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Abstract To solve the problem of controlling mining in the open-pit mine end slope fire-burned area, applying multivariate function fitting to the roof and floor modeling of multi-coal seam open pit mines, introducing the factor of coal quality changes in the fire-burned area, determining coal quality information at each location through proximate analysis of coal, to establish the net profit model of the mining area, it is determined the net profit of each mining position by numerical integration, the final mining position was determined without failure by calculating the slope stability based on the numerical simulation of strength reduction. Taking the Dananhu No. 2 open-pit mine in Hami, Xinjiang, China as the engineering background, the fire-burned area III within the southern end slope boundary of the first mining area is 240 m. It was finally determined that the optimal mining position is when the advancement degree is 182 m, the ultimate pit slope angle is 25°, the three-dimensional slope stability is 1.305, the profit is 671.96 million yuan, The deep boundary of the southern end slope fire-burned area of the slope is reduced by 58 m. This paper solves the problem of end slope mining in Dananhu No. 2 mine, and maximizes its net profit under the condition of ensuring safe production.

Abstract Open-pit mine pavement dust dries and breaks easily. As such, a composite pavement dust suppressant with good wettability, moisturizing, coagulation, and antifreezing properties in winter was investigated. Monomer screening and orthogonal experiments were conducted, using evaporation rate, permeability rate, viscosity, and freezing point as evaluation indexes. Consequently, a dust suppressant solution is a mixture of glycerol (GLY), sodium dodecylbenzene sulfonate (SDBS), polyacrylamide (PAM), compound propylene glycol (PG), and potassium acetate (PA). The characteristics of the dust suppressant and its interaction mechanism with road dust were measured and analyzed. The results showed that the optimal ratio of the antifreeze-type composite dust suppressant is 3%GLY, 0.30%SDBS, 0.07% PAM, and 50%PG + 10%PA; the contact angle is 27.62°, which can effectively wet coal dust. Moreover, it easily forms hydrogen bonds with water molecules to release free -OH, which increases the oxygen-containing functional groups in the dust. The maximum viscosity is 25.4 mPa·s, and the hydrophobic groups adsorbed on the surface of the dust can condense and agglomerate the dust to form large particles, and effectively inhibit the occurrence of dust. It freezes at − 34.2 ℃, resists a temperature of − 30 ℃ without freezing, and improves dust suppression efficiency and antifreezing effect in cold areas.

Objective: To increase the yield of Sophora flavescens polysaccharides and elucidate their antioxidant and hypolipidemic properties, this study optimised the polysaccharide extraction process through orthogonal experiments, followed by evaluation of their antioxidant and hypolipidemic activities in vitro. Methods: Using polysaccharide yield as the primary metric, this study performed orthogonal experiments to optimise the extraction process, building on preliminary one-way experiments. This study investigated the effect of extraction temperature, number of extractions, material-liquid ratio and extraction time on the polysaccharide yield of Sophora flavescens. Furthermore, this study evaluated the in vitro antioxidant activity of the polysaccharides by investigating their scavenging potential against DPPH radicals, hydroxyl radicals and superoxide anion radicals. In addition, the in vitro hypolipidemic activity of the polysaccharides was evaluated by their binding affinity to sodium cholate (SC), sodium taurocholate (STC), sodium glycylcholate (SGC) and mixed bile salts (MBS). Results: The optimal conditions for the extraction of Sophora flavescens polysaccharide were determined as follows: a temperature of 85 ℃, a material-liquid ratio of 1:35 (g:mL), and an extraction duration of 3.5 hours, yielding an average polysaccharide content of 3.07%±0.07%. The scavenging efficiencies of Sophora flavescens polysaccharides against DPPH radicals, hydroxyl radicals, and superoxide anion radicals at a concentration of 5 mg/mL were measured at 60.1%±3.6%, 39.6%±3.1% and 45.1%±4.1%, respectively. Furthermore, the binding affinities of Sophora flavescens polysaccharides to SC, STC, SGC and MBS at a concentration of 10 mg/mL were determined to be 34.4%±0.75%, 45.4%±0.15%, 19.7%±0.94% and 37.7%±0.64%, respectively. Conclusion: Sophora flavescens polysaccharide exhibits notable in vitro antioxidant and hypolipidemic activities. This investigation furnishes a foundational understanding for the potential development and exploitation of Sophora flavescens polysaccharide.

To investigate the role of Vanadium element in Ti2AlNb-based alloy, Ti–22Al–26Nb-xV (x = 0, 2, 8) alloys were cooled from the B2 single-phase temperature (1300 °C) at controlled process parameters. The isothermal preheating in the B2 single-phase zone contributes to the homogenization of microstructure and the elimination of micro-segregation in subsequent microstructure evolution. Two typical microstructures after temperature-controlled cooling experiments can be obtained: B2+O two-phase and α2+B2+O three-phase microstructures. The effects of Vanadium content and cooling rate on phase transformation and microstructure evolution were analyzed. The crystallographic relationship between B2, α2 and O phases was identified as follows: {011}B2/β//{0001}α2, B2/β//α2, {110}B2/β//{001}O, < 1‾ 11> B2/β//O, {0001}α2//{001}B2/β, α2// O. Last, the compression tests of these heat-treated samples were performed, and the microstructure-dependent mechanical properties were discussed.

Accurately tracking and analyzing human motion during aerobic exercise poses significant challenges due to the dynamic complexity of human biomechanics. Traditional methods often fail to capture this complexity, resulting in training plans that lack personalization and an increased risk of exercise-related injuries. Therefore, developing a method capable of accurately understanding and analyzing the dynamics of human motion has become particularly important. The motivation behind this study is to enhance the safety and effectiveness of aerobic exercise training. By accurately monitoring and analyzing the movements of athletes during their training, it aims to prevent injuries and create personalized training plans. To this end, we believe a new approach is needed to deeply understand human motion, one that can adapt to various environmental changes and provide real-time feedback. We propose a framework that combines 3D pose estimation with kinematic modeling. This method employs self-attention mechanisms and machine learning techniques to precisely capture the complexity of human motion. Our core technology includes a self-attention-based pose estimation system capable of accurately tracking 3D joint positions in various environments, and a detailed kinematic model for biomechanical analysis, including the calculation of joint angles, velocities, and accelerations. Our model was validated using a custom aerobic exercise dataset, demonstrating superior accuracy and adaptability compared to existing models. Comparative analyses with other models highlight the advanced capabilities of our model in accurately interpreting and analyzing human motion. Our experiments confirm that the model excels in precision, robustness to environmental changes, real-time feedback, and injury prevention. Notably, it significantly reduces injury risks by identifying potential stress points and facilitates the generation of personalized training plans.

