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Abstract Background New daily persistent headache (NDPH) is a rare primary headache with unclear pathogenesis. Neuroimaging studies of NDPH are limited, and controversy still exists. Diffusion tensor imaging (DTI) is commonly used to study the white matter. However, lacking specificity, the potential pathological mechanisms of white matter microstructural changes remain poorly understood. In addition, the intricacy of gray matter structures impedes the application of the DTI model. Here, we applied an advanced diffusion model of neurite orientation dispersion and density imaging (NODDI) to study the white matter and cortical gray matter microstructure in patients with NDPH. Methods This study assessed brain microstructure, including 27 patients with NDPH, and matched 28 healthy controls (HCs) by NODDI. The differences between the two groups were assessed by tract-based spatial statistics (TBSS) and surface-based analysis (SBA), focusing on the NODDI metrics (neurite density index (NDI), orientation dispersion index (ODI), and isotropic volume fraction (ISOVF)). Furthermore, we performed Pearson’s correlation analysis between the NODDI indicators and clinical characteristics. Results Compared to HCs, patients with NDPH had a reduction of density and complexity in several fiber tracts. For robust results, the fiber tracts were defined as comprising more than 100 voxels, including bilateral inferior fronto-occipital fasciculus (IFOF), left superior longitudinal fasciculus (SLF) and inferior longitudinal fasciculus (ILF), as well as right corticospinal tract (CST). Moreover, the reduction of neurite density was uncovered in the left superior and middle frontal cortex, left precentral cortex, and right lateral orbitofrontal cortex and insula. There was no correlation between the NODDI metrics of these brain regions and clinical variables or scales of relevance after the Bonferroni correction. Conclusions Our research indicated that neurite loss was detected in both white matter and cortical gray matter of patients with NDPH.

Underground engineering often passes through water-rich fractured rock masses, which are prone to fracture and instability under the long-term coupling of in-situ stress field and pore water (P-W) pressure, ultimately threatening the stability of underground structures. In order to explore the mechanical properties of rocks under H-M coupling, the corresponding damage constitutive (D-C) model has become the focus of attention. Considering the inadequacy of the current research on rock strength parameters, energy evolution characteristics and D-C model under H-M coupling, the mechanical properties of typical sandstone samples are discussed based on laboratory tests. The results show that the variation of characteristic stresses of sandstone under H-M coupling conforms to the normalized attenuation equation and Mohr-Coulomb (M−C) criterion. The P-W pressure mechanism of sandstone exhibits a dynamic change from softening effect to H-M fracturing effect. The closure stress is mainly provided by cohesive strength, while the initiation stress, damage stress, and peak stress are jointly dominated by cohesive strength and friction strength. In addition, residual stress is attributed to the friction strength formed by the bite of the fracture surface. Subsequently, the energy evolution characteristics of sandstone under H-M coupling were studied, and it was found that P-W pressure weakened the energy storage capacity and energy dissipation capacity of sandstone, and H-M fracturing was an important factor in reducing its energy storage efficiency. Finally, combined with energy dissipation theory and statistical damage theory, two types of D-C models considering P-W pressure are proposed accordingly, and the model parameters can be determined by four methods. The application results indicate that the proposed and modified D-C models have high reliability, and can characterize the mechanical behavior of sandstone under H-M coupling, overcome the inconvenience of existing D-C models due to excessive mechanical parameters, and can be applied to the full-range stress–strain process. The results are conducive to revealing the deformation and damage mechanisms of rocks under H-M coupling, and can provide theoretical guidance for related engineering problems.

Corrosion damage mechanisms of nickel-based alloy G3 at 600 °C with a mixture of H2O, CO2, H2S and H2 were explored using ultra-high-temperature and high-pressure corrosion experiments, slow strain rate tensile tests and a series of microscopic characterization methods. Results unveil that G3 alloy exhibited a low corrosion rate on average. The corrosion product film consists of two layers – an inner layer of Cr2O3 and an outer layer of a mixture of Ni3S2 and Cr2O3. The material experienced plasticity losses of 49.5 % and 24.3 % after corrosion and aging, respectively. Precipitation of M23C6 at grain boundary occurred after corrosion and aging, resulting in chromium depletion and intergranular corrosion within weak grain boundary regions, which reduced plasticity of G3 alloy.

Societal Impact Statement With the rapid development of modern agriculture and its reliance on high‐yielding and genetically uniform varieties, many traditional agricultural systems are gradually being abandoned. The genetic diversity contained in landraces is crucial for modern eco‐agriculture. An indicator evaluation model combined with machine learning could help to locate and conserve these existing traditional agricultural systems, called agricultural heritage systems (AHS). Here, this method provided the first map of potential areas of Tea‐AHS in China. These results could help policymakers to confirm priorities and rationally allocate conservation resources based on the distribution status and endangerment of AHS. This could also help local people to receive additional support for the transfer of germplasm resources and indigenous knowledge. Summary Modern agriculture is overly dependent on high‐yielding and genetically uniform varieties, whereas traditional agricultural systems contain a large number of genetically diverse landraces and the indigenous knowledge associated with them. We call traditional agricultural systems that survive to the present‐day agricultural heritage systems (AHS). Under the impact of modernization, AHS are gradually disappearing. Identifying these systems is the first step towards conserving them, but the potential areas of AHS related to agro‐biodiversity are not yet clear. Using Chinese tea as an example, this paper provides the first universal method for identifying potential areas of AHS based on agro‐biodiversity and the first map of potential areas of Tea‐AHS in China. The map is constructed based on the maximum entropy model (Maxent) of tea germplasm resources and related indicator functions and has been validated by existing Tea‐AHS in China. The study identified 54 potential areas of Tea‐AHS. These potential areas are mainly concentrated in the southern region, in 15 provinces, including Anhui, Fujian, Guangdong, Yunnan, Guizhou, Guangxi, Hubei, and Hunan. Mangshi, Qimen County, and Chaisang District are among the high potential areas for Tea‐AHS and are the next priority for exploration and conservation work. We have verified the validity of the proposed method, which can help conserve the germplasm resources and traditional wisdom in the global AHS in a timely manner, and contribute to the development of modern and eco‐agriculture.

The collapse of goaf is one of the most serious geological disasters in cities where underground mineral resources are mined. The ground subsidence caused by the goaf limits the social and economic development of the area, while also endangering the safety of residents and property near the mining area. At present, support and grouting treatment methods are commonly used for the treatment of goaf. The cost of support treatment is relatively high, and it is difficult to control the collapse of the deeper goaf. Grouting treatment is suitable for conducting detailed investigations of underground spaces. The cost of complete grouting is high, and the timing of grouting termination is difficult to control. This paper aims to explore the optimization of grouting efficiency in the treatment of underground subsidence in goaf areas using the reserved pillar mining method. Through the stability calculation of the goaf pillars and roof, it can be concluded that the goaf pillars are unstable pillars under current conditions and are prone to damage under load interference. At present, surface subsidence has occurred in the goaf and requires treatment. Consider the comparison between the collapse control effect under different grouting rates and the complete grouting, and ultimately select the condition of 90% grouting rate to achieve the control effect. This conclusion can provide a certain theoretical reference basis for the treatment of similar goaf collapse, and has certain practical significance.

The subsidiary of Yunnan Phosphate Group Co., Ltd., Kunyang Phosphate Mine’s mining area is the subject of study. The mining of open-pit phosphate mines has caused significant damage to the ecological environment. Therefore, carrying out ecological restoration and green reclamation of the ecosystem in the mining area has become the top priority for current development. This article establishes an evaluation system for ecological restoration indicators, selecting four indicators including vegetation coverage, soil and water conservation, restoration of native plants, and Plant Species Diversity Index to assess the effects of ecological restoration and green reclamation of phosphate mines. The techniques of reconstructing soil ecological structure using phosphate tailings substrate and improving acidic soil with soil conditioner and calcium-magnesium phosphate compound fertilizer were applied. A series of other measures were taken, including: drafting scientific ecological restoration plans; employing physical, chemical, and biological methods for ecological restoration and green reclamation; selecting suitable plant species for planting; enhancing planting techniques; and strengthening post-restoration ecological monitoring and regulation. After ecological restoration and green reclamation, the Ecological Remediation Effect Index (EREI) for the years 2020, 2021, and 2022 were 48.40, 87.38, and 93.23 respectively, indicating significant improvement in the ecological environment. Furthermore, the difficulties encountered during the ecological system restoration process of the mine and the future development directions were summarized, providing practical and guiding significance for ecological restoration and green reclamation of abandoned mining areas both domestically and internationally.

