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Pine wilt disease is caused by the pine wood nematode (Bursaphelenchus xylophilus) and leads to wilting and death of pines. It is one of the most damaging diseases of pines worldwide. Therefore, accurate and rapid detection methods are of great importance for the control of B. xylophilus. Traditional detection methods have some problems, such as being time-consuming and requiring expensive instruments. In this study, the loop-mediated isothermal amplification (LAMP) and clustered regularly interspaced short palindromic repeats (CRISPR) were used to establish a set of intelligent detection and analysis system for B. xylophilus, called LAMP-CRISPR/Cas12a analysis, which integrated field sampling, rapid detection and intelligent control analysis. The process can be completed within 1 hour, from sample pretreatment and detection to data analysis. Compared with the single LAMP method, the LAMP-CRISPR/Cas12a assay uses species-specific fluorescence cleavage to detect target amplicons. This process confirms the amplicon identity, thereby avoiding false-positive results from non-specific amplicons, and the large amounts of irrelevant background DNA do not interfere with the reaction. The LAMP-CRISPR/Cas12a assay was applied to 46 pine wood samples and the samples carrying B. xylophilus nematodes were successfully identified. To meet the needs of different environments, we designed three methods to interpret the data: 1) naked eye interpretation; 2) lateral flow biosensor assay; and 3) integrated molecular analysis system to standardize and intellectualize the detection process. Application of the B. xylophilus detection and analysis system will reduce the professional and technical requirements for the operating environment and operators and help to ensure the accuracy of the detection results, which is important in grass-root B. xylophilus detection institutions.

The quality of fresh products through cross-regional sales has been uncertain to consumers. To improve the quality of fresh products, some fresh product supply chains have implemented blockchain technology to provide traceable information for their products, and some regional governments have subsidized their local firms to incentivize them to implement blockchain-driven traceability systems. However, with regional government subsidy heterogeneity, cross-regional fresh product supply chain firms lack theoretical guidance on their operation decisions. Based on the research gap, we investigate optimal operation policies in a fresh product supply chain consisting of a manufacturer and a retailer located in different regions. The local governments may subsidize the manufacturer or the retailer located in their own regions, which construct four subsidy strategies (SS, SN, NS, and NN) along the supply chain. We find that the optimal operation policies under four subsidy strategies can be affected by the sensitivity to traceability level, cost-sharing rate of the manufacturer, rate of products left after corrosion, and subsidy rate to the manufacturer. Moreover, the government subsidy to the retailer is always beneficial to the retailer and the supply chain but does not affect the manufacturer’s operation policies and profits. The government subsidy to the manufacturer is always beneficial to the manufacturer but not always beneficial to the retailer and the supply chain. Hence the desired subsidy strategy for the manufacturer is SS and SN, and the one for the retailer and the supply chain is either NS or SS with different conditions.

Whereas the existing literature on the relationship between parental behavior and family business succession mainly focuses on parental behavior in the business domain, we highlight the importance of parental behavior in the family domain. Integrating attachment theory, the family business succession literature, and person-job fit literature, our study proposes a theoretical framework hypothesizing that general self-efficacy and perceived person-job fit mediate the association between perceived parental care (an underrepresented family-domain-specific parental behavior) and next-generation family members’ succession intentions. This framework is tested by data from two surveys and further verified by qualitative interviews of next-generation family members. Multivariate analysis results suggest that next-generation family members’ general self-efficacy and perceived person-job fit played a sequential-mediating role in the relationship between perceived parental care and next-generation family members’ succession intentions. Our interviews not only confirm these results but also reveal new insights, particularly into the specific Chinese context in the study of family business succession.

