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Acute lung injury (ALI) or its more severe form, acute respiratory distress syndrome, is a life-threatening disease closely associated with an imbalance of M1/M2 macrophage polarization. However, current therapeutic strategies for ALI are controversial due to their side effects, restricted administration routes, or poor targeted delivery. The development of herbal medicine has uncovered numerous anti-inflammatory compounds potentially beneficial for ALI therapy. One such compound is the bergapten, a coumarin, which has been isolated from Ficus simplicissima Lour. However, it's been used as an anti-cancer drug and it's effects on ALI remain unexplored. The poor solubility and biodistribution of bergapten heavily limit its application. In this timely report, we developed a bioactive and lung-targeting lipid-nanomedicine by integrating bergapten and DPPC liposome, named as Ber-lipo. A comprehensive series of in vitro experiments confirmed the anti-inflammatory effects of Ber-lipo and its protective roles in maintaining the homeostasis of macrophage polarization and epithelial–endothelial integrity. In a lipopolysaccharide (LPS)-induced ALI mouse model, Ber-lipo can target inflamed lungs and significantly improve lung edema, tissue injury, and pulmonary function, relieve body weight loss, pulmonary permeability, and proinflammatory status, and especially maintain a balance of M1/M2 macrophage polarization. Furthermore, RNA sequencing analysis showed Ber-lipo's potential in effectively treating inflammatory lung diseases such as pneumonia, inhibiting proinflammatory signals, and altering the transcriptome of M1/M2 macrophages-associated genes in lung tissues. Molecular docking and Western blot analyses validated that Ber-lipo suppressed the activation of the TLR4/MyD88/NF-κB signaling axis responsible for ALI progression. In conclusion, this study demonstrates for the first time that new inhalable nanomedicine (Ber-lipo) can target inflamed lungs and ameliorates ALI by reprogramming macrophage polarization to an anti-inflammatory state via inactivating the TLR4/MyD88/NF-κB pathway, hence providing a promising strategy for enhanced ALI therapy in the clinic.

This study evaluated the effects of four highland barley proteins (HBPs), namely albumin, globulin, gliadin and glutenin, on the retrogradation and in vitro digestion properties of highland barley starch (HBS). The results showed globulin had the most significant effect on inhibiting short-term retrogradation of HBS, which was reflected in the reduction of G' and G''. Compare with HBS, four HBPs could significantly inhibit long-term recrystallization process. For albumin, globulin, gliadin and glutenin, the degree of retrogradation reduced from 51.55 % to 48.20 %, 35.06 %, 42.22 % and 32.63 %, respectively, which was reflected in the decrease of water migration rate, crystal enthalpy, crystallinity and short-range order. It could be found that glutenin had the most significant effect on inhibiting long-term retrogradation of HBS. Moreover, the anti-digestion properties of retrograded HBS with HBPs intervention significantly increased, with glutenin most significantly. Compared with HBS, resistant starch (RS) content increased by 59.76 % at 28 d of retrogradation.

A 79-year-old man underwent operative drainage and 2-week cephalosporin treatment due to a maxillofacial space infection (bilateral submaxillaris, submentum, and left face). However, he experienced anorexia, nausea, vomiting, and emaciation in the following 2 months. It was initially considered that a malignancy might be present, thus a series of examinations were performed. Laboratory investigations showed increases in inflammatory markers and a significant eosinophilia, which seemed to be a hematological system disease. Combined with the gastrointestinal endoscopes and histology examination, the patient was diagnosed with eosinophilic gastroenteritis (EGE). After cessation of antibiotic treatment and administration of corticosteroid, our patient experienced a rapid progress in his clinical condition. Despite the low incidence, EGE should be considered in patients with unknown cause of gastrointestinal disorder, elevated eosinophilia, and so on.

