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The fruits of Aronia melanocarpa (Michx.) Elliot have high nutritional value and medicinal value. This fruit is rich in flavonoids, anthocyanins and anthocyanins and presents good biological activity and pharmacological effects in antioxidant, anti-aging, anti-inflammatory, antibacterial, hypolipidemic, hypoglycemic, anti-cancer, antidepressant, anti-fatigue, etc. It is necessary for the development of this fruit material to explore more chemical constituents. The Global Natural Products Social (GNPS) molecular network based on mass spectrometry technology can establish an association network with the similarity and fingerprint characteristics of similar components, and quickly analyze unknown components in natural products. In this study, ultra-high performance liquid chromatography Orbitrap tandem mass spectrometry (UPLC-Qrbitrap-MS/MS) combined GNPS molecular network was developed for the rapid analysis of constituents in fruits of Aronia melanocarpa (Michx.) Elliot. Under the positive and negative ion modes, the high resolution mass data were acquired. The multiple tandem mass and fragmentation rules were summarized. The molecular network was established based on the similarity of characteristic fragmentation. According to the retention time, accurate molecular mass and fragment ions of references, the constituents in the fruits were identified and deduced. The molecular network of anthocyanins, proanthocyanidins, flavonoids and organic acids were built. Totally 42 compounds are identified in the fruits of Aronia melanocarpa (Michx.) Elliot, including 20 anthocyanins, 3 proanthocyanidins, 12 flavonoids and 7 organic acids. It was concluded that UPLC-Qrbitrap-MS/MS combined with GNPS molecular network can be used to rapidly and accurately identify the constituents in fruits of Aronia melanocarpa (Michx.) Elliot. This results provides a basis for the research of efficacy substances, and the development and utilization of Aronia melanocarpa (Michx.) Elliot fruits.

Abstract Undifferentiated pleomorphic sarcoma (UPS) and related tumors are the most common type of soft tissue sarcoma. However, this spectrum of tumors has different etiologies with varying rates of metastasis and survival. Two dermal-based neoplasms in this class of pleomorphic sarcomas, atypical fibroxanthoma (AFX) and pleomorphic dermal sarcoma (PDS), are challenging to differentiate at initial biopsy but vary significantly in prognosis. We performed single-cell transcriptomics on five AFX and PDS biopsy specimens as well as both single-cell and spatial transcriptomics on one PDS excision specimen to better characterize these tumors. The top differential genes between AFX and PDS were predictive of overall survival in 17 other cancers included in the Human Protein Atlas. Of these genes, COL6A3 and BGN predicted overall survival and metastasis-free survival in independent cohorts of 46 and 38 UPS tumors, respectively. COL6A3 was most predictive of overall survival in UPS patients and outperformed an established sarcoma prognostic gene panel at predicting metastasis in UPS.

Abstract To address the limitations of traditional coal pillar design methods in engineering practice for deep retreat mining roadways, this research focuses on the retreat mining face at the Pinggang Coal Mine in Heilongjiang Province. Combining mechanical experiments, theoretical calculations, numerical simulations, and field tests, this study calculates the ultimate equilibrium size of coal pillars. It also analyses the stress transfer and surrounding rock plastic evolution characteristics under different coal pillar sizes in deep retreat mining faces and carries out a field engineering application. After the factors mentioned above are analysed, the appropriate size for coal pillars that align with the current state of the surrounding rock in deep mines is established. The research findings indicate a correlation between the theoretically calculated ultimate stability range of coal pillars and the numerical simulation results on coal pillar size, suggesting a close consistency. The determined ultimate equilibrium coal pillar size falls within the range of 7.12–8.22 m. When the coal pillar size changes, the stress around the deep retreat mining roadway is transferred, and the plastic state of the surrounding rock also gradually changes. When the coal pillar width is 3–6 m, a stress concentration appears in the coal body, and the coal pillar has a lower bearing capacity and is prone to plastic failure. When the width is 7–8 m, the stress concentration gradually shifts to the sides of the coal pillar, enhancing its control over the roof, and a loosening zone forms in the surrounding rock. When the coal pillar width reaches 9–10 m, the stress concentration shifts completely from the coal body side to the coal pillar side, and the bearing performance of the coal pillar no longer improves. Plastic failure of the coal pillar disappears, but a greater degree of stress concentration occurs on the side of the coal pillar. The optimal size of the coal pillar is determined to be 7–8 m. Verified by the coal pillar retention engineering application at the Pinggang Coal Mine, when an 8 m coal pillar is retained, a peak stress of 27.54 MPa appears 12 m from the roadway, and the maximum deformations of both sides, the roof, and the coal pillar side are within the ideal range, indicating a relatively good overall state of the roadway. These research results provide new theoretical and practical guidance for minimizing coal loss and eliminating the safety hazards posed by unreasonable coal pillar retention at the Pinggang Coal Mine and offer a reference for the reasonable retention of coal pillars under similar conditions in the Northeast China mining area, thereby promoting the sustainable development of the coal industry.

Abstract Numerous studies have suggested that the hemoglobin-to-red blood cell distribution width ratio (HRR) is associated with the onset, progression, and prognosis of various diseases. However, to the best of our knowledge, no research has conducted statistical analyses to determine the association between HRR and stroke. This cross-sectional study was conducted among adults with complete data on hemoglobin-red cell distribution width ratio (HRR) and stroke from the 2005–2018 National Health and Nutrition Examination Survey (NHANES). HRR was calculated by dividing hemoglobin (HGB) in grams per deciliter (g/dL) by the red blood cell distribution width (RDW). Weighted multivariable logistic regression and generalized additive models were employed to investigate the independent and nonlinear relationships between HRR and stroke. Threshold effects were assessed using two-piece linear regression models. Additionally, subgroup analyses and interaction tests were performed. A total of 36,215 participants were included, with 2.92% classified as stroke patients. The prevalence of stroke decreased across increasing tertiles of HRR (Q1: 5.07%; Q2: 2.63%; Q3: 1.69%; P 30. Using a two-piece linear regression model, a threshold effect was identified at a BMI of 30 (K = 1.16). To the left of this breakpoint, there was a negative association between HRR and stroke (OR = 0.55, 95% CI: 0.27–0.97), whereas no such association was detected to the right of the breakpoint (OR = 6.49, 95% CI: 0.75–56.11). HRR is negatively associated with the likelihood of stroke, with a lower risk of stroke in individuals with higher HRR levels.

Abstract Background Mesenchymal stem cells (MSCs) are widely dispersed in vivo and are isolated from several tissues, including bone marrow, heart, body fluids, skin, and perinatal tissues. Bone marrow MSCs have a multidirectional differentiation potential, which can be induced to differentiate the medium in a specific direction or by adding specific regulatory factors. MSCs repair damaged tissues through lineage differentiation, and the ex vivo transplantation of bone marrow MSCs can heal injured sites. MSCs have different propensities for lineage differentiation and pathological evolution for different diseases, which are crucial in disease progression. In this study, we describe various lineage analysis methods to explore lineage ontology in vitro and in vivo, elucidate the impact of MSC lineage differentiation on diseases, advance our understanding of the role of MSC differentiation in physiological and pathological states, and explore new targets and ideas associated with disease diagnosis and treatment.

Abstract Background The study focuses on the effect of temperature and relative humidity on hospitalization for acute lower respiratory tract infections (LRTI) in children, respectively. Methods In this study, the Distributed Lag Nonlinear Model (DLNM) based on quasi-Poisson distribution was used to investigate the effect of temperature and relative humidity on LRTI hospitalization in children, and subgroup analyses were conducted to identify sensitive populations by gender and age. Results A total of 43,951 children were hospitalized for LRTI from 1 January 2014 to 31 December 2019 in Lanzhou. The mean temperature during the study period was 11.34 °C and the mean relative humidity was 51.03%. With reference to the median temperature of 12.7 °C during the study period, both low (-4.1 °C) and high (25.43 °C) temperature had a detrimental effect on LRTI hospitalization, and the maximum effect was reached at lag0-10 and lag0-9, respectively, with RR values of 1.645 (95%CI: 1.533, 1.764) and 1.098 (95%CI: 1.018, 1.184). With a reference to the median relative humidity of 51.17% during the study period, both low relative humidity (26.71%) and high relative humidity (76.70%, P95) had a detrimental effect on LRTI hospitalization, and the maximum effect was reached at lag0-21 and lag21, respectively, with RR values of 1.235 (95% CI: 1.163, 1.311) and 1.044 (95% CI: 1.036, 1.051). The results of subgroup analyses showed that changes in meteorological factors had a stronger effect on Female and children aged 5–14 years. Conclusions The meteorological factors all have different degrees of influence on LRTI hospitalization in children. Girls and the children aged 5–14 years are more sensitive. Attention to these meteorological risks can inform targeted interventions.

