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The frequent occurrence of coal burst seriously threatens the safe and efficient recovery of coal resources. The research on the mechanism of coal burst is the basis of prediction and disaster prevention. Aiming at the coal burst event under the condition that the stress environment is stable and not affected by dynamic load, the concept of local mine stiffness (LMS) is introduced. Taking the mining area with complex mining layout of the mine as the engineering background, the mechanical response of coal pillar in the process of large-scale mining is analyzed by comprehensively using numerical analysis and field measurement, The evolution of LMS in this process is investigated. It is pointed out that the mining leads to the reduction of LMS, the rapid accumulation of energy in the coal seam and its roof and floor system, and the rapid release of energy when the coal pillar is unstable, resulting in impact damage. The engineering verification is carried out by comparing the evolution of LMS with the mining and the field measured ground sound and microseismic data. The research shows that:①the deformation, load and elastic energy accumulation of coal pillar increase with the overall mining operation, but the LMS decreases. The mining space size and the distance between the mining space and the research area are the main influencing factors. The response degree of the two to the mining of the working face is significantly greater than that of the roadway excavation. The significant influence range of the mining of the working face on the LMS reduction is 3.67 times that of the roadway excavation, and the LMS reduction under the unit advancing distance is 6.41 times that of the roadway excavation.②The good correspondence between the evolution of local mine stiffness with the advancement of the working face and the on-site ground sound and microseismic data indicates that the reduction of local mine stiffness caused by coal mining directly affects the failure mode of coal pillars. The energy in the coal seams and their roof and floor systems accumulates rapidly with the reduction of local mine stiffness and is released rapidly when the bearing capacity of coal pillars decreases, resulting in impact damage. ③After using large-diameter drilling to weaken the coal body, the microseismic energy and frequency are significantly reduced, indicating that large-diameter drilling destroys the coal body in this area, reduces its post peak stiffness, and effectively realizes the impact prevention effect.

Abstract Depression is a mood disorder mainly clinically characterized by significant and persistent low spirits. Chronic stress is the leading cause of depression. However, traditional medicine has severe side effects in treating depression, ineffective treatment, and easy recurrence. Therefore, it is of great significance to prevent depression in the environment of chronic stress. In this study, aromatherapy was used for the prevention of depression. To solve the defects of intense volatility and inconvenience in using essential oils, we designed bionic nano-aromatic drugs and adhered them to the wallpaper. Inspired by the moldy wallpaper, we successively prepared the morphology-bionic nano-aromatic drugs, the function-bionic nano-aromatic drugs, and the bionic plus nano-aromatic drugs by referring to the morphology of microorganisms and substances in bacterial biofilms. Bionic nano-aromatic drugs remarkably promoted their adhesion on wallpaper. Molecular dynamics simulation explored its molecular mechanism. The essential oils, which were slowly released from the bionic nano-aromatic drugs, showed excellent biosecurity and depression prevention. These sustainedly released essential oils could significantly increase monoamine neurotransmitters in the brain under a chronic stress environment and had excellent neuroprotection. Besides, the bionic nano-aromatic drugs with simple preparation process and low cost had excellent application potential.

Uncaria rhynchophylla (Gouteng), as an evergreen woody vine belong to Rubiaceae family, is a traditional medicinal herb in China. Its terpenoid indole alkaloids (TIAs), which have good antidepressant and combined therapeutic effects on Alzheimer's disease, have attracted widespread attention. However, the content of TIAs is relatively low in U.rhynchophylla, which is unable to meet the growing market demand. The basic helix loop-helix (bHLH) transcription factor family exists in all three eukaryotic kingdoms and can participate in regulating secondary metabolite pathways. So far, there has been no comprehensive analysis of the bHLH gene in U. rhynchophylla, and their role in TIAs is almost unknown. In this study, a total of 171 UrbHLH genes (UrbHLHs) were unevenly distributed on 22 chromosomes and divided into 23 subfamilies. In addition, the physicochemical properties of UrbHLHs were analyzed. Most UrbHLHs in each subgroup had similar gene structures and conserved motifs. Intraspecific collinearity analysis showed that UrbHLH1 may be related to the biosynthesis of TIAs. Subcellular localization experiments revealed that UrbHLH1 is located in the nucleus; Dual luciferase reporter gene analysis (Dual-LUC) showed that UrbHLH1 could activate the expression of UrG10H and Ur10HGO in the TIAs synthesis pathway of U. rhynchophylla. Finally, using yeast one hybrid (Y1H) it was found that the promoter regions of these two genes both have E-box binding elements, which can be bound by UrbHLH1 and produced strong interactions. Therefore, UrbHLH1 may participate in the synthesis of TIAs pathway. In conclusion, this study provides foundation data on the role of UrbHLH transcription factors in regulating TIAs of U. rhynchophylla.

Abstract The post-peak characteristics of coal serve as a direct reflection of its failure process and are essential parameters for evaluating brittleness and bursting liability. Understanding the significant factors that influence post-peak characteristics can offer valuable insights for the prevention of coal bursts. In this study, the Synthetic Rock Mass method is employed to establish a numerical model, and the factors affecting coal post-peak characteristics are analyzed from four perspectives: coal matrix mechanical parameters, structural weak surface properties, height-to-width ratio, and loading rate. The research identifies four significant influencing factors: deformation modulus, density of discrete fracture networks, height-to-width ratio, and loading rate. The response and sensitivity of post-peak characteristics to single-factor and multi-factor interactions are assessed. The result suggested that feasible prevention and control measures for coal bursts can be formulated through four approaches: weakening the mechanical properties of coal pillars, increasing the number of structural weak surfaces in coal pillars, reducing the width of coal pillars, and optimizing mining and excavation speed. The efficacy of measures aimed at weakening the mechanical properties of coal is successfully demonstrated through a case study on coal burst prevention using large-diameter borehole drilling.

Reactive oxygen species (ROS)-mediated oxidative stress exacerbates chronic diseases such as organ damage and neurodegenerative disorders. The Keap1-Nrf2-ARE pathway is a widely distributed endogenous antioxidant system. However, ROS under redox homeostasis regulates a wide range of life activities. Therefore, smart scavenging of excess ROS under pathological conditions is essential to treat chronic diseases safely. This study reports a smart antioxidant function enhancement (SAFE) strategy. On-demand release of nucleic acid drugs in a pathological ROS environment smartly activates the endogenous antioxidant system, thereby smartly alleviating oxidative stress in an exogenous antioxidant-independent manner. Through structural modulation and ligand modification, we develop SAFE nanoparticles based on nanohybrid complexes (SAFE-complex) adapted to brain delivery of nucleic acid drugs. SAFE-complex with homogeneous monodisperse structure efficiently treat ROS-related neurodegenerative diseases while protecting the major organ from oxidative stress damage. Moreover, SAFE-complex can stabilize storage in the form of freeze-dried powder. These data indicate that SAFE nanoparticles hold promise for treating ROS-related chronic diseases and comorbidities through rational transformation.