Treatment of large and complex irregular bone defects is a major clinical challenge in orthopedic surgery. The current treatment includes bone transportation using the Ilizarov technique and bone cement repair using the Masquelet technique, but they require long-term manual intervention or secondary operation. To improve this situation, we compared the different implanting materials in the literature published in the past 10 years, finding that glycolic acid copolymer (PLGA) and Calcium sulfate (CaSO4) are appropriated to be used as synthetic bone materials due to their advantages of easy-availability, nontoxicity, osteogenic properties and rapid degradation. Meanwhile, the development of 3D printing technique and devices makes it relatively easier to synthetize customized bio-mimetic porous scaffolds, thus facilitating the release of modified protein. In this study, we compounded BMP-2/PLGA microspheres with polylactic glycolic acid copolymer/CaSO4 (PC) 3D printed scaffold to improve the osteogenic properties of the scaffold. The result of our in vitro experiment demonstrated that the prepared PCB scaffold not only had satisfactory bio-compatibility, but also promoted osteogenic differentiation. This 3D printed scaffold is capable to accelerate the repair of complex bone defects by promoting new bone formation, suggesting that it may prove to be a potential bone tissue engineering substitute.

Abstract Background DNA damage repair is a crucial mechanism highly related to therapy resistance for various therapeutic strategies. Our previous results have shown that the degree of drug resistance in small‐cell lung cancer (SCLC) cell lines was proportional to both the transcription and expression levels of Wee1, indicating that Wee1, an evolutionarily highly conserved kinase, plays a vital role in the therapeutic resistance of SCLC. In the present study, we aim to determine the nonclassical mechanism of Wee1 on DNA repair regulation. Methods Western blot was conducted to determine the mono‐ubiquitination level of H2Bub. Comet assay was used to evaluate the degree of DNA damage. Immunofluorescence was conducted to determine the DNA repair markers. Co‐immunoprecipitation was utilized to assess the potential interactions with H2BY37ph. MTT assays were used to evaluate the survival rates of SCLC cells. Results Overexpression of Wee1 increases the level of H2BK120ub and alleviates ionizing radiation (IR)‐induced DNA damage in SCLC cells. Moreover, H2BK120ub is a crucial molecule in Wee1‐mediated double‐strain break (DSB) repair in SCLC cells. Mechanisms study indicated that H2BY37ph is involved in Wee1‐mediated H2BK120ub through interaction with the E3 ubiquitin ligase RNF20–RNF40 complex and upregulates its phosphorylation, mutation of H2BY37 phosphorylation sites attenuated DSB repair and enhanced the sensitivity of IR‐induced SCLC cell death. Conclusion H2BY37ph produces crosstalk with H2BK120ub in an E3 ubiquitin ligase‐dependent manner, promoting Wee1‐mediated DSB repair in SCLC cells. This study clarifies the nonclassical mechanism of Wee1 regulation of DSB repair, which provides a theoretical basis for the clinical understanding of the regulatory network of Wee1 and its use as a target for overcoming multiple types of therapeutic resistance.

In order to increase the development and utilization value of polysaccharides from Olea europaea L. leaves, the extraction process of polysaccharides from Olea europaea L. leaves (OLP) was optimized by orthogonal experiment, the molecular weight was determined by high performance gel permeation chromatography combined with multi-angle laser light scattering (HPGPC-MALLS), and the monosaccharide composition of OLP was analyzed by PMP pre-column derivatization and its antioxidant activity was evaluated. The results showed that the optimal extraction conditions were material-liquid ratio of 1:27.5 g/mL, extraction temperature of 95 ℃ and extraction time of 3.5 h. Under these conditions, the yield of OLP was 2.75%. The average weight molecular weight (Mw) of OLP was 25.36 kDa, the average number molecular weight (Mn) was 19.32 kDa, and the polydispersity was 1.313. OLP was mainly composed of glucose (Glc), galactose (Gal) and galactose amino (GalN), but also contains rhamnose (Rha), arabinose (Ara), xylose (Xyl), mannose (Man) and glucosamine (GlcN), and the relative molar ratio of monosaccharide was 56.2:15.9:10.3:8.3:5.9:2.6:0.5:0.3. The results showed that OLP had good antioxidant activity, with IC50 of 0.422, 0.302 and 0.268 mg/mL for hydroxyl free radical, superoxide anion free radical and DPPH free radical, respectively. The optimum technology of OLP is simple, the yield is high, and the antioxidant activity is good, which provides an essential reference for the further research, development and utilization of OLP.

Abstract Background To investigate the prognostic significance of station 4R lymph node (LN) dissection in patients who underwent operations for right primary non-small cell lung cancer (NSCLC). Methods We performed a retrospective study involving patients with right primary NSCLC who received lobotomy or pneumonectomy with mediastinal LN dissection between January 2011 and December 2017. Propensity score matching was performed. Disease-free survival (DFS) and overall survival (OS) were compared between patients with and without station 4R dissection. Results Our study included 2070 patients, with 207 patients having no station 4R dissection (S4RD− group) and 1863 patients having station 4R dissection (S4RD+ group). The 4R LN metastasis rate was 13.4% (142/1748), higher than that for other mediastinal LN metastases. Compared with the S4RD− group, the S4RD+ group had higher 5-year DFS (48.1% vs. 39.1%, P = 0.009) and OS (54.4% vs. 42.8%, P = 0.025). Station 4R dissection was an independent risk factor for DFS (odds ratio, OR, 1.28, 95% confidence interval, CI, 1.08–1.64, P = 0.007) and OS (OR 1.31, 95% CI 1.04–1.63, P = 0.018). Patients with adjuvant chemotherapy had a better prognosis after station 4R dissection than those without adjuvant chemotherapy (57.4% vs. 52.3%, P = 0.006). The 5-year OS in the station 4R metastasis group was lower than that in the station 4R non-metastasis group (26.9% vs. 44.3%, P = 0.006) among N2 patients. The 5-year OS of the single-station 4R metastasis group was lower than that of the single-station 7 metastasis group (15.7% vs. 51.6%, P = 0.002). Conclusions Station 4R metastasis was the highest among all the mediastinal station metastases in right primary NSCLC patients. Station 4R dissection can improve the prognosis and should be recommended as a routine procedure for these patients.

Background: The complexity and rapid progression of lesions in diabetic kidney disease pose significant challenges for clinical diagnosis and treatment. The advantages of Traditional Chinese Medicine (TCM) in diagnosing and treating this condition have gradually become evident. However, due to the disease’s complexity and the individualized approach to diagnosis and treatment in Traditional Chinese Medicine, Traditional Chinese Medicine guidelines have limitations in guiding the treatment of diabetic kidney disease. Most medical knowledge is currently stored in the process of recording medical records, which hinders the understanding of diseases and the acquisition of diagnostic and treatment knowledge among young doctors. Consequently, there is a lack of sufficient clinical knowledge to support the diagnosis and treatment of diabetic kidney disease in Traditional Chinese Medicine.Objective: To build a comprehensive knowledge graph for the diagnosis and treatment of diabetic kidney disease in Traditional Chinese Medicine, utilizing clinical guidelines, consensus, and real-world clinical data. On this basis, the knowledge of Traditional Chinese Medicine diagnosis and treatment of diabetic kidney disease was systematically combed and mined.Methods: Normative guideline data and actual medical records were used to construct a knowledge graph of Traditional Chinese Medicine diagnosis and treatment for diabetic kidney disease and the results obtained by data mining techniques enrich the relational attributes. Neo4j graph database was used for knowledge storage, visual knowledge display, and semantic query. Utilizing multi-dimensional relations with hierarchical weights as the core, a reverse retrieval verification process is conducted to address the critical problems of diagnosis and treatment put forward by experts.Results: 903 nodes and 1670 relationships were constructed under nine concepts and 20 relationships. Preliminarily a knowledge graph for Traditional Chinese Medicine diagnosis and treatment of diabetic kidney disease was constructed. Based on the multi-dimensional relationships, the diagnosis and treatment questions proposed by experts were validated through multi-hop queries of the graphs. The results were confirmed by experts and showed good outcomes.Conclusion: This study systematically combed the Traditional Chinese Medicine diagnosis and treatment knowledge of diabetic kidney disease by constructing the knowledge graph. Furthermore, it effectively solved the problem of “knowledge island”. Through visual display and semantic retrieval, the discovery and sharing of diagnosis and treatment knowledge of diabetic kidney disease were realized.