Objective: The present investigation was designed to devise a rapid and straightforward technique for the isolation of rat precartilaginous stem cells (PCSCs) that eschews the use of immunomagnetic bead sorting. Method: Rat neonates within 24 h of birth were selected for this study. Microsurgical techniques were used to harvest the femur, tibia, and the musculature of the knee joint. The ring of LaCroix between the metaphysis of the femur and the epiphysis was excised and divided into fragments of approximately 1 mm³. Tissue sections were cultured in Dulbecco's modified Eagle's medium(DMEM)/F12 medium supplemented with 20 % fetal bovine serum and 1 % penicillin-streptomycin. Cell digestion and passaging were performed using trypsin when cells reached 70%–80 % confluence. Third-generation cells underwent immunofluorescence staining and flow cytometry to evaluate fibroblast growth factor receptor-3(FGFR-3) and proliferating cell nuclear antigen(PCNA) expression, while β-galactosidase staining was used to determine cellular senescence. Results: Within two days of isolation, numerous short spindle-shaped cells exhibiting distinct refractive properties were observed around the tissue fragments. These cells began to proliferate within 2–3 days and displayed ample cytoplasm. Adherent cells adopted various morphologies, including angular, triangular, and elongated spindles. By the fifth day, more than 80 % of the culture dish surface was covered with elongated cells, with some arranged in patterns reminiscent of whirlpools. Significant FGFR-3 and PCNA expression was confirmed via immunofluorescence in the third-generation cells. Additionally, flow cytometry identified that the proportion of cells positive for FGFR-3 and PCNA exceeded 98 %. Notably, the cells preserved their proliferative capacity through nine passages in vitro, with a marginal proportion showing senescence as indicated by β-galactosidase staining alone. Conclusion: The developed tissue adherence protocol was used to successfully isolate PCSCs with positive FGFR-3 and PCNA expression, rendering the immunomagnetic bead sorting superfluous. The expression of FGFR-3 and PCNA in the isolated cells persisted through the ninth passage in vitro with minimal senescence.

Carbamate is a key structural motif in the development of fungicidal compounds, which is still promising and robust in the discovery of green pesticides. Herein, we report the synthesis and evaluation of the fungicidal activity of 35 carbamate derivatives, among which 19 compounds were synthesized in our previous report. These derivatives were synthesized from aromatic amides in a single step, which was a green oxidation process for Hofmann rearrangement using oxone, KCl and NaOH. Their chemical structures were characterized by 1H NMR, 13C NMR and high-resolution mass spectrometry. Their antifungal activity was tested against seven plant fungal pathogens. Many of the compounds exhibited good antifungal activity in vitro (inhibitory rate > 60% at 50 μg/mL). Compound 1ag exhibited excellent broad-spectrum antifungal activities with inhibition rates close to or higher than 70% at 50 μg/mL. Notably, compound 1af demonstrated the most potent inhibition against F. graminearum, with an EC50 value of 12.50 μg/mL, while compound 1z was the most promising candidate fungicide against F. oxysporum (EC50 = 16.65 μg/mL). The structure–activity relationships are also discussed in this paper. These results suggest that the N-aryl carbamate derivatives secured by our green protocol warrant further investigation as potential lead compounds for novel antifungal agents.

Abstract Chronic obstructive pulmonary disease (COPD) is a serious chronic lung disease. Schisandrin A (SchA) is one of the most important active ingredients in Schisandra chinensis and has been used to treat various lung diseases in several countries. Here, we studied the pharmacological effect of SchA on airway inflammation induced by cigarette smoke (CS) and explored the therapeutic mechanism of SchA in COPD model mice. Our results showed that SchA treatment significantly improved the lung function of CS-induced COPD model mice and reduced the recruitment of leukocytes and hypersecretion of interleukin-6 (IL-6), interleukin-1β (IL-1β) and tumor necrosis factor α (TNF-α) in bronchoalveolar lavage fluid (BALF). H&E staining showed that SchA treatment could effectively reduce emphysema, immune cell infiltration and airway wall destruction. In addition, we found that SchA treatment can stimulate the expression of heme oxygenase-1 (HO-1) through the nuclear factor-erythroid 2-related factor (Nrf2) pathway, significantly reduce oxidative stress, increase catalase (CAT) and superoxide dismutase (SOD) levels, and suppress the level of malondialdehyde (MDA) in COPD model mice. Moreover, SchA treatment suppressed the generation of the NLRP3/ASC/Caspase1 inflammasome complex to inhibit the inflammatory response caused by IL-1β and IL-18 and pyroptosis caused by GSDMD. In conclusion, our study shows that SchA treatment can inhibit the production of ROS and the activation of the NLRP3 inflammasome by upregulating Nrf-2, thereby producing anti-inflammatory effects and reducing lung injury in COPD model mice. More importantly, SchA exhibited similar anti-inflammatory effects to dexamethasone in COPD model mice, and we did not observe substantial side effects of SchA treatment. The high safety of SchA makes it a potential candidate drug for the treatment of COPD.