The loading mine stiffness and the post-peak stiffness of a coal pillar are important factors affecting the occurrence of coal bursts. In order to systematically study the mechanism of coal bursts and pillar bursts based on local mine stiffness theory, a laboratory-scale coal burst experiment system has been developed. The system is mainly composed of static loading system, energy storage system, variable stiffness loading system, excavation system and multi-source information monitoring system. The main innovations of the test system are as follows: ① An excavation device is added to the loading system, which can induce the stress concentration of the specimen and the reduction of local mine stiffness through excavation in the pressure-holding state. Coal bursts will occur when the specimen is stressed to its bearing capacity and the local system stiffness is lower than the post-peak stiffness of the specimen. ② The loading system is equipped with an energy storage device of oil cylinder airbag accumulator, which can store energy during loading. ③ A variable stiffness loading device is set up to adjust different loading stiffnesses by adjusting the initial airbag pressure of airbag accumulator. ④ The experiment system can reproduce the whole process of specimen from loading-stabilization-excavation-burst in laboratory, which makes it possible to monitor the strain of coal pillar during the whole process of coal bursts and observe the burst process. The accuracy and reliability of the simulation equipment are verified by preliminary laboratory tests on high-strength concrete blocks and realistic coal samples. The test results show that under the condition of low stiffness loading, the unstable failure of coal pillars can be effectively induced by excavating bottom samples, and the failure position extends from the low stiffness side to the high stiffness side. The damaged central residual coal pillar is dumbbell shaped under the action of top and bottom plate friction, and is cut off at the center by a transverse sawtooth crack penetrating the sample, resulting in a significant reduction in the bearing capacity of the coal pillar. The development of the experiment system can reproduce the whole process of coal bursts from loading, pressure stabilization, excavation and unstable failure in the laboratory from the perspective of local mine stiffness, and can provide an experimental basis for the mechanism of coal bursts in coal mines.

Green total factor productivity (GTFP) is a major driver of environmental governance, climate change mitigation, and green transformation in China. This study aims to improve GTFP, reduce regional differences, and promote sustainable development. Herein, the slacks-based measure-global Malmquist–Luenberger index was used for the scientifically rigorous measurement of China’s GTFP from 2000 to 2019. Dagum’s Gini coefficient decomposition and kernel density estimation methods were used to explore GTFP regional differences and distributional dynamics. Finally, spatial GTFP heterogeneity driving factors were analyzed using a geodetector tool. We found that China’s GTFP is on an overall upward trend, driven mainly by technological progress. There were substantial spatial differences in China’s GTFP, primarily caused by transvariation intensity, the average contribution of which is 43.26%. Differences in GTFP between and within regions decreased to varying degrees over time. Spatial heterogeneities in China’s GTFP were primarily caused by driving factors interactions, which were stronger than their individual effects. Thus, we recommend that China should accelerate the establishment of a new coordinated regional development mode, improve its green technology innovation capacity, increase openness, and push for a green model of development.

Among all malignancies worldwide, gastric cancer is the fifth most common cancer with the third highest mortality rate. One of the main reasons for the low survival rate is the recurrence and metastasis that occurs in many patients after surgery. Numerous studies have shown that abnormal TRIM33 expression is associated with the progression of malignant tumors. TRIM33 can function either as a tumor suppressor or tumor promoter in different cancers. Our data showed that TRIM33 was highly expressed in stomach cancer, and in human gastric cancer tissues, low expression of TRIM33 was associated with poor prognosis in patients with gastric cancer. To clarify the function of TRIM33 in survival and epithelial–mesenchymal transition in gastric cancer cells, we investigated the effect of TRIM33 knockdown in several gastric cancer cell lines. Downregulation of TRIM33 in BGC-823 and SGC-7901 cells enhanced the proliferation, colony formation, and migratory ability of these gastric cancer cells. It also promoted epithelial–mesenchymal transition; transfection of cells with siRNA targeting TRIM33 led to the upregulation of vimentin and N-Cadherin expression, and downregulation of E-Cadherin expression. Meanwhile, the transforming growth factor beta pathway was activated: levels of transforming growth factor beta were elevated and the expressions of p-Smad2, Smad2, Smad3, and Smad4 were activated. To confirm the role of TRIM33 in vivo, a xenograft model was established in nude mice. Immunohistochemical analysis identified that the protein levels of TRIM33, p-Smad2, Smad2, Smad3, Smad4, vimentin, and N-Cadherin were increased, and E-Cadherin levels were decreased, in xenograft tumors from the si-TRIM33 group. Taken together, these results suggest that TRIM33 may be a potential marker for the diagnosis and prognosis of gastric cancer. Furthermore, it may also serve as a novel target for gastric cancer treatment.

Hibiscus syriacus, a woody ornamental plant with great economic value, is vulnerable to salinity. Hence, its cultivation in saline areas is severely restricted. Although grafting H. syriacus onto H. hamabo rootstock can greatly improve H. syriacus’s salt resistance, the photosynthetic response of H. syriacus to grafting and salt stress remains largely unknown. To address this question, self-rooted (Hs), self-grafted (Hs/Hs), and H. hamabo-grafted (Hs/Hh) H. syriacus were exposed to 0 or 300 mM NaCl. Salt significantly reduced the net and maximum photosynthetic rates, chlorophyll content, and maximum (Fv/Fm) and actual (ΦPSII) photochemical quantum yield of photosystem II (PSII), as well as the apparent electron transport rate, in Hs and Hs/Hs. However, these reductions were largely alleviated when H. syriacus was grafted onto H. hamabo. In line with the changes in the chlorophyll fluorescence parameters, the expression of genes encoding subunits of PSII and PSI in Hs/Hh was higher than that in Hs and Hs/Hs under saline conditions. Moreover, H. hamabo rootstock grafting upregulated the genes involved in the Calvin–Benson–Bassham cycle in H. syriacus under salt conditions. These results indicate that grafting can ameliorate the inhibition of salinity on the photosynthetic capacity of H. syriacus, mainly resulting from alleviated limitations on photosynthetic pigments, photochemical efficiency, and the Calvin–Benson–Bassham cycle.

Protoplast-based engineering has become an important tool for basic plant molecular biology research and developing genome-edited crops. Uncaria rhynchophylla is a traditional Chinese medicinal plant with a variety of pharmaceutically important indole alkaloids. In this study, an optimized protocol for U. rhynchophylla protoplast isolation, purification, and transient gene expression was developed. The best protoplast separation protocol was found to be 0.8 M D-mannitol, 1.25% Cellulase R-10, and 0.6% Macerozyme R-10 enzymolysis for 5 h at 26 °C in the dark with constant oscillation at 40 rpm/min. The protoplast yield was as high as 1.5 × 107 protoplasts/g fresh weight, and the survival rate of protoplasts was greater than 90%. Furthermore, polyethylene glycol (PEG)-mediated transient transformation of U. rhynchophylla protoplasts was investigated by optimizing different crucial factors affecting transfection efficiency, including plasmid DNA amount, PEG concentration, and transfection duration. The U. rhynchophylla protoplast transfection rate was highest (71%) when protoplasts were transfected overnight at 24 °C with the 40 µg of plasmid DNA for 40 min in a solution containing 40% PEG. This highly efficient protoplast-based transient expression system was used for subcellular localization of transcription factor UrWRKY37. Finally, a dual-luciferase assay was used to detect a transcription factor promoter interaction by co-expressing UrWRKY37 with a UrTDC-promoter reporter plasmid. Taken together, our optimized protocols provide a foundation for future molecular studies of gene function and expression in U. rhynchophylla.