Passive heat dissipation was a prospective solution to gratify the thermal management requirements of the continuously compact and miniaturized package. In here, we proposed an embedded heat pipe SiC interposer for the distributed power devices. The thermal effects of wick shape and filling ratio were investigated through the established VOF (volume of fluid) models. The hotspots' arrangement was identified by comparing thermal performance with hotspots' placing at 22.5°, 45°, and 90° in the vertical coordinate system. The 45° arrangement was settled by analyzing the effects on refilling path between the evaporation and condensation areas. Profited from the SiC substrate transparency, the embedded thermography visualization platform was deployed to verify the two-phase flow behaviors inside the SiC interposer with various heat fluxes. Through the Infrared imager and non–contact Raman–based thermometry, the heat transfer coefficient (90 kW/m2·°C @ 160 W/cm2), maximum temperature difference (within 2.6 °C @ 160 W/cm2), and the distributed radial and axial thermal resistances (0.167–0.178 °C/W and 0.157–0.163 °C/W) of the SiC interposer were ascertained, respectively. Towards the distributed power devices embedded heat pipe interposer, the substrate material, the wick geometry, the filling ratio, and hotspots’ arrangement need to be comprehensively optimized.

Some photosensitive resins have poor mechanical properties after 3D printing. To overcome these limitations, a polyurethane acrylate oligomer (PUA) microsphere was prepared using the Pickering emulsion template method and ultraviolet (UV) curing technology in this paper. The prepared PUA microspheres were added to PUA-1,6-hexanediol diacrylate (HDDA) photosensitive resin system for digital light processing (DLP) 3D printing technology. The preparation process of PUA microspheres was discussed based on micromorphology, and it was found that the oil-water ratio of the Pickering emulsion and the emulsification speed had a certain effect on the microsphere size. As the oil-water ratio and the emulsification speed increased, the microsphere particle size decreased to a certain extent. Adding a suitable proportion of PUA microspheres to the photosensitive resin can improve the mechanical properties and thermal stability. When the modified photosensitive resin microsphere content was 0.5%, the tensile strength, elongation at break, bending strength, and initial thermal decomposition temperature were increased by 79.14%, 47.26%, 26.69%, and 10.65%, respectively, compared with the unmodified photosensitive resin. This study provides a new way to improve the mechanical properties of photosensitive resin 3D printing. The resin materials studied in this work have potential application value in the fields of ceramic 3D printing and dental temporary replacement materials.

Faced with difficulties stemming from the complex interactions between tight gas sand bodies and fractures, when describing and identifying reservoirs, a composite reservoir model was established. By setting the supply boundary to characterize the superposition characteristics of sand bodies, a mathematical model of unstable seepage in fractured vertical wells in tight sandstone gas reservoirs was developed, considering factors such as stress sensitivity, fracture density and fracture symmetry. The seepage law and pressure response characteristics of gas wells in tight sandstone discontinuous reservoirs with stress sensitivity, semi-permeable supply boundary and complex fracture topology were determined, and the reliability of the model was verified. The research results more accurately display the pressure characteristic of a vertical well in the superimposed sand body with complex fractures and provide a more comprehensive model for tight gas production dynamic analysis and well test data analysis, which can more accurately guide the dynamic inversion of reservoir and fracture parameters.

Restoring vegetation on waste dumps is imperative because soil erosion heavily impacts these areas and creates erosion micro-topographies, including bare slopes, rills, ephemeral gullies, and deposit bodies. These micro-topographies may affect seedling emergence by forming special micro-habitats, although the mechanism is vague. This study determined the substrate chemical (i.e., pH and electrical conductivity) and physical (i.e., capillary porosity, capillary water content, and mechanical composition) properties of different micro-topographies. In addition, the temporal dynamics of micro-climates (i.e., air temperature and air humidity), substrate hydrothermal conditions (i.e., substrate temperature and water content), and seedling emergence were investigated. Redundancy analysis (RDA), random forest (RF), and receiver operating characteristic (ROC) curve analysis were then used to identify the main factors affecting seedling emergence and clarify the relationships among the environmental conditions. Our results demonstrate that seedling densities in the rill, ephemeral gully, and deposit body were 1.78 times, 3.42 times, and 3.97 times higher than those on the bare slope, respectively. More species were found in the rill, ephemeral gully, and deposit body (Artemisia annua, Salsola collina, Setaria viridis, and Tribulus terrestris) than on the bare slope (Salsola collina). The main factors affecting seedling emergence were air humidity, substrate temperature, and substrate water content. The mechanical composition may have affected substrate water content during the initial stage of seedling emergence and substrate temperature during the entire period. We demonstrate that the ephemeral gully and deposit body may provide micro-habitats with a lower substrate temperature and higher substrate water content, which are favorable to seedling emergence, thus guiding vegetation restoration on waste dumps or other disturbed areas.

Abstract Background CITED4 belongs to the CBP/p300‐interacting transactivator with glutamic acid and aspartic acid‐rich tail (CITED) family which is induced by various cytokines and participates in cytokine‐induced proliferation and differentiation. CITED4 is induced by HB‐EGF in lung cancer cells. However, it is unclear whether and how CITED4 contributes to the invasion and metastasis of lung adenocarcinoma (ADC). Methods CITED4 expression in lung adenocarcinoma and its association with disease‐free survival (DFS) and overall survival were analyzed based on a cohort of 261 patients. The roles of CITED4 were validated via loss‐of‐function and gain‐of‐function experiments. The relationship between CITED4 and CLDN3 was validated by immunohistochemistry, Western blotting, and luciferase reporter assays. The function of the CITED4‐CTNNB1‐CLDN3 complex was fully validated and described. Results CITED4 expression was significantly upregulated in ADC tissues and cells and a predictor for DFS. Downregulation of CITED4 attenuated the proliferation and invasion, whereas CITED4 overexpression enhanced these effects. Overexpression and knockdown of CITED4 resulted in the upregulation and downregulation of CLDN3, respectively. Moreover, CITED4 downregulation suppressed CLDN3‐mediated ADC cell metastasis in vivo. CITED4 was highly expressed and positively correlated with CLDN3. Mechanistically, CITED4 interacted with CTNNB1 and functioned synergistically to enhance CLDN3 transcription. Importantly, CITED4 induced ADC invasion via a CLDN3‐dependent pathway. CITED4 determined the level of CLDN3, which in turn affected the sensitivity of tumors to Clostridium perfringens enterotoxin treatment. Conclusions The CITED4‐CTNNB1‐CLDN3 axis plays a key role in the invasion and metastasis of ADC and provides a novel therapeutic target for lung cancer treatment.