Additively manufactured mould tools offer advantages compared to conventional tools, including cooling performance and cost savings. Certain moulds require inserts with high aspect ratio (>3) where using traditional tool steel, with low thermal conductivity, is insufficient for cooling. This necessitates the manual addition of high thermal conductivity pins, such as copper. Recent advances in selective powder deposition enable the fabrication of multi-material components with multi-material interface perpendicular to the build plate (vertical interface). This work investigates, for the first time, the manufacturability of tool steel and CuCrZr multi-material components with vertical interfaces. EDS and EBSD across multiple vertical interfaces revealed that metallurgically sound interfaces were obtained with porosity along the intermixed zone, attributed to using one set of parameters per material, without correction. Anisotropy in the intermixing zone was observed along the recoating direction (1.5 mm) compared to the other direction (0.5 mm), leading to increased porosity. This study establishes the manufacturability of multi-material tools and paves the way for adapting multi-material dosing and LPBF process parameters to manufacture defect-free interfaces.

This research proposes the utilization of a geopolymer-based blasting sealing material to improve the profitability of coal sales and reduce the rate of coal fragmentation during blasting in open pit mines. The study first focused on optimizing the strength of the sealant material and reducing curing time. This was achieved by regulating the slag doping and sodium silicate solution modulus. The findings demonstrated that increasing slag content and improving the material resulted in an early rise in strength while increasing the modulus of the sodium silicate solution extended the curing time. The slag doping level was fixed at 80 g, and the sodium silicate solution modulus was set at 1.5. To achieve a strength of 3.12 MPa, the water/gel ratio was set at 0.5. The initial setting time was determined to be 33 min, meeting the required field test duration. Secondly, the strength requirements for field implementation were assessed by simulating the action time and force destruction process of the sealing material during blasting using ANSYS/LS-DYNA software. The results indicated that the modified material meets these requirements. Finally, the Shengli Open Pit Coal Mine served as the site for the field test. It was observed that the hole-sealing material’s hydration reaction created a laminated and flocculated gel inside it. This enhanced the density of the modified material. Additionally, the pregelatinized starch, functioning as an organic binder, filled the gaps between the gels, enhancing the cohesion and bonding coefficient of the material. Upon analyzing the post-blasting shooting effect diagram using the Split-Desktop software, it was determined that the utilization of the modified blast hole plugging material resulted in a decrease in the rate of coal fragmentation from 33.2% to 21.1%. This reduction exhibited a minimal error of 1.63% when compared to the field measurement, thereby providing further confirmation of the exceptional plugging capabilities of the modified material. This study significantly contributes to establishing a solid theoretical basis for enhancing the blasting efficiency of open pit mines and, in turn, enhancing their economic advantages.

Abstract Background The brain functional network topology in new daily persistent headache (NDPH) is not well understood. In this study, we aim to assess the cortical functional network topological characteristics of NDPH using non-invasive neural signal recordings. Methods Resting-state magnetoencephalography (MEG) was used to measure power fluctuations in neuronal oscillations from distributed cortical parcels in 35 patients with NDPH and 40 healthy controls (HCs). Their structural data were collected by 3T MRI. Functional connectivity (FC) of neural networks from 1 to 80 Hz frequency ranges was analyzed with topographic patterns and calculated network topological parameters with graph theory. Results In the delta (1–4 Hz) and beta (13–30 Hz) bands, the lateral occipital cortex and superior frontal gyrus FC were increased in NDPH groups compared to HCs. Graph theory analysis revealed that the NDPH had significantly increased global efficiency in the delta band and decreased nodal clustering coefficient (left medial orbitofrontal cortex) in the theta (4–8 Hz) band. The clinical characteristics had a significant correlation with network topological parameters. Age at onset of patients showed a positive correlation with global efficiency in the delta band. The degree of depression of patients showed a negative correlation with the nodal clustering coefficient (left medial orbitofrontal cortex) in the theta band. Conclusion The FC and topology of NDPH in brain networks may be altered, potentially leading to cortical hyperexcitability. Moreover, medial orbitofrontal cortex is involved in the pathophysiological mechanism of depression in patients with NDPH. Increased FC observed in the lateral occipital cortex and superior frontal gyrus during resting-state MEG could serve as one of the imaging characteristics associated with NDPH.

Although early diagnosis and therapeutic advances have transformed the living quality and outcome of cancer patients, the poor prognosis for metastatic patients has not been significantly improved. Mechanisms underlying the complexity of metastasis cannot be simply determined by the straightforward ‘cause‐and‐effect relationships’. We have developed a ‘dry‐lab‐driven knowledge discovery and wet‐lab validation’ approach to embrace the complexity of cancer and metastasis. We have revealed for the first time that polymetastatic (POL) melanoma cells can utilize both the secretory protein pathway (S100A11–Sec23a) and the exosomal crosstalk (miR‐487a‐5p) to transfer their ‘polymetastatic competency’ to the oligometastatic (OL) melanoma cells, via synergistic co‐targeting of the tumor‐suppressor Nudt21. The downstream deregulated glycolysis was verified to regulate metastatic colonization efficiency. Further, two gene sets conferring independent prognosis in melanoma were identified, which have the potential for clinical translation and merit future clinical validation.

Tetrastigma hemsleyanum Diels et Gilg (T. hemsleyanum) is a homology medicine and food that is rich in bioactive ingredients such as flavonoids and phenolic acids. A strategy that integrates ultrahigh-performance liquid chromatography–electrospray ionization mass spectrometry (UHPLC–ESI/MS) and desorption electrospray ionization mass spectrometry imaging (DESI-MSI) spatial metabolomics analysis was proposed and applied to different parts of T. hemsleyanum for the first time. A total of 132 compounds were tentatively identified, and 3, 7, and 24 components were found only in tuberous roots (TRs), fibrous roots (FRs), and leaves, respectively, using UHPLC–ESI/MS. The DESI-MSI results showed that the spatial distribution of flavonoids between the aerial and underground parts was diverse; for example, vitexin-2″-O-glucoside was largely localized in the epidermis and xylem of TRs, while a small amount was restricted to the xylem of the leaf margin and FRs. There was a higher abundance of most organic acids and flavonoids in the leaves than in the underground parts. Some flavonoids showed the same abundance in FRs and TRs, but the levels of most compounds were considerably higher in FRs. It is possible for leaves and FRs to become new medicinal parts of T. hemsleyanum. Through chemometrics statistics analysis, 19 key differential compounds in different parts of T. hemsleyanum were found, and the pharmacological mechanisms of the main differential metabolites were predicted by network pharmacology. This study provides a novel method for the medicinal development of T. hemsleyanum, showing its great potential in the development of medicinal resources.

BackgroundThere is still a controversy about the superiority of liposomal bupivacaine (LB) over traditional local anesthetics in postoperative analgesia after thoracic surgery. This study aims to determine the effect of LB versus bupivacaine hydrochloride (HCl) for preoperative ultrasound-guided erector spinae plane block (ESPB) on postoperative acute and chronic pain in patients undergoing video-assisted thoracoscopic lung surgery.MethodsThis multicenter, randomized, double-blind, controlled trial will include 272 adult patients scheduled for elective video-assisted thoracoscopic lung surgery. Patients will be randomly assigned, 1:1 and stratified by site, to the liposomal bupivacaine (LB) group or the bupivacaine (BUPI) HCl group. All patients will receive ultrasound-guided ESPB with either LB or bupivacaine HCl before surgery and patient-controlled intravenous analgesia (PCIA) as rescue analgesia after surgery. The numeric rating scale (NRS) score will be assessed after surgery. The primary outcome is the area under the curve of pain scores at rest for 0–72 h postoperatively. The secondary outcomes include the total amount of opioid rescue analgesics through 0–72 h postoperatively, time to the first press on the PCIA device as rescue analgesia, the area under the curve of pain scores on activity for 0–72 h postoperatively, NRS scores at rest and on activity at different time points during the 0–72 h postoperative period, Quality of Recovery 15 scores at 72 h after surgery, and NRS scores on activity on postsurgical day 14 and postsurgical 3 months. Adverse events after the surgery are followed up to the postsurgical day 7, including postoperative nausea and vomiting, fever, constipation, dizziness, headache, insomnia, itching, prolonged chest tube leakage, new-onset atrial fibrillation, severe ventricular arrhythmia, deep venous thrombosis, pulmonary embolism, pulmonary atelectasis, cardiac arrest, ileus, urinary retention, chylothorax, pneumothorax, and organ failure. Analyzes will be performed first according to the intention to treat principle and second with the per-protocol analysis.DiscussionWe hypothesize that LB for preoperative ultrasound-guided ESPB would be more effective than bupivacaine HCl in reducing postoperative pain in video-assisted thoracoscopic lung surgery. Our results will contribute to the optimization of postoperative analgesia regimens for patients undergoing video-assisted thoracoscopic lung surgery.Clinical trial registration:http://www.chictr.org.cn, identifier ChiCTR2300074852.