Astronauts are under high stress for a long time because of the microgravity condition, which leads to anxiety, affects their learning and memory abilities, and seriously impairs the health of astronauts. Aromatherapy can improve the physical and mental health of astronauts in a way that moisturizes them softly and silently. However, the strong volatility of fragrances and inconvenience of aroma treatment greatly limit their application in the field of spaceflight. In this study, reactive mesoporous silica nanoparticles were prepared to encapsulate and slowly release limonene. The limonene loaded nanoparticles were named limonene@mesoporous silica nanoparticles-cyanuric chloride (LE@MSNs-CYC). LE@MSNs-CYC were then applied to wallpaper to improve the convenience of aromatherapy. LE@MSNs-CYC could chemically react with the wallpaper, thus firmly adsorbed on the wallpaper. In the following, the mice were treated with hindlimb unloading (HU) to simulate a microgravity environment. The results showed that 28-day HU led to an increase in the level of anxiety and declines in learning, memory, and physical health in mice. LE@MSNs-CYC showed significant relief effects on anxiety, learning, memory, and physical health of HU treated mice. Subsequently, the molecular mechanisms were explored by hypothalamic-pituitary-adrenal axis related hormones, immune-related cytokines, learning, and memory-related neurotransmitters and proteins.

Taxodium hybrid ‘Zhongshanshan’ has been widely used as a timber tree in river network areas and coastal regions and is mainly propagated by cuttings. However, when trees age, their capacity to form adventitious roots becomes weaker. We successfully enhanced the rooting ability of shoots in T. hybrid ‘Zhongshanshan 302’ by their rejuvenation based on grafting. We recorded temporal variation in endogenous auxin, abscisic acid (ABA), gibberellins (GAs), trans-zeatin-riboside (TZR), soluble sugar and H2O2 after root induction. Auxin, soluble sugars and H2O2 levels were higher in rejuvenated shoots than in mature shoots, whereas the opposite was true for ABA and GAs. Notably, indole-3-acetic acid (IAA) and GA3 presented higher contents with more obvious differences in T. hybrid ‘Zhongshanshan 302’ rejuvenated shoots vs. mature shoots compared with other kinds of auxin and GAs. The evident improvement in the rooting ability of rejuvenated shoots after grafting likely resulted from the differential regulation of plant hormones, carbohydrates and redox signaling. In addition to the physiological basis of improved rooting ability by grafting, this study provided a theoretical basis for the optimization of subsequent propagation techniques in T. hybrid ‘Zhongshanshan’ and potentially other Taxodium spp.

Taxodium hybrid Zhongshanshan has been widely planted in the Yangtze River Basin (YRB) for soil and carbon conservation, with quantities over 50 million. The objective of this study was to determine how T. hybrid Zhongshanshan plantations affected soil physicochemical properties and bacterial community structure in the YRB, and to examine the consistency of changes by afforestation. Soils under T. Zhongshanshan plantations across six sites of the YRB were compared with soils of adjacent non-forested sites. Soil physicochemical properties and bacterial community structure were determined to clarify edaphic driving factors and reveal the effects of afforestation on bacteria. The results indicated that most soil attributes manifested improvements, e.g., total nitrogen in Jiangxi and Shanghai; available phosphorus in Hubei, Chongqing and Yunnan, exhibited the potential to maintain or ameliorate soil quality. A decrease in soil bulk density caused by plantation was also observed at the expense of soil macro-aggregates augment. Afforestation of T. Zhongshanshan plantation has habitually improved Shannon diversity and Chao1 richness, of which dominant phyla were Proteobacteria, Acidobacteria, and Actinobacteria, and increased the relative abundance of the phyla Proteobacteria and Nitrospirae, and the classes Flavobacteriia, Acidobacteria_Gp5, and Bacilli. We concluded that T. Zhongshanshan plantation can be employed to facilitate soil nutrient accumulation in the YRB, but that the degree, rate and direction of changes in soil attributes are sites dependent. It is recommended that afforestation of nutrient-depleted and less productive lands in the YRB should utilize this fast-growing species in combination with proper fertilization.

In some existing omnidirectional mobile robots, the movement of each wheel is generally controlled by one driven motor cooperates with one steering motor, such design will increase the energy consumption. This paper investigates an omnidirectional mobile robot based on a special coupling system, so as to solve the above problem. We propose a unique robot's steering method by designing the parallelogram connecting rod as the coupling system, which makes each wheel only need to be equipped with one motor to complete omnidirectional motion and always keep unchanged robot's attitude. In theory, we conduct the structural analysis, dynamic analysis and kinematic analysis of the mobile robot and explain why our system is under-actuated. In experiments, the square trajectory and the serpentine trajectory are exploited to verify the rationality of design and theoretical derivation by comparing the simulation results with the experimental results. By performing mobile robot walking experiments under different ground condition respectively, the stability and adaption of the under-actuated omnidirectional mobile robot is also favourably confirmed. After detailed theoretical analysis and the support of experiments, it is carried out that the under-actuated mechanism proposed in this paper can indeed realize the movement of the robot in all directions. As well as the attitude of the robot always keeps constant, as we expected, enables to realize the steering of robot flexibly even in a narrow space.

Mining above confined aquifer has become an important task for water inrush prevention in China. To study the failure characteristics of stope floor along the strike, a mechanical model under combined action of mining and confined aquifer was constructed, and the distribution of vertical stress, horizontal stress, and shear stress was obtained. Based on the Mohr–Coulomb criterion, the failure range of the floor is determined and verified by the in situ test. The results indicate the following. (1) Both vertical stress and horizontal stress in the stope floor take the junction of stress increasing area and stress decreasing area as the dividing line, forming two groups of “convex arches” at the solid coal side and the goaf side, respectively. (2) The vertical stress gradient in the solid coal side is significantly higher than that in the goaf side, while the horizontal stress gradient in the solid coal side is similar to that in the goaf side. The shear stress distribution is divided into three regions by the boundary between positive and negative shear stress, which makes the stope floor in this area to show compression shear or tension shear failure. (3) According to the in situ test, the maximum floor failure depth of 41503 working face is 11.38 m, which is quite close to the theoretical calculation result of 9.68 m. (4) Applying the mechanical model to five other coal mines with different mining conditions and stress states, the maximum absolute error between the measured and theoretical values of floor failure depth is 1.1 m, the average absolute error is 0.8 m, the maximum relative error is 8.2%, and the average relative error is 6.5%. The study provides a certain mechanical basis and reference for the floor failure mechanism induced by mining and confined aquifer.

The multi-locomotion robot (MLR), including bionic insect microrobot, bionic animal robot and so on, should choose different locomotion modes according to the obstacles it faces. However, under different locomotion modes, the power consumption, moving speed, and falling risk of MLR are different, and in most cases, they are mutually exclusive. This paper proposes a path planning algorithm for MLR based on a multi-objective genetic algorithm with elitist strategy (MLRMOEGA), which has four optimization objectives: power consumption, time consumption, path falling risk, and path smoothness. We propose two operators: a map analysis operator and a population diversity expansion operator, to improve the global search ability of the algorithm and solve the problem so that it is easy to fall into the local optimal solution. We conduct simulations on MATLAB, and the results show that the proposed algorithm can effectively optimize the objective function value compared with the traditional genetic algorithm under the equal weight of the four optimization objectives, and, under alternative weights, the proposed algorithm can effectively generate the corresponding path of the decision maker’s intention under the weight of preference. Compared with the traditional genetic algorithm, the global search ability is improved effectively.