Platinum‐based chemotherapy has been the cornerstone treatment for small cell lung cancer (SCLC) for decades, but no major progress has been made in the past 20 years with regard to overcoming chemoresistance. As the cell cycle checkpoint kinase 1 (Chk1) plays a key role in DNA damage response to chemotherapeutic drugs, we explored the mechanisms of acquired drug resistance to the Chk1 inhibitor prexasertib in SCLC. We established prexasertib resistance in two SCLC cell lines and found that DNA copy number, messengerRNA (mRNA) and protein levels of the cell cycle regulator Wee1 significantly correlate with the level of acquired resistance. Wee1 small interfering RNA (siRNA) or Wee1 inhibitor reversed prexasertib resistance, whereas Wee1 transfection induced prexasertib resistance in parental cells. Reverse phase protein microarray identified up‐regulated proteins in the resistant cell lines that are involved in apoptosis, cell proliferation and cell cycle. Down‐regulation of CDK1 and CDC25C kinases promoted acquired resistance in parental cells, whereas down‐regulation of p38MAPK reversed the resistance. High Wee1 expression was significantly correlated with better prognosis of resected SCLC patients. Our results indicate that Wee1 overexpression plays an important role in acquired resistance to Chk1 inhibition. We also show that bypass activation of the p38MAPK signaling pathway may contribute to acquired resistance to Chk1 inhibition. The combination of Chk1 and Wee1 inhibitors may provide a new therapeutic strategy for the treatment of SCLC.

Static experiments and dynamic displacement experiments were conducted to quantitatively determine the amount of precipitate generated by the CO2-formation water reaction at different temperatures, pressures, and scaling ion concentrations during CO2 flooding in the Chang 8 block of Changqing Oilfield, the influence of precipitate on the physical properties of reservoirs was investigated, and the corresponding mathematical characterization model was established. The mathematical characterization equation was used to correct the numerical simulation model of E300 module in Eclipse software. The distribution pattern of inorganic salt precipitates during continuous CO2 flooding in Chang 8 block was simulated, and the influence of inorganic salt precipitates on oil recovery was predicted. The inorganic salt precipitate generated during CO2-formation water reaction was mainly CaCO3, and the pressure difference and scaling ion concentration were proportional to the amount of precipitate generated, while the temperature was inversely proportional to the amount of precipitate. The rate of core porosity change before and after CO2 flooding was positively correlated with temperature and flooding pressure difference. The core porosity increase in the CO2-formation water-core reaction experiment was always lower than that of CO2-distilled water-core reaction experiment because of precipitation. The area around the production wells had the most precipitates generated with the injection of CO2. The oil field became poor in development because of the widely distributed precipitate and the recovery decreased to 33.45% from 37.64% after 20-year-CO2 flooding when considering of precipitation.

Organic-inorganic halide perovskite solar cells (PSCs) have attracted much attention in recent years due to their simple manufacturing process, low cost, and high efficiency. So far, all efficient organic-inorganic halide PSCs are mainly made of polycrystalline perovskite films. There are transmission barriers and high-density defects on the surface, interface, and grain boundary of the films. Among them, the deep-level traps caused by specific charged defects are the main non-radiative recombination centers, which is the most important factor in limiting the photoelectric conversion efficiency of PSCs devices to the Shockley-Queisser (S-Q) theoretical efficiency limit. Therefore, it is imperative to select appropriate passivation materials and passivation strategies to effectively eliminate defects in perovskite films to improve their photovoltaic performance and stability. There are various passivation strategies for different components of PSCs, including interface engineering, additive engineering, antisolvent engineering, dopant engineering, etc. In this review, we summarize a large number of defect passivation work to illustrate the latest progress of different types of passivators in regulating the morphology, grain boundary, grain size, charge recombination, and defect density of states of perovskite films. In addition, we discuss the inherent defects of key materials in carrier transporting layers and the corresponding passivation strategies to further optimize PSCs components. Finally, some perspectives on the opportunities and challenges of PSCs in future development are highlighted.

Predicting the deliverability change laws of a gas well in the early stage is one of the technical difficulties in natural gas development. The commonly used steady seepage analysis methods have relatively large errors. And this problem cannot be solved effectively by the classical methods of production decline analysis and pressure transient well test analysis. To solve this problem, this paper did calculation based on the well test model of constant-pressure production, changed the previous approximate method of simplifying the calculation of the exponential integral function, and accurately calculated the analytical solution of absolute open flow potential of a gas well. In addition, the deliverability instability characteristics of different types of gas wells were quantitatively described by taking vertical wells in homogeneous reservoirs as the reference benchmark. Then, combined with the deliverability evaluation needs of a new well, a new practical method focusing on solving the problems of gas formation testing analysis was researched and developed, and also applied on site at some key wells in the hot spots of natural gas development in the Sichuan Basin. And the following research results were obtained. First, the accurate formula for the analytical solution of well test model significantly enhances the adaptability to short-term test conditions. Second, the newly established chart briefly reveals the quantitative relationship between the unstable deliverability characteristics of a gas well and the main influencing factors. Third, if the characteristic parameter of turbulence effect is unknown, it is necessary to perform iterative calculation of the variable skin factor when the well test model of constant-pressure production is used to analyze the change trend of the absolute open flow potential of a gas well. Fourth, by conducting comparative analysis on the calculation results of typical cases, the decline laws of the absolute open flow potential of different types of gas wells can be understood further. It is concluded that this new method is capable of improving the prediction accuracy of the unstable deliverability of gas wells. Therefore, it can be widely applied to the deliverability evaluation of gas wells in the exploration stage, the evaluation stage of early development and the commissioning stage of new development and production wells, which is conducive to the formulation of natural gas exploration and development decision.

With the development of the petroleum industry, the importance of low-permeability reservoirs becomes clear. The fracture, which serves as the notable characteristic of a low-permeability reservoir, controls the flow system of reservoir fluid and restrains the development effect. Finding ways to recognize the fracture by using the normal data and building the fracture 3-D model are the important and difficult points of low-permeability development. According to this problem, the authors use a helpful probe. First, from similar outcrop and drilling core study of the fractured original model, the knowledge base of the fracture was built. Second, based on the analysis of the principle of dual-later log identification fracture, the core calibration was used to make logging, and using dual-later log, the fracture in wells was recognized. Third, based on the analysis of the principle of the fractal kriging method, the inter-well fractures were predicted. Finally, the 3-D model of fracture was built with fractural random simulation. The result shows that the 3-D model is in accordance with the fact of the development. So, the method is correct.