Introduction: Taking a phosphate mine in Yunnan as the engineering research background, the fractured rock mass of the No. 1 belt roadway is selected as the research object.Methods: To reduce the cost of tunnel surrounding rock support and optimize construction technology, a combination of numerical simulation software Midas and on-site experiments was used to compare and analyze the distribution characteristics of the plastic zone of tunnel surrounding rock, deformation characteristics of tunnel surrounding rock, and stress characteristics of tunnel support anchor bolts under two support methods: double-layer spray anchor mesh and single-layer spray anchor mesh with steel bar.Results: Research findings indicate that adopting the single-layer spray anchor mesh with steel bar support method results in a more uniform distribution of the plastic zone at the top of the tunnel surrounding rock, with a smaller range. The settlement of the roof and bulging of the bottom plate in the roadway’s surrounding rock, supported by a single-layer spray anchor mesh and steel bars, measure at 75.033 mm and 82.165 mm, respectively. Additionally, the internal bulging on both sides of the roadway’s surrounding rock is recorded as 37.835 mm and 37.470 mm, respectively. On the other hand, when utilizing a double-layer spray anchor mesh for support, the settlement of the roof and bulging of the bottom plate in the roadway’s surrounding rock are measured at 84.199 mm and 85.255 mm, respectively. Correspondingly, the internal bulging on both sides of the roadway’s surrounding rock records measurements of 41.670 mm and 41.756 mm, respectively. Furthermore, adopting the single-layer spray anchor mesh with steel bar support method ensures a more even transfer of axial forces to the steel bars, thereby increasing the overall load-bearing capacity. In contrast, the anchor bolts in the double-layer spray anchor mesh support method experience higher axial forces, leading to more pronounced stress concentration.Discussion: By comparing the field monitoring data, it is evident that the single-layer spray anchor mesh with steel bar support method exhibits significantly better control over the tunnel surrounding rock than the double-layer spray anchor mesh support method. Therefore, replacing the double-layer spray anchor net support with a single-layer spray anchor net with steel bar support method is entirely feasible and can meet on-site practical production requirements. The research results hold significant value in providing guidance and reference for selecting cost-effective support schemes for tunnel surrounding rock.

Abstract Surface coal mining procedures include piercing—blasting—mining and loading—transportation—discharging, blasting link exists due to the poor blasting effect leads to low loading efficiency, blasting dust caused by environmental pollution and other problems. In this paper, from the mechanical characteristics of the water medium, we analyze in detail the transferring effect, transducing effect and bubble pulsation phenomenon of the water medium in the blasting process. The results show that when the blasting medium is water medium, the maximum principal stress is 1.53 times that of air medium; the peak energy transfer can be up to 2.73 times that of air medium. With the help of TrueGrid/LS-DYNA finite element analysis software to simulate the dynamic process of blasting, the study of the maximum principal stresses around the hole, the top of the slope, the foot of the slope on the maximum principal stress changes, the results show that the maximum principal stresses around the hole, the top of the slope, the foot of the slope unit with the increase in the water content is gradually increasing trend. Finally, combined with the actual mine production conditions for blasting field test, water-mediated blasting dust reduction rate of 75%, the use of AHP—fuzzy comprehensive evaluation method of two groups of traditional dry hole blasting and three groups of water-mediated blasting comprehensive evaluation, the results show that the water-mediated blasting scores are higher than the traditional dry hole blasting, proving that the water-mediated blasting has a certain prospect of engineering applications.

Abstract Background Cell-based immunotherapy shows the therapeutic potential in sarcomas, in addition to angiogenesis-targeted tyrosine kinase inhibitor (TKI) and immune checkpoint inhibitor (ICI). Multi-antigen stimulated cell therapy-I (MASCT-I) technology is a sequential immune cell therapy for cancer, which composes of multiple antigen-loaded dendritic cell (DC) vaccines followed by the adoptive transfer of anti-tumor effector T-cells. Methods In this phase 1 study, we assessed MASCT-I plus camrelizumab (an ICI against PD-1) and apatinib (a highly selective TKI targeting VEGFR2) in patients with unresectable recurrent or metastatic bone and soft-tissue sarcoma after at least one line of prior systemic therapy. One MASCT-I course consisted of 3 DC subcutaneous injections, followed by 3 active T cell infusions administered 18–27 days after each DC injection. In schedule-I group, 3 DC injections were administered with a 28-day interval in all courses; in schedule-II group, 3 DC injections were administered with a 7-day interval in the first course and with a 28-day interval thereafter. All patients received intravenous camrelizumab 200 mg every 3 weeks and oral apatinib 250 mg daily. Results From October 30, 2019, to August 12, 2021, 19 patients were enrolled and randomly assigned to schedule-I group (n = 9) and schedule-II group (n = 10). Of the 19 patients, 11 (57.9%) experienced grade 3 or 4 treatment-related adverse events. No treatment-related deaths occurred. Patients in schedule-II group showed similar objective response rate (ORR) with those in schedule-I group (30.0% versus 33.3%) but had higher disease control rate (DCR; 90.0% versus 44.4%) and longer median progression-free survival (PFS; 7.7 versus 4.0 months). For the 13 patients with soft-tissue sarcomas, the ORR was 30.8%, DCR was 76.9%, and median PFS was 12.9 months; for the 6 patients with osteosarcomas, the ORR was 33.3%, the DCR was 50.0%, and median PFS was 5.7 months. Conclusions Overall, MASCT-I plus camrelizumab and apatinib was safe and showed encouraging efficacy in advanced bone and soft-tissue sarcoma, and schedule-II administration method was recommended. Trial registration ClinicalTrials.gov, NCT04074564.

Abstract Inlay celadon was a type of high-end ceramics of the Koryŏ dynasty (918–1392 AD) produced in the Korean Peninsula. It was conveyed to China during the Yuan dynasty (1279–1368 AD) as tribute or trade goods. In this study, the authors analyzed six samples of inlay celadon recently discovered at the prosperous Taicang Port of the Yuan and Ming dynasties in the lower Yangtze River, China. With scanning electron microscopy coupled with energy dispersive spectroscopy (SEM–EDS) and X-ray diffraction (XRD), the authors investigated the production technique, and compositional characteristics of these samples for the purpose of tracking their provenances. While the bodies are made of porcelain stone, the glazes are of porcelain stone and calcium-rich flux. The white inlay material in these samples is kaolinite-dominant, and the black one is made of quartz with high Fe content or a compound of quartz and raw materials with high Fe content. The results link the samples uncovered at the Taicang Port to the Samhǔngni Kiln in Kangjin-gun and the Uch'ǒlli and Chinsǒri Kilns in Buan-gun in Southern Korea. The products from these kilns were shipped to China in several shipments.

Two critical factors, namely intense precipitation and intricate excavation, can trigger rock mass disasters in mining operations. In this study, an indoor rainfall system was developed to precisely regulate the flow and intensity of precipitation. A large-scale model experiment was conducted on a self-designed physical simulation experiment platform to investigate the failure and instability of high-steep rock slopes under unsaturated conditions. The real-time reproduction of the progressive failure process in high-steep rock slopes enabled the determination of the critical rainfall intensity and revealed the mechanism underlying slope instability. Experiment results indicated that rainfall may be the primary factor contributing to rock mass instability, while continuous pillar mining exacerbates the extent of rock mass failure. The critical failure stage of high-steep rock slopes occurs at a rainfall intensity of 40 mm/h, whereas a rainfall exceeding 50 mm can induce critical instability and precipitation reaching up to 60 mm will result in slope failure. The improved region growing segmentation method (IRGSM) was subsequently employed for image recognition of rock mass deformation in underground mines. Herein an error comparison with the simple linear iterative cluster (SLIC) superpixel method and the original region growing segmentation method (ORGSM) showed that the average identification error in the X and Y directions by the method was reduced significantly (1.82% and 1.80% in IRGSM; 4.70% and 6.26% in SLIC; 9.45% and 12.40% in ORGSM). Ultimately, the relationship between rainfall intensity and failure probability was analyzed using the Monte Carlo method. Moreover, the stability assessment criteria of rock slope under unsaturated condition were quantitatively and accurately evaluated.