Walnut oil (WO), known for abundant polyunsaturated fatty acids and an array of bioactive substances such as tocopherols, phytosterols, squalene, melatonin, and polyphenols, which is endowed with numerous health advantages. The primary objective of this research was to ascertain the impact of WO on cognitive deficits in learning and memory impairment mice caused by scopolamine (SCOP). The Morris water maze and the step-down avoidance test were utilized to assess the memory and learning capabilities. WO notably counteracted the detrimental effects of SCOP on learning and memory in the Morris water maze, as indicated by a reduction in escape latency and swimming distance. Likewise, WO administration led to a notably reduced number of errors in training trial and an increased latency in testing trial when compared to the SCOP group in the step-down avoidance test,. Moreover, WO activated the cholinergic system of the brain by upregulating choline acetyltransferase activity and reducing acetylcholinesterase activity. These results suggest that WO has the potential to protect against memory decline in mice, offering a promising strategy for the prevention of memory-related disorders.

Abstract Hypertrophic scars arise from aberrant wound healing and can lead to functional and aesthetic impairments. One of the common interventions for treating hypertrophic scars is fractional carbon dioxide (CO2) laser, which employs narrow laser beams to stimulate dermal collagen deposition. Recent studies and reports have suggested that combining laser therapy with other interventions such as botulinum toxin type A (BTX-A) and topical growth factors may enhance treatment outcomes. Here, we examine the efficacy and safety of a sequential combination of BTX-A, fractional CO2 laser, and topical growth factors, referred to as combined therapy, for treating hypertrophic scars compared with only using fractional CO2 laser and topical growth factors, referred to as monotherapy. Our retrospective study includes 128 patients with hypertrophic scars (56 underwent monotherapy and 72 underwent combined therapy), which were followed-up for up to 15 months after the initiation of treatment to collect demographic and clinical data. Our analysis showed that the combined therapy significantly outperformed monotherapy in improving Vancouver scar scale scores (P

Abstract Acute severe stress may induce fear memory and anxiety. Their mechanisms are expectedly revealed to explore therapeutic strategies. We have investigated the recruitment of associative memory cells that encode stress signals to cause fear memory and anxiety by multidisciplinary approaches. In addition to fear memory and anxiety, the social stress by the resident/intruder paradigm leads to synapse interconnections between somatosensory S1-Tr and auditory cortical neurons in intruder mice. These S1-Tr cortical neurons become to receive convergent synapse innervations newly from the auditory cortex and innately from the thalamus as well as encode the stress signals including battle sound and somatic pain, i.e., associative memory neurons. Neuroligin-3 mRNA knockdown in the S1-Tr cortex precludes the recruitment of associative memory neurons and the onset of fear memory and anxiety. The stress-induced recruitment of associative memory cells in sensory cortices for stress-relevant fear memory and anxiety is based on neuroligin-3-mediated new synapse formation.

Objective: To evaluate the immunomodulatory function and safety of compound preparation containing Ganoderma lucidum polysaccharides. Methods: According to the Technical Standards for Testing and Assessment of Health Food (2003 Edition), the immunomodulatory function of compound preparation containing Ganoderma lucidum polysaccharides was evaluated comprehensively from cellular immunity, humoral immunity and non-specific immunity by measuring the ability of lymphocyte proliferation, degree of ear swelling, number of hemolytic plaques, phagocytic percentage, phagocytic index and natural killer (NK) cells activity in normal mice. Its safety was evaluated comprehensively by acute oral toxicity test in mice, Ames test and 30 d feeding test in rats. Results: In cellular immunity test, the tested substance had no significant effect on lymphocyte proliferation induced by concanavalin A and degree of ear swelling (P>0.05). In the humoral immunity test, the low dose group (0.17 g/kg), the middle dose group (0.33 g/kg) and the high dose group (1.00 g/kg) could increase the level of antibody-producing cells by 10.98%, 12.08%, 17.63% (P0.05), and no obvious pathological changes were found by histological examination. Conclusion: Compound preparation containing Ganoderma lucidum polysaccharides had a positive effect on immunomodulatory function in mice, and it had a good safety as a health food.

Creep, as a long-term deformation characteristic of shotcrete, significantly influences the load-bearing performance and durability of tunnel support structures. This study conducted creep tests on shotcrete under varying stress levels. The results reveal that shotcrete exhibits linear creep response within the stress range of 30%–40%, while the critical stress range for nonlinear creep response occurs between 40% and 50%. Employing SEM-EDS and XRD analysis methods, the impact of accelerator on the microstructure evolution and creep mechanism of shotcrete is explored. The accelerator accelerates the hydration of C3S, promoting the generation of AFt and C–S–H gel, leading to rapid solidification of the matrix and enhanced early strength. With the consumption of SO42− ions, AFt gradually transforms into AFm, resulting in increased matrix porosity. This phenomenon contributes to the reduced later-stage strength and substantial creep deformation of shotcrete. Based on experimental outcomes, this study evaluates the applicability of existing creep calculation models to shotcrete.

Significance: As the hardest material, diamond is widely used in various cutting and grinding tools. During the preparation process of diamond tools, thermal damage to diamonds is almost inevitable. The thermal damage to diamonds primarily includes graphitization, breakage, cracking, and chemical erosion. Graphitization of diamonds is a lattice transformation process of C atoms essentially, which requires sufficient energy to overcome the energy barrier. Consequently, during the preparation process of diamond tools, diamonds undergo varying degrees of graphitization due to high temperatures and catalyst elements. Breakage and cracking of diamonds primarily orginate from thermal mismatch between the diamond and the matrix metal, including its carbides, where carbides act as inducers of local residual stress, facilitating crack propagation. Chemical erosion of diamonds mainly refers to the process in which C atoms on the surface of diamonds react with active elements through diffusion during the sintering process, therefore deteriorating the diamonds. However, due to the poor wettability of diamonds, it often necessitates the addition of active elements such as Ti, Cr, V, etc., to react with diamonds and improve the holding force. Current suppression technologies for diamond thermal damage can be roughly divided into surface coating of diamonds, adjustment of matrix material properties, and optimization of forming technology. Progress: Diamond surface coating utilizes the unbonded atoms present on the diamond surface, which can react with certain elements at sufficiently high temperatures to form carbides, thereby enhancing the wettability between the matrix metal and the diamonds. Depending on the type of coating, it can generally be classified into metal and non-metal coatings. Metal coatings not only fill and repair defects in diamonds but also improve the bonding strength between the metal and diamonds. Common coating metals include Ni, Ti, W, Cr, and alloys are also selected as coating materials. For non-metal coatings, elements such as B and Si are typically chosen, as they can form carbide layers on the diamond surface, protect the diamond structure, reduce diamond oxidation, and prevent diamonds from being eroded and damaged by strong carbon elements in the matrix material. The choice of matrix material plays a crucial role in mitigating thermal damage to diamonds. Low-melting-point matrix materials can effectively reduce sintering temperature and inhibit the graphitization of diamonds consequently. Furthermore, incorporating appropriate active elements into the matrix material can enhance the interfacial strength between diamond and the matrix, thereby improving the performance of diamond tools. Currently, the modulation of matrix material properties is primarily focused on alloy optimization and composite material development. Alloy optimization aims to reduce diamond thermal damage by refining the alloy composition of the matrix material. Researchers have experimented with elements such as Si, Hf, and Zr, discovering that these elements can mitigate the erosion of diamonds by active elements and reduce diamond thermal damage. Additionally, amorphous Ni-based alloys, due to their low melting point and narrow melting range, have been used as brazing materials to enhance the performance of diamond tools. Composite material development seeks to improve mechanical properties while utilizing suitable reinforcing phases to absorb catalytic elements within the matrix, thereby reducing diamond graphitization. Additionally, reinforcing phases could optimize the diamond interface condition, leading to both increased interfacial strength and reduced diamond thermal damage. Molding technology significantly impacts the lifespan and performance of diamond tools, particularly through parameters such as molding temperature, soaking time, molding pressure, and atmosphere. Molding temperature and soaking time determine grain growth in the matrix, diamond thermal damage, and the interfacial growth between diamond and the matrix. Molding pressure affects the density of the matrix material, which in turn influences its mechanical properties. The atmosphere, typically vacuum or protective, must be carefully controlled, as even trace amounts of moisture or oxygen could lead to diamond oxidation, degrading tool performance and lifespan. Diamond tools are typically manufactured through methods such as hot-press sintering and brazing, while additive manufacturing is emerging as a promising direction in tool fabrication. Conclusions and Prospects: Future research to mitigate diamond thermal damage could focus on three main areas: theoretical analysis of diamond interfaces at the microscale, the establishment of a guidance system matching diamond tool matrix materials with service environments, and investigation of the mechanical behavior of diamonds interfaced during the molding process.