Abstract Background Oligomannuronates (OM) are natural products from alginate that is frequently used as food supplement. The aim of this study was to investigate the in vitro protective effects of OM on RINm5F cells against human Islet amyloid polypeptide (IAPP) induced mitochondrial dysfunction, as well as the underlying mechanisms. Methods In the present study, we obtained several kinds of OM with different molecular masses, and then we used RINm5F cells as a model to elucidate the involvement of JNK signal pathway in hIAPP-induced mitochondrial dysfunction in pancreatic beta cells, and the protective effects of OM are associated with its ability to attenuate the mitochondrial dysfunction. Results Our results demonstrated that human IAPP induced mitochondrial dysfunction, as evidence by loss of ΔΨm and ATP content, and decrease in oxygen consumption and complex activities, was accompanied by JNK activation, changes in the expressions of Bcl-2 and Bax proteins, release of cytochrome c (Cyto-c) and apoptosis inducing factor (AIF) from mitochondria into cytosol. Interestingly, the human IAPP induced damage in RINm5F cells were effectively restored by co-treatment of OM. Moreover, JNK activation was required for the OM mediated changes in RINm5F cells. Conclusions OM prevented mitochondrial dysfunction induced by human IAPP in RINm5F islet cells through JNK dependent signaling pathways.

Background and objective Da Vinci robotic system is currently widely used in thoracic surgery. The ports employment and procedures vary in different medical center in China. Usually, a small incision was used for assistant. Methods Based on clinical practice, we summarized domestic and foreign experience, combined with the characteristics of the Chinese body anatomy, employ portal technique and artificial pneumothorax, summarized a set of simplified and easier surgical method. Results Port-only artificial pneumothorax robot-assisted lobectomy has further improvement in anatomical safety, hemostatic effect and aesthetic appearance of the wound. Conclusion This study optimizes the procedure of port-only artificial pneumothorax robot-assisted lobectomy in order to serve lung cancer patients better.

Immune checkpoint inhibitor-induced sarcoid-like reactions and tertiary lymphoid structures (TLSs) are increasingly recognized but rarely reported in the same patient. We report a patient with lung adenocarcinoma who displayed sarcoid-like reactions in intrathoracic lymph nodes and tertiary lymphoid structures in surgical tumor after neoadjuvant therapy with nivolumab plus ipilimumab. Pathological examination revealed 50% residual tumor cells after treatment, and the CT evaluation of the primary tumor showed a stable disease. The patient experienced a recurrence eight months after surgery. To identify immune correlates of the limited response to immunotherapy, we conducted genomic and transcriptional assays, multiplex immunoassay, and multiplex immunohistochemistry on the pre- and post-immunotherapy tumor, lymph node, and plasma samples. TP53 R181C, KRAS G12C and SMAD4 R361H were identified as driver mutations of the tumor. In addition to abundant infiltrated lymphocytes, immunotherapy induced high levels of inhibitory components in post-treatment tissue samples, especially the FOXP3+ regulatory T cells in tumor and PD-L1 expression in the lymph node. Despite abundant TLSs in the post-treatment tumor, most TLSs were immature. Moreover, increasing levels of circulating checkpoint proteins BTLA, TIM-3, LAG-3, PD-1, PD-L1, and CTLA4 were observed during immunotherapy. Collectively, our observations revealed that high levels of immunosuppressive molecules in tumor, lymph nodes and/or in peripheral blood might indicate poor outcomes after immunotherapy, even in the setting of a patient with concurrent sarcoid-like reactions and tertiary lymphoid structures.

In an effort to address the load adjustment time in the thermal and electrical load distribution of thermal power plant units, we propose an optimal load distribution method based on load prediction among multiple units in thermal power plants. The proposed method utilizes optimization by attention to fine-tune a deep convolutional long-short-term memory network (CNN-LSTM-A) model for accurately predicting the heat supply load of two 30 MW extraction back pressure units. First, the inherent relationship between the heat supply load and thermal power plant unit parameters is qualitatively analyzed, and the influencing factors of the power load are screened based on a data-driven analysis. Then, a mathematical model for load distribution optimization is established by analyzing and fitting the unit’s energy consumption characteristic curves on the boiler and turbine sides. Subsequently, by using a randomly chosen operating point as an example, a genetic algorithm is used to optimize the distribution of thermal and electrical loads among the units. The results showed that the combined deep learning model has a high prediction accuracy, with a mean absolute percentage error (MAPE) of less than 1.3%. By predicting heat supply load variations, the preparedness for load adjustments is done in advance. At the same time, this helps reduce the real-time load adjustment response time while enhancing the unit load’s overall competitiveness. After that, the genetic algorithm optimizes the load distribution, and the overall steam consumption rate from power generation on the turbine side is reduced by 0.488 t/MWh. Consequently, the coal consumption rate of steam generation on the boiler side decreases by 0.197 kg (coal)/t (steam). These described changes can greatly increase the power plant’s revenue by CNY 6.2673 million per year. The thermal power plant used in this case study is in Zhejiang Province, China.

Background To assess the potential prognostic value of the albumin to alkaline phosphatase ratio (AAPR) in patients with non‐small cell lung cancer (NSCLC) after surgery. Methods The log‐rank and Kaplan‐Meier analyses were performed to detect differences in survival levels between different groups. A model of Cox proportional hazards was used to perform univariate and multivariate survival analyses. Comparisons of receiver operating characteristic (ROC) curves and the likelihood ratio test (LRT) were also utilized to compare the prognostic abilities of different systems for overall survival (OS) prediction. Results The optimal cut‐off value of the preoperative AAPR was 0.64. A decreased AAPR was associated with several clinicopathological and clinicolaboratory variables related to cancer progression. The preoperative AAPR of patients was positively correlated with the poor prognosis of NSCLC. In multivariate analyses, the preoperative AAPR was identified as an independent prognostic factor for disease‐free survival (DFS; P = 0.001) and overall survival (OS; P = 0.003). The LRT showed that the AAPR tumor‐node‐metastasis (TNM) system presented a significantly larger χ2 value (112.4 vs. 89.2, respectively, P

Magnolia officinalis Rehd. et Wils. and Magnolia officinalis Rehd. et Wils. var. biloba Rehd. et Wils, as the legal botanical origins of Magnoliae Officinalis Cortex, are almost impossible to distinguish according to their appearance traits with respect to medicinal bark. The application of AFLP molecular markers for differentiating the two origins has not yet been successful. In this study, a combination of e-nose measurements, e-tongue measurements, and chemical analyses coupled with multiple-source data fusion was used to differentiate the two origins. Linear discriminant analysis (LDA) and quadratic discriminant analysis (QDA) were applied to compare the discrimination results. It was shown that the e-nose system presented a good discriminant ability with a low classification error for both LDA and QDA compared with e-tongue measurements and chemical analyses. In addition, the discriminating capacity of LDA for low-level fusion with original data, similar to a combined system, was superior or equal to that acquired individually with the three approaches. For mid-level fusion, the combination of different principals extracted by PCA and variables obtained on the basis of PLS-VIP exhibited an analogous discrimination ability for LDA (classification error 0.0%) and was significantly superior to QDA (classification error 1.67–3.33%). As a result, the combined e-nose, e-tongue, and chemical analysis approach proved to be a powerful tool for differentiating the two origins of Magnoliae Officinalis Cortex.