NAC transcription factor is one of the largest plant gene families, participating in the regulation of plant biological and abiotic stresses. In this study, 182 NAC proteins (HhNACs) were identified based on genomic datasets of Hibiscus hamabo Sieb. et Zucc (H. hamabo). These proteins were divided into 19 subfamilies based on their phylogenetic relationship, motif pattern, and gene structure analysis. Expression analysis with RNA-seq revealed that most HhNACs were expressed in response to drought and salt stress. Research of quantitative real-time PCR analysis of nine selected HhNACs supported the transcriptome data’s dependability and suggested that HhNAC54 was significantly upregulated under multiple abiotic stresses. Overexpression of HhNAC54 in Arabidopsis thaliana (A. thaliana) significantly increased its tolerance to salt. This study provides a basis for a comprehensive analysis of NAC transcription factor and insight into the abiotic stress response mechanism in H. hamabo.

In order to achieve the normal walking of hemiplegic patients, this paper proposes a single-legged exoskeleton robot according to the bionics principle, and presents an adaptive adjustment strategy for walking characteristics. The least square regression analysis is used to fit the angle data of healthy leg joints by cubic polynomials, and then the parametric design of the fitted curve is carried out to obtain the influence of the user’s stride frequency and stride length on the joint angle, so that the gait of the exoskeleton can be adjusted in real time according to the stride length and stride frequency of the healthy leg to realize normal walking. In order to verify the effectiveness of the adaptive adjustment strategy proposed in this paper, the angle of leg joints under normal gait is collected in advance. In addition, an adult male is chosen as the subject to walk on the horizontal ground wearing the single-legged exoskeleton as the experiment. The experimental results show that the designed exoskeleton is reasonable, and the adaptive adjustment strategy proposed in this paper can make the exoskeleton adapt well and follow the gait of healthy legs to achieve a more natural walking state.

Diabetes mellitus has been described as a chronic endocrine and metabolic disease, which is characterized by hyperglycemia and the coexistence of multiple complications. At present, the drugs widely applied in clinical treatment of diabetes mellitus mainly include insulin, insulin analogs, non-insulin oral hypoglycemic drugs and genetic drugs. Nevertheless, there is still no complete therapy strategy for diabetes mellitus management by far due to the intrinsic deficiencies of drugs and limits in administration routes such as the adverse reactions caused by long-term subcutaneous injection and various challenges in oral administration, such as enzymatic degradation, chemical instability and poor gastrointestinal absorption. Therefore, it is remarkably necessary to develop appropriate delivery systems and explore complete therapy strategies according to the characters of drugs and diabetes mellitus. Delivery systems have been found to be potentially beneficial in many aspects for effective diabetes treatment, such as improving the stability of drugs, overcoming different biological barriers in vivo to increase bioavailability, and acting as an intelligent automatized system to mimic endogenous insulin delivery and reduce the risk of hypoglycemia. This review aims to provide an overview related with the research advances, development trend of drug therapy and the application of delivery systems in the treatment diabetes mellitus, which could offer reference for the application of various drugs in the field of diabetes mellitus treatment.

Numerical simulations have often been used in close-distance coal seam studies. However, numerical simulations can contain certain subjective and objective limitations, such as high randomness and excessively simplified models. In this study, close-distance coal seams were mechanically modeled based on the half-plane theory. An analytical solution of the floor stress distribution was derived and visualized using Mathematica software. The principal stress difference was regarded as a stability criterion for the rock surrounding the roadway. Then, the evolution laws of the floor principal stress difference under different factors that influence stability were further examined. Finally, stability control measures for the rock surrounding the roadway in the lower coal seam were proposed. The results indicated the following: (1) The principal stress difference of the floor considers the centerline of the upper coal pillar as a symmetry axis and transmits radially downward. The principal stress difference in the rock surrounding the roadway gradually decreases as the distance from the upper coal pillar increases and can be ranked in the following order: left rib > roof > right rib. (2) The minimum principal stress difference zones are located at the center of the left and right “spirals,” which are obliquely below the edge of the upper coal pillar. This is an ideal position for the lower coal seam roadway. (3) The shallowness of the roadway, a small stress concentration coefficient, high level of coal cohesion, large coal internal friction angle, and appropriate lengthening of the working face of the upper coal seam are conducive to the stability of the lower coal seam roadway. (4) Through bolt (cable) support, borehole pressure relief, and pregrouting measures, the roof-to-floor and rib-to-rib convergence of the 13313 return airway is significantly reduced, and the stability of the rock surrounding the roadway is substantially improved. This research provides a theoretical basis and field experience for stabilizing the lower coal seam roadways in close-distance coal seams.

Abstract Alzheimer's disease (AD) is a devastating neurodegenerative disorder characterized by progressive cognitive and memory loss. The vicious circle between dysfunctional microglia and amyloid‐β (Aβ) is a crucial pathological event and accelerates the progression of AD. Herein, a zwitterionic poly(carboxybetaine) (PCB)‐based nanoparticle (MCPZFS NP) with normalizing the dysfunctional microglia and Aβ recruitment is established for the treatment of AD. Compared with the neural polyethylene glycol (PEG)‐based nanoparticles (MEPZFS NPs), the MCPZFS NPs significantly alleviate the priming of microglia by decreasing the level of proinflammatory mediators and promoting the secretion of BDNF. Most importantly, quite different from PEG, the PCB‐based NPs exhibit the behavior to recruit Aβ into microglia, which significantly enhances the Aβ phagocytosis. Moreover, the Aβ degradation is changed from the conventional lysosomal/autophagy to the proteasomal pathway in the presence of MCPZFS NPs. After the treatment with MCPZFS NPs, the Aβ burden, neuron damages, memory deficits, and neuroinflammation of APPswe/PS1dE9 mice are significantly attenuated in the brain. Therefore, the PCB‐based MCPZFS NPs have great potential to serve as an “Aβ cleaner” and provide a new insight into the therapeutic strategy for AD therapy.

Irregular shape workface would result in the presence of coal pillar, which leads to high stress concentration and possibly induces coal bumps. In order to study the coal bump mechanism of pillars, static and dynamic stress overlapping (SDSO) method was proposed to explain the impacts of static stress concentration and tremors induced by mining activities. The stress and deformation in surrounding rock of mining face were analyzed based on the field case study at 1303 workface in Zhaolou Coal Mine in China. The results illustrate that the surrounding rock of a workface could be divided into four different zones, i.e., residual stress zone, stress decrease zone, stress increase zone and original stress zone. The stress increase zone is prone to failure under the SDSO impact loading conditions and will provide elastic energy for inducing coal bump. Based on the numerical modelling results, the evolution of static stress in coal pillar as the size of gob increasing was studied, and the impact of dynamic stress was investigated through analyzing the characteristics of tremor activities. The numerical results demonstrate the peak value of vertical stress in coal pillar rises from about 30 MPa with mining distance 10 m to 52.6 MPa with mining distance 120 m, and the location of peak stress transfers to the inner zone of coal pillars as the workface moves forward. For the daily tremor activities, tremors with high energy released indicate high dynamic stress disturbance on the surrounding rock, therefore, the impact of dynamic stressing is more serious during workface extension period because the tremor frequency and average energy after workface extension are higher than those before the workface extension. Keywords: Coal bump, Coal pillar, Tremor, Irregular shape longwall face, Static and dynamic stress overlapping

To elucidate the transcriptomic regulation mechanisms that underlie the response of Ginkgo biloba to dehydration and rehydration, we used ginkgo saplings exposed to osmotically driven water stress and subsequent rewatering. When compared with a control group, 137, 1453, 1148, and 679 genes were differentially expressed in ginkgo leaves responding to 2, 6, 12, and 24 h of water deficit, and 796 and 1530 genes were differentially expressed responding to 24 and 48 h of rewatering. Upregulated genes participated in the biosynthesis of abscisic acid, eliminating reactive oxygen species (ROS), and biosynthesis of flavonoids and bilobalide, and downregulated genes were involved in water transport and cell wall enlargement in water stress-treated ginkgo leaves. Under rehydration conditions, the genes associated with water transport and cell wall enlargement were upregulated, and the genes that participated in eliminating ROS and the biosynthesis of flavonoids and bilobalide were downregulated in the leaves of G. biloba. Furthermore, the weighted gene coexpression networks were established and correlated with distinct water stress and rewatering time-point samples. Hub genes that act as key players in the networks were identified. Overall, these results indicate that the gene coexpression networks play essential roles in the transcriptional reconfiguration of ginkgo leaves in response to water stress and rewatering.