On the basis of the structure of natural product lansiumamide B (1), a total of 27 novel cis-enamide compounds were designed and synthesized via Intermediate Derivatization Method. Their chemical structures were characterized by 1H and 13C nuclear magnetic resonance and high-resolution mass spectrometry. The in vitro antifungal activities against Sclerotinia sclerotiorum, Thanatephorus cucumeris and Botrytis cinerea were evaluated by the mycelium linear growth rate method. Most of the compounds showed some activity against each of the fungi at 25 or 50 μg/mL. The relationship between structure and antifungal activity was also discussed, which showed the cinnamic double bond was critical to maintain the antifungal activity. Notably, among the title compounds, 3e and 3h could inhibit mycelia growth of Botrytis cinerea by approximately 50% (EC50) at 39.17 and 41.25 μg/mL respectively, which showed better antifungal activity than lansiumamide B (1) with more concise chemical structure. The present study pointed out the correct direction for the development and optimization of lansiumamide B derivatives as potential inhibitors of pathogenic fungi.

Previous studies have shown that feeding mice with food containing mantle tissue from Japanese scallops results in aggravated liver and kidney damage, ultimately resulting in mortality within weeks. The aim of this study is to evaluate the toxicity of scallop mantle in China’s coastal areas and explore the impact of scallop mantle toxins (SMT) on intestinal barrier integrity and gut microbiota in mice. The Illumina MiSeq sequencing of V3-V4 hypervariable regions of 16S ribosomal RNA was employed to study the alterations in gut microbiota in the feces of SMT mice. The results showed that intestinal flora abundance and diversity in the SMT group were decreased. Compared with the control group, significant increases were observed in serum indexes related to liver, intestine, inflammation, and kidney functions among SMT-exposed mice. Accompanied by varying degrees of tissue damage observed within these organs, the beneficial bacteria of Muribaculaceae and Marinifilaceae significantly reduced, while the harmful bacteria of Enterobacteriaceae and Helicobacter were significantly increased. Taken together, this article elucidates the inflammation and glucose metabolism disorder caused by scallop mantle toxin in mice from the angle of gut microbiota and metabolism. SMT can destroy the equilibrium of intestinal flora and damage the intestinal mucosal barrier, which leads to glucose metabolism disorder and intestinal dysfunction and may ultimately bring about systemic toxicity.

This study evaluated the effects of four highland barley proteins (HBPs), namely, albumin, globulin, gliadin and glutenin, on the short-term retrogradation of highland barley starch (HBS). The findings reveal that HBPs could reduce the viscosity, storage modulus and hardness of HBS, with albumin and globulin showing more prominent effects. Furthermore, with the addition of HBPs, the loss tangent (tan δ) of HBS loss increased from 0.07 to 0.10, and the enthalpy of gelatinization decreased from 8.33 to 7.23. The degree of retrogradation (DR%) of HBS was 5.57%, and the DR% decreased by 26.65%, 38.78%, 11.67% and 20.29% with the addition of albumin, globulin, gliadin and glutenin, respectively. Moreover, the relative crystallinity (RC) and the double helix structures were inhibited with the HBPs’ incorporation. Meanwhile, the HBPs also could inhibit water migration and improve the structure of HBS gels. In summary, HBPs could inhibit the retrogradation behavior of HBS, which provides new theoretical insights for the production studies of highland barley foods.