A superior combination of yield strength (1001 MPa) and − 20 °C impact toughness (166 J) was obtained in Nb–V–Ti-microalloyed Ni–Cr–Mo–Cu steel treated by direct quenching and tempering route (DQT). The tested steels treated by DQT route and re-austenitization and tempering route (QT) were compared with each other in terms of mechanical properties and microstructures characterized by optical microscopy, transmission electron microscopy, X-ray diffraction, electron back-scattered diffraction method and so on. Strength and Vickers hardness of the tested steel treated by the above two routes vary with isothermal aging temperature (400–600 °C), shown as under-aged state, peak-aged state and over-aged state. All DQT specimens show higher strength and Vickers hardness than QT specimens with the same aging condition. Furthermore, the largest difference of yield strength between DQT and QT specimens was shown in DQT600 and QT600 specimens. DQT600 or QT600 specimens refers to direct quenched (DQ) or quenched (Q) specimens isothermally aged at 600 °C. The main disparities in quenched microstructure between DQ and Q specimens are mainly in morphology of prior austenite grains, dislocation density of martensite matrix and solution amount of Nb and Mo elements dissolving in martensite matrix, which play key roles in affecting microstructure and mechanical properties of DQT and QT specimens. Higher dislocation density of matrix and finer average diameter of both MC (M is any combination of Nb, Mo and V) and Cu-rich particles were shown in DQT600 specimens than in QT600 specimens. Strengthening from dislocations and nanosized MC and Cu-rich particles mainly leads to the largest difference of yield strength between DQT600 and QT600 specimens. In addition, strong dislocation strengthening and precipitation strengthening in DQT600 specimen also elevated its ductile-to-brittle-transition-temperature, compared with QT600 specimen.

The problem of off-policy evaluation (OPE) has long been advocated as one of the foremost challenges in reinforcement learning. Gradient-based and emphasis-based temporal-difference (TD) learning algorithms comprise the major part of off-policy TD learning methods. In this work, we investigate the derivation of efficient OPE algorithms from a novel perspective based on the advantages of these two categories. The gradient-based framework is adopted, and the emphatic approach is used to improve convergence performance. We begin by proposing a new analogue of the on-policy objective, called the distribution-correction-based mean square projected Bellman error (DC-MSPBE). The key to the construction of DC-MSPBE is the use of emphatic weightings on the representable subspace of the original MSPBE. Based on this objective function, the emphatic TD with lower-variance gradient correction (ETD-LVC) algorithm is proposed. Under standard off-policy and stochastic approximation conditions, we provide the convergence analysis of the ETD-LVC algorithm in the case of linear function approximation. Further, we generalize the algorithm to nonlinear smooth function approximation. Finally, we empirically demonstrate the improved performance of our ETD-LVC algorithm on off-policy benchmarks. Taken together, we hope that our work can guide the future discovery of a better alternative in the off-policy TD learning algorithm family.

Existing studies of coal self-ignition and impact frictional sparks do not provide valid support for the analysis of ignition sources in all cases of methane explosions in the gob. In this paper, the explosion in the gob of the Renlou coal mine is used to investigate the piezoelectric effect and ignition characteristics of roof collapse in identifying a new ignition source of gas explosion. Experimental and theoretical analyses conclude that the piezoelectric effect is produced by quartz, which is the main constituent of the roof sandstone. During the loading process, the piezoelectric effect and compressive strength are key factors in the gathering of free charges on rock tips. During rupture, the rock tip retains a large number of charges, forming a ″point-surface″ effect, which triggers an electron avalanche accompanied by an orange-yellow spark lasting over 22 ms, far exceeding the ionization energy and ignition induction period of methane–air mixtures. The piezoelectric effect and compressive strength of the rock cause the generation of electrical sparks, which is the ignition source of the explosion in the gob of Renlou mine II7322.

Post-translational modification (PTM) on protein plays important roles in the regulation of cellular function and disease pathogenesis. The systematic analysis of PTM dynamics presents great opportunities to enlarge the target space by PTM allosteric regulation. Here, we presented a framework by integrating the sequence, structural topology, and particular dynamics features to characterize the functional context and druggabilities of PTMs in the well-known kinase family. The machine learning models with these biophysical features could successfully predict PTMs. On the other hand, PTMs were identified to be significantly enriched in the reported allosteric pockets and the allosteric potential of PTM pockets were thus proposed through these biophysical features. In the end, the covalent inhibitor DC-Srci-6668 targeting the PTM pocket in c-Src kinase was identified, which inhibited the phosphorylation and locked c-Src in the inactive state. Our findings represent a crucial step toward PTM-inspired drug design in the kinase family.