Almanac is an elegant design to help Global Navigation Satellite Systems (GNSS) signal acquisition, which has been adopted by all global satellite navigation systems. For the future low Earth orbit (LEO) navigation constellation, the almanac will be more critical due to larger constellation and signal Doppler variation, while the LEO orbit prediction is more challenging due to complex perturbation forces, especially atmospheric drag. This study introduces a novel 9-parameter almanac model for LEO constellation, leveraging the Empirical Mode Decomposition (EMD) method. Our innovative approach uniquely balances almanac accuracy and simplicity by considering the atmosphere drag effects, addressing a critical gap in existing models. The proposed almanac model is validated with four in-orbit LEO satellites at various altitudes. For the LEO with a 600 km orbit or lower, our model achieves a 50% improvement in 23-day orbit prediction accuracy compared to the classical GPS almanac model. This significant enhancement extends to visibility prediction and signal acquisition performance. Our design limits the maximum elevation angle error to less than 1.5 degrees, efficiently excluding invisible satellites during LEO navigation signal acquisition. Furthermore, for visible satellite, the proposed LEO almanac reduces the signal frequency searching range by about 20 times during acquisition, with Doppler prediction errors better than 0.5 kHz/0.3 kHz for 95% of cases. These advancements represent a substantial leap in LEO navigation technology, offering improved efficiency and accuracy for future satellite systems.

Abstract Human actions are predominantly presented in 2D format in video surveillance scenarios, which hinders the accurate determination of action details not apparent in 2D data. Depth estimation can aid human action recognition tasks, enhancing accuracy with neural networks. However, reliance on images for depth estimation requires extensive computational resources and cannot utilise the connectivity between human body structures. Besides, the depth information may not accurately reflect actual depth ranges, necessitating improved reliability. Therefore, a 2D human skeleton action recognition method with spatial constraints (2D‐SCHAR) is introduced. 2D‐SCHAR employs graph convolution networks to process graph‐structured human action skeleton data comprising three parts: depth estimation, spatial transformation, and action recognition. The initial two components, which infer 3D information from 2D human skeleton actions and generate spatial transformation parameters to correct abnormal deviations in action data, support the latter in the model to enhance the accuracy of action recognition. The model is designed in an end‐to‐end, multitasking manner, allowing parameter sharing among these three components to boost performance. The experimental results validate the model's effectiveness and superiority in human skeleton action recognition.

The Land surface of the Sichuan Basin is characterized by complexity and diversity， with frequent occurrences of heavy rainfall.This study utilizes global reanalysis data from the U.S.National Centers for Environmental Prediction and various categories of land use data， including default land use data from the WRF model， MODIS （Moderate Resolution Imaging Spectroradiometer）， and USGS （United States Geological Survey）.Additionally， the 2015 LUCC2015 （Land use datasets in China 2015） datasets and the 2015 GLASS （Global Land Surface Satellite） land use datasets are incorporated.The WRF（Weather Research and Forecasting）model is used to simulate a heavy rainfall event in Sichuan Province.The impact of changes in land surface classification and variations in terrain height on heavy rainfall is discussed through four sets of land use experiments and two sets of terrain sensitivity experiments.The results indicate that the experiments involving different land use types have a significant impact on regions experiencing heavy precipitation.In comparison to the MODIS experiment， the precipitation distribution from the USGS experiment is more concentrated， with a larger coverage area for intense precipitation centers； the LUCC2015 experiment results in a reduction in rainfall intensity in the northeastern part of the Sichuan Basin， accompanied by a more concentrated precipitation distribution； the GLASS experiment simulation， characterized by a relatively uniform land use， results in a reduction in the intensity of both intense precipitation centers.Additionally， the precipitation centers in the northeastern part of Sichuan shift southward.Various land use types also exert influence on near-surface meteorological parameter fields.Through a comprehensive analysis of the various land use experiments， it is evident that a reduction in urban built-up areas results in a decrease in 2 m temperature by 0.5 to 1 ℃； the reduction in vegetation coverage results in an increase in 2 m temperature and an enhancement of 10 m wind speed； the decrease in surface roughness leads to a significant enhancement in 10 m wind speed， with a magnitude of change ranging from 2 to 4 m·s-1.Compared to the default land use types in WRF， the simulated results under the underlying surface types in the LUCC2015 experiment are better.The topography exerts a pronounced influence on heavy rainfall.Following the reduction in elevation of the western mountainous region in the basin， the absence of mountain barriers allows for a more abundant presence of lower-level water vapor and energy.Consequently， moisture and energy can be transported to more northern regions of Sichuan.With the reduction in elevation of the terrain， the low-level airflow intensifies convergence ahead of the mountains， triggering stronger upward motion of air and resulting in enhanced precipitation intensity.This phenomenon leads to a westward shift in the precipitation location and a more concentrated coverage of rainfall.Conversely， with the uplift of the terrain， the mountainous barrier impedes the entry of warm and moist airflow from the south.As a result， energy and moisture become more dispersed， causing a reduction in airflow convergence in the western and eastern parts of the basin.The weakening of low-level airflow ascent leads to a decrease in precipitation intensity and a more dispersed distribution of rainfall.

The Qinghai-Xizang Plateau （QXP） is an important herbage producing area， ecological barrier and water conservation area， the vegetation ecological process on which can directly affect the changes of China and even East Asia.With global warming， the phenological period of vegetation on the QXP is constantly changing， affecting climate and ecosystem through carbon cycle and hydrothermal cycle， etc.The study of phenological change and its influencing factors has become a key issue， and the construction of models that can realize future phenological prediction is of great scientific significance.In this paper， based on the Normalized Difference Vegetation Index acquired by satellites during 2000 -2020 （MODIS NDVI）， the dynamic threshold method was used to extract the start of growing season （SOS） on the QXP， and its spatiotemporal variation was analyzed in combination with vegetation types， so as to construct multiple phenological models of SOS， air temperature and soil moisture， exploring the hydrothermal conditions required for different regions and types of vegetation to start growing.The results showed that： （1） From 2000 to 2020， the overall SOS advance trend of the QXP was most significant in the eastern part of the region， where the SOS advance rate exceeded 10 d·（10a）-1.Coniferous forests， scrub， meadows， and alpine vegetation cover areas had a high percentage of SOS advance， and grasslands had about 50 % of slightly delayed areas.（2） The eastern and northern regions of the QXP showed an obvious warming and humidification trend.The average annual temperature rise rate was about 0.36 ℃·（10a）-1， and the average annual soil moisture increase rate was about 3.8×10-4 m3·m-3 （p

Abstract A light (GeV mass) long-lived (cτ around dozens of millimeters) CP-odd scalar can be readily predicted in new physics models. In this work we investigate the Higgs decay into such a light scalar plus a Z-boson and take the aligned two-Higgs-doublet model (2HDM) as an example. This light long-lived scalar, with the dominant decay to tau leptons, will fly over a distance from the production point and present a displaced vertex in an Inner Detector of a generally purposed experiment like ATLAS or CMS. In our study we focus on the LHC experiment and perform Monte Carlo simulations for the signal and backgrounds. We demonstrate some benchmark points for the aligned 2HDM and find the signal to be detectable when the luminosity is accumulated to 300 fb −1. So our study suggests an experimental search for this process in the ongoing LHC.