AbstractA significant number of ionic rare earth tailings slopes were generated during the process of rare earth mining and the factor of safety of these slopes continued to decrease under the action of rainfall. This study focussed on a specific tailings slope located in Dayu County, Ganzhou City. Through the utilization of MatDEM numerical simulation software, the variations in infiltration distribution and destabilization evolution of the tailings slope between different seasons were comparatively examined. The results indicated that during the rainy season (May to June), increased rainfall led to increased rate of water infiltration, consequently reducing the stability of the slope and exacerbating landslide damage. Furthermore, the study provided analyses of safety distances under different seasons of rainfall, taking into account the geographical location of the tailings slope in Dayu County, Ganzhou City, and the results of the analyses provided theoretical foundation into ensuring the safety of buildings and residents downstream of the slope.

The journal retracts the article titled “Forecasting the Landslide Blocking River Process and Cascading Dam Breach Flood Propagation by an Integrated Numerical Approach: A Reservoir Area Case Study” [...]

Introduction: Taking Yunnan Phosphate Group Co., Ltd. Kunyang Phosphate Mine No. 2 as the engineering background, this study aims to explore mining methods for deep ore bodies in phosphorus mines. Three mining schemes, namely open-pit mining, open-pit deep concave mining, and underground mining, were carefully selected for optimization. This article thoroughly analyzes the three schemes from various perspectives, including technical, economic, safety, and other aspects.Methods: The assessment of these aspects was conducted using the entropy weighted TOPSIS method. The technical aspects focused on evaluating the mining methods employed in each scheme. The economic aspects considered factors such as initial investment, resource recovery rate, phosphate content, production scale, infrastructure, and mining costs. Safety aspects took into account transportation safety and production safety. Additionally, the analysis considered environmental impact as one of the key factors. In total, 10 indicators were quantified to provide a comprehensive evaluation. To assess the schemes, the positive and negative ideal distances (Di+, Di−) and the relative proximity (Ci) for open-pit mining, open-pit deep concave mining, and open-pit to underground mining were calculated. These calculations helped to determine the relative performance of each scheme.Results: The relative closeness values (Ci) for Scheme 1, Scheme 2, and Scheme 3 are determined as 1.00, 0.09, and 0.68, respectively.The evaluation results indicate that the relative closeness (Ci) for open-pit mining in Scheme 1 is 1.00, for open-pit deep concave mining in Scheme 2 is 0.09, and for underground mining in Scheme 3 is 0.68. Through comparison and analysis of these results, it can be concluded that open-pit mining is the most optimal method. However, considering the fact that the open-pit portion of Kunyang Phosphate Mine No. 2 has already been extensively mined, the study recommends underground mining as the best mining plan for the phosphate mine.Discussion: By applying the entropy weight TOPSIS method to underground mining, this study overcomes the challenge of transitioning from qualitative to quantitative analysis for selecting mining methods. The mathematical approach enables the presentation of optimal mining techniques in a more precise manner. Through comparison of relative closeness, an optimal solution can be selected. This method holds significant value not only for selecting suitable mining methods for phosphorus mines but also for choosing optimal solutions for underground mining methods, drainage, ventilation, and other relevant considerations.

This study is grounded in research conducted at the Kunyang Phosphate Mine No. 2, a Chinese open-pit phosphate mining enterprise owned by the Yunnan Phosphate Group Co., Ltd. Due to the small inclination angle and the presence of weak interlayers in the middle of the gently inclined thin to medium thick phosphate ore layer, mining such ore bodies cannot rely on self weight migration, making roof management difficult and mining costs high technical challenges. The methods utilized on-site research, engineering comparisons, and theoretical analysis experiments to address the gently inclined phosphorus deposits. Based on the actual technical and economic conditions of current phosphorus mines, the advantages, disadvantages, and practical conditions of upward horizontal layered filling mining method, upward horizontal layered drift filling mining method, and pseudo inclined segmented strip filling mining method are compared. Priority should be given to using the pseudo inclined segmented strip method as the main method for mining, supplemented by the upward horizontal layered filling method in the panel area. And theoretical calculation methods were applied to obtain various numerical values of the filling capacity of the 2 million t/a mine filling test section, providing technical support for the mining design and equipment selection of the filling test system. The relevant research results can provide guidance for the selection of mining methods for gently inclined thin to medium thick phosphate deposits with an average inclination angle of 15°. The theoretical calculation method used can provide technical guidance for the filling system and filling equipment.

The peak adjustment of seismic wave is often realized by the method based on the peak ground acceleration (PGA), while the peak acceleration of the design response spectrum in the current specification is the effective peak acceleration (EPA), and EPA is recommended for peak adjustment. Firstly, the meaning and internal relations of PGA and EPA were analyzed, and the existing EPA calculation methods at home and abroad were summarized. According to the different characteristics of bridge structure and building structure, the calculation formula of EPA for bridge structure time history analysis was modified. Secondly, the smoothing processing problem of seismic wave response spectrum in EPA calculation was studied, and three peak smoothing methods were proposed to analyze the value determination of relevant parameter and the advantages and disadvantages of each method. Finally, this method was applied to the time history analysis of a long-span cable-stayed bridge, and the displacement and internal force results of the structure based on PGA and EPA were compared. The results showed that the time history analysis results obtained by the peak adjustment method based on EPA were more reliable.

This research examines how rainfall and mining affect the slope damage resulting from the transition from open-pit mining to underground mining. Using an unmanned aerial vehicle (UAV), the Huangniu slope of the Dexing Copper Mine was fully characterized, and experiments were conducted on rock samples from appropriate sites. First, the mechanical properties of the samples were measured. Then, the parameters of the similarity simulation experiments were derived based on the similarity theory. Subsequently, the rainfall, rock slope, data acquisition, and monitoring systems were designed. Finally, the rock mass failure with different slope angles was analyzed, and the deformation and damage patterns under the coupling effect were obtained. The results show that rainfall increases pore water pressure and moisture content. Rainfall and slope-slip water have more of an impact on the open-pit platform. The pore water pressure values on the upper rock mass rise faster than inside it. In the open-pit mining stage, the rock mass shifts slightly to the upper left. In the room mining stage, vertical fractures and goaf sinking occur. The fractures above the mine form a semi-ellipse. In the pillar mining stage, overlying rock displacement is evident and fractures persist. In the continuous pillar mining stage, the overlying rock collapses. The 65° slope model was the most damaged, while the 55° slope model was the least damaged. The results also suggest that the UAV guides sample selection.

Apocynum venetum L. is an economically valuable plant with tolerance to drought and salinity. Its leaves are utilized in tea production and pharmaceuticals, while the stem bark serves as a high-quality fiber material. To gain insights into the gene expression patterns of A. venetum using quantitative real-time PCR (qRT-PCR), it is crucial to identify appropriate reference genes. This study selected nine candidate genes, including α-tubulin (TUA), β-tubulin (TUB), actin (ACT), cyclophilin (CYP), elongation factor-1α (EF-1α), the B family of regulatory subunits of protein phosphatase (PPP2R2, PPP2R3, and PPP2R5), and phosphoglycerate kinase (PGK), to determine the most appropriate reference genes in the leaf, stem, and root tissues of A. venetum. A comprehensive ranking by geNorm, NormFinder, BestKeeper, and RefFinder software and Venn diagrams was used to screen more stable reference genes in different tissues. The two most stable reference genes were CYP and TUA in leaves, PGK and PPP2R3 in stems, and TUA and EF-1α in roots, respectively. The relative expression values of the four genes involved in proline metabolism under polyethylene glycol treatment were used to validate the screened reference genes, and they exhibited highly stable expression levels. These findings represent the first set of stable reference genes for future gene expression studies in A. venetum. They significantly contribute to enhancing the accuracy and reliability of gene expression analyses in this economically important plant species.