Gallic acid (GA) is a natural ingredient in functional foods, which has various health-promoting and antitumour effects. Peptidyl-prolyl cis/trans isomerase Pin1 plays an important role in preventing the development of some malignant tumours. However, whether there was an interaction between Pin1 and GA remains unknown. In this work, the binding information of GA and Pin1 was investigated systematically using multiple spectral and computational methods. GA bound to Pin1 directly with moderate binding affinity in the order of 104 mol/L, therefore decreasing the activity of Pin1. Also, the binding process of GA to Pin1 was driven through weak van der Waals forces, hydrogen bonds, and electrostatic forces. In addition, the important residues Lys63, Arg68, and Arg69 played a significant role in maintaining the binding stability between Pin1 and GA. Interestingly, GA reduced the activity of Pin1 by affecting its conformational characteristics. Our present work showed that GA binds to Pin1 and inhibits its activity, affecting its structural and functional properties, which may contribute to the therapy of Pin1-related diseases.

The scarcity of reliable methods for synthesizing chiral gem-diarylmethine borons limits their applications. Herein, we report a method for highly enantioselective dirhodium-catalyzed B-H bond insertion reactions with diaryl diazomethanes as carbene precursors. These reactions afforded chiral gem-diarylmethine borane compounds in high yield (up to 99 % yield), high activity (turnover numbers up to 14 300), high enantioselectivity (up to 99 % ee) and showed unprecedented broad functional group tolerance. The borane compounds synthesized by this method could be efficiently transformed into diaryl methanol, diaryl methyl amine, and triaryl methane derivatives with good stereospecificity. Mechanistic studies suggested that the borane adduct coordinated to the rhodium catalyst and thus interfered with decomposition of the diazomethane, and that insertion of a rhodium carbene (generated from the diaryl diazomethane) into the B-H bond was most likely the rate-determining step.

In reinforcement learning an agent may explore ineffectively when dealing with sparse reward tasks where finding a reward point is difficult. To solve the problem, we propose an algorithm called hierarchical deep reinforcement learning with automatic sub-goal identification via computer vision (HADS) which takes advantage of hierarchical reinforcement learning to alleviate the sparse reward problem and improve efficiency of exploration by utilizing a sub-goal mechanism. HADS uses a computer vision method to identify sub-goals automatically for hierarchical deep reinforcement learning. Due to the fact that not all sub-goal points are reachable, a mechanism is proposed to remove unreachable sub-goal points so as to further improve the performance of the algorithm. HADS involves contour recognition to identify sub-goals from the state image where some salient states in the state image may be recognized as sub-goals, while those that are not will be removed based on prior knowledge. Our experiments verified the effect of the algorithm.

Objective The upregulation of long noncoding RNA intersectin 1-2 (lnc ITSN1-2) is associated with poor prognosis in acute ischemic stroke (AIS) patients, but the role and mechanism of lnc ITSN1-2 in AIS are rarely reported, which, thus, are highlighted in this study. Methods AIS cell model was constructed by oxygen glucose deprivation and reoxygenation (OGD/R). The quantitative real-time PCR was used to detect the expression of lnc ITSN1-2 in HT22 cells. The effects of lnc ITSN1-2 overexpression or knockdown on viability, LDH release, apoptosis, inflammatory and apoptotic factor expressions in OGD/R-induced HT22 cells were measured by cell counting kit-8 assay, LDH release kit, flow cytometry, ELISA and western blot, respectively. Starbase was used to screen the target genes of lnc ITSN1-2. The targeting relationship between lnc ITSN1-2 and miR-195-5p was predicted by starbase and verified by dual-luciferase report assay. The above assays were conducted again to study the function of miR-195-5p. Lastly, the levels of activated mitogen-activated protein kinases (MAPK) pathway-related proteins were determined by western blot. Results OGD/R treatment reduced the HT22 cell viability and enhanced LDH release rate and lnc ITSN1-2 expression. Lnc ITSN1-2 overexpression promoted the cell injury, apoptosis and inflammation in OGD/R-induced HT22 cells, while lnc ITSN1-2 knockdown generated the opposite effect and deactivated the MAPK pathways. However, the effect of lnc ITSN1-2 knockdown in OGD/R-induced HT22 cells was reversed by miR-195-5p inhibitor. Conclusion Lnc ITSN1-2 knockdown suppressed the inflammation and apoptosis in OGD/R-induced HT22 cells by regulating the miR-195-5p-mediated MAPK pathways.