Affected by reservoir heterogeneity, developed natural fractures, and bedding fractures, the fracturing pressure curves in fracturing of shale gas horizontal wells present complex shapes. A large amount of information contained in the fracturing curves is still not fully excavated. Based on the theory of shale gas fracture network fracturing, the calculation model of bottom hole net pressure is established by integrating the real-time data such as casing pressure, pump rate, and proppant concentration. Net pressure slope and net pressure index are constructed as key parameters, and the net pressure curve is divided dynamically to describe the mechanical conditions corresponding to the fracture propagation behavior during the fracturing process. Six fracture propagation modes were identified, including fracture network propagation, fracture propagation blockage, normal fracture propagation, fracture propagation long bedding, fracture height growth, and rapid fluid filtration, and then the operation pressure curve diagnosis and identification method were formed for shale gas fracture network fracturing in horizontal wells. The shortcomings of conventional operation curve diagnosis and identification methods are abandoned and the fracture network complexity index is presented. The higher index indicates more time of fracture network propagation and fracture propagation along bedding and the better reservoir stimulation effect. The model is applied to shale gas wells in the southeastern margin of Sichuan Basin, and the average fracture network complexity index of a single well is 0.3, which is in good agreement with the microseismic monitoring results. This proves the good reliability of the method developed. The method is helpful to improve the potential and level of fracturing stimulation of shale reservoirs and is of great significance for improving the post-fracturing evaluation technology of fracture network and guiding the real-time dynamic adjustment of field fracturing operations.

When deep and ultra-deep shale gas well fracturing is carried out, multi-cluster fracturing can hardly realize synchronous initiation and propagation of hydraulic fractures due to the combined effects of heterogeneity of deep in-situ stress and ''dense cluster'' fracture arrangement, and the strong interference between fractures aggravates the unbalanced fracture propagation degree. Field practice proves that the fracture-opening temporary plugging fracturing technology can effectively control the unbalanced propagation of multiple fractures. In addition, the application effect of temporary plugging process can be improved by developing a method for simulating fracture control during fracture-opening temporary plugging fracturing of deep/ultra-deep shale-gas horizontal wells. Based on rock mechanics, elasticity mechanics, fluid mechanics and fracture propagation theory, combined with the flow distribution equation of horizontal-well multi-cluster fracturing and the plugging equation of temporary plugging balls, this paper establishes a fracture propagation model and a fracture control simulation method for the fracture-opening temporary plugging fracturing of deep/ultra-deep shale gas horizontal wells. Then, the influences of the number of temporary plugging balls and the times and timing of temporary plugging on temporary plugging control are simulated, and the influences of temporary plugging balls on fracture propagation morphology and SRV (stimulated reservoir volume) distribution are analyzed by taking Sinopec's one deep shale gas well in Dingshan-Dongxi structure of southeast Sichuan Basin as an example. And the following research results are obtained. First, fracture-opening temporary plugging can significantly promote the balanced propagation of multiple fractures, and the simulation confirms that the number of temporary plugging balls and the times and timing of temporary plugging play an important role in fracture control. Second, as the number of temporary plugging balls increase, the SRV increases firstly and then decreases, so there is an optimal number of temporary plugging balls. Third, increasing the times of temporary plugging can improve the fault tolerance rate of temporary plugging and diverting process, but it is necessary to increase the number of temporary plugging balls appropriately. Fourth, when the timing of temporary plugging is appropriate, the balanced propagation of multiple fractures is achieved and the maximum SRV is reached. In conclusion, this method is of great significance to optimizing the design of temporary plugging fracturing, improve the implementation level of field process and develop deep and ultra-deep shale gas efficiently.