Abstract This study explores the reflection and dialog feedback of preservice teachers (PTs) in a one-semester chemistry teaching design and practice course with the aim of improving their situated and dynamic pedagogical content knowledge (PCK). Using a collective case study method, reflections and dialogs from 18 PTs across six teaching cycles were analyzed. The research results indicate that teaching reflection focuses on five themes: the diversity of student situations, the functionality of teaching contexts, the consistency of teaching content, the construction of teacher‒student dialog, and the progression of subject practice activities. The reflection of the PTs strengthened meaningful teaching content and corresponding specific skills, and effective dialog feedback provided external evaluation standards. The reflection prompted teachers to evaluate from multiple perspectives and levels and provided important insights to promote the development of situated and dynamic PCK. This study concludes with a discussion of the practical implications and potential for future research to develop a situated and dynamic PCK for PTs.

Abstract The objective of this research was to establish a rat model for cardiopulmonary bypass (CPB) with cardiac arrest and resuscitation that is both practical and economical and simulates clinical cardiac surgery. Concurrently, the study aimed to evaluate the myocardial protective effects conferred by histidine–tryptophan–ketoglutarate (HTK) cardioplegia. Thirty rats were randomly assigned to three groups: the histidine–tryptophan–ketoglutarate (HTK), 4:1 blood cardioplegia (BC) and del Nido cardioplegia (DN) groups. The cardiopulmonary bypass (CPB) procedure was implemented and sustained for a duration of one hour. Subsequent to the cessation of CPB, the rats were subjected to monitoring and observation for an additional two hours. Following this observation period, the heart and blood samples were procured for subsequent analysis. During CPB, the average hematocrit level was significantly below the typical physiological range (P

Abstract This study investigates the expressions of ADAM9, CDCP1 and t-PA in OSCC and their impacts on patient prognosis. Previous research has demonstrated the overexpression of ADAM9 and activation of plasminogen activator in OSCC, but CDCP1's role remains unexplored. While these biomolecules are known to contribute to lung cancer metastasis, their concurrent expressions in OSCC have not been thoroughly examined. Our aim is to assess the expressions of ADAM9, CDCP1, and t-PA in OSCC specimens, compare them with normal oral tissues, and explore their correlation with OSCC's clinicopathological features and patient survival outcomes.

Abstract The twin boundaries and inherent lattice strain of five-fold twin (5-FT) structures offer a promising and innovative approach to tune nanocrystal configurations and properties, enriching nanomaterial performance. However, a comprehensive understanding of the nonclassical growth models governing 5-FT nanocrystals remains elusive, largely due to the constraints of their small thermodynamically stable size and complex twin configurations. Here, we conducted in situ investigations to elucidate the atomic-scale mechanisms driving size-dependent and twin configuration-related aggregation phenomena between 5-FT and other nanoparticles at the atomic scale. Our results reveal that surface diffusion significantly shapes the morphology of aggregated nanoparticles, promoting the symmetrical formation of 5-FT, especially in smaller nanoparticles. Moreover, the inherent structural characteristics of 5-FT mitigate the dominance of surface diffusion in its morphological evolution, retarding the aggregation evolution process and fostering intricate twin structures. These findings contribute to advancing our capacity to manipulate the configuration of twinned particles, enabling more predictable synthesis of functional nanomaterials for advanced engineering applications.

Abstract Background The influence of the small Rho GTPase Rif (RHOF) on tumor growth, glycolysis, endothelial–mesenchymal transition (EMT), and the potential mechanism of RHOF in pancreatic cancer (PC) were explored. Methods RHOF expression in PC tissues and cells was assessed by qRT-PCR and western blotting. The viability, proliferation, apoptosis, migration, and invasion of PC cells were assessed using CCK-8, colony formation, EdU, flow cytometry, scratch, and Transwell assays. The expression of EMT- and glycolysis-related proteins was determined using western blotting. The potential mechanisms of action of RHOF in PC were identified using bioinformatic analysis. The effects of RHOF were assessed in vivo using a xenograft mouse model. Results PC cell proliferation, migration, and invasion are accelerated by RHOF overexpression, which inhibited apoptosis. RHOF overexpression promoted EMT and glycolysis as evidenced by a decrease in E-cadherin expression and an increase in N-cadherin, Vimentin, HK2, PKM2, and LDHA expression. Bioinformatic analysis indicated that RHOF activated EMT, glycolysis, and Myc targets and that c-Myc could bind to the PKM2 promoter. RHOF overexpression promotes the lactylation and nuclear translocation of Snail1. Silencing Snail1 reversed the promoting effects of RHOF and lactate on cell migration, invasion, and EMT. Moreover, in vivo tumor growth and EMT were inhibited by RHOF silencing. Conclusion RHOF plays an oncogenic role in PC. c-Myc is upregulated by RHOF and promotes PKM2 transcription. PKM2 further induces glycolysis, and the lactate produced by glycolysis causes the lactylation of Snail1, ultimately promoting EMT.

Abstract The D14 protein, an alpha/beta hydrolase, is a key receptor in the strigolactone (SL) signaling pathway. However, the response of VvD14 to SL signals and its role in grapevine root architecture formation remain unclear. This study demonstrated that VvD14c was highly expressed in grapevine tissues and fruit stages than other VvD14 isoforms. Application of GR24, an SL analog, enhanced the elongation and diameter of adventitious roots but inhibited the elongation and density of lateral roots (LRs) and increased VvD14c expression. Additionally, GR24 is nested within the VvD14c pocket and strongly bound to the VvD14c protein, with an affinity of 5.65 × 10−9 M. Furthermore, VvD14c interacted with grapevine MORE AXILLARY GROWTH 2 (VvMAX2) in a GR24-dependent manner. Overexpression of VvD14c in the d14 mutant and VvMAX2 in the max2 Arabidopsis mutant reversed the increased LR number and density, as well as primary root elongation. Conversely, homologous overexpression of VvD14c and VvMAX2 resulted in reduced LR number and density in grapevines. VvMAX2 directly interacted with LATERAL ORGAN BOUNDARY (VvLOB) and VvLBD19, thereby positively regulating LR density. These findings highlight the role of SLs in regulating grapevine root architecture, potentially via the VvD14c-VvMAX2-VvLOB/VvLBD19 module, providing new insights into the regulation of root growth and development in grapevines.

Abstract Background The role of histone methyltransferase SETDB1 in renal ischemia–reperfusion (I/R) injury has not been explored yet. This study aims to investigate the potential mechanism of SETDB1 in regulating renal I/R injury and its impact on mitochondrial damage and oxidative stress. Methods The in vivo model of renal I/R in mice and the in vitro model of hypoxia/reoxygenation (H/R) in human renal tubular epithelial cells (HK-2) were constructed to detect the expression of SETDB1. Next, the specific inhibitor (R,R)-59 and knockdown viruses were used to inhibit SETDB1 and verify its effects on mitochondrial damage and oxidative stress. Chromatin immunoprecipitation (ChIP) and coimmunoprecipitation (CoIP) were implemented to explore the in-depth mechanism of SETDB1 regulating renal I/R injury. Results The study found that SETDB1 had a regulatory role in mitochondrial damage and oxidative stress during renal I/R injury. Notably, SESN2 was identified as a target of SETDB1, and its expression was under the influence of SETDB1. Besides, SESN2 mediated the regulation of SETDB1 on renal I/R injury. Through deeper mechanistic studies, we uncovered that SETDB1 collaborates with heterochromatin HP1β, facilitating the labeling of H3K9me3 on the SESN2 promoter and impeding SESN2 expression. Conclusions The SETDB1/HP1β-SESN2 axis emerges as a potential therapeutic strategy for mitigating renal I/R injury.

Peptides are native binders involved in numerous physiological life procedures, such as cellular signaling, and serve as ready-made regulators of biochemical processes. Meanwhile, small molecules compose many drugs owing to their outstanding advantages of physiochemical properties and synthetic convenience. A novel field of research is converting peptides into small molecules, providing a convenient portable solution for drug design or peptidomic research. Endowing properties of peptides onto small molecules can evolutionarily combine the advantages of both moieties and improve the biological druggability of molecules. Herein, we present eight representative recent cases in this conversion and elaborate on the transformation process of each case. We discuss the innovative technological methods and research approaches involved, and analyze the applicability conditions of the approaches and methods in each case, guiding further modifications of peptides to small molecules. Finally, based on the aforementioned cases, we summarize a general procedure for peptide-to-small molecule modifications, listing the technological methods available for each transformation step and providing our insights on the applicable scenarios for these methods. This review aims to present the progress of peptide-to-small molecule modifications and propose our thoughts and perspectives for future research in this field.