Desiccation is a kind of extreme form of drought stress and desiccation tolerance (DT) is an ancient trait of plants that allows them to survive tissue water potentials reaching −100 MPa or lower. ScDREB10 is a DREB A-5 transcription factor gene from a DT moss named Syntrichia caninervis, which has strong comprehensive tolerance to osmotic and salt stresses. This study delves further into the molecular mechanism of ScDREB10 stress tolerance based on the transcriptome data of the overexpression of ScDREB10 in Arabidopsis under control, osmotic and salt treatments. The transcriptional analysis of weight gene co-expression network analysis (WGCNA) showed that “phenylpropanoid biosynthesis” and “starch and sucrose metabolism” were key pathways in the network of cyan and yellow modules. Meanwhile, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis of differentially expressed genes (DEGs) also showed that “phenylpropanoid biosynthesis” and “starch and sucrose metabolism” pathways demonstrate the highest enrichment in response to osmotic and salt stress, respectively. Quantitative real-time PCR (qRT-PCR) results confirmed that most genes related to phenylpropanoid biosynthesis” and “starch and sucrose metabolism” pathways in overexpressing ScDREB10 Arabidopsis were up-regulated in response to osmotic and salt stresses, respectively. In line with the results, the corresponding lignin, sucrose, and trehalose contents and sucrose phosphate synthase activities were also increased in overexpressing ScDREB10 Arabidopsis under osmotic and salt stress treatments. Additionally, cis-acting promoter element analyses and yeast one-hybrid experiments showed that ScDREB10 was not only able to bind with classical cis-elements, such as DRE and TATCCC (MYBST1), but also bind with unknown element CGTCCA. All of these findings suggest that ScDREB10 may regulate plant stress tolerance by effecting phenylpropanoid biosynthesis, and starch and sucrose metabolism pathways. This research provides insights into the molecular mechanisms underpinning ScDREB10-mediated stress tolerance and contributes to deeply understanding the A-5 DREB regulatory mechanism.

Syntrichia caninervis is the dominant species of biological soil crust in the desert, including the Gurbantunggut Desert in China. It is widely distributed in drylands and considered to be a new model of vegetative desiccation tolerance moss. Here, we cloned an ATG8 gene from S. caninervis and confirmed its function under multiple abiotic stresses, both in situ and in Physcomitrium patens. The results showed that the ScATG8 gene encoded a protein with a highly conserved ATG8 functional domain. ScATG8 gene was increasingly expressed under different abiotic stresses. Under desiccation stress, the overexpression of ScATG8 enhanced the tolerance of S. caninervis and its ability to scavenge ROS. In addition, ScATG8 overexpression promoted the growth of P. patens under multiple stress conditions. Thus, ScATG8 may be a multifunctional gene, and it plays a critical role in the survival of S. caninervis under various abiotic stresses. Our results provide new insights into the function of ATG8 in enabling desiccation tolerance and open up more possibilities for subsequent plant molecular breeding and the mining of the resistance genes of S. caninervis and other moss species.

IntroductionColorectal adenoma can develop into colorectal cancer. Determining the risk of tumorigenesis in colorectal adenoma would be critical for avoiding the development of colorectal cancer; however, genomic features that could help predict the risk of tumorigenesis remain uncertain.MethodsIn this work, DNA and RNA parallel capture sequencing data covering 519 genes from colorectal adenoma and colorectal cancer samples were collected. The somatic mutation profiles were obtained from DNA sequencing data, and the expression profiles were obtained from RNA sequencing data.ResultsDespite some similarities between the adenoma samples and the cancer samples, different mutation frequencies, co-occurrences, and mutually exclusive patterns were detected in the mutation profiles of patients with colorectal adenoma and colorectal cancer. Differentially expressed genes were also detected between the two patient groups using RNA sequencing. Finally, two random forest classification models were built, one based on mutation profiles and one based on expression profiles. The models distinguished adenoma and cancer samples with accuracy levels of 81.48% and 100.00%, respectively, showing the potential of the 519-gene panel for monitoring adenoma patients in clinical practice.ConclusionThis study revealed molecular characteristics and correlations between colorectal adenoma and colorectal cancer, and it demonstrated that the 519-gene panel may be used for early monitoring of the progression of colorectal adenoma to cancer.

Abstract Background Main pancreatic duct (MPD) dilation is a high-risk stigmata/worrisome feature of malignancy in intraductal papillary mucinous neoplasms (IPMNs). The threshold of MPD diameter in predicting malignancy may be related to the lesion location. This study aimed to separately identify the thresholds of MPD for malignancy of IPMNs separately for the head-neck and body-tail. Materials and methods A total of 185 patients with pathologically confirmed IPMNs were included. Patient demographic information, clinical data, and pathological features were obtained from the medical records. Those IPMNs with high-grade dysplasia or with associated invasive carcinoma were considered as malignant tumor. Radiological data including lesion location, tumor size, diameter of the MPD, mural nodule, and IPMN types (main duct, MD; branch duct, BD; and mixed type, MT), were collected on computed tomography or magnetic resonance imaging. Serum carbohydrate antigen 19-9 levels, serum carcinoembryonic antigen levels, and the medical history of diabetes mellitus, chronic cholecystitis, and pancreatitis were also collected. Results Malignant IPMNs were detected in 31.6% of 117 patients with lesions in the pancreatic head-neck and 20.9% of 67 patients with lesions in the pancreatic body-tail. In MPD-involved IPMNs, malignancy was observed in 54.1% of patients with lesions in the pancreatic head-neck and 30.8% of patients with lesions in the pancreatic body-tail (p

Abstract Melanoma, one of the most aggressive malignancies, its high mortality and low survival rates are associated with effective metastatic colonization. Melanoma metastasis hinges on the bidirectional cell-cell communication within the complex metastatic microenvironments (MME). Extracellular vesicles (EVs) are recognized as a new class of molecular mediator in MME programing. Published studies show that melanoma EVs can educate MME stromal cells to acquire the pro-metastatic phenotype to enhance metastatic colonization. Whether EVs can mediate the interactions between heterogenous cancer cells within the MME that alter the course of metastasis has not been investigated at the mechanistic level. In this study, melanoma parental cells (MPCs) and paired derivative cancer stem cell line melanoma stem cells (MSCs) that were derived from melanoma cell line M14 were used. We demonstrate that the EVs-mediated crosstalk between the MSCs and the MPCs is a novel mechanism for melanoma metastasis. We characterized miR-592, a relatively novel microRNA of prognostic potential, in mediation of such intercellular crosstalk. EVs can encapsulate and deliver miR-592 to target MPCs. Upon entering, miR-592 inhibits the expression of its gene target protein tyrosine phosphatase non-receptor type7 (PTPN7), a phosphatase targeting MAPKs. This leads to the relief of the inhibitory effect of PTPN7 on MAPK/ERK signaling and consequently the augmentation of metastatic colonization of MPCs. Thus, via the extracellular vesicle miR-592/PTPN7/MAPK axis, melanoma-CSCs can transfer their metastatic ability to the low-metastatic non-CSC melanoma cells.

Abstract Background Metastatic melanoma has a high mortality rate and poor survival. This is associated with efficient metastatic colonization, but the underlying mechanisms remain elusive. Communication between cancer stem cells (CSCs) and cancer cells plays an important role in metastatic dissemination. Whether cancer stem cells can alter the metastatic properties of non-CSC cells; and whether exosomal crosstalk can mediate such interaction, have not been demonstrated in melanoma prior to this report. Results The results revealed that exosomes secreted by highly metastatic melanoma CSCs (OL-SCs) promoted the invasiveness of the low metastatic melanoma cells (OL) and accelerated metastatic progression. miR-1268a was up-regulated in cells and exosomes of OL-SCs. Moreover, OL-SCs-derived exosomal miR-1268a, upon taking up by OL cells, promoted the metastatic colonization ability of OL cells in vitro and in vivo. In addition, the pro-metastatic activity of exosomal miR-1268a is achieved through inhibition of autophagy. Conclusion Our study demonstrates that OL cells can acquire the “metastatic ability” from OL-SCs cells. OL-SCs cells achieves this goal by utilizing its exosomes to deliver functional miRNAs, such as miR-1268a, to the targeted OL cells which in turn augments metastatic colonization by inactivating the autophagy pathway in OL cells.

To investigate the toppling displacement evolution characteristics of anti-dip rock slopes, the Xiaodongcao-Zhengjiadagou bank slope is taken as an engineering case, and firstly, the geological geometric distribution characteristics of the slope are obtained by superimposing the lithology, slope, and elevation raster layers of the slope through ArcGIS, and the geological partition with the largest area is the Lower Triassic Daye Formation, bottom elevation, and medium slope; based on the actual surface displacement monitoring data, the spatio-temporal evolution nephogram of toppling displacement of bank slope every half year is interpolated by Inverse Distance Weight method, and then the last displacement nephogram is assigned to the thousandth and superimposed with the geological geometric partition to obtain the displacement superposition characteristics. The results show that: the obvious zone of horizontal displacement deformation mainly occurs in the front and middle of the bank slope, mainly shear deformation, vertical displacement is primarily in the front and the back edge of the bank slope and the total displacement deformation is more similar to the horizontal displacement; the horizontal displacement value is larger than the vertical displacement value, the horizontal displacement deformation controls the overall deformation of the bank slope; through the analysis of the geometric superposition evolution of the anti-dip rock slope, the displacement superposition strong deformation zone is located at the boundary between the Triassic Jialingjiang Formation (T1j) and the Triassic Daye Formation (T1d).