The first fractured shale gas well of China was constructed in 2010. After 10 years of development, China has become the second country that possesses the core technology of shale gas development around the world, realized the shale gas fracturing techniques from zero to one and from lagging to partially leading, and constructed the fracturing theory and technology system suitable for middle–shallow marine shale gas exploitation. In order to provide beneficial guidance for the efficient exploitation of shale gas in China in the future, this paper comprehensively reviews development history and status of domestic fundamental theories, optimized design methods, fluid systems, tools and technologies of shale gas fracturing and summarizes the research results in fundamental theories and optimized design methods, such as fracturing sweet-spot cognition, fracture network propagation simulation and control, rock hydration and flowback control, and SRV (stimulated reservoir volume) evaluation and characterization. The development and application of slick-water fracturing fluid system and new fracturing fluid with little or no water is discussed. The development and independent research & development level of multi-stage fracturing tools are evaluated, including drillable composite plug, soluble plug, large-diameter plug and casing cementing sleeve. The implementation situations of field technologies and processes are illustrated, including the early conventional multi-stage multi-cluster fracturing and the current “dense cluster” fracturing and temporary plugging fracturing. Based on this, the current challenges to domestic shale gas fracturing technologies are analyzed systematically, and the development direction of related technologies is forecast. In conclusion, it is necessary for China to continuously research the fracturing theories, technologies and methods suitable for domestic deep and ultra-deep marine shale gas, terrestrial shale gas and transitional shale gas to facilitate the future efficient development of shale gas in China.

This study aims to solve the problem of limited learning efficiency caused by information overload and resource diversity in online course learning. We adopt a recommendation algorithm that combines knowledge graph and collaborative filtering, aiming to provide an application that can meet users’ personalized learning needs and consider the semantic information of learning resources. In addition, this article collects and models implicit data in online courses and compares the impact of video and text learning resources on user learning needs under different weights in order to deeply understand the different contributions of video and text learning resources to meeting learning needs. The experimental results show that the video high-weight experimental group performs better than the text high-weight experimental group; students tend to prefer video resources. This experiment can help students cope with the challenges brought by numerous types of learning resources and provide personalized and high-quality learning experiences for learners. At the same time, adjusting and innovating teaching models for teachers has great reference value.

The stimulation effect of oil wells is seriously affected by the complexity of hydraulic fractures, and the analysis of the factors that control the fracture complexity index has become the key to fracturing design in sandy conglomerate reservoirs. Based on the intrinsic relationship between geological engineering parameters and the fractures complexity index, a Genetic Expression Programming (GEP) method, which has broad advantages in solving multi-factor nonlinear fitting and black-box prediction problems, is proposed to analyze the hydraulic fracture complexity index. Combined with the geoengineering factors that affect the hydraulic fractures propagation, a comprehensive index calculation method is established to analyze the relative importance of these features and 18 reconstructed features were obtained by collecting the geoengineering parameter data of 118 fracturing sections in 8 fracturing wells in Jinlong oilfield. The principal component analysis was performed to eliminate the interaction between the features, and then a GEP-based fractures complexity index calculation model was developed. The partial dependence plot is used to analyze the influence of the main control feature (variable) on the hydraulic fracture complexity index. It showed that GEP model can achieve satisfactory performance (Training set: R = 0.861; Test set: R = 0.817) by statistical parameters. The results showed that the model can calculate the hydraulic fracture complexity index quickly and precisely. The influence of geological engineering control factors can be obtained. It proved that the GEP method can effectively analyze and evaluate the complexity in sandy conglomerate reservoirs.

On the basis of the three-component synthetic methodology developed by us, a total of twenty-six pyrazole compounds bearing aryl OCF3 were designed and synthesized. Their chemical structures were characterized by 1H and 13C nuclear magnetic resonance and high-resolution mass spectrometry. These compounds were evaluated systematically for antifungal activities in vitro against six plant pathogenic fungi by the mycelium growth rate method. Most of the compounds showed some activity against each of the fungi at 100 μg/mL. Compounds 1t and 1v exhibited higher activity against all the tested fungi, and 1v displayed the highest activity against F. graminearum with an EC50 value of 0.0530 μM, which was comparable with commercial pyraclostrobin. Structure–activity relationship analysis showed that, with respect to the R1 substituent, the straight chain or cycloalkyl ring moiety was a key structural moiety for the activity, and the R2 substituent on the pyrazole ring could have significant effects on the activity. Simple and readily available pyrazoles with potent antifungal activity were obtained, which are ready for further elaboration to serve as a pharmacophore in new potential antifungal agents.