This paper introduces a planar positioning sensing system based on orthogonal wheels and encoders for some surfaces that may float (such as ship decks). The positioning sensing system can obtain the desired position and angle information on any such ground that floats. In view of the current method of using the IMU gyroscope for positioning, the odometer data on these floating grounds are not consistent with the real-time data in the world coordinate system. The system takes advantage of the characteristic of the orthogonal wheel, using four vertical omnidirectional wheels and encoders to position on the floating ground. We design a new structure and obtain the position and angle information of a mobile robot by solving the encoder installed on four sets of omnidirectional wheels. Each orthogonal wheel is provided with a sliding mechanism. This is a good solution to the problem of irregular motion of the system facing the floating grounds. In the experiment, it is found that under the condition that the parameters of the four omnidirectional wheels are obtained by the encoder, the influence of the angle change of the robot in the world coordinate system caused by the flotation of the ground can be ignored, and the position and pose of the robot on the fluctuating ground can be well obtained. Regardless of straight or curved motion, the error can reach the centimeter level. In the mobile floating platform experiment, the maximum error of irregular movement process is 2.43 (±0.075) cm and the RMSE is 1.51 cm.

Combining diagnosis with therapy, magnetic iron oxide nanoparticles (INOPs) act as an important vehicle for drug delivery. However, poor biocompatibility of INOPs limits their application. To improve the shortcomings, various surface modifications have been developed, including small molecules coatings, polymers coatings, lipid coatings and lipopolymer coatings. These surface modifications facilitate iron nanoparticles to cross the blood-brain-barrier, which is essential for diagnosis and treatments of brain diseases. Here we focus on the characteristics of different coated INOPs and their application in brain disease, particularly gliomas, Alzheimer’s disease (AD) and Parkinson’s disease (PD). Moreover, we summarize the current progress and expect to provide help for future researches.

In many previous tunnel analyses, the axial in-situ stress was ignored. In this work, its effect on the deformation and failure of the surrounding rock of a deep tunnel was revealed, considering the objective strain softening and dilatancy behavior of the surrounding rock. Analysis based on the incremental plastic flow theory was conducted, and C++ was used to write a constitutive model for numerical simulation to verify and further analyze this effect. Then, the results were validated by the field monitoring data of a coal mine gateway. Results show that the effect of the axial in-situ stress σa0 is more significant when strain softening is considered, compared with the results of a perfectly elastoplastic model. When the axial stress σa is σ1 or σ3 at the initial yield, an increase or decrease in σa0 intensifies the deformation and failure of the surrounding rock. When σa is σ2 at the initial yield, 3D plastic flow partly controlled by σa may occur, and an increase in σa0 intensifies the deformation and failure of the surrounding rock. The effect of σa0 will be amplified by considering dilatancy. Considering both strain softening and dilatancy, when σa0 is close to the tangential in-situ stress σt0 or significantly greater than σt0 (1.5 times), σa will be σ2 or σ1 at the initial yield, and then 3D plastic flow will occur. In the deformation prediction and support design of a deep tunnel, σa0 should not be ignored, and the strain softening and dilatancy behavior of the surrounding rock should be accurately considered.

Textual representations play an important role in the field of natural language processing (NLP). The efficiency of NLP tasks, such as text comprehension and information extraction, can be significantly improved with proper textual representations. As neural networks are gradually applied to learn the representation of words and phrases, fairly efficient models of learning short text representations have been developed, such as the continuous bag of words (CBOW) and skip-gram models, and they have been extensively employed in a variety of NLP tasks. Because of the complex structure generated by the longer text lengths, such as sentences, algorithms appropriate for learning short textual representations are not applicable for learning long textual representations. One method of learning long textual representations is the Long Short-Term Memory (LSTM) network, which is suitable for processing sequences. However, the standard LSTM does not adequately address the primary sentence structure (subject, predicate and object), which is an important factor for producing appropriate sentence representations. To resolve this issue, this paper proposes the dependency-based LSTM model (D-LSTM). The D-LSTM divides a sentence representation into two parts: a basic component and a supporting component. The D-LSTM uses a pre-trained dependency parser to obtain the primary sentence information and generate supporting components, and it also uses a standard LSTM model to generate the basic sentence components. A weight factor that can adjust the ratio of the basic and supporting components in a sentence is introduced to generate the sentence representation. Compared with the representation learned by the standard LSTM, the sentence representation learned by the D-LSTM contains a greater amount of useful information. The experimental results show that the D-LSTM is superior to the standard LSTM for sentences involving compositional knowledge (SICK) data.

Text representation can map text into a vector space for subsequent use in numerical calculations and processing tasks. Word embedding is an important component of text representation. Most existing word embedding models focus on writing and utilize context, weight, dependency, morphology, etc., to optimize the training. However, from the linguistic point of view, spoken language is a more direct expression of semantics; writing has meaning only as a recording of spoken language. Therefore, this paper proposes the concept of a pronunciation-enhanced word embedding model (PWE) that integrates speech information into training to fully apply the roles of both speech and writing to meaning. This paper uses the Chinese language, English language and Spanish language as examples and presents several models that integrate word pronunciation characteristics into word embedding. Word similarity and text classification experiments show that the PWE outperforms the baseline model that does not include speech information. Language is a storehouse of sound-images; therefore, the PWE can be applied to most languages.

Because both faults and cleats exist in coal, sharp stress drops occur during loading when coal is deformed. These drops occur during the pre-peak stage and are accompanied by sudden energy releases. After a stress drop, the stress climbs slowly following a zigzag path and the energy accumulated during the pre-peak stage is unstable. A stress−strain curve is the basic tool used to evaluate the bursting liability of coal. Based on energy accumulation in an unsteady state, the pre-peak stress−strain curve is divided into three stages: pre-extreme, stress drop, and re-rising stage. The energy evolution of the specimen during each stage is analyzed. In this paper, an index called the effective elastic strain energy release rate (EESERR) index is proposed and used to evaluate the coal’s bursting liability. The paper shows that the propagation and coalescence of cracks is accompanied by energy release. The stress climb following a zigzag path prolongs the plastic deformation stage. This causes a significant difference between the work done by a hydraulic press during a laboratory uniaxial compression experiment and the elastic strain energy stored in the specimen during the experiment, so the evaluation result of the burst energy index would be too high. The determination of bursting liability is a comprehensive evaluation of the elastic strain energy accumulated in coal that is released when the specimen is damaged. The index proposed in this paper fully integrates the energy evolution of coal samples being damaged by loading, the amount of elastic strain energy released during the sample failure divided by the failure time is the energy release rate. The calculation method is simplified so that the uniaxial compressive strength and elastic modulus are included which makes the new index more universal and comprehensive. Theoretical analysis and physical compression experiments validate the reliability of the evaluation.