Biosensors have been flourishing in the field of drug discovery with pronounced developments in the past few years. They facilitate the screening and discovery of innovative drugs. However, there is still a lack of critical reviews that compare the merits and shortcomings of these biosensors from a pharmaceutical point of view. This contribution presents a critical and up-to-date overview on the recent progress of tailored biosensors, including surface plasmon resonance, fluorescent, photoelectrochemical, and electrochemical systems with emphasis on their mechanisms and applications in drug screening, efficacy assessment, and toxicity evaluation. Multiple functional nanomaterials have also been incorporated into the biosensors. Representative examples of each type of biosensors are discussed in terms of design strategy, response mechanism, and potential applications. In the end, we also compare the results and summarize the major insights gained from the works, demonstrating the challenges and prospects of biosensors-assisted drug discovery.

Herein we report the first method for highly enantioselective Brønsted acid catalyzed Heyns rearrangements. These reactions, catalyzed by a chiral spiro phosphoric acid, afforded synthetically valuable chiral α-aryl-α-aminoketones which cannot be obtained by means of previously reported Heyns rearrangement methods. This method features low catalyst loadings, high yields and high enantioselectivities, making these reactions highly practical. We used the method to efficiently synthesize various chiral amines, including some biologically active molecules. We experimentally proved that these acid-catalyzed Heyns rearrangements proceeded via a proton-transfer process involving an enol intermediate and the stereocontrol was realized during the proton-transfer step.

As human activity increases, coastal ecosystems are becoming increasingly vulnerable to a range of challenges. Oyster reefs are coastal ecosystems that provide habitats for a diverse range of marine species while also purifying water and providing natural coastal defense. However, because of human activity, global oyster reef areas have drastically diminished and are in grave danger. Simultaneously, it is impossible to determine the negative impact of human engineering activity on oyster reefs, due to the lack of intuitive and quantitative study methodologies. To address this issue, we applied a hydrodynamic model to analyze the impact on oyster reefs. First, we considered that human engineering activity, that is, coastal engineering, mainly affects the development of Liyashan Oyster Reefs by influencing hydrodynamics, sediment concentration, and bed-level evolution. We then applied MIKE3 to establish and validate a 3D hydrodynamic model of the southern part of the Yellow Sea around oyster reefs. Results showed that regional variations in flow velocity and suspended sediment concentration occurred in oyster reef waters, but the magnitude of these variations was limited. However, seabed elevation increased substantially in the Center Protection Area, which had a negative impact on oyster reefs. In general, our study provided a paradigm for analyzing the degree of impact on oyster reefs, showed the advantages of hydrodynamic models in quantitatively analyzing impact factors, and had reliable results.

The aim of this study was to evaluate the safety and effectiveness of robot-assisted thymectomy (RAT) in large anterior mediastinal tumors (AMTs) (size ≥6 cm) compared with video-assisted thymectomy (VAT) and open surgery.A total of 132 patients with large AMTs who underwent surgical resection from January 2016 to June 2022 were included in this study. A total of 61 patients underwent RAT, 36 patients underwent VAT and 35 patients underwent open surgery. Perioperative outcomes were compared.There were no significant differences in tumor size (p = 0.141), or pathological types (p = 0.903). Compared with the open group, the RAT and VAT groups were associated with a shorter operation time (115.00 vs. 160.00, p = 0.012; 122.50 vs. 160.00, p = 0.071), and less blood loss (50.00 vs. 200.00, p 0.001; 50.00 vs. 200.00, p 0.001), respectively. The rate of conversion in the RAT group was similar to that in the VAT group (6.56% vs. 13.89%, p = 0.229). Concomitant resection was less frequently performed in the VAT group than in the RAT and open groups (5.56% vs. 31.15%, p = 0.040; 5.56% vs. 31.43%, p = 0.006). VAT patients had a lower drainage volume (365.00 vs. 700.00 and 910.00 mL, p 0.001), shorter duration of chest tube (2.00 vs. 3.00 and 4.00, p 0.001), and shorter hospital stay (5.00 vs. 6.00 and 7.00, p 0.001) than the RAT and open groups. There was no 30-day mortality in any group. No difference was seen in R0 resection rates (p = 0.846). The postoperative complication rates were similar among the three groups (p = 0.309). Total in-hospital costs (66493.90 vs. 33581.05 and 42876.40, p 0.001) were significantly higher in the RAT group.RAT is safe and effective for the resection of large AMTs compared to VAT and open surgery. Vascular resection in RAT is technically feasible. A long-term follow-up is required.