Fibroblasts, in particular myofibroblasts, are the critical effector cells in idiopathic pulmonary fibrosis (IPF), a deadly lung disease characterized by abnormal lung remodeling and the formation of “fibroblastic foci”. Aberrant activation of TGF-β1 is frequently encountered and promotes fibroblast proliferation, activation, and differentiation in pulmonary fibrosis. Hence, the inhibition of TGF-β1-induced lung fibroblast activation holds promise as a therapeutic strategy for IPF. The present study aimed to investigate the potential effect and underlying mechanisms of bone morphogenetic protein 4 (BMP4) on TGF-β1-induced proliferation, apoptosis, activation and myofibroblast differentiation of adult lung fibroblasts. Here, we demonstrated that BMP4 expression was significantly decreased in TGF-β1-stimulated mouse primary lung fibroblasts (PLFs). BMP4 inhibited proliferation and apoptosis resistance of TGF-β1-stimulated mouse PLFs. BMP4 suppressed TGF-β1-induced fibroblast activation and differentiation in mouse PLFs. We also found that BMP4 inhibited TGF-β1-induced ERK and p38 MAPK phosphorylation. Our findings indicate that BMP4 exerts its anti-fibrotic effects by regulating fibroblast proliferation, apoptosis, activation and differentiation via the inhibition of the ERK/p38 MAPK signaling pathway, and thus has a potential for the treatment of pulmonary fibrosis.

PurposeUnstable femoral shaft fractures (UFSFs) in children aged 5–11 years remain challenging due to their intrinsic instability. The aim of this study was to evaluate the clinical and radiographic outcomes of UFSF in children aged 5 to 11 years managed by the combined use of ESIN and temporary EF.MethodsChildren with UFSF (long oblique and comminuted) treated by ESIN and temporary EF were retrospectively reviewed. Sex, age at injury, side involved, type of fracture, presence or absence of associated lesions or neurovascular complications, type of treatment, time from trauma to surgery, duration of surgery, radiation exposure and length of postoperative immobilization were collected from the medical charts. Radiological and functional outcomes were evaluated according to Beaty's and Flynn's criteria, respectively.ResultsA total of 28 consecutive patients with closed or open (Gustilo type I or II) UFSF were reviewed (18 boys and 10 girls). The mean age at injury was 8.7 ± 1.6 years (range, 5–11); the average weight was 38.1 ± 7.6 kg (range, 26–55). The mean hospital stay was 3.7 ± 1.4 days (range, 2–7), and the mean time to EF and ESIN removal was 6.5 ± 1.1 weeks (range, 4–8) and 9.4 ± 1.6 months (range, 6–12), respectively. Twenty-seven out of 28 patients had excellent radiographic outcomes according to Beaty's criteria, and 24/28 had excellent functional outcomes according to Flynn's criteria. Overall, 4 complications (14.3%) were recorded. No statistically significant correlation was found between complication rates and sex, age, weight or fracture characteristics (P < 0.05).ConclusionsThe combined use of ESIN and temporary EF provides good clinical and radiological outcomes in children with UFSF aged between 5 and 11 years, with a reduced complication rate.

Background and Objectives: The femoral neck system (FNS) is a new minimally invasive internal fixation system for femoral neck fractures (FNFs), but its use has not been reported in adolescents. The aim of this study was to compare the clinical and radiographic outcomes of displaced FNF in adolescents treated with FNS or a cannulated compression screw (CCS). Materials and Methods: A retrospective study of 58 consecutive patients with displaced FNF treated surgically was performed; overall, 28 patients underwent FNS and 30 CCS fixation. Sex, age at injury, type of fracture, associated lesions, duration of surgery, radiation exposure, and blood loss were collected from the hospital database. The clinical and radiographic results, as well as complications, were recorded and compared. Results: The patients were followed up for 16.4 ± 3.1 months on average after index surgery (range, 12 to 24). Consolidation time among patients treated with FNS was significantly lower than those managed by CCS (p = 0.000). The functional scores of patients treated with FNS were significantly higher than those managed by CCS (p = 0.030). Unplanned hardware removal in patients treated with FNS was significantly lower than in those managed by CCS (p = 0.024). Conclusions: FNS has a lower complication rate and better functional outcome than CCS. It may be a good alternative to treat femoral neck fractures in adolescents.