This paper focuses on planning patterns for biped walking on complex terrains. Two problems are solved: ZMP (zero moment point) cannot be used on uneven terrain, and the conventional cart-table model does not allow vertical CM (centre of mass) motion. For the ZMP definition problem, we propose the extended ZMP (EZMP) concept as an extension of ZMP to uneven terrains. It can be used to judge dynamic balance on universal terrains. We achieve a deeper insight into the connection and difference between ZMP and EZMP by adding different constraints. For the model problem, we extend the cart-table model by using a dynamic constraint instead of constant height constraint, which results in a mathematically symmetric set of three equations. In this way, the vertical motion is enabled and the resultant equations are still linear. Based on the extended ZMP concept and extended cart-table model, a biped pattern generator using triple preview controllers is constructed and implemented simultaneously to three dimensions. Using the proposed pattern generator, the Atlas robot is simulated. The simulation results show the robot can walk stably on rather complex terrains by accurately tracking extended ZMP.

Abstract Background Our previous studies demonstrated that 1-Pyrroline-5-carboxylate (P5C) released by prostate cancer cells inhibits T cell proliferation and function by increasing SHP1 expression. We designed this study to further explore the influence of P5C on T cell metabolism, and produced an antibody for targeting P5C to restore the functions of T cells. Method We co-immunoprecipated SHP1 from T cells and analyzed the proteins that were bound to it using liquid chromatography mass spectrometry (LC/MS-MS). The influence of P5C on T cells metabolism was also detected by LC/MS-MS. Seahorse XF96 analyzer was further used to identify the effect of P5C on T cells glycolysis. We subsequently designed and produced an antibody for targeting P5C by monoclonal technique and verified its effectiveness to restore the function of T cells in vitro and in vivo. Result PKM2 and LDHB bind SHP1 in T cells, and P5C could increase the levels of p-PKM2 while having no effect on the levels of PKM2 and LDHB. We further found that P5C influences T cell energy metabolism and carbohydrate metabolism. P5C also inhibits the activity of PKM2 and decreases the content of intracellular lactic acid while increasing the activity of LDH. Using seahorse XF96 analyzer, we confirmed that P5C remarkably inhibits glycolysis in T cells. We produced an antibody for targeting P5C by monoclonal technique and verified that the antibody could oppose the influence of P5C to restore the process of glycolysis and function in T cells. Meanwhile, the antibody also inhibits the growth of prostate tumors in an animal model. Conclusion Our study revealed that P5C inhibits the process of glycolysis in T cells by targeting SHP1/PKM2/LDHB complexes. Moreover, it is important that the antibody for targeting P5C could restore the function of T cells and inhibit the growth of prostate tumors.

In this communication, we used electrochemical sensor for recording the electrochemical profiles of eleven species of Yulania spp. from leaf extract. Two solvents and two buffer conditions were used for electrochemical fingerprints collection. Their electrochemical fingerprints can be converted to different patterns and consequently for species recognition. The results indicate the pattern recognition is much convenient than that of the recognition of species directly using voltammetric signal. The current information in electrochemical fingerprinting represents the type and amount of electrochemically active molecules, which linked to the genetic differences among the plants. Therefore, the electrochemical fingerprints were applied for further phylogenetic study. The phylogenetic tree deduced from voltametric curves is divided into three main groups. The first clade contains Y. denudate, Liriodendron chinense, Y. cylindrica, Y. biondii, Y. sprengeri. The second clade contains Y. zenii, Y. liliiflora, Y. kobus, and Y. amoena. The third clade contains Y. × soulangeana, Manglietia fordiana and Y. sinostellata. In addition, Y. salicifolia is not in these main clades. The results demonstrate that electrochemical fingerprinting can be used as a com-plementary tool in the study of phylogenetics. [ABSTRACT FROM AUTHOR]

Previous resting-state functional magnetic resonance imaging (rs-fMRI) studies have widely explored the temporal connection changes in the human brain following long-term sleep deprivation (SD). However, the frequency-specific topological properties of sleep-deprived functional networks remain virtually unclear. In this study, thirty-seven healthy male subjects underwent resting-state fMRI during rested wakefulness (RW) and after 36 hours of SD, and we examined frequency-specific spectral connection changes (0.01–0.08 Hz, interval = 0.01 Hz) caused by SD. First, we conducted a multivariate pattern analysis combining linear SVM classifiers with a robust feature selection algorithm, and the results revealed that accuracies of 74.29%-84.29% could be achieved in the classification between RW and SD states in leave-one-out cross-validation at different frequency bands, moreover, the spectral connection at the lowest and highest frequency bands exhibited higher discriminative power. Connection involving the cingulo-opercular network increased most, while connection involving the default-mode network decreased most following SD. Then we performed a graph-theoretic analysis and observed reduced low-frequency modularity and high-frequency global efficiency in the SD state. Moreover, hub regions, which were primarily situated in the cerebellum and the cingulo-opercular network after SD, exhibited high discriminative power in the aforementioned classification consistently. The findings may indicate the frequency-dependent effects of SD on the functional network topology and its efficiency of information exchange, providing new insights into the impact of SD on the human brain.

Abstract Background Previous studies on cancer of unknown primary (CUP) mainly focus on treatment and prognosis in western populations and lacked clinical evaluation of different IHC markers, so this study aimed to evaluate characteristics of CUP and recommend a diagnostic strategy from a single center in China. Methods and results Data of 625 patients with CUP were retrospectively collected and reviewed. The patients ranged in age from 20 to 91 years, with a female-to-male ratio of 1.3:1. The predominant histological type was poor or undifferentiated adenocarcinomas (308; 49.3%). The results of Canhelp-Origin molecular testing for the identification of the tissue of origin in 262 of 369 patients (71.0%) were considered predictable (similarity score > 45), with the most common predicted primary tumor site being the breast (57, 21.8%). Unpredictable molecular results correlated with more aggressive clinical parameters and poor survival. Thee positivity rates of several targeted antibodies (GATA3, GCDFP15, TTF1, Napsin A, and PAX8), based on the clinically predicted site, were lower than those reported for the corresponding primary tumors. Nonetheless, TRPS1 and INSM1 were reliable markers of predicted breast carcinoma (75.0%) and neuroendocrine tumors (83.3%), respectively. P16 expression, as well as HPV and EBER testing contributed significantly to the diagnosis of squamous cell carcinomas. Survival analysis revealed that older ages (> 57), ≥ 3 metastatic sites, non-squamous cell carcinomas, bone/liver/lung metastases, unpredictable molecular results, and palliative treatment correlated with poor overall survival. Conclusions We recommend a CUP diagnostic strategy involving the use of targeted antibody panels as per histological findings that is potentially applicable in clinical practice. The markers TRPS1, INSM1, and P16 expression, as well as HPV and EBER testing are particularly valuable in this aspect. Molecular testing is also predictive of survival rates.