The aim of this study was to analyze the influence of non-predominant micropapillary pattern in small sized invasive lung adenocarcinoma. A total of 986 lung adenocarcinoma patients with tumor size ≤3 cm were identified and classified according to the IALSC/ATS/ERS classification. Emphasis was placed on the impact of non-predominant micropapillary pattern on disease-free survival (DFS) and overall survival (OS). The relationship between lung adenocarcinoma subtype and lymph node involvement, EGFR mutation and KRAS mutation was also evaluated. A nomogram was developed to predict the probability of 3- and 5-year OS for these patients. The concordance index and calibration plot were used to validate this model. Among all 986 patients, the percentages of lymph node involvement were: 58.1, 50.0, 33.5, 21.4, 21.1, 10.9, 0, and 0% for micropapillary predominant, solid predominant, acinar predominant, papillary predominant, invasive mucinous adenocarcinoma (IMA), lepidic predominant, minimally invasive adenocarcinoma (MIA), adenocarcinoma in situ (AIS), respectively. The frequency of EGFR mutation in the cases of lepidic predominant, acinar predominant, MIA, micropapillary predominant, papillary predominant, solid predominant, IMA, and AIS were 51.1, 45.2, 44.4, 36.8, 29.3, 26.8, 8.3, and 0%, respectively. A non-predominant micropapillary pattern was observed in 344 (38.4%) invasive adenocarcinoma (IAC), and its presence predicted a poorer DFS (median: 56.0 months vs. 66.0 months, P

Antibiotics are widely detected in the water environment, posing a serious threat to the health of humans and animals. The effect of levofloxacin (LOFL) on pollutant removal and the difference in the influence mechanisms at normal and low temperatures in constructed wetlands are worth discussing. A hydroponic culture experiment was designed with Iris pseudacorus L. at low and normal temperatures. LOFL (0–100 µg/L) was added to the systems. The results indicated that the removal of pollutants was affected most by temperature, followed by LOFL concentration. At the same concentration of LOFL, the pollutant removal rate was significantly higher at normal temperature than at low temperature. Low concentrations of LOFL promoted the degradation of pollutants except TN under normal-temperature conditions. Compared with the results at low temperature, the bacterial community richness was higher and the diversity of bacterial communities was lower under normal-temperature conditions. The genera and the function of bacteria were greatly affected by antibiotic concentration, temperature and test time. A series of microorganisms resistant to antibiotics and low temperature were identified in this study. The results will provide valuable information and a reference for our understanding of the ecological effects of LOFL.

The management of postoperative and inflammatory pain has been a pressing challenge in clinical settings. Sinomenine (SN) is a morphinan derived alkaloid with remarkable analgesic properties in various kinds of pain models. The aim of the current study is to investigate if SN can enhance the effect of ligustrazine hydrochloride (LGZ) or paracetamol (PCM) in animal models of postoperative and inflammatory pain. And to determine if the combined therapeutic efficacies can be explained by pharmacokinetics changes. Pharmacological studies were performed using a rat model of incisional pain, and a mouse model of carrageenan induced inflammatory pain. Pharmacokinetic studies were performed using a microdialysis sampling and HPLC-MS/MS assay method to quantify SN, LGZ, and PCM levels in blood and extracellular fluid in brain. We found that SN plus LGZ or SN plus PCM produced marked synergistic analgesic effects. However, such synergy was subjected to pain modalities, and differed among pain models. Pharmacological discoveries could be partially linked to pharmacokinetic alterations in SN combinations. Though further evaluation is needed, our findings advocate the potential benefits of SN plus LGZ for postoperative pain management, and SN plus PCM for controlling inflammatory pain.

Study shows that decline exponents of gas wells in Sulige Tight Gas Field vary during their life cycle. However, decline analysis methods with variable decline exponent have not been developed so far. To address this problem, a simple-yet-effective method is proposed. In this method, the fracture linear flow regime and the channel linear flow regime, which appear two straight lines on the coordinate axis (1/q vs. t), respectively, are used to carry out the decline analysis. Each regime has a different slope and intercept (in the form of 1/q vs. t), which leads to a useful graphical technique for predicting gas rate. The graphical technique is verified by matching actual gas rate and predicting future gas rate trend. Theoretically, the influence of the two slopes and intercepts in the graphical technique on the rate decline is also studied. Aiming at decline analysis for tight gas wells with variable decline exponents, this paper proposes a novel method using linear flow characteristics, which ingeniously avoids the establishment of an empirical method to deal with variable decline exponent. The method in this study can help for better understanding of decline analysis of tight gas wells in a theoretical manner.

Natural hydrogels are growing in interest as a priority for wound healing. Plant polysaccharides have a variety of biological pharmacological activities, and chitosan hydrogels have proven strong antimicrobial effects, but hydrogels prepared with polysaccharides alone have certain deficiencies. Polysaccharides from flowers of Lonicera japonica Thunb. (LP) and the aerial parts of Mentha canadensis L. (MP) were extracted and oxidized by sodium periodate (NaIO4) and then cross-linked with oxidized-carboxymethylated chitosan (O-CCS) to develop oxidized plant- polysaccharides-chitosan hydrogels (OPHs). SEM observation showed that OPHs had porous interior structures with interconnecting pores. The OPHs showed good swelling, water-retention ability, blood coagulation, cytocompatibility properties, and low cytotoxicity (classed as grade 1 according to United States Pharmacopoeia), which met the requirements for wound dressings. Then the cutaneous wound-healing effect was evaluated in BALB/C mice model, after 7 days treatment, the wound-closure rate of OPHs groups were all greater than 50%, and after 14 days, all were greater than 90%, while the value of the control group was only 72.6%. Of them, OPH-2 and OPH-3 were more favorable to the wound-healing process, as the promotion was more significant. The plant polysaccharides and CS-based hydrogel should be a candidate for cutaneous wound dressings.

In the process of CO2 enhanced oil recovery (CO2-EOR), CO2 interacts with formation brine containing high concentrations of scale-forming ions to produce inorganic salt precipitation, which blocks the rock pore throats, changes the characteristics of the reservoir, and thereby reduces the oil recovery rate. In this study, a series of experiments on the static reaction of CO2–formation brine was conducted. The amounts of precipitation formed from the interaction of CO2–formation brine under various conditions were tested. Using the PHREEQC software, the mathematical characterization formulas between the precipitation amount and various environmental factors (e.g., temperature, pressure difference, scale-forming ion concentration, and pH) were established. On this basis, a numerical simulation model of CO2 flooding in a typical area of oil field C was established. The distribution of inorganic salt precipitation during continuous gas flooding was predicted, and the effect of inorganic salt precipitation on oil field recovery was analyzed.

Abstract To meet the requirement of fuel cells and metal–air batteries, non‐noble metal catalysts have to be developed to replace precious platinum‐based catalysts. Herein, Co nanoclusters (≈2 nm) are anchored on nitrogen‐doped reduced graphene oxide (Co/N‐r‐GO) by using DUT‐58 (Co) metal–organic framework and GO as precursors. Compared with single‐atom catalysts usually with ultralow concentration (

Recurrent connections are thought to be a common feature of the neural circuits that encode memories, but how memories are laid down in such circuits is not fully understood. Here we present evidence that courtship memory in Drosophila relies on the recurrent circuit between mushroom body gamma (MBγ), M6 output, and aSP13 dopaminergic neurons. We demonstrate persistent neuronal activity of aSP13 neurons and show that it transiently potentiates synaptic transmission from MBγ>M6 neurons. M6 neurons in turn provide input to aSP13 neurons, prolonging potentiation of MBγ>M6 synapses over time periods that match short-term memory. These data support a model in which persistent aSP13 activity within a recurrent circuit lays the foundation for a short-term memory.