When horizontal well staged cluster fracturing is applied in shale gas reservoirs, the cluster spacing is essential to fracturing performance. If the cluster spacing is too small, the stimulated area between major fractures will be overlapped, and the efficiency of fracturing stimulation will be decreased. If the cluster spacing is too large, the area between major fractures cannot be stimulated completely and reservoir recovery extent will be adversely impacted. At present, cluster spacing design is mainly based on the static model with the potential reservoir stimulation area as the target, and there is no cluster spacing design method in accordance with the actual fracturing process and targets dynamic stimulated reservoir volume (SRV). In this paper, a dynamic SRV calculation model for cluster fracture propagation was established by analyzing the coupling mechanisms among fracture propagation, fracturing fluid loss and stress. Then, the cluster spacing was optimized to reach the target of the optimal SRVs. This model was applied for validation on site in the Jiaoshiba shale gasfield in the Fuling area of the Sichuan Basin. The key geological engineering parameters influencing the optimal cluster spacing intervals were analyzed. The reference charts for the optimal cluster spacing design were prepared based on the geological characteristics of south and north blocks in the Jiaoshiba shale gasfield. It is concluded that the cluster spacing optimal design method proposed in this paper is of great significance in overcoming the blindness in current cluster perforation design and guiding the optimal design of volume fracturing in shale gas reservoirs. Keywords: Shale gas, Horizontal well, Staged fracturing, Cluster spacing, Reservoir, Stimulated reservoir volume (SRV), Mathematical model, Optimal method, Sichuan basin, Jiaoshiba shale gasfield

The acyclic organic alkynes and carbyne bonds exhibit linear shapes. Metallabenzynes and metallapentalynes are six- or five-membered metallacycles containing carbynes, whose carbine-carbon bond angles are less than 180°. Such distortion results in considerable ring strain, resulting in the unprecedented reactivity compared with acyclic carbynes. Meanwhile, the aromaticity of these metallacycles would stabilize the ring system. The fascinating combination of ring strain and aromaticity would lead to interesting reactivities. This mini review summarized recent findings on the reactivity of the metal–carbon triple bonds and the aromatic ring system. In the case of metallabenzynes, aromaticity would prevail over ring strain. The reactions are similar to those of organic aromatics, especially in electrophilic reactions. Meanwhile, fragmentation of metallacarbynes might be observed via migratory insertion if the aromaticity of metallacarbynes is strongly affected. In the case of metallapentalynes, the extremely small bond angle would result in high reactivity of the carbyne moiety, which would undergo typical reactions for organic alkynes, including interaction with coinage metal complexes, electrophilic reactions, nucleophilic reactions and cycloaddition reactions, whereas the strong aromaticity ensured the integrity of the bicyclic framework of metallapentalynes throughout all reported reaction conditions.

The total synthesis of potent anti-obesity lansiumamide B was accomplished in four steps using commercially available materials. The synthetic strategy, featured with copper-catalyzed Buchwald coupling, is concise, convergent, practical and can be carried out on a one-gram scale. This approach could give either Z- or E-configured enamide moiety in natural products with absolute stereocontrol and was applied in the total synthesis of natural products.

Dove tree, Davidia involucrata Baill. which is endemic in western China, is not only one of the best known relict species of the tertiary, but also a famous ornamental plant with dove-shaped flowers. A diverse array of secondary metabolites have been isolated and identified from Davidia involucrata. The 58 structures of the secondary metabolites were presented and classified as triterpenoids, tannins, phenolic compounds, lignans, flavonoids, alkaloids, and sterol. In addition, the biosynthetic route of some triterpenoids was proposed. Moreover, the advances in the discovery of unprecedented compounds and uncovering of notable bioactivities were highlighted in this review.