Abstract Previous hospitality research typically focuses on consumers’ positive attitudes and intentions toward addressing an existing research gap in the literature on consumer attitude and behaviour in green hotel marketing. Those studies have frequently neglected to investigate the effects of negative attitudes and perspectives. This study aims to explore the relationships between seven indicators of perceived risk, familiarity, novelty, trust, attitude, subjective norm, perceived behavioural control, and intention to visit green hotels. A total of 606 questionnaires were collected and analysed using structural equation modelling. Results showed that perceived risk negatively influences trust, subjective norm, and perceived behavioural control. Familiarity positively influences perceived risk but negatively influences attitude. Novelty negatively influences perceived risk and attitude, while trust positively influences attitude and intention. Subjective norm positively influences attitude, perceived behavioural control, and intention, and attitude influences intention. This study provides an alternative negative factor perspective on green hotel visitation using a theoretically driven approach.

Abstract The controlled shock wave (CSW) fracturing is an effective method for enhancing permeability of coal seam to promote gas extraction. Based on Fick’s law, Darcy’s law, the ideal gas law and the Langmuir equation, a damage-seepage-deformation coupling mathematical model of CSW fracturing in coal seam combined with the maximum tensile stress and the Mohr-Coulomb criterion is established. This model is implemented into COMSOL Multiphysics to simulate the coal seam CSW fracturing and subsequent gas extraction. When the shock wave and isotropic in-situ stress are applied on the borehole wall, the coal damage zone is an annular shape, and the permeability in the damage zone increases sharply. The CSW can effectively increase the efficiency of gas extraction and reduce the gas pressure and gas content in coal seam. With the increase of CSW action times, the damage in coal mass reaches a threshold and tends to be stable after several shocks. The damage area and the gas extraction efficiency are positively correlated with the shock intensity. Under the anisotropic ground stress, the larger diversity of the stress in different directions is, the more obvious damage extension in the fractured coal along the maximum stress direction is. Ground stress can inhibit the extension of cracks in the CSW fractured coal seam. This inhibition effect becomes more obvious with the increase of in-situ stress. Parameters are substantiated of controlled shock wave impact on the coal seam, which ensures increased methane extraction from low-permeability reservoirs, are substantiated.

Abstract This study investigates whether duration of working hours affect residents’ preferences for the micro-features of Small Urban Green Spaces (SUGS), and explores differences across genders and visitation purposes. Little is known about this subject, yet it is crucial for creating more equitable green spaces. In phase 1, participants (n = 209; 30.9 ± 6.73 years, 59.3%male) were categorized by average daily working hours (0–8 h, 8–10 h, 10 h+), and rated 41 micro-feature images on their importance for visiting SUGS. Phase 2 included the top ten features ranked from phase 1, with participants (n = 256; 30.8 ± 5.12 years, 35.2% female) completing the Kano model survey to identify and explain the importance of features and different types of needs. Findings reveal a clear trend: extended work hours pivot resident preferences towards green space attributes promoting physical activity. For residents of 0–8 h valued aesthetic elements like sculptures and vegetation, while lighting became paramount for those with 8–10 h, and for those working over 10 h prioritized facilities for active engagement, such as playground equipment and slow runway. These distinctions provide valuable guidance for designing SUGS with diverse feature combinations that cater to the needs of residential areas with varying socio-economic backgrounds and occupational lifestyles, thereby enhancing urban livability.

The initial section of the Arctic Northeast Passage is located in the Yellow Sea and Bohai Sea of China. The severe weather types that may threaten the safety of shipping in this area are mainly strong winds and heavy precipitation. Among them the cold air gale accompanied by the cold wave process, as well as the disastrous weather such as strong wind and heavy precipitation caused by weather systems such as tropical cyclones and extratropical cyclones, have a great impact on shipping safety in this area. Based on the National Centers for Environmental Prediction (NCEP) global daily reanalysis data from 1991 to 2020, we analyze the energy propagation characteristics of the Rossby wave along the upper-level jet stream during the seaworthiness period (July to October) of the Arctic Northeast Passage and its impact on the weather in the initial section of the Arctic Northeast Passage, especially on heavy precipitation. The results are as follows. (1) The meridional wind along the 250 hPa westerly jet axis in the subtropical region of the Northern Hemisphere shows a zonal three-wave quasi-stationary Rossby wave pattern. (2) The atmospheric quasi-stationary Rossby wave source at 250 hPa is located in the Mediterranean region. The wave is excited here and propagates eastward along the jet stream. Although the wave energy is dissipated during the propagation process, continuous input of energy from the Mediterranean region maintains and strengthens the wave. (3) The absolute value of the correlation coefficient between the key area of the wave action flux divergence and the precipitation and wind speed in the initial section of the Arctic Northeast Passage is greater than 0.5. While the absolute value of the correlation coefficient between the key area wave action flux index and the precipitation and wind speed is close to 0.9, indicating a strong correlation, it shows that the energy of the Rossby wave is concentrated and strengthened when it propagates along the upper jet stream, significantly influencing the precipitation and wind speed in the initial section of the Northeast Passage of the Arctic, thus triggering disastrous weather such as heavy precipitation and strong winds. (4) When the Rossby wave disturbance is stronger, the downstream propagation energy is also stronger. The westerly jet is then strengthened, and the vertical upward motion is enhanced. This results in an abnormal increase in precipitation in the initial section of the Arctic Northeast Passage.

Abstract Background Fish gut microbiota undergo dynamic changes under the influence of many factors and play an important role in the nutrition, immunity and development in fish. Although common carp (Cyprinus carpio L.) is an economically important freshwater fish, there are few reports on its gut microbiota changes at different early developmental stages. In the present study, the gut microbiota of common carp during the early developmental stages and its correlation with the feed and pond water flora were studied using the Illumina MiSeq sequencing platform. Results The results showed that the gut microbiota of common carp underwent continuous and mild changes over the development process, and the pond water environment might provide bacterial resources and have a certain influence on the changes in the gut microbiota of common carp. However, host selection pressure played a more important role in shaping the gut microbiota. Although the gut microbiota was affected by many factors, the presence of core microbiota indicated that some bacterial species adapt to the gut microenvironment of common carp and played a role in its growth process. Conclusions The dynamic changes of gut microbiota of carp in early development stage were related to the feed, water environment and host selection. The results of this study provide a theoretical basis for healthy farming and disease prevention of common carp.

Abstract The aberrant acetylation of mitochondrial proteins is involved in the pathogenesis of multiple diseases including neurodegenerative diseases and cerebral ischemic injury. Previous studies have shown that depletion of mitochondrial NAD+, which is necessary for mitochondrial deacetylase activity, leads to decreased activity of mitochondrial deacetylase and thus causes hyperacetylation of mitochondrial proteins in ischemic brain tissues, which results in altered mitochondrial dynamics. However, it remains largely unknown about how mitochondrial dynamics-related protein Drp1 is acetylated in ischemic neuronal cells and brain tissues. Here, we showed that Drp1 and GCN5L1 expression was up-regulated in OGD-treated neuronal cells and ischemic brain tissues induced by dMCAO, accompanied by the increased mitochondrial fission, mtROS accumulation, and cell apoptosis. Further, we confirmed that ischemia/hypoxia promoted Drp1 interaction with GCN5L1 in neuronal cells and brain tissues. GCN5L1 knockdown attenuated, while its overexpression enhanced Drp1 acetylation and mitochondrial fission, indicating that GCN5L1 plays a crucial role in ischemia/hypoxia-induced mitochondrial fission by acetylating Drp1. Mechanistically, ischemia/hypoxia induced Drp1 phosphorylation by CDK5 upregulation-mediated activation of AMPK in neuronal cells, which in turn facilitated the interaction of GCN5L1 with Drp1, thus enhancing Drp1 acetylation and mitochondrial fission. Accordingly, inhibition of AMPK alleviated ischemia/hypoxia- induced Drp1 acetylation and mitochondrial fission and protected brain tissues from ischemic damage. These findings provide a novel insight into the functional roles of GCN5L1 in regulating Drp1 acetylation and identify a previously unrecognized CDK5-AMPK-GCN5L1 pathway that mediates the acetylation of Drp1 in ischemic brain tissues.

