary representation of data features is extended to ensure the diversity of data feature attributes. In order to mine some correlation features in data, a heuristic feature mining method based on minimum support was studied to discover the frequency of correlation features and construct the optimal feature subset. Based on the frequent items of data features, this study observes the heuristic algorithm of digital art feature association mining based on minimum confidence and carries out feature matching based on digital art feature association mining under different situation modes. The validity of the proposed algorithm is verified by using the experimental data of health and medical situations in the machine learning library.

Current hydraulic fracture models are mainly based on elastic theories, which fail to give accurate prediction of fracture parameters in plasticity formation. This paper proposes a fluid–solid coupling model for fracture propagation in elastoplastic formations. The rock plastic deformation in the model satisfies the Mohr-Coulomb yield criterion and plastic strain increment theory. The extended finite-element method (XFEM) combined with the cohesive zone method (CZM) is used to solve the coupled model. The accuracy of the model is validated against existing models. The effects of stress difference, friction angle, and dilation angle on fracture shape (length, width), injection pressure, plastic deformation, induced stress, and pore pressure are investigated through the model. The results indicate that compared with elastic formation, fracture propagation in elastoplastic formation is more difficult, the breakdown pressure and extending pressure are greater, and fracture shape is wider and shorter. The plastic deformation causes the fracture tip to become blunt. Under the condition of high stress difference or low friction angle formation, it is prone to occur large plastic deformation zones and form wide and short fracture. Compared with friction angle, dilation angle is less sensitive to plastic deformation, fracture parameters, and fracture geometry. For the formation with high stress difference and friction angle, the effect of plasticity deformation on fracture propagation should not be ignored.

Zn pollution is a potential toxicant for agriculture and the environment. Sedum alfredii is a Zn/Cd hyperaccumulator found in China and has been proven as a useful resource for the phytoremediation of Zn-contaminated sites. However, the molecular mechanism of Zn uptake in S. alfredii is limited. In this study, the function of SaPCR2 on Zn uptake in S. alfredii was identified by gene expression analysis, yeast function assays, Zn accumulation and root morphology analysis in transgenic lines to further elucidate the mechanisms of uptake and translocation of Zn in S. alfredii. The results showed that SaPCR2 was highly expressed in the root elongation zone of the hyperaccumulating ecotype (HE) S. alfredii, and high Zn exposure downregulated the expression of SaPCR2 in the HE S. alfredii root. The heterologous expression of SaPCR2 in yeast suggested that SaPCR2 was responsible for Zn influx. The overexpression of SaPCR2 in the non-hyperaccumulating ecotype (NHE) S. alfredii significantly increased the root uptake of Zn, but did not influence Mn, Cu or Fe. SR-μ-XRF technology showed that more Zn was distributed in the vascular buddle tissues, as well as in the cortex and epidermis in the transgenic lines. Root morphology was also altered after SaPCR2 overexpression, and a severe inhibition was observed. In the transgenic lines, the meristematic and elongation zones of the root were lower compared to the WT, and Zn accumulation in meristem cells was also reduced. These results indicate that SaPCR2 is responsible for Zn uptake, and mainly functions in the root elongation zone. This research on SaPCR2 could provide a theoretical basis for the use of genetic engineering technology in the modification of crops for their safe production and biological enhancement.

Abstract With the rapid development of wireless communication, the spectrum resource becomes rare, and research on utilization of limited spectrum resource becomes more popular, especially in fifth generation (5G) mobile communication system. Some efficient frequency division multiplexing systems, such as spectrally efficient frequency division multiplexing (SEFDM) system, can improve spectrum utilization by further compression of the distance between subcarriers with respect to orthogonal frequency division multiplexing (OFDM) carrier structure. This idea of further compressing bands will efficiently solve the problem of scarce spectrum resource in future. However, this kind of systems exist strong self-caused inter-carrier interference (ICI) due to non-orthogonal subcarriers employment, which poses a great challenge to the design of receiver. In this paper, a receiver designed with iterative ICI compensation (IIC) for SEFDM is proposed, which has excellent bit error rate (BER) performance and low complexity. Simulation results show that the BER performance of system under iterative ICI compensation receiver is almost same as traditional combining iterative detection and fixed sphere detection (ID-FSD) scheme with large bandwidth compression factor (BCF). But the complexity of the proposed method is lower than that of ID-FSD.

