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Background & Aims: Tumor-initiating cells (TICs) drive pancreatic cancer tumorigenesis, therapeutic resistance, and metastasis. However, TICs are highly plastic and heterogenous, which impede the robust identification and targeted therapy of such a population. The aim of this study is to identify the surface marker and therapeutic target for pancreatic TICs. Methods: We isolated voltage-gated calcium channel α2δ1 subunit (isoform 5)-positive subpopulation from pancreatic cancer cell lines and freshly resected primary tissues by fluorescence-activated cell sorting and evaluated their TIC properties by spheroid formation and tumorigenic assays. Coimmunoprecipitation was used to identify the direct substrate of CaMKⅡδ. Results: We demonstrate that the voltage-gated calcium channel α2δ1 subunit (isoform 5) marks a subpopulation of pancreatic TICs with the highest TIC frequency among the known pancreatic TIC markers tested. Furthermore, α2δ1 is functionally sufficient and indispensable to promote TIC properties by mediating Ca2+ influx, which activates CaMKⅡδ to directly phosphorylate PKM2 at T454 that results in subsequent phosphorylation at Y105 to translocate into nucleus, enhancing the stem-like properties. Interestingly, blocking α2δ1 with its specific antibody has remarkably therapeutic effects on pancreatic cancer xenografts by reducing TICs. Conclusions: α2δ1 promotes pancreatic TIC properties through sequential phosphorylation of PKM2 mediated by CaMKⅡδ, and targeting α2δ1 provides a therapeutic strategy against TICs for pancreatic cancer.

Coal gangue and slime water are difficult to dispose and utilize on a large scale, which could cause environmental pollution and waste of resources. Therefore, the co-treatment of coal gangue and slime water can serve as an environmentally friendly and novel way for the collaborative resource of solid wastes. Based on this, a method for preparation of slime water-based cementitious material (SWCM) was developed, and the enhanced mechanical property of a coal gangue pile modified by SWCM (CGSWCM) was investigated. For the preparation of SWCM, 6 types of additives were selected, and solidification was achieved with a liquid to solid ratio of 3:1. A compressive strength of 0.45 MPa was acquired with raw SWCM, and the value decreased to 0.38 MPa, then increased to 0.44 MPa when the mass of the kaolin increased from 2 to 10 g. X-ray diffraction and scanning electron microscopy results showed that the pore size of the coal gangue pile decreased and the rod-like ettringite transferred to a linear shape when mass of kaolin increased. The analysis of thermogravimetry proved that the increased mass of kaolin improved the thermal stability, thus decreasing the mass loss. Therefore, it was proposed that the mechanical properties of CGSWCM was affected by evolved hydration product, gap between coal gangue particles and ettringite (AFT) morphology.

Broken waste rock as backfill materials is filled into the underground goaf and will encounter particle breakage under the overburden pressure. The damage degree of the crushed waste rock materials directly affects the compression properties of the backfill body and the control effect of strata movement and surface subsidence. Fractal theory can be used to quantify the breakage degree of waste rock particles. In this study, compression tests are carried out on the broken waste rock materials with different particle size distributions to investigate the influence of the particle size distribution on the fractal characteristics of waste rock backfill materials under compression. The results show that the waste rock specimens with discontinuous size grading and containing more coarse particles have higher stress when entering the stable deformation stage, larger strain if at the same stress level and larger breakage ratio after compression. The particle size distribution of the crushed waste rock specimens after compressive loading has superior fractal characteristics and the fractal dimension increases with the content of fine particles and decreases significantly under discontinuous size grading. The fractal dimension has significant negative exponential function regression relationship with the strain and the breakage ratio. The strain and the breakage ratio decline with the growing fractal dimension. If the waste rock specimens have continuous particle size gradation and higher content of fine particles, the fractal dimension, the strain and the breakage ratio of the waste rock backfill materials tend to be optimal and stable, proving a desirable initial particle size distribution of the waste rock backfill materials.

The optimal design about the packing structure of W and Cu particles has become a focus of attention for developing the high performance W–Cu composites. In the present work, a series of numerical simulations and physical experiments were conducted to optimize the packing structure of W and Cu particles and establish the relation between particle size and sintering properties. The results reveal that the relative density and uniformity of the binary W–20Cu system showed a negative correlation with increasing size ratio of W and Cu particles. The optimal binary W–20Cu system can be formed when the size ratio of W/Cu particle is 1.5 and the peaked uniformity can reach 0.986. The (W45–20Cu30)-20(W10–20Cu10) size ratio in ternary W–20Cu mixture was identified as the best packing structure by optimization calculation for multi-component system. The relative density of best ternary (W45–20Cu30)-20(W10–20Cu10) system can reach 0.625, which was 10.7% higher than that of binary W45–20Cu30 system. In the best packing structure with size ratio, the sintering properties of ternary W–20Cu composites were efficiently improved by reducing particle size. The W–20Cu composite with small particles showed a tensile/compressive strength over 147/442 MPa (1.73/1.62 times that of the W–20Cu composite with large particles), an electrical conductivity of 36 %IACS, and a hardness of 190 HV. These highlighted results can provide some valuable references for the design and optimization of high performance W–Cu composite in the route of powder metallurgy.