Abstract SARS-CoV-2 JN.1 with an additional L455S mutation on spike when compared with its parental variant BA.2.86 has outcompeted all earlier variants to become the dominant circulating variant. Recent studies investigated the immune resistance of SARS-CoV-2 JN.1 but additional factors are speculated to contribute to its global dominance, which remain elusive until today. Here, we find that SARS-CoV-2 JN.1 has a higher infectivity than BA.2.86 in differentiated primary human nasal epithelial cells (hNECs). Mechanistically, we demonstrate that the gained infectivity of SARS-CoV-2 JN.1 over BA.2.86 associates with increased entry efficiency conferred by L455S and better spike cleavage in hNECs. Structurally, S455 altered the mode of binding of JN.1 spike protein to ACE2 when compared to BA.2.86 spike at ACE2H34, and modified the internal structure of JN.1 spike protein by increasing the number of hydrogen bonds with neighboring residues. These findings indicate that a single mutation (L455S) enhances virus entry in hNECs and increases immune evasiveness, which contribute to the robust transmissibility of SARS-CoV-2 JN.1. We further evaluate the in vitro and in vivo virological characteristics between SARS-CoV-2 BA.2.86/JN.1 and EG.5.1/HK.3, and identify key lineage-specific features of the two Omicron sublineages that contribute to our understanding on Omicron antigenicity, transmissibility, and pathogenicity.

Abstract Background Organisms have evolved a range of phenotypic and genetic adaptations to live in different environments along an altitudinal gradient. Herein, we studied the widely distributed Chinese toad, Bufo gargarizans, as a model and used an integrated phenotype-genotype approach to assess adaptations to different altitudinal environments. Results Comparison of populations from four altitudes (50 m, 1200 m, 2300 m, and 3400 m) showed more effective defenses among high-altitude toads. These included thickened epidermis, more epidermal capillaries and granular glands, greater gland size in skin, and higher antioxidant enzyme activities in plasma. High-altitude toads also showed increased erythrocytes and hematocrit and elevated hemoglobin concentration, potentially improving oxygen delivery. Elevated altitude led to a metabolic shift from aerobic to anaerobic metabolism, and high-altitude populations favored carbohydrates over fatty acids to fuel for energy metabolism. Differentially expressed genes were associated with adaptive phenotypic changes. For instance, expression of genes associated with fatty acid metabolism showed greater suppression at high altitude (3400 m), consistent with decreased flux of β-hydroxybutyric acid and lower free fatty acids levels. Moreover, down-regulation of genes involved in carbon metabolism processes at high altitude (3400 m) were coincident with reduced TCA cycle flux. These results suggest that high-altitude toads adopt a metabolic suppression strategy for survival under harsh environmental conditions. Moreover, the hypoxia-inducible factor signaling cascade was activated at high altitude. Conclusions Collectively, these results advance our comprehension of adaptation to high-altitude environments by revealing physiological and genetic mechanisms at work in Chinese toads living along altitudinal gradients.

To solve problems of the low yields and dark color of Sargassum horneri polysaccharides which were produced according to the traditional extraction method under the high-temperature and alkalic condition, this study attempted to produce S. horneri polysaccharides at a lower alkaline treatment temperature of 60 ℃ and optimize the process parameters by the response surface methodology. The combined scores of alginate and fucoidan yields and whiteness index (WI) were used as assessment indices to identify the optimal process condition. Under the optimal extraction condition, the concentration of NaClO addition was changed to investigate its effect on various characteristics of the produced alginate and fucoidan. The results showed that the polysaccharide comprehensive score was significantly correlated with the alkaline concentration, the extraction time, and the dosage of NaClO (P

Summary Pedicle screw loosening after posterior lumbar fusion is associated with poor bone quality, which often determines screw pull‐out strength, insertion torque, and vertebral body loading characteristics. Magnetic resonance imaging (MRI)‐based vertebral bone quality (VBQ) score were associated with poor bone quality. Current evidence suggests that pedicle bone quality (PBQ) has a greater impact on screw stability. However, the correlation between MRI‐based PBQ score and screw loosening has not been reported. Purpose To introduce and evaluate an MRI‐based PBQ score to determine its effectiveness in predicting pedicle screw loosening following lumbar fusion surgery. Methods The retrospective study analyzed 244 patients who underwent posterior lumbar interbody fusion (PLIF) with pedicle screws between December 2017 and December 2021, with CT and MRI imaging before surgery. Data collected included patient demographics and preoperative radiological data. Radiographic screw loosening was measured at 12 months postoperatively. Clinical assessments included pain visual analog scale (VAS) and Oswestry Disability Index (ODI) scores. The PBQ score was measured using MRI scans. We use univariate analysis for preliminary screening of the risk factors of screw loosening. Subsequent analysis involved multivariate logistic regression to identify independent predictive factors for screw loosening. We constructed the receiver operating characteristic (ROC) curve to ascertain the discriminative capacity of the PBQ score. The area under the curve (AUC) quantified its predictive accuracy. Additionally, we evaluated the association between PBQ score and screw loosening using Spearman's correlation analysis. Results Overall, 244 patients who underwent PLIF with pedicle screw fixation participated in this study, including 35 in the loosening group and 209 in the non‐loosening group. PBQ score in the loosening group was significantly higher than that in the non‐loosening group. On multivariate logistic regression, the higher PBQ score (OR = 8.481, 95% CI: 3.158–22.774; p

Abstract Background Burkholderia is a phosphorus solubilizing microorganism discovered in recent years, which can dissolve insoluble phosphorus compounds into soluble phosphorus. To investigate the effects of Burkholderia and calcium phosphate on the composting of Torreya grandis branches and leaves, as well as to explain the nutritional and metabolic markers related to the composting process. Methods In this study, we employed amplicon sequencing and untargeted metabolomics analysis to examine the interplay among phosphorus (P) components, microbial communities, and metabolites during T. grandis branch and leaf waste composting that underwent treatment with calcium phosphate and phosphate-solubilizing bacteria (Burkholderia). There were four composting treatments, 10% calcium phosphate (CaP) or 5 ml/kg (1 × 108/ml Burkholderia) microbial inoculum (WJP) or both (CaP + WJP), and the control group (CK). Results The results indicated that Burkholderia inoculation and calcium phosphate treatment affected the phosphorus composition, pH, EC, and nitrogen content. Furthermore, these treatments significantly affected the diversity and structure of bacterial and fungal communities, altering microbial and metabolite interactions. The differential metabolites associated with lipids and organic acids and derivatives treated with calcium phosphate treatment are twice as high as those treated with Burkholderia in both 21d and 42d. The results suggest that calcium phosphate treatment alters the formation of some biological macromolecules. Conclusion Both Burkholderia inoculation and calcium phosphate treatment affected the phosphorus composition, nitrogen content and metabolites of T. grandis branch and leaf waste compost.These results extend our comprehension of the coupling of matter transformation and community succession in composting with the addition of calcium phosphate and phosphate-solubilizing bacteria.

Abstract Background Aberrant activation of mesenchymal epithelial transition (MET) has been considered to mediate primary and acquired resistance to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) in EGFR-mutant non-small cell lung cancer (NSCLC). However, mechanisms underlying this process are not wholly clear and the effective therapeutic strategy remains to be determined. Methods The gefitinib-resistant NSCLC cell lines were induced by concentration increase method in vitro. Western blot and qPCR were used to investigate the relationship between MET and vascular endothelial growth factor (VEGF)/VEGF receptor 2 (VEGFR2) signaling pathway. Double luciferase reporter gene and co-immunoprecipitation were used to further reveal the regulation mechanism between MET and VEGF/VEGFR2. The effect of combined inhibition of MET and VEGF/VEGFR2 signaling pathway on the therapeutic sensitivity of EGFR-TKI in gefitinib resistant cell lines with MET aberration was verified ex vivo and in vivo. Results We successfully obtained two gefitinib-resistant NSCLC cell lines with EGFR mutation and abnormal activation of MET. We observed that MET formed a positive feedback loop with the VEGF/VEGFR2 signaling, leading to persistent downstream signaling activation. Specifically, MET up-regulated VEGFR2 expression in a MAPK/ERK/ETS1-dependent manner, while VEGF promoted physical interaction between VEGFR2 and MET, thereby facilitating MET phosphorylation. A MET inhibitor, crizotinib, combined with an anti-VEGF antibody, bevacizumab, enhanced the sensitivity of NSCLC cells to gefitinib and synergistically inhibited the activation of downstream signaling in vitro. Dual inhibition of MET and VEGF combined with EGFR TKIs markedly restrained tumor growth in both human NSCLC xenograft models and in an EGFR/MET co-altered case. Conclusions Our work reveals a positive feedback loop between MET and VEGF/VEGFR2, resulting in continuous downstream signal activation. Combined inhibition of MET and VEGF/VEGFR2 signaling pathway may be beneficial for reversing EGFR TKIs resistance.