An apigalacturonan (AGA)-rich polysaccharide, ZCMP, was isolated from the sea grass Zostera caespitosa Miki. The depolymerized fragments derived from ZCMP were obtained by either acidic degradation or pectinase degradation, and their structures were characterized by electrospray ionization collision-induced-dissociation mass spectrometry (ESI-CID-MS2) and nuclear magnetic resonance (NMR) spectroscopy. The average molecular weight of ZCMP was 77.2 kD and it consisted of galacturonic acid (GalA), apiosefuranose (Api), galactose (Gal), rhamnose (Rha), arabinose (Ara), xylose (Xyl), and mannose (Man), at a molar ratio of 51.4꞉15.5꞉6.0꞉11.8꞉4.2꞉4.4꞉4.2. There were two regions of AGA (70%) and rhamnogalacturonan-I (RG-Ι, 30%) in ZCMP. AGA was composed of an α-1,4-D-galactopyranosyluronan backbone mainly substituted at the O-3 position by single Api residues. RG-Ι possessed a backbone of repeating disaccharide units of →4GalAα1,2Rhaα1→, with a few α-L-arabinose and β-D-galactose residues as side chains. The anti-angiogenesis assay showed that ZCMP inhibited the migratory activity of human umbilical vein endothelial cell (HUVECs), with no influence on endothelial cells growth. ZCMP also promoted macrophage phagocytosis. These findings of the present study demonstrated the potential anti-tumor activity of ZCMP through anti-angiogenic and immunoregulatory pathways.

The precondition of well testing interpretation is to determine the appropriate well testing model. In numerous attempts in the past, automatic classification and identification of well testing plots have been limited to fully connected neural networks (FCNN). Compared with FCNN, the convolutional neural network (CNN) has a better performance in the domain of image recognition. Utilizing the newly proposed CNN, we develop a new automatic identification approach to evaluate the type of well testing curves. The field data in tight reservoirs such as the Ordos Basin exhibit various well test models. With those models, the corresponding well test curves are chosen as training samples. One-hot encoding, Xavier normal initialization, regularization technique, and Adam algorithm are combined to optimize the established model. The evaluation results show that the CNN has a better result when the ReLU function is used. For the learning rate and dropout rate, the optimized values respectively are 0.005 and 0.4. Meanwhile, when the number of training samples was greater than 2000, the performance of the established CNN tended to be stable. Compared with the FCNN of similar structure, the CNN is more suitable for classification of well testing plots. What is more, the practical application shows that the CNN can successfully classify 21 of the 25 cases.

Females of many animal species emit chemical signals that attract and arouse males for mating. For example, the major aphrodisiac pheromone of Drosophila melanogaster females, 7,11-heptacosadiene (7,11-HD), is a potent inducer of male-specific courtship and copulatory behaviors. Here, we demonstrate that a set of gustatory sensory neurons on the male foreleg, defined by expression of the ppk23 marker, respond to 7,11-HD. Activity of these neurons is required for males to robustly court females or to court males perfumed with 7,11-HD. Artificial activation of these ppk23+ neurons stimulates male-male courtship even without 7,11-HD perfuming. These data identify the ppk23+ sensory neurons as the primary targets for female sex pheromones in Drosophila.

As an important glycosaminoglycan, keratan sulfate (KS) mainly exists in corneal and cartilage, possessing various biological activities. In this study, we purified KS from blue shark (Prionace glauca) cartilage and prepared KS oligosaccharides (KSO) through keratanase II-catalyzed hydrolysis. The structures of KS and KSO were characterized using multi-dimensional nuclear magnetic resonance (NMR) spectra and liquid chromatography-mass spectrometry (LC-MS). Shark cartilage KS was highly sulfated and modified with ~2.69% N-acetylneuraminic acid (NeuAc) through α(2,3)-linked to galactose. Additionally, KS exhibited binding affinity to Ricinus communis agglutinin I (RCA120) in a concentration-dependent manner, a highly toxic lectin from beans of the castor plant. Furthermore, KSO from dp2 to dp8 bound to RCA120 in the increasing trend while the binding affinity of dp8 was superior to polysaccharide. These results define novel structural features for KS from Prionace glauca cartilage and demonstrate the potential application on ricin-antidote exploitation.

As shown in our previous study, sinomenine hydrochloride (SH), the major bioactive alkaloid isolated from Sinomenium acutum Rehd. et Wils. (Fam. Menispermaceae), initiates the autophagy-mediated death of human glioblastoma cells by generating reactive oxygen species and activating the autophagy-lysosome pathway. However, its effects on the migration and invasion of human glioblastoma cells have not yet been elucidated. Therefore, human glioblastoma U87 and SF767 cells were treated with SH (0.125 and 0.25 mM) for 24 h, and cell migration and invasion were assessed using scratch wound healing, migration and invasion assays. SH promoted G0/G1 phase arrest, inhibited the migration and invasion of the two cell lines, suppressed the activation of nuclear factor kappa B (NFκB) and the expression of matrix metalloproteinase (MMP)-2/-9, triggered endoplasmic reticulum (ER) stress, reversed the exogenous epithelial-mesenchymal transition (EMT) induced by the inflammatory microenvironment and the endogenous EMT. Additionally, NFκB p65 overexpression blocked the SH-mediated inhibitory effects on MMP-2/-9 expression and cell invasion. SH-induced autophagy was reduced in CCAAT/enhancer binding protein (C/EBP) homologous protein (CHOP) or autophagy-related 5 (ATG5)-silenced human glioblastoma cells and cells treated with 4-phenylbutyric acid (4-PBA) or 3-methyladenine (3-MA), as shown by the decreased levels of the microtubule-associated protein light chain 3B (LC3B)-II and autophagic vacuoles (AVs) stained with monodansylcadaverine (MDC), respectively. Moreover, knockdown of CHOP or ATG5 and treatment with 4-PBA or 3-MA abolished the SH-mediated inhibition of mesenchymal markers (vimentin, Snail and Slug) expression and cell invasion, respectively. Importantly, SH also regulated the above related pathways in nude mice. Based on these findings, SH inhibited cell proliferation by inducing cell cycle arrest, and attenuated the metastasis of U87 and SF767 cells by suppressing MMP-2/-9 expression and reversing the endogenous and exogenous EMT in vitro and/or in vivo. Thus, SH might be a new potential anti-metastasis agent for the treatment of human glioblastoma.