In this study, the 1991 rock avalanche, in Touzhai, Zhaotong, Yunnan, China, was considered the study object. The investigation of the landslide accumulation body revealed that the Touzhai rock avalanche accumulation body has the characteristics of wide gradation and poor sorting. A combination of field investigations, indoor and outdoor experiments, and numerical simulations were used to invert the occurrence and spreading range of rock avalanche-debris flow hazards. To invert and analyze its dynamics and the crushing process, a three-dimensional discrete element modeling was performed on the real terrain data. Simulation results showed that the movement time of the numerically simulated Touzhai rock avalanche was approximately 200 s. After 50 s of movement, the peak velocity reached 32 m/s, and the velocity gradually decayed after the sliding mass rubbed violently against the valley floor and collided with the mountain. Due to the meandering nature of the gully, the sliding mass makes its way down the gully and constantly collides with the mountain, making particles appear to climb, with some particles being blocked by the valley. After 150 s of movement, the average velocity rate decreased substantially, and the landslide-avalanche debris reached the mouth of the trench. After 200 s of movement, the average sliding velocity tends to 0 m/s, where the avalanche debris tends to stop and accumulate. When the rock avalanche movement reaches the mouth of the gully, the avalanche debris spreads to the sides as it is no longer bounded by the hills on either side of the narrow gully, eventually forming a ‘trumpet-shaped’ accumulation, and the granular flow simulation matched the findings of the landslide site accumulation.

Eremosparton songoricum (Litv.) Vass. is a rare and extremely drought-tolerant legume shrub that is distributed in Central Asia. E. songoricum naturally grows on bare sand and can tolerate multiple extreme environmental conditions. It is a valuable and important plant resource for desertification prevention and environmental protection, as well as a good material for the exploration of stress tolerance mechanisms and excellent tolerant gene mining. However, the regeneration system for E. songoricum has not yet been established, which markedly limits the conservation and utilization of this endangered and valuable desert legume. Assimilated branches derived from seedlings were cultured on several MS mediums supplemented with various concentrations of TDZ or 6-BA in different combinations with NAA. The results showed that the most efficient multiplication medium was MS medium supplemented with 0.4 mg/L 6-BA and 0.1 mg/L NAA. The most efficient rooting medium was WPM + 25 g/L sucrose. The highest survival rate (77.8%) of transplantation was achieved when the ratio of sand to vermiculite was 1:1. In addition, the optimal callus induction medium was MS + 30 g/L sucrose + 2 mg/L TDZ + 0.5 mg/L NAA in darkness. The E. songoricum callus treated with 100 mM NaCl and 300 mM mannitol on MS medium could be used in proper salt and drought stress treatments in subsequent gene function tests. A rapid and efficient regeneration system for E. songoricum that allowed regeneration within 3 months was developed. The protocol will contribute to the conservation and utilization of this rare and endangered desert stress-tolerant species and also provide a fundamental basis for gene functional analysis in E. songoricum.

This paper aims to introduce a numerical technique for forecasting the hazard caused by the disaster chain of landslide blocking river-dam breach floods through an integration of the distinct element method (DEM) and a well-balanced finite volume type shallow water model (SFLOW). A toppling slope in a reservoir area, the southeastern Tibetan Plateau, was chosen for the study. Creep has been observed in the potential instability area, and a possible sliding surface was identified based on the data collected from adits and boreholes. Catastrophic rock avalanches may be triggered after reservoir impoundment, and the associated landslide disaster chain needed to be predicted. First, the landslide blocking river process was modeled by the DEM using the three-dimensional particle flow code (PFC 3D). The landslide duration, runout distance, and kinematic characteristics were obtained. In addition, the landslide dam and barrier lake were constructed. Then, the cascading dam breach flood propagation was simulated using the self-developed SFLOW. The flow velocity, inundation depth, and area were obtained. The hazard maps derived from the combined numerical technique provided a quantitative reference for risk mitigation. The influences of two involved parameters on the final hazard-affected area are discussed herein. It is expected that the presented model will be applied in more prediction cases.

Abstract The mean survival of metastatic melanoma is less than 1 year. While the high mortality rate is associated with the efficient metastatic colonization of the involved organs, the underlying mechanisms remain elusive. The role of exosomes in facilitating the interactions between cancer cells and the metastatic microenvironment has received increasing attention. Previous studies on the role of exosomes in metastasis have been heavily focused on cancer cell-derived exosomes in modulating the functions of stromal cells. Whether the extravasated neighboring cancer cells at the distant organ can alter the metastatic properties of one another, a new mechanism of metastatic colonization, has not been demonstrated prior to this report. In this study, a paired M4 melanoma derivative cell lines, i.e., M14-OL and POL, that we established and characterized were employed. They exhibit high (POL cells) and low (OL cells) metastatic colonization efficiency in vivo, respectively. We show that exosomal crosstalk between metastatic cancer cells is a new mechanism that underlies cancer metastasis and heterogeneity. Low metastatic melanoma cells (OL) can acquire the “metastatic power” from highly metastatic melanoma cells (POL). POL achieves this goal by utilizing its exosomes to deliver functional miRNAs, such as miR-199a-1-5p, to the targeted OL cell which in turn inactivates cell cycle inhibitor CDKN1B and augments metastatic colonization.

Carbonic oxide(CO) can effectively reduce the risk of hydrogen embrittlement(HE) of hydrogen pipelines by inhibiting the adsorption of hydrogen molecules on the inner wall, which provides a potential solution to ensure the safe hydrogen transportation by the in-service pipelines. However, the influence of CO on HE index is related to the microstructure of steel materials. A case study was carried out to X80 steel, for which slow strain rate tension tests were conducted on the base material, pre-strained base material and two different types of root weld under the conditions of nitrogen, hydrogen and hydrogen + 0.1% CO(by partial pressure, the same below), so as to study the HE index and CO influence degree of pipe body in different states. According to the results, the HE indexes of the base material, pre-strained base material, automatic weld and manual weld under the condition of 12 MPa pure hydrogen are 35.75%, 43.72%, 39.28% and 33.66%, respectively, showing a very high risk of hydrogen embrittlement. However, the hydrogen embrittlement sensitivity could be reduced greatly with the addition of CO. Specifically, adding 0.1% CO can lower the HE index of the four kinds of specimens to 15.66%, 17.54%, 23.16% and 25.33%, respectively. Among them, the HE index of manual weld has the minimum reduction, which is least affected by CO among the studying objects. Therefore, it is recommended to study the minimum CO addition that could inhibit the HE at various hydrogen partial pressures for the manual weld area in future.

Abstract Background The genesis and developments of solid tumors, analogous to the renewal of healthy tissues, are driven by a subpopulation of dedicated stem cells, known as cancer stem cells (CSCs), that exhibit long-term clonal repopulation and self-renewal capacity. CSCs may regulate tumor initiation, growth, dormancy, metastasis, recurrence and chemoresistance. While autophagy has been proposed as a regulator of the stemness of CSCs, the underlying mechanisms requires further elucidation. Methods The CSC component in human melanoma cell lines M14 and A375 was isolated and purified by repetitive enrichments for cells that consistently display anchorage-independent spheroid growth. The stemness properties of the CSCs were confirmed in vitro by the expressions of stemness marker genes, the single-cell cloning assay and the serial spheroid formation assay. Subcutaneous tumor transplantation assay in BALB/c nude mice was performed to test the stemness properties of the CSCs in vivo. The autophagic activity was confirmed by the protein level of LC3 and P62, mRFP-LC3B punta and cytoplasmic accumulation of autolysosomes. The morphology of ER was detected with transmission electron microscopy. Results In the present study, by employing stable CSC cell lines derived from human melanoma cell lines M14 and A375, we show for the first time that Sec23a inhibits the self-renewal of melanoma CSCs via inactivation of ER-phagy. Mechanistically, inhibition of Sec23a reduces ER stress and consequently FAM134B-induced ER-phagy. Furthermore, TCGA data mining and analysis show that Sec23a is a favorable diagnostic and prognostic marker for human skin cutaneous melanoma. Conclusion This study has elucidated a new mechanism underlying the regulation of autophagy on stemness, i.e. CSCs can exploit the SEC23A/ER-stress/FAM134B/ER-phagy axis for the self-renewal. These observations provide new ideas for exploration of the regulatory network of CSC self-renewal to develop CSCs-based therapy strategies for malignant tumors. Video Abstract