Abstract This study integrates pharmacology databases with bulk RNA-seq and scRNA-seq to reveal the latent anti-PDAC capacities of BBR. Target genes of BBR were sifted through TargetNet, CTD, SwissTargetPrediction, and Binding Database. Based on the GSE183795 dataset, DEG analysis, GSEA, and WGCNA were sequentially run to build a disease network. Through sub-network filtration acquired PDAC-related hub genes. A PPI network was established using the shared genes. Degree algorithm from cytoHubba screened the key cluster in the network. Analysis of differential mRNA expression and ROC curves gauged the diagnostic performance of clustered genes. CYBERSORT uncovered the potential role of the key cluster on PDAC immunomodulation. ScRNA-seq analysis evaluated the distribution and expression profile of the key cluster at the single-cell level, assessing enrichment within annotated cell subpopulations to delineate the target distribution of BBR in PDAC. We identified 425 drug target genes and 771 disease target genes, using 57 intersecting genes to construct the PPI network. CytoHubba anchored the top 10 highest contributing genes to be the key cluster. mRNA expression levels and ROC curves confirmed that these genes showed good robustness for PDAC. CYBERSORT revealed that the key cluster influenced immune pathways predominantly associated with Macrophages M0, CD8 T cells, and naïve B cells. ScRNA-seq analysis clarified that BBR mainly acted on epithelial cells and macrophages in PDAC tissues. BBR potentially targets CDK1, CCNB1, CTNNB1, CDK2, TOP2A, MCM2, RUNX2, MYC, PLK1, and AURKA to exert therapeutic effects on PDAC. The mechanisms of action appear to significantly involve macrophage polarization-related immunological responses.

Abstract Oil-in-water emulsion is a system with extensive applications in foods, cosmetics and coating industries, and it could also be designed into an artificial lipid droplet in recent works. However, the insights into the biophysical dynamic behaviors of such artificial lipid droplets are lacking. Here, we reveal an enzymatic reaction triggered endocytosis-like behavior in the oil-in-water emulsion lipid droplets. A thermodynamically favored recruitment of lipases onto the membrane of the droplets is demonstrated. We confirm that the hydrolysis of tributyrin by lipases can decrease the interfacial tension and increase the compressive force on the membrane, which are the two main driving forces for triggering the endocytosis-like behavior. The endocytosis-like behavior induced various emerging functionalities of the lipid droplets, including proteins, DNA or inorganic particles being efficiently sequestered into the oil droplet with reversible release as well as enhanced cascade enzymatic reaction. Overall, our studies are expected to open up a way to functionalize oil-in-water emulsions capable of life-inspired behaviors and tackle emerging challenges in bottom-up synthetic biology, revealing the unknown dynamic behaviors of lipid droplets in living organisms.

Abstract Tumor draining lymph nodes (TDLN) represent a key component of the tumor-immunity cycle. There are few studies describing how TDLNs impact lymphocyte infiltration into tumors. Here we directly compare tumor-free TDLNs draining “cold” and “hot” human triple negative breast cancers (TDLNCold and TDLNHot). Using machine-learning-based self-correlation analysis of immune gene expression, we find unbalanced intranodal regulations within TDLNCold. Two gene pairs (TBX21/GATA3-CXCR1) with opposite correlations suggest preferential priming of T helper 2 (Th2) cells by mature dendritic cells (DC) within TDLNCold. This is validated by multiplex immunofluorescent staining, identifying more mature-DC-Th2 spatial clusters within TDLNCold versus TDLNHot. Associated with this Th2 priming preference, more IL4 producing mast cells (MC) are found within sinus regions of TDLNCold. Downstream, Th2-associated fibrotic TME is found in paired cold tumors with increased Th2/T-helper-1-cell (Th1) ratio, upregulated fibrosis growth factors, and stromal enrichment of cancer associated fibroblasts. These findings are further confirmed in a validation cohort and public genomic data. Our results reveal a potential role of IL4+ MCs within TDLNs, associated with Th2 polarization and reduced immune infiltration into tumors.

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

Abstract Background Developmental dysplasia of the hip (DDH) is a common pediatric orthopedic condition characterized by varying degrees of acetabular dysplasia and hip dislocation. Current 2D imaging methods often fail to provide sufficient anatomical detail for effective treatment planning, leading to higher rates of misdiagnosis and missed diagnoses. MRI, with its advantages of being radiation-free, multi-planar, and containing more anatomical information, can provide the crucial morphological and volumetric data needed to evaluate DDH. However, manual techniques for measuring parameters like the center–edge angle (CEA) and acetabular index (AI) are time-consuming. Automating these processes is essential for accurate clinical assessments and personalized treatment strategies. Methods This study employed a U-Net-based CNN model to automate the segmentation of hip MRI images in children. The segmentation process was validated using a leave-one-out method during training. Subsequently, the segmented hip joint images were utilized in clinical settings to perform automated measurements of key angles: AI, femoral neck angle (FNA), and CEA. This automated approach aimed to replace manual measurements and provide an objective reference for clinical assessments. Results The U-Net-based network demonstrates high effectiveness in hip segmentation compared to manual radiologist segmentations. In test data, it achieves average DSC values of 0.9109 (acetabulum) and 0.9244 (proximal femur), with a 91.76% segmentation success rate. The average ASD values are 0.3160 mm (acetabulum) and 0.6395 mm (proximal femur) in test data, with Ground Truth (GT) edge points and predicted segmentation maps having a mean distance of less than 1 mm. Using automated segmentation models for clinical hip angle measurements (CEA, AI, FNA) shows no statistical difference compared to manual measurements (p > 0.05). Conclusion Utilizing U-Net-based image segmentation and automated measurement of morphological parameters significantly enhances the accuracy and efficiency of DDH assessment. These methods improve precision in automatic measurements and provide an objective basis for clinical diagnosis and treatment of DDH.

Abstract Patients with germline pathogenic variants of BRCA1/2 genes have a particular predisposition to develop breast cancer. No clinical test has been developed to accurately and quantitatively evaluate their risk of developing breast cancer. We hypothesized that aberrant cell clonal expansion may be initiated in normal breast tissues without manifesting pathologic changes. To assess the prevalence of clonal expansion in the normal breast, we collected normal breast tissue from 24 breast cancer patients who had undergone surgical resection and 5 carriers of pathogenic BRCA1/2 variant who had undergone prophylactic mastectomy. Whole-exome sequencing (WES) was conducted in 97 specimens from 14 individuals, and TOP panel, a gene panel targeting 464 genes, was conducted in 321 specimens from 26 individuals, including 8 individuals with germline pathogenic variants of BRCA1/2 genes. Recurrent oncogenic mutations within PIK3CA, ARHGAP35, HRAS, and NF1 were identified in normal breast tissue at considerable variant allelic frequencies (VAF), suggesting clonal expansion. In addition, 937 normal breast tissues were evaluated using the Breast Cancer Panel (BCP) targeting 25 genes to determine the exact prevalence and distribution of clonal expansion. To assess the clonal expansion, we developed the clonality score, which is the mean value of clonal cell fractions for samples obtained from a given breast. The average clonality score in macroscopically normal breast tissue was 0.95 (0–2.46), with a significant difference between cases with and without a history of breast cancer of stage 2 or more advanced stage (p = 0.01). Additional WES on 42 samples with relatively large clone size (VAF > 3%) confirmed that these cell clones harbored multiple mutations (10.7 mutations/sample), and the number of existing mutations was consistent with the clone size (R = 0.50). The results suggest that clonal changes occur in normal breast tissue of women at high risk for breast cancer even before cancer is detected pathologically and/or radiologically, and the clonality score shows the potential to be a valid method of evaluating clonal expansion for cancer-risk assessment that provides appropriate preventive options for patients at high risk for breast cancer.