Summary: The cognitive and behavioral functions of the human brain are supported by its frequency multiplexing mechanism. However, there is limited understanding of the dynamics of the functional network topology. This study aims to investigate the frequency-specific topology of the functional human brain using 7T rs-fMRI data. Frequency-specific parcellations were first performed, revealing frequency-dependent dynamics within the frontoparietal control, parietal memory, and visual networks. An intrinsic functional atlas containing 456 parcels was proposed and validated using stereo-EEG. Graph theory analysis suggested that, in addition to the task-positive vs. task-negative organization observed in static networks, there was a cognitive control system additionally from a frequency perspective. The reproducibility and plausibility of the identified hub sets were confirmed through 3T fMRI analysis, and their artificial removal had distinct effects on network topology. These results indicate a more intricate and subtle dynamics of the functional human brain and emphasize the significance of accurate topography.

Abstract Purpose Metastatic ocular and orbital melanomas are extremely rare. The clinical characteristics and standard treatments for these patients are not fully established. Materials and Methods We retrospectively analyzed patients with metastatic ocular and orbital melanoma from Fudan University Shanghai Cancer Center and Eye & ENT Hospital of Fudan University between January 2012 and May 2022. Results Overall, 51 patients with metastatic ocular and orbital melanoma were included. The most common primary sites were uvea (73%), followed by conjunctiva (22%), lacrimal sac (4%), and orbit (2%). Patients with uveal melanoma (UM) had a significantly younger age (48 vs. 68 years, p

Abstract Background Melanoma frequently harbors BRAF, NRAS, or KIT mutations which influence both tumor development and treatment strategies. For example, it is still controversial whether adjuvant anti‐PD‐1 monotherapy or BRAF/MEK inhibitors may better improve the survival for resected BRAF‐mutant melanoma. Furthermore, outcomes for melanoma with NRAS and KIT mutation receiving adjuvant immunotherapy remain unclear. Methods One hundred seventy‐four stage III melanoma patients who underwent radical surgery in Fudan University Shanghai Cancer Center (FUSCC) during January 2017 to December 2021 were included in this real‐world study. Patients were followed up until death or May 30th, 2022. Pearson's chi‐squared test or Fisher's exact test was performed for univariable analysis of the different category groups. Log‐rank analysis was used to identify the prognostic factors for disease‐free survival (DFS). Results There were 41 (23.6%) patients with BRAF mutation, 31 (17.8%) with NRAS mutation, 17 (9.8%) with KIT mutation, and 85 (48.9%) wild‐type patients without either genomic alteration of those three genes. Most ( n = 118, 67.8%) of them were acral melanoma, while 45 (25.9%) were cutaneous subtype, and 11 were (6.3%) primary unknown. Among them, 115 (66.1%) patients received pembrolizumab or toripalimab monotherapy as adjuvant therapy; 22 (12.6%) patients received high‐dose interferon (IFN), and 37 (21.3%) patients were just for observation. There was no statistical difference in clinicopathologic factors between anti‐PD‐1 group and IFN/OBS group. Of all the enrolled patients, anti‐PD‐1 group had a better DFS than IFN/OBS group ( p = 0.039). In anti‐PD‐1 group, patients with BRAF or NRAS mutations had poorer DFS than wild‐type group. No survival difference was found among patients harboring different gene mutations in IFN/OBS group. In wild‐type patients, anti‐PD‐1 group had a better DFS than IFN/OBS group ( p = 0.003), while no survival benefits were found for patients with BRAF, NRAS, or KIT mutations. Conclusion Although anti‐PD‐1 adjuvant therapy provides a better DFS in the general population and in wild‐type patients, patients with BRAF, KIT or, especially, NRAS mutation may not benefit further from immunotherapy than conventional IFN treatment or observation.

Abstract Background BRAF V600 mutation is the most common oncogenic alternation in melanoma and is visible in around 50% of cutaneous and 10%–15% of acral or mucosal subtypes. Currently, immunotherapy with anti‐PD‐1 blockade and dual‐targeted therapy with Dabrafenib plus trametinib (D + T) target therapy have been approved as adjuvant therapies for Stage III melanoma with BRAF V600 mutation. According to their phase III clinical trials, 3‐year recurrence‐free survival (RFS) is around 60% for both types of treatment. However, early disease control was slightly more effective with targeted therapy than immunotherapy. With different drug approval deadlines in China, anti‐PD1 monotherapy, D + T combination, and Vemurafenib (V) monotherapy have all been used in real clinical practice as adjuvant settings for stage III BRAF‐mut melanoma in recent years. We conducted this retrospective study to evaluate the efficacy of different treatments in the Chinese melanoma population. Methods Patients who underwent radical surgery and were diagnosed as Stage III melanoma harboring BRAF V600 mutation by pathological report were retrospectively identified at Fudan University Shanghai Cancer Center from January 2017 to December 2021. Patients with mucosal melanoma, or with follow‐up of

Radiation resistance has always been one of the main obstacles to tumor radiotherapy. Therefore, understanding the mechanisms underlying radiotherapy resistance is a focus of research. In this study, we induced two radiation-resistant cell lines to mimic the radiation resistance of NSCLC and investigated the mechanisms of radiotherapy resistance. Cell radiosensitivity was analyzed by single-cell gel electrophoresis, colony formation and tumor sphere formation assays. A wound healing assay was used to analyze cell migration. Western blotting and siRNA were used to identify the potential mechanism. In animal model experiments, xenograft tumors were used to verify the difference between radiotherapy-resistant and nonresistant NSCLC models after radiotherapy. Our results showed that NSCLC radiation-resistant cells exhibited more radioresistance and migratory abilities under low-dose irradiation. The expression of LIMK2 and p-CFL1 were upregulated in NSCLC radiation-resistant cells. Knockdown of LIMK2 significantly enhanced the radiosensitivity of NSCLC-resistant cells. In vivo, low-dose radiotherapy suppressed tumor growth, induced apoptosis and upregulated the expression of LIMK2 in xenograft tumors. However, radiotherapy had little effect on the NSCLC radiation resistance model. In conclusion, NSCLC radiation-resistant cells exhibit more radioresistance and migratory ability under low-dose irradiation. Strikingly, knockdown of LIMK2 enhanced the radiosensitivity of NSCLC-resistant cells.

Abstract Background Pucotenlimab is a novel recombinant humanized anti-PD-1 (Programmed death-1) monoclonal antibody, which belongs to the human IgG4/kappa subtype, and can selectively block the binding of PD-1 with its ligands PD-L1 and PD-L2. Methods In this phase 2 trial, patients with locally advanced or metastatic melanoma who had failed conventional treatment (chemotherapy, targeted therapy, interferon, IL-2, et al.) were recruited. The patients were administrated with Pucotenlimab of 3 mg/kg every 3 weeks until disease progression, intolerable toxicity, or treatment discontinuation for any other reasons. The primary endpoint was the overall response rate (ORR). The secondary endpoints were disease control rate (DCR), duration of response (DOR), progression-free survival (PFS), overall survival (OS), and toxicity. Results One-hundred and nineteen patients were enrolled and followed up for 19.32 (ranging from 15.901 to 24.608) months by the cutoff date of July 30th, 2021. The ORR was 20.17% (24/119, 95% CI, 13.370%-28.506%) based on both independent review committee (IRC) and the investigator’s assessment per RECIST v1.1. The median PFS were 2.89 (95% CI, 2.037–4.074) months and 2.46 (95% CI, 2.004–4.008) months based on IRC and investigator’s assessment, respectively, per RECIST v1.1. The median OS was 16.59 (95% CI, 13.963–26.973) months. Treatment-related adverse events (TRAEs) occurred in 77.3% (92/119) of the patients. The incidence of Grade ≥ 3 TRAEs was 15.1% (18/119). In addition, none of the patients died because of TRAEs. As for biomarker analysis, Eotaxin (CCL11) and MCP-1 (CCL2) were related to treatment response, while TNF-α and VEGF were related to treatment failure. Conclusions Pucotenlimab as a ≥ 2nd line therapy showed promising efficacy and tolerable toxicity for patients with locally advanced or metastatic melanoma. Trial registration Clinicaltrials.gov Identifier: NCT04749485 (registered retrospectively on 11/02/2021).