The heavy consumption of ethanol can lead to alcohol use disorders (AUDs) which impact patients, their families, and societies. Yet the genetic and physiological factors that predispose humans to AUDs remain unclear. One hypothesis is that alterations in mitochondrial function modulate neuronal sensitivity to ethanol exposure. Using Drosophila genetics we report that inactivation of the mitochondrial outer membrane translocator protein 18kDa (TSPO), also known as the peripheral benzodiazepine receptor, affects ethanol sedation and tolerance in male flies. Knockdown of dTSPO in adult male neurons results in increased sensitivity to ethanol sedation, and this effect requires the dTSPO depletion-mediated increase in reactive oxygen species (ROS) production and inhibition of caspase activity in fly heads. Systemic loss of dTSPO in male flies blocks the development of tolerance to repeated ethanol exposures, an effect that is not seen when dTSPO is only inactivated in neurons. Female flies are naturally more sensitive to ethanol than males, and female fly heads have strikingly lower levels of dTSPO mRNA than males. Hence, mitochondrial TSPO function plays an important role in ethanol sensitivity and tolerance. Since a large array of benzodiazepine analogues have been developed that interact with the peripheral benzodiazepine receptor, the mitochondrial TSPO might provide an important new target for treating AUDs.

When considering disintegration of spatial networks, the topological relationships between nodes and their geographical positions are taken into account. In the case of regional attacks, the targeted nodes are determined based on the size of the region and the geographical relationships between nodes. In this paper, a new metric is proposed on top of region centrality (RC) to describe the importance of nodes within local regions in spatial networks. We define the weighted sum of the number of connections between nodes within a local region and the number of connections between nodes within the local region and nodes outside the local region as local connectivity. This metric integrates topological information with geographical information. From a mathematical perspective, RC is a special case of local connectivity. In addition, we propose a hybrid spatial network disintegration strategy based on two metrics, namely local connectivity and RC. From experimental results, our strategy outperforms traditional approaches and demonstrates a stronger ability to completely disintegrate the network. [ABSTRACT FROM AUTHOR]

To promote the theoretical and empirical research on the impact of data assets on the operation and development of enterprises, this paper reviews the relevant research on the impact of data assets on the operation and development of enterprises. At present, scholars' research on the impact of data assets on the operation and development of enterprises mainly focuses on the impact of data assets on the micro-operation efficiency of enterprises (including: impact mechanism, impact law, impact core), the impact of data assets on the high-quality development of enterprises (including: theoretical logic, impact mechanism), and the impact of data asset information disclosure on the enterprise value (including: impact mechanism, analyst attention). In general, scholars' research on the impact of data assets on the operational risk of enterprises is relatively weak; in addition, scholars have rarely studied the impact mechanism of data assets on the credit risk and debt financing of enterprises. In the context of the digital economy, scholars' theoretical and empirical research on the impact of data assets on the operation and development of enterprises needs to be further deepened. [ABSTRACT FROM AUTHOR]

Deep shale gas reserves that have been fractured typically have many relatively close perforation holes. Due to the proximity of each fracture during the formation of the fracture network, there is significant stress interference, which results in uneven fracture propagation. It is common practice to use "balls" to temporarily plug fracture openings in order to lessen liquid intake and achieve uniform propagation in each cluster. In this study, a diameter optimization model is introduced for these plugging balls based on a multi-cluster fracture propagation model and a perforation dynamic abrasion model. This approach relies on proper consideration of the multiphase nature of the considered problem and the interaction force between the involved fluid and solid phases. Accordingly, it can take into account the behavior of the gradually changing hole diameter due to proppant continuous perforation erosion. Moreover, it can provide useful information about the fluid-dynamic behavior of the considered system before and after plugging. It is shown that when the diameter of the temporary plugging ball is 1.2 times that of the perforation hole, the perforation holes of each cluster can be effectively blocked. [ABSTRACT FROM AUTHOR]