The mining of extra-thick coal seams features severe deformation of the stoping roadway and section coal pillars due to the large mining thickness of the coal seams and the intense movement of the overlying strata. The adjacent goaf and secondary mining disturbance in the current working face further challenge the roadway deformation control. This study explores the effect of the overlying strata structural evolution in the fully mechanized caving face of the extra-thick seam on the failure of section roadway and coal pillars. Physical analog modeling was carried out. A MatchID non-contact full-field displacement- and strain-measuring system was used to determine the evolutionary characteristics of the overlying strata breakage in the extra-thick coal seam, including the displacement variation pattern and stress/strain distribution in coal pillars. The results indicated that following the primary mining disturbance in the adjacent working face, the section roadway and coal pillars underwent initial deformation due to the primary mining-induced stress. As the mining of the current working face continued, the section roadway and coal pillars were subjected to secondary mining disturbance to the effect that the structure of the broken overlying strata gradually formed a triangular support structure. Thus, the overlying strata tilted downwards and subsided, forming a layered hanging roof structure. The additional load was then imposed on the stoping roadway and upper part of the section coal pillars. Meanwhile, the overlying strata failure caused a significant increase in the stress within the section coal pillars. Following the secondary mining disturbance, the peak stress reached a maximum of 33.62 KPa, leading to deformation and instability failure of the section roadway and coal pillars. Finally, distinctive evolutionary features of the overlying strata structure in the extra-thick and ordinary coal seams were identified, and their effect on the deformation and failure of the section roadway and coal pillars were analyzed in detail. These findings are considered instrumental in substantiating the deformation control of the stoping roadway and coal pillars in the extra-thick coal seams.

Objective: There are many researches on using bone marrow mesenchymal stem cells (BMSCs) in the treatment of acute kidney injury (AKI), which has certain effects, but the mechanism of action is still unclear. Previous researches show that glioma-associated oncogene homolog 1 (Gli 1) can promote the proliferation and migration of cells, which can also promote renal fibrosis. Therefore, we investigate the influence of Gli-regulated BMSCs on repairing AKI and renal fibrosis induced by limb Ischemia-Reperfusion (I/R). Methods: The Crispr-Cas9 technique was adopted to knock out the Gli1 gene from the mouse BMSCs according to green fluorescent tracing, and the BMSCs (BMSCs-Gliko) with Gli1 gene knocked out and the BMSCs as control group were obtained. The cell proliferation, apoptosis, cycle and SHH signal pathway gene level were tested. The mice were built to the AKI model with inducing I/R injury, then the BMSCs-Gliko and BMSCs cells were injected into the mice, and their IL-1, IL-1B, TNF-a, serum creatinine (Scr) and blood urea nitrogen (BUN) levels were tested; Western blot was employed to test the expression of α-SMA, SMAD2 and SMAD4 in the renal tissues of mice. Finally, flow cytometry was used to test the content of BMSCs containing green fluorescence in the blood of mice. Results: The BMSCs-Gliko containing green fluorescence and the mouse AKI model were built; both BMSCs and BMSCs-Gliko can reduce the damage level, and BMSCs-Gliko outperformed BMSCs in protecting renal tubules and anti-fibrosis. Our study also shows that BMSCs-Gliko stayed longer in the blood of mice, which might also be one of the reasons why BMSCs-Gliko outperformed BMSCs in preventing renal tubules and fibrosis. To sum it up, could be key target of using.

Objective: Meniscus tear is a common problem in sports trauma, and its imaging diagnosis mainly relies on MRI. To improve the diagnostic accuracy and efficiency, a deep learning model was employed in this study and the identification efficiency was evaluated. Methods: Standard knee MRI images from 924 individual patients were used to complete the training, validation and testing processes. Mask regional convolutional neural network (R–CNN) was used to build the deep learning network structure, and ResNet50 was adopted to develop the backbone network. The deep learning model was trained and validated with a dataset containing 504 and 220 patients, respectively. Internal testing was performed based on a dataset of 200 patients, and 180 patients from 8 hospitals were regarded as an external dataset for model validation. Additionally, 40 patients who were diagnosed by the arthroscopic surgery were enrolled as the final test dataset. Results: After training and validation, the deep learning model effectively recognized healthy and injured menisci. Average precision for the three types of menisci (healthy, torn and degenerated menisci) ranged from 68% to 80%. Diagnostic accuracy for healthy, torn and degenerated menisci was 87.50%, 86.96%, and 84.78%, respectively. Validation results from external dataset demonstrated that the accuracy of diagnosing torn and intact meniscus tear through 3.0T MRI images was higher than 80%, while the accuracy verified by arthroscopic surgery was 87.50%. Conclusion: Mask R–CNN effectively identified and diagnosed meniscal injuries, especially for tears that occurred in different parts of the meniscus. The recognition ability was admirable, and the diagnostic accuracy could be further improved with increased training sample size. Therefore, this deep learning model showed great potential in diagnosing meniscus injuries. Translational potential of this article: Deep learning model exerted unique effect in terms of reducing doctors’ workload and improving diagnostic accuracy. Injured and healthy menisci could be more accurately identified and classified based on training and learning datasets. This model could also distinguish torn from degenerated menisci, making it an effective tool for MRI-assisted diagnosis of meniscus injuries in clinical practice.

This paper reports the control method for the core power of the China initiative Accelerator Driven System (CiADS) facility. In the