Abstract Objective Constructing a demand-oriented Internet + community home care service indicator system, starting from the actual needs of the elderly, and quantifying the demand into specific service contents that can be provided, so as to realize the effective supply of services. It aims to provide a theoretical basis for the government to formulate relevant aging policies and provide a reference basis for promoting the innovation and development of the Internet + elderly care model. Methods Based on existence needs, relationship needs and growth needs abbreviated as “Existence, Relatedness, Growth (ERG)” demand theory, through the discussion in the group meeting, form the expert consultation questionnaire of the demand-oriented Internet + community home care service indicator system, select experts in related fields to conduct two rounds of Delphi expert consultation, summarize the experts’ opinions to determine the indicator system items, and use the Analytic Hierarchy Process (AHP) method to construct the judgment matrix to derive the weighting coefficients of the indicators, and establish the ultimate demand-oriented Internet + community home care service indicator system. Results The effective recovery rates for the two rounds of expert consoulation questionnaires were 100%, with expert authority coefficients of 0.852 and 0.868, respectively. The Kendall coefficients for the second round of expert views varied from 0.226 to 0.431, with coefficients of variation for all indexes less than 0.25.The finalized demand-oriented Internet + community home care service indicator system includes 3 first-level indicators, 10 s-level indicators, and 46 third-level indicators. The consistency ratios of indicator judgment matrices at all levels are less than 0.10, suggesting that the hierarchical analysis findings are consistent, implying that the weight coefficient distribution is appropriate. Conclusion The demand-oriented Internet + community home care service Indicator System, which was created through expert consultation and AHP method, has reasonable content and is more dependable as an evaluation tool for reliably assessing demand for elderly servic.

Abstract Spectrum map is a database that stores multidimensional representations of spectrum situation information. It provides support for spectrum sensing and endows wireless communication networks with intelligence. However, the ubiquitous deployment of monitoring devices leads to huge costs of operation and maintenance. It indicates that an approach is needed to reduce the number of monitoring devices, but prevent the degradation of data granularity. Therefore, this paper focuses on the accurate construction of the spectrum map. It aims to infer the fine‐grained spectrum situation of the target region based on coarse‐grained observation. In order to solve this problem, an inference framework based on deep residual network is developed in this paper. In the case of rule deployment for sensing nodes, it adopts the idea of super resolution to improve the accuracy of the spectrum map. The framework is composed of two major parts: an inference network, which generates fine‐grained spectrum maps from coarse‐grained counterparts by using feature extraction module and upsampling construction module; and a fusion network, which considers the influence of environmental factors to further improve the performance. A large number of experiments on simulated datasets verify the effectiveness of the proposed method.

As the next-generation power system, smart grid presents challenges to enterprises in managing and analyzing massive data, meeting complex operational and decision-making demands, and predicting future power demand for grid optimization. This paper aims to proposed a fusion algorithm for smart grid enterprise decision-making and economic benefit analysis, enhancing the accuracy of decision-making and predictive capability of economic benefits. The proposed method combines techniques such as Long Short-Term Memory (LSTM), Generative Adversarial Networks (GAN), and edge computing. The LSTM model is employed to model historical data of the smart grid. The GAN model generates diverse scenarios for future power demand and economic benefits. The proposed method is evaluated on four public datasets, including the ENTSO-E Dataset, and outperforms several traditional algorithms in terms of prediction accuracy, efficiency, and stability. Notably, on the ENTSO-E Dataset, the proposed algorithm achieves a reduction of over 46.6% in FLOP, and a decrease in inference time by over 48.3%, and an improvement of 38% in MAPE. The novel fusion algorithm proposed in this paper demonstrates significant advantages in accuracy and predictive capability, providing a scientific basis for smart grid enterprise decision-making and economic benefit analysis while offering practical value for real-world applications.

In the demand response process involving multi-agent participation, multiple parties’ interests are involved and response execution status supervision is required. Traditional centralized demand response systems lack trust attributes. At the same time, traditional centralized cloud management can no longer support massive terminal services, resulting in delays in demand response services. We build a distributed trusted demand response architecture based on blockchain, illustrating the information interaction process in the demand bidding process and container-based edge-side heterogeneous resource management. We also propose a demand bidding algorithm that takes into account both the day-ahead market and the intraday market, aiming to maximize the aggregator’s benefits. In addition, a virtual resource management algorithm to support demand response tasks is also proposed to optimize computing resource allocation and meet business latency requirements. Simulation results demonstrate that compared with only cloud computing or edge computing, the solution we proposed can reduce response delay by more than 39% for the sample system. Energy cost is saved by about 10.25% during container scheduling.

Background: To delineate the levels of serum Hepatitis B virus (HBV) RNA in patients with HBV-related hepatocellular carcinoma (HCC) and study comparisons with those of individuals afflicted with cirrhosis. Methods: Adult patients diagnosed with HBV-related cirrhosis or HCC (initial diagnosis) were enrolled in the cross-sectional study. Serum HBV DNA level was quantified through a real-time polymerase chain reaction assay with a lower limit of quantification (LLQ) of 20 IU/ml. Additionally, serum HBV RNA was quantified employing RNA real-time fluorescence thermostatic amplification detection technology with LLQ of 100 copies/ml. Propensity score matching (PSM) was conducted to ensure balance in between-group confounders. Results: A total of 187 patients (47 with HCC and 140 with cirrhosis) were recruited, among whom 140 (74.9%) had undergone antiviral therapy prior to their inclusion, with varying durations. Serum HBV RNA was detectable in 89.4% of HCC patients at the time of carcinoma diagnosis. After PSM, individuals with HCC exhibited significantly elevated levels of serum HBV DNA and HBV RNA compared to those with cirrhosis (median lgHBV RNA 3.1 vs 2.0 copies/ml, P = 0.001). Subgroup analysis, including 38 patients who exhibited ultrasensitive HBV DNA negativity, revealed similar results (median lgHBV RNA 3.0 vs 0.0 copies/ml, P < 0.001). Conclusions: Serum HBV RNA levels were significantly higher in HBV-related HCC patients compared to cirrhotic patients. The presence of serum HBV RNA positivity or elevated levels was associated with the onset of HCC.

Abstract This work proposes two differential magnetic‐field resonant probes, consisting of a U‐shaped single‐loop resonant probe (S_probe) and a dual‐loops resonant probe (D_probe). These resonant probes are composed of a pair of LC resonant circuits, a pair of strip‐lines with two outputs, two rows of via fences, and two different sensing structures (single‐loop and dual‐loops). Among them, a pair of open stubs as capacitor and shorted stubs as inductor is used to form the LC resonant circuit, via fences are utilized to suppress unwanted electromagnetic wave modes, a U‐shaped single‐loop and a pair of differential dual‐loops is used to receive the electromagnetic signal. In order to prove the rationality of the design, simulation models of the S_probe and D_probe are optimized and manufactured based on four‐layers PCBs. In addition, a near‐field scanning system with a standard 50 Ω straight microstrip line as calibration kit is used to measure and calibrate these resonant probes. The tested results indicate that these designed magnetic‐field probes could operate at 1.575 GHz and have high detection sensitivity and electric‐field suppression.

In view of the energy occurrence structure of “rich coal, poor oil and little gas” in China, and the situation that coal will occupy the dominant position of energy consumption for a long time,The development history of frozen shaft mechanized drilling and blasting is reviewed in the field of coal mining in China. As the main construction method of shaft construction, the application of dynamite greatly improves the drilling efficiency of frozen shaft. The application of supporting large mechanized equipment such as umbrella drilling, rock grabbing machine loading, large derrick and equipment hoisting, and large formwork building, greatly improve the wellbore completion speed; Shaft drilling rig, reverse drilling rig and shaft boring machine as special shaft sinking methods under special formation conditions, also have their own application range. Aiming at the characteristics of water-rich weakly consolidated formation and the development trend of smart mine in western China, there are shortcomings in using freezing & borehole-blasting method and large drilling equipment to develop the shaft of weakly consolidated formation at kilometer level, while using freezing & shaft boring machine is one of the trends of ultra-deep shaft construction. Combining with the construction cases of freezing & shaft boring machine abroad, reasonable suggestions are put forward for shaft excavation of water-rich weak consolidated rock formation in western China. The freezing wall thickness and strength are calculated according to the current design theory, the permanent shaft support adopts double-layer reinforced concrete wall structure, the rock-breaking form of shaft boring machine under low temperature environment, and the method of hierarchical slag discharge to realize the parallel operation of digging - supporting - transporting. Finally, the next research focus of this construction method is put forward. The synergistic mechanism between shaft wall structure and weakly consolidated surrounding rock should be clarified to realize optimization of shaft wall structure, and the support - operation cooperation mode of shaft boring machine to improve shaft excavation and support efficiency and improve informatization level. Realize shaft driving towards mechanization and intelligence.