Purpose: To study the effect of dexmedetomidine on ischemia-reperfusion injury (IRI)–induced inflammatory response, as well as its underlying mechanism of action. Methods: Three groups of healthy adult Sprague Dawley (SD) rats (mean weight, 275 ± 10 g): control, IRI and treatment groups were used. With the exception of control group, ligation was performed on left anterior descending coronary arteries for 30 min and blood perfusion was restored within 100 min to establish IRI. Control group rats were without left ligation. Rats in control and IRI groups received normal saline intraperitoneally 30 min prior to surgery, while the treatment group received 100 μg/kg dexmedetomidine via intraperitoneal injection 30 min before operation. Infarct volume was determined using triphenyl tetrazolium chloride (TTC) staining. IL-6) and TNF-α levels ofmyocardial tissues and serum were determined using enzyme-linked immunosorbent assay (ELISA). Western blotting was used to determine protein expressions of NF-ΚB and TLR-4 in myocardial tissues. Results: Pretreatment with dexmedetomidine markedly decreased infarct volume caused by IRI (p < 0.05). Serum and myocardial TNF-α and IL-6 were significantly upregulated in IRI group, relative to control group, but were downregulated by pretreatment with dexmedetomidine (p < 0.05). There was marked upregulation of NF-ΚB and TLR-4 proteins in IRI rats, relative to untreated rats (p < 0.05). Dexmedetomidine also down-regulated the expressions of these proteins (p < 0.05). Conclusion: Pretreatment with dexmedetomidine alleviates IRI-induced inflammatory reaction via suppression of TLR-4/NF-ΚB signaling pathway. This finding provides a basis for large-scale clinical trials with dexmedetomidine. [ABSTRACT FROM AUTHOR]

Hemp, with very strong vitality, is a kind of annual tall herbaceous plant. Hemp is naturally hardy and drought tolerant which grows well in a cold climate. Hemp plants can resist various plant diseases. Besides, hemp can fight against insect pests without toxic pesticides and chemical fertilizers and thus effectively improve the soil salinization. In this work, two strains of pathogenic fungi (DN1 and DN2) were isolated from lesion site of the hemp plant, by an observation of hypha and spore morphology, the DN1 and the DN2 are respectively determined as deuteromycotina Alternaria (Alternaria alternata) and Verticillium (M.Verticillium). At pH values between 4 and 14, the two fungi can grow normally and show a great ability to adapt to the environment. Effects of hemp on soil pH were determined by pot experiment. The results showed that hemp could repair the weak alkaline soil. [ABSTRACT FROM AUTHOR]

Interleukin 17 (IL-17)-producing T helper cells (TH-17 cells) are increasingly recognized as key participants in various autoimmune diseases, including multiple sclerosis. Although sets of transcription factors and cytokines are known to regulate TH-17 differentiation, the role of noncoding RNA is poorly understood. Here we identify a TH-17 cell–associated microRNA, miR-326, whose expression was highly correlated with disease severity in patients with multiple sclerosis and mice with experimental autoimmune encephalomyelitis (EAE). In vivo silencing of miR-326 resulted in fewer TH-17 cells and mild EAE, and its overexpression led to more TH-17 cells and severe EAE. We also found that miR-326 promoted TH-17 differentiation by targeting Ets-1, a negative regulator of TH-17 differentiation. Our data show a critical role for microRNA in TH-17 differentiation and the pathogenesis of multiple sclerosis. [ABSTRACT FROM AUTHOR]

Adenosine is a key endogenous signaling molecule that regulates immune responses. A2B adenosine receptor (AR) is a relatively low-affinity receptor for adenosine, and the activation of AA2BAR is believed to require pathological level of adenosine that is associated with ischemia, inflammation, trauma, or other types of stress. The role of A2BAR in the pathogenesis of multiple sclerosis (MS) is still unclear. In this study, we discovered that A2BAR was upregulated both in the peripheral blood leukocytes of MS patients and the peripheral lymphoid tissues of experimental autoimmune encephalomyelitis (EAE) mice. A2BAR-specific antagonists, CVT-6883 and MRS-1754, alleviated the clinical symptoms of EAE and protected the CNS from immune damage. A2BAR-knockout mice also developed less severe EAE. Further study indicated that blocking or deleting A2BAR inhibited Thl7 cell differentiation by blocking IL-6 production from APCs such as dendritic cells. In dendritic cells, A2BAR was also upregulated during the development of EAE. CVT-6883 and genetic deletion of A2BAR significantly reduced adenosine-mediated IL-6 pro-duction. The phospholipase CP-protein kinase C and p38 MAPK pathways were found to be involved in the A2BAR-mediated IL-6 production. Our findings not only revealed the pathological role of A2BAR in EAE, but also suggested that this receptor might be a new therapeutic target for the development of anti-MS drugs. [ABSTRACT FROM AUTHOR]

Maintaining a constant number and ratio of immune cells is one critical aspect of the tight regulation of immune homeostasis. Breakdown of this balance will lead to autoimmune diseases such as multiple sclerosis (MS). The antiepileptic drug valproic acid (VPA) was reported to regulate the growth, survival, and differentiation of many cells. However, its function in T cell homeostasis andMStreatment remains unknown. In this study, VPA was found to reduce spinal cord inflammation, demyelination, and disease scores in experimental autoimmune encephalomyelitis, a mouse model of MS. Further study indicated that VPA induces apoptosis in activated T cells and maintains the immune homeostasis. This effect was found to be mainly mediated by the caspase-8/caspase-3 pathway. Interestingly, this phenomenon was also confirmed in T cells from normal human subjects and MS patients. Considering the long history of clinical use and our new findings, we believeVPAmight be a safe and effective therapy for autoimmune diseases, such as multiple sclerosis. [ABSTRACT FROM AUTHOR]