The improper stockpiling of lead/zinc mine tailings results in significant toxic impurities releasing, which threatens both the surrounding environment and human health. Cemented paste backfill (CPB) is considered an effective in-situ remediation way for managing lead/zinc mine tailings. In this study, the mechanical performance and heavy metal retention of CPB were evaluated by comparing the different binder strategies of ordinary Portland cement (OPC), Ca-bentonite, and Na-bentonite. The engineering properties of the mixtures were verified by uniaxial compressive strength (UCS) tests. The phase composition and internal microstructure were obtained by X-ray diffraction (XRD) and scanning electron microscopy (SEM). Toxicity characteristic leaching procedure (TCLP) was performed to ascertain the effectiveness of heavy metal retention capacity. The results showed that the use of bentonite effectively optimized the UCS at early ages. Despite the deterioration is observed at 28 days, the UCS values are still qualified for the engineering application. With XRD and SEM analysis, a great content of amorphous was quantitatively characterized, highlighting the importance of amorphous content in the regulation of mechanical properties. TCLP results indicate that all the Pb, Cd, and As are predominantly incorporated within the cementitious matrix, whereas the Zn is the only concern in which the leachability decreases with the Ca-bentonite proportion. The leachates met the regulation limits (0.1 mg/L) at the CPB samples with 1.28 wt% of Ca-bentonite. Overall, bentonite could be an attractive alternative for the in-situ remediation of lead/zinc mine tailings to revive the stockpile site and reduce the environmental influence of this solid waste.

Syntrichia caninervis is a desiccation tolerant moss and is the dominant bryophyte found in biological soil crusts in the Gurbantunggut desert. In this study, we assessed the transcriptome profiles of S. caninervis gametophytes during the dehydration-rehydration (D-R) process (across 9 time points) using Illumina sequencing. In total, 22489 transcripts were identified, including 5337 novel transcripts, that mapped to the reference genome. A total of 12548 transcripts exhibited significant alterations in the D-R samples compared with the control samples. The differentially expressed transcripts (DETs) possessed several enriched Gene Ontology terms, such as “water stress response”, “oxidation-reduction process”, “membrane metabolism”, “photosynthesis”, and “transcription factor activity”. Moreover, during early dehydration stress, the DETs were significantly enriched in stress-related pathways from the Kyoto Encyclopedia of Genes and Genomes, such as “phenylpropanoid biosynthesis”, “alpha-linolenic acid metabolism”, and “fructose and mannose metabolism”. Photosynthesis-related transcripts (e.g., ScPsa H, ScRubisco, and ScLhcb1) were inhibited during the dehydration treatment and significantly accumulated during the late rehydration period. Most transcripts from the late embryogenesis abundant proteins (LEA) and early light-inducible protein (ELIP) families strongly accumulated at the late dehydration stage. These pathways were positively correlated with the content changes of absolute water content and Fv/Fm values, alongside peroxidase and superoxide dismutase activities. Seven transcription factor families, including AP2-ERF, bHLH, G2-like, MYB, NAC, WRKY, and bZIP, were enriched in DETs during D-R treatment. This study is the first transcriptome analysis using the S. caninervis genome for gene annotation and multigroup D-R treatment points. Our results demonstrated the detailed dynamic changes in the transcriptome of S. caninervis during the D-R process. These results also improve understanding of desiccation tolerant plants’ adaptations to desiccation stress at the transcription level and provide promising gene resources for transgenic crop breeding.

Overtopping dam break is a frequent accident in tailings reservoirs. However, little attention has been paid to the study of overtopping hydraulic erosion damage characteristics of tailings dam after adding reinforcement. Nowadays, there were few people have researched the prediction of the overtopping failure process of the reinforced tailings dam. It is important significance to establish a prediction model for the overtopping of reinforced tailings dam which aims at the problem of overtopping erosion of reinforced tailings. For the anti-erosion and anti-collapse effects of the reinforced tailings dam, a mathematical model for the development of the overtopping breach of the reinforced tailings dam is established. The formula of reinforced erosion rate derived from water flow shear stress theory, simulation of breach erosion development by time iteration method in the mathematical model. Secondly, the limit equilibrium method is used to analyze the stability of the reinforced breach slope. Then, the physical test is used to reproduce the dam failure process of the tailings dam. In addition, the development process of the breach and discharge are monitored. Ultimately, the maximum depth and width of the breach are in brilliant agreement with the calculated values.

Adding a type of municipal solid waste (incinerator slag) into ultrafine tailings can effectively enhance the mechanical properties of tailings. With an aim to study the macro- and micro-mechanical properties of the tailings slag mixture (TSM), the strength parameters (internal friction angle, cohesion) and micro-mechanical properties with different slag contents were analyzed by geotechnical experiments and particle flow simulations, respectively. The macroscale experimental results demonstrated that the strength parameters of TSM were much higher than that of tailings. Strength parameters also showed non-linear-rising trends with increasing slag content. For the slag content of 40%, the maximum cohesiveness of TSM was determined at 65.2 kPa, and the corresponding friction angle was 39.9°C. Furthermore, the Particle Flow Code (PFC) micro-simulation software was used to analyze the micro-mechanical characteristics of the TSM at different slag contents. The microscale simulation outcomes indicated that the particle transport, particularly in their moving directions, became increasingly chaotic with an increase in the slag content; also, the slag particles significantly impacted the shear processing zone of the TSM. These experimental and numerical results brought more scientific insights into the shear failure mechanism of TSM.

Abstract Background Freezing temperatures are an abiotic stress that has a serious impact on plant growth and development in temperate regions and even threatens plant survival. The wild apple tree (Malus sieversii) needs to undergo a cold acclimation process to enhance its freezing tolerance in winter. Changes that occur at the molecular level in response to low temperatures are poorly understood in wild apple trees. Results Phytohormone and physiology profiles and transcriptome analysis were used to elaborate on the dynamic response mechanism. We determined that JA, IAA, and ABA accumulated in the cold acclimation stage and decreased during freezing stress in response to freezing stress. To elucidate the molecular mechanisms of freezing stress after cold acclimation, we employed single molecular real-time (SMRT) and RNA-seq technologies to study genome-wide expression profiles in wild apple. Using the PacBio and Illumina platform, we obtained 20.79G subreads. These reads were assembled into 61,908 transcripts, and 24,716 differentially expressed transcripts were obtained. Among them, 4410 transcripts were differentially expressed during the whole process of freezing stress, and these were examined for enrichment via GO and KEGG analyses. Pathway analysis indicated that “plant hormone signal transduction”, “starch and sucrose metabolism”, “peroxisome” and “photosynthesis” might play a vital role in wild apple responses to freezing stress. Furthermore, the transcription factors DREB1/CBF, MYC2, WRKY70, WRKY71, MYB4 and MYB88 were strongly induced during the whole stress period. Conclusions Our study presents a global survey of the transcriptome profiles of wild apple trees in dynamic response to freezing stress after two days cold acclimation and provides insights into the molecular mechanisms of freezing adaptation of wild apple plants for the first time. The study also provides valuable information for further research on the antifreezing reaction mechanism and genetic improvement of M. sieversii after cold acclimation.

Chitinases are responsible for catalyzing the hydrolysis of chitin and contribute to plant defense against fungal pathogens by degrading fungal chitin. In this study, genome-wide identification of the chitinase gene family of wild apple (Malus sieversii) and domesticated apple (Malus domestica) was conducted, and the expression profile was analyzed in response to Valsa mali infection. A total of 36 and 47 chitinase genes belonging to the glycosyl hydrolase 18 (GH18) and 19 (GH19) families were identified in the genomes of M. sieversii and M. domestica, respectively. These genes were classified into five classes based on their phylogenetic relationships and conserved catalytic domains. The genes were randomly distributed on the chromosomes and exhibited expansion by tandem and segmental duplication. Eight of the 36 MsChi genes and 17 of the 47 MdChi genes were differentially expressed in response to V. mali inoculation. In particular, MsChi35 and its ortholog MdChi41, a class IV chitinase, were constitutively expressed at high levels in M. sieversii and domesticated apple, respectively, and may play a crucial role in the defense response against V. mali. These results improve knowledge of the chitinase gene family in apple species and provide a foundation for further studies of fungal disease prevention in apple.