Background Young breast cancer survivors with body image disturbance have poor quality of life. Self-compassion and different coping styles can influence their body image. The purpose of the study was to investigate the relationship between self-compassion, coping styles, and body image disturbance, and examined the mediation role of coping styles between self-compassion and body image disturbance among young breast cancer survivors in China. Methods In the cross-sectional study, a total of 310 young women with breast cancer were assessed on self-compassion, coping styles, and body image disturbance by self-reported questionnaires in China. Spearman’s correlation was used to test the links between variables and to verify the indirect effects between variables by constructing a structural equation model. Results There were correlations between self-compassion, different coping styles, and body image disturbance. Confrontation, avoidance, and acceptance-resignation coping had significant mediation effects on the association between self-compassion and body image disturbance. The mediation effects of confrontation coping were greater than avoidance, and acceptance-resignation coping. Conclusions In this study, different coping styles acted as mediators between self-compassion and body image disturbance, providing support for further understanding the mechanism between self-compassion and body image disturbance, and developing comprehensive interventions for body image disturbance. Oncology nurses should pay attention to the breast cancer survivors’ self-compassion and coping styles and encourage them to adopt adaptive coping strategies, which can reduce body image disturbance.

Inorganic pyrophosphate (PPi) is an important biological functional anion and plays crucial roles in life science, environmental science, medicine, and chemical process. Quantification of PPi in water has far-reaching significance for life exploration, disease diagnosis, and water pollution control. The label-free quantitative detection of PPi anions with a nanofluidic sensing device based on a conical single nanochannel is demonstrated. The channel surface is functionalized with a synthetic PPi receptor, triazol-methanaminium-functionalized pillar[5]arene (TAMAP5), using carbodiimide coupling chemistry. Due to the specific binding between TAMAP5 and PPi, the functionalized nanochannel can discriminate PPi from other inorganic anions with high selectivity through ionic current recording, even in the presence of various interfering anions. The current response exhibits a linear correlation with PPi concentration in the range from 1 × 10

Ferroptosis has recently been associated with immunological changes in sepsis. However, the clinical significance of ferroptosis-associated genes (FAGs) remains unknown. In this paper, a FAG-based prognostic model was constructed for sepsis patients using an integrated machine learning approach. The prognosis model was composed of 14 FAGs that classify the patients as high or low risk. Based on immunological study, it was found that the immune status differed between the high-risk and low-risk clusters. Cox regression analysis revealed that FAGs were independent risk factors for the overall survival of sepsis patients. ROC curves and nomograms revealed that the FAG-based model was robust for prognosis prediction. Lastly, NEDD4L was identified from the 14 FAGs as a potential hub gene for sepsis prediction.

Our work aims to investigate the functions of a natural compound, Albiflorin (AF) in cerebral ischemia-reperfusion (IR) injury. The cerebral IR models were established by OGD/R in PC12 cells and MCAO/IR in rats. The cells in a glucose-free medium were placed in an anaerobic chamber containing 95% N₂ and 5% CO₂ for 3 h at 37°C, returned to a normal medium, and incubated for 24 h to accomplish OGD/R. Focal cerebral ischemia was conducted by thread occlusion of the right middle cerebral artery for 2 h followed by 24 h reperfusion in rats. CCK-8 assay indicated that AF had no toxicity to PC12 cells. Flow cytometry, Western blot, or TUNEL showed that AF treatment reduced apoptosis of cells or rat brain tissues. qRT-PCR and ELISA showed that AF decreased IL-1β, IL-6, and TNF-α levels in vitro and in vivo. Elevated levels of MDA, SOD, and ROS induced by IR injury were mitigated by AF in vitro and in vivo. HE and TTC staining revealed that AF ameliorated pathological injury in MCAO/IR rats. Western blot showed that Nrf2, NQO1, and HO-1 expression was activated by AF, and ML385 treatment suppressed the inhibition effects of AF in cerebral IR injury models. Overall, AF alleviates cerebral IR injury via regulating the Nrf2/HO-1 pathway.