Background: Emotions are thought to be related to distinct patterns of neural oscillations, but the interactions among multi-frequency neural oscillations during different emotional states lack full exploration. Phase-amplitude coupling is a promising tool for understanding the complexity of the neurophysiological system, thereby playing a crucial role in revealing the physiological mechanisms underlying emotional electroencephalogram (EEG). However, the non-sinusoidal characteristics of EEG lead to the non-uniform distribution of phase angles, which could potentially affect the analysis of phase-amplitude coupling. Removing phase clustering bias (PCB) can uniform the distribution of phase angles, but the effect of this approach is unknown on emotional EEG phase-amplitude coupling. This study aims to explore the effect of PCB on cross-frequency phase-amplitude coupling for emotional EEG. Methods: The technique of removing PCB was implemented on a publicly accessible emotional EEG dataset to calculate debiased phase-amplitude coupling. Statistical analysis and classification were conducted to compare the difference in emotional EEG phase-amplitude coupling prior to and post the removal of PCB. Results: Emotional EEG phase-amplitude coupling values are overestimated due to PCB. Removing PCB enhances the difference in coupling strength between fear and happy emotions in the frontal lobe. Comparable emotion recognition performance was achieved with fewer features after removing PCB. Conclusions: These findings suggest that removing PCB enhances the difference in emotional EEG phase-amplitude coupling patterns and generates features that contain more emotional information. Removing PCB may be advantageous for analyzing emotional EEG phase-amplitude coupling and recognizing human emotions.

IntroductionEmotion recognition plays a crucial role in affective computing. Recent studies have demonstrated that the fuzzy boundaries among negative emotions make recognition difficult. However, to the best of our knowledge, no formal study has been conducted thus far to explore the effects of increased negative emotion categories on emotion recognition.MethodsA dataset of three sessions containing consistent non-negative emotions and increased types of negative emotions was designed and built which consisted the electroencephalogram (EEG) and the electrocardiogram (ECG) recording of 45 participants.ResultsThe results revealed that as negative emotion categories increased, the recognition rates decreased by more than 9%. Further analysis depicted that the discriminative features gradually reduced with an increase in the negative emotion types, particularly in the θ, α, and β frequency bands.DiscussionThis study provided new insight into the balance of emotion-inducing stimuli materials.

Background2’,5’-oligoadenylate synthetase 1 (OAS1), has been reported as a tumor driver gene in breast carcinoma and pancreatic carcinoma. However, the role of OAS1 in most tumors has not been reported.MethodsThe original data of 35 tumor types were down load from the TCGA (The Cancer Genome Atlas) database and Human Protein Atlas (HPA) database. TIMER2, Kmplot, UALCAN, and TISIDB tools were used to investigate the expression and function of OAS1, and the role of OAS1 in prognosis, diagnostic value, and immune characteristics of pan-cancer. LUAD and PRAD cell lines, A549, H1975, PC-3 and C4-2 were utilized to perform cell function tests.ResultsOAS1 expression was up-regulated in 12 tumor types and down-regulated in 2 tumor types. High OAS1 expression was correlated with poor prognosis in 6 tumor types, while high OAS1 expression was correlated with good prognosis in 2 tumor types. OAS1 was correlated with molecular subtypes in 8 tumor types and immune subtypes in 12 tumor types. OAS1 was positively associated with the expression of numerous immune checkpoint genes and tumor mutational burden (TMB). OAS1 had potential diagnostic value in 15 tumor types. Silence of OAS1 significantly inhibited the cell proliferation ability, and promoted G2/M cell cycle arrest of LUAD and PRAD cells. Meanwhile, silence of OAS1 enhanced cisplatin-induced apoptosis of LUAD and PRAD cells, but weakened cell migration.ConclusionThis pan-cancer study suggests that OAS1can be used as a molecular biomarker for prognosis in pan-cancer and may play an important role in tumor immune response.

Abstract Background HL-085 is a selective, orally administered MEK1/2 inhibitor. We aimed to evaluate the safety and efficacy of HL-085 in patients with advanced melanoma harboring NRAS mutations. Methods This was a multicenter phase 1 study. HL-085 was administered twice daily in a standard 3 + 3 dose-escalation design (10 dose cohorts; 0.5–18 mg twice daily), followed by dose expansion at the recommended phase II dose (RP2D). The primary endpoints included tolerability, dose-limiting toxicity (DLT), maximum tolerated dose (MTD) and RP2D. Results Between September 13, 2017, and January 18, 2021, 42 patients were enrolled (dose escalation phase: n = 30; dose expansion phase: n = 12). No DLT was reported during dose escalation and MTD was not reached with HL-085 doses up to 18 mg twice daily. The RP2D was 12 mg twice daily. The most common all-grade drug-related adverse events (AEs) across all dose levels were rash (61.9%), increased creatine phosphokinase (CK, 59.5%), face edema (50.0%), increased aspartate aminotransferase (47.6%), peripheral edema (40.5%), diarrhea (33.3%), alanine aminotransferase (33.3%), and paronychia (19.0%), most of which were grade 1 and 2. Most frequency of grade ≥ 3 AEs were CK (14.2%), asthenia (7.1%), peripheral edema (4.8%), and acneiform dermatitis (4.8%). In the cohort of 12 mg twice daily dose (15 patients), confirmed objective response rate was 26.7%; disease control rate was 86.7%; median duration of response was 2.9 months; median progression-free survival was 3.6 months. Conclusions The HL-085 showed acceptable tolerability and substantial clinical activity in patients with advanced melanoma harboring NRAS mutations. Trial registration Trial registration ClinicalTrials.gov number: NCT03973151.

Background: Affective computing has gained increasing attention in the area of the human-computer interface where electroencephalography (EEG)-based emotion recognition occupies an important position. Nevertheless, the diversity of emotions and the complexity of EEG signals result in unexplored relationships between emotion and multichannel EEG signal frequency, as well as spatial and temporal information. Methods: Audio-video stimulus materials were used that elicited four types of emotions (sad, fearful, happy, neutral) in 32 male and female subjects (age 21–42 years) while collecting EEG signals. We developed a multidimensional analysis framework using a fusion of phase-locking value (PLV), microstates, and power spectral densities (PSDs) of EEG features to improve emotion recognition. Results: An increasing trend of PSDs was observed as emotional valence increased, and connections in the prefrontal, temporal, and occipital lobes in high-frequency bands showed more differentiation between emotions. Transition probability between microstates was likely related to emotional valence. The average cross-subject classification accuracy of features fused by Discriminant Correlation Analysis achieved 64.69%, higher than that of single mode and direct-concatenated features, with an increase of more than 7%. Conclusions: Different types of EEG features have complementary properties in emotion recognition, and combining EEG data from three types of features in a correlated way, improves the performance of emotion classification.