Peptic ulcer disease (PUD) is a common disease and frequently encountered in the clinic. Accumulating evidence suggests that PUD is associated with the gastrointestinal microbiota. Electroacupuncture (EA) is an improved version of acupuncture, which can improve the clinical effect by increasing the stimulation and delivering appropriate electrical pulses to needles. This method has been widely used in the treatment of peptic ulcer disease. However, its effect on gastrointestinal microbiota remains unclear. Therefore, in the present study, the ameliorative effect of EA was evaluated on the gastroduodenal mucosa, and the regulatory effect of the gastroduodenal microbiota was assessed in PUD mice. A total of 48 male Kun Ming mice were randomly divided into the following groups: normal control group (NC), PUD model group (PUD), Shousanli group (LI10), and Zusanli group (ST36) (n=12). The mice in groups LI10 and ST36 were treated with EA at LI10 and ST36, respectively. This intervention was continued for 7 days. Subsequently, we evaluated the morphological changes in the gastric and duodenal mucosa, and specific indices were measured, including the contents of serum dopamine (DA), the trefoil factor (TFF), and the vasoactive intestinal peptide (VIP). In addition, the gastric and duodenal microbiota were assessed via 16S ribosomal DNA sequencing. The results indicated that EA at LI10 or ST36 significantly reduced the injury of the gastroduodenal mucosa in PUD mice. The gastric microbial community structure of the groups LI10 and ST36 was similar to that of the NC group following comparison with the microbial community structure of the PUD model group. Moreover, the abundance of Firmicutes in the stomach was decreased, whereas that of Bacteroidetes was increased, and the abundance of Firmicutes in the duodenum was decreased. Furthermore, the microbial diversity and richness of the gastric microbiota in group LI10 were also significantly increased, and the serum dopamine and trefoil factor levels in group ST36 were significantly increased. Therefore, it is suggested that EA ameliorating PUD is in association with improving the levels of DA and TFF and regulating the relative abundances of Firmicutes and Bacteroidetes in the gastric microbiota.

Eremosparton songoricum (Litv.) Vass. is a rare leafless legume shrub endemic to central Asia which grows on bare sand. It shows extreme drought tolerance and is being developed as a model organism for investigating morphological, physiological, and molecular adaptations to harsh desert environments. APETALA2/Ethylene Responsive Factor (AP2/ERF) is a large plant transcription factor family that plays important roles in plant responses to various biotic and abiotic stresses and has been extensively studied in several plants. However, our knowledge on the AP2/ERF family in legume species is limited, and no respective study was conducted so far on the desert shrubby legume E. songoricum. Here, 153 AP2/ERF genes were identified based on the E. songoricum genome data. EsAP2/ERFs covered AP2 (24 genes), DREB (59 genes), ERF (68 genes), and Soloist (2 genes) subfamilies, and lacked canonical RAV subfamily genes based on the widely used classification method. The DREB and ERF subfamilies were further divided into A1–A6 and B1–B6 groups, respectively. Protein motifs and exon-intron structures of EsAP2/ERFs were also examined, which matched the subfamily/group classification. Cis-acting element analysis suggested that EsAP2/ERF genes shared many stress- and hormone-related cis-regulatory elements. Moreover, the gene numbers and the ratio of each subfamily and the intron-exon structures were systematically compared with other model plants ranging from algae to angiosperms, including ten legumes. Our results supported the view that AP2 and ERF evolved early and already existed in algae, whereas RAV and DREB began to appear in moss species. Almost all plant AP2 and Soloist genes contained introns, whereas most DREB and ERF genes did not. The majority of EsAP2/ERFs were induced by drought stress based on RNA-seq data, EsDREBs were highly induced and had the largest number of differentially expressed genes in response to drought. Eight out of twelve representative EsAP2/ERFs were significantly up-regulated as assessed by RT-qPCR. This study provides detailed insights into the classification, gene structure, motifs, chromosome distribution, and gene expression of AP2/ERF genes in E. songoricum and lays a foundation for better understanding of drought stress tolerance mechanisms in legume plants. Moreover, candidate genes for drought-resistant plant breeding are proposed.

Under seismic action, the stock of phosphogypsum (PG) affects the security risk significantly, so it is crucial to study the dynamic characteristics of PG. In this article, unidirectional and bidirectional vibration tests on typical PG in Yunnan under different consolidation-confining pressure and vibration conditions were carried out using a dynamic triaxial apparatus that can be used for bidirectional vibration. The results show that the pore pressure growth of PG under both unidirectional and bidirectional vibrations has obvious stages and can be fitted by the BiDoseResp function. The dynamic strength of PG does not increase monotonically with the increase in consolidation-confining pressure and dynamic stress under the same cyclic stress ratio (CSR) but varies under a specific critical condition. The dynamic strength of PG decreases significantly with the increase in CSR under unidirectional and bidirectional vibrations. The number of vibrations required for liquefaction by bidirectional vibrations is much larger than that by unidirectional vibrations under the same CSR conditions, and the specimens have significant softening characteristics after liquefaction by bidirectional vibrations. The study results can provide theoretical references for studying the dynamic stability of PG reservoirs under seismic action.

With the improvement in tailing mining-grade requirements and in mineral processing technology, tailing materials tend to be fine-grained. Under the action of earthquakes, a tailing dam is prone to liquefaction, which endangers the safety and stability of the dam. To further explore the dynamic properties of tailing silt under cyclic stress, through a series of dynamic triaxial experiments, we investigated the growth of the hysteresis curve, the development of pore pressure, and the energy dissipation law of tailing silt. The experimental findings indicated that increasing the density of the sample significantly improves its liquefaction resistance and the pore pressure development curve can be fitted using the BiDoseResp function. At the same cyclic stress ratio, the sample’s anti-liquefaction strength did not rise monotonically with increasing confining pressure but changed variably at values near a specified low confining pressure; when the sample density rose under the same settings, the specific confining pressure reduced. We also further discussed the evolution law of the stress–strain curves of tailing silt. The results further explored the dynamic characteristics of tailing silt, which can provide some reference for the seismic design and reinforcement measures of many fine-grained tailing dams.

Syntrichia caninervis can survive under 80–90% protoplasmic water losses, and it is a model plant in desiccation tolerance research. A previous study has revealed that S. caninervis would accumulate ABA under dehydration stress, while the ABA biosynthesis genes in S. caninervis are still unknown. This study identified one ScABA1, two ScABA4s, five ScNCEDs, twenty-nine ScABA2s, one ScABA3, and four ScAAOs genes, indicating that the ABA biosynthesis genes were complete in S. caninervis. Gene location analysis showed that the ABA biosynthesis genes were evenly distributed in chromosomes but were not allocated to sex chromosomes. Collinear analysis revealed that ScABA1, ScNCED, and ScABA2 had homologous genes in Physcomitrella patens. RT-qPCR detection found that all of the ABA biosynthesis genes responded to abiotic stress; it further indicated that ABA plays an important role in S. caninervis. Moreover, the ABA biosynthesis genes in 19 representative plants were compared to study their phylogenetic and conserved motifs; the results suggested that the ABA biosynthesis genes were closely associated with plant taxa, but these genes had the same conserved domain in each plant. In contrast, there is a huge variation in the exon number between different plant taxa; it revealed that ABA biosynthesis gene structures are closely related to plant taxa. Above all, this study provides strong evidence demonstrating that ABA biosynthesis genes were conserved in the plant kingdom and deepens our understanding of the evolution of the phytohormone ABA.

Transcription factor (TF) families play important roles in plant stress responses. S. caninervis is a new model moss for plant desiccation tolerance studies. Here, we report a high-confidence identification and characterization of 591 TFs representing 52 families that covered all chromosomes in S. caninervis. GO term and KEGG pathway analysis showed that TFs were involved in the regulation of transcription, DNA-templated, gene expression, binding activities, plant hormone signal transduction, and circadian rhythm. A number of TF promoter regions have a mixture of various hormones-related cis-regulatory elements. AP2/ERF, bHLH, MYB, and C2H2-zinc finger TFs were the overrepresented TF families in S. caninervis, and the detailed classification of each family is performed based on structural features. Transcriptome analysis revealed the transcript abundances of some ScAP2/ERF, bHLH, MYB, and C2H2 genes were accumulated in the treated S. caninervis under cold, dehydration, and rehydration stresses. The RT-qPCR results strongly agreed with RNA-seq analysis, indicating these TFs might play a key role in S. caninervis response to abiotic stress. Our comparative TF characterization and classification provide the foundations for functional investigations of the dominant TF genes involved in S. caninervis stress response, as well as excellent stress tolerance gene resources for plant stress resistance breeding.