In our previous studies, we prepared novel oligomannuronate-chromium(III) complexes (OM2, OM4) from marine alginate, and found that these compounds sensitize insulin action better than oligomannuronate(OM), chromium, and metformin in C2C12 skeletal muscle cells. In the present study, we studied their effects on mitochondrial biogenesis, lipid metabolism, and the underlying molecular mechanisms in differentiated 3T3-L1 adipocytes.We firstly used the pGL3-PGC1α and pGL3-ATGL promoter plasmids to compare their effects on PGC1α and ATGL transcription activities. Then mitochondrial biogenesis was quantified by transmission electron microscopy and MitoTracker staining. Mitochondrial oxygen consumption and fatty acid oxidation were measured by an oxygen biosensor system and ³H-labelled water scintillation. The mitochondrial DNA and mRNA involved in mitochondrial biogenesis and lipid oxidation were evaluated by real-time PCR. AMPK together with other protein expression levels were measured by western blotting. The inhibitor compound C and siRNA of PGC1α were used to inhibit the OM2-induced AMPK-PGC1α signaling pathway. And we found that OM2 stimulated AMPK-PGC1α pathway in the 3T3-L1 adipocytes, which were correlated with induced mitochondrial biogenesis, improved mitochondrial function, and reduced lipid accumulation by enhanced fatty acid β-oxidation and augmented ATGL protein expression.Our data indicated that the marine oligosaccharide-derived OM2 might represent a novel class of molecules that could be useful for type 2 diabetes prevention and treatment by up-regulating AMPK-PGC1α signaling pathway.

Glioblastoma is the most common malignant primary brain tumor, and it is one of the causes of cancer fatality in both adult and pediatric populations. Patients with glioblastoma require chemotherapy after surgical resection and radiotherapy. Therefore, chemotherapy constitutes a viable approach for the eradication of glioblastoma cells. In this study, the anti-tumor activity of sinomenine hydrochloride (SH) was evaluated in U87 and SF767 cells in vitro and in vivo. The results showed that SH potently inhibited U87 and SF767 cell viability and did not cause caspase-dependent cell death, as demonstrated by the absence of significant early apoptosis and caspase-3 cleavage. Instead, SH activated an autophagy-mediated cell death pathway, as indicated by the accumulated microtubule-associated protein light chain 3B (LC3B)-II, triggered autophagic flux and enhanced cell viability after pretreatment with autophagy inhibitors. SH-mediated autophagy in the two cell lines was implicated in reactive oxygen species (ROS) generation, protein kinase B (Akt)-mammalian target of rapamycin (mTOR) pathway suppression and c-Jun NH2-terminal kinase (JNK) pathway activation. The ROS antioxidant N-acetylcysteine (NAC), the Akt-specific activator insulin-like growth factor-1 (IGF-1) and the JNK-specific inhibitor SP600125 attenuated SH-induced autophagy. Moreover, ROS activated autophagy via the Akt-mTOR and JNK pathways. Additionally, SH treatment may promote lysosome biogenesis through activating transcription factor EB (TFEB). The in vivo study found that SH effectively suppressed glioblastoma growth without exhibiting significant toxicity. In conclusion, our findings reveal a novel mechanism of action of SH in cancer cells via the induction of autophagy through ROS generation and autophagy-lysosome pathway activation; these findings also supply a new potential therapeutic agent for the treatment of human glioblastoma.

Agarose (AP) from red algae has a long history as food ingredients in East Asia. Agaro-oligosaccharides (AO) derived from AP have shown potential prebiotic effects. However, the human gut microbes responsible for the degradation of AO and AP have not yet been fully investigated. Here, we reported that AO and AP can be degraded and utilized at various rates by fecal microbiota obtained from different individuals. Bacteroides uniformis L8 isolated from human feces showed a pronounced ability to degrade AO and generate D-galactose as its final end product. PCR-DGGE analysis showed B. uniformis to be common in the fecal samples, but only B. uniformis L8 had the ability to degrade AO. A synergistic strain, here classified as Escherichia coli B2, was also identified because it could utilize the D-galactose as the growth substrate. The cross-feeding interaction between B. uniformis L8 and E. coli B2 led to exhaustion of the AO supply. Bifidobacterium infantis and Bifidobacterium adolescentis can utilize one of the intermediates of AO hydrolysis, agarotriose. Growth curves indicated that AO was the substrate that most favorably sustained the growth of B. uniformis L8. In contrast, κ-carrageenan oligosaccharides (KCO), guluronic acid oligosaccharides (GO), and mannuronic acid oligosaccharides (MO) were found to be unusable to B. uniformis L8. Current results indicate that B. uniformis L8 is a special degrader of AO in the gut microbiota. Because B. uniformis can mitigate high-fat-diet-induced metabolic disorders, further study is required to determine the potential applications of AO.

The low-molecular-weight fucosylated chondroitin sulfate (LFCS) was prepared from native fucosylated chondroitin sulfate (FCS), which was extracted and isolated from sea cucumber Cucumaria frondosa, and the anti-cancer mechanism of LFCS on mouse Lewis lung carcinoma (LLC) was investigated. The results showed that LFCS remarkably inhibited LLC growth and metastasis in a dose-dependent manner. LFCS induced cell cycle arrest by increasing p53/p21 expression and apoptosis through activation of caspase-3 activity in LLC cells. Meanwhile, LFCS suppressed the expression of vascular endothelial growth factor (VEGF), increased the expression of tissue inhibitor of metalloproteinase-1 (TIMP-1) and downregulated the matrix metalloproteinases (MMPs) level. Furthermore, LFCS significantly suppressed the activation of ERK1/2/p38 MAPK/NF-κB pathway, which played a prime role in expression of MMPs. All of these data indicate LFCS may be used as anti-cancer drug candidates and deserve further study.

The SARI (suppressor of AP-1, regulated by IFN) gene, which is also called BATF2, is associated with the risk of several kinds of cancer, and loss of SARI expression is frequently detected in aggressive and metastatic cancer. However, the functional role of SARI in lung adenocarcinoma remains unknown. We have shown that loss of SARI expression initiates epithelial-mesenchymal transition (EMT), which is visualized by repression of E-cadherin and up-regulation of vimentin in lung adenocarcinoma cell lines and in clinical lung adenocarcinoma specimens. Using a human lung xenograft-mouse model, we observed that knocking down endogenous SARI in human carcinoma cells leads to the development of multiple lymph node metastases. Moreover, we showed that SARI functions as a critical protein in regulating EMT by modulating the (GSK)-3β-β-catenin signaling pathway. These results demonstrate the mechanism of SARI function in EMT and suggest that assessment of SARI may serve as a prognostic biomarker and potential therapeutic target for lung adenocarcinoma metastasis.

Treatment of large and complex irregular bone defects is a major clinical challenge in orthopedic surgery. The current treatment includes bone transportation using the Ilizarov technique and bone cement repair using the Masquelet technique, but they require long-term manual intervention or secondary operation. To improve this situation, we compared the different implanting materials in the literature published in the past 10 years, finding that glycolic acid copolymer (PLGA) and Calcium sulfate (CaSO4) are appropriated to be used as synthetic bone materials due to their advantages of easy-availability, nontoxicity, osteogenic properties and rapid degradation. Meanwhile, the development of 3D printing technique and devices makes it relatively easier to synthetize customized bio-mimetic porous scaffolds, thus facilitating the release of modified protein. In this study, we compounded BMP-2/PLGA microspheres with polylactic glycolic acid copolymer/CaSO4 (PC) 3D printed scaffold to improve the osteogenic properties of the scaffold. The result of our in vitro experiment demonstrated that the prepared PCB scaffold not only had satisfactory bio-compatibility, but also promoted osteogenic differentiation. This 3D printed scaffold is capable to accelerate the repair of complex bone defects by promoting new bone formation, suggesting that it may prove to be a potential bone tissue engineering substitute. [ABSTRACT FROM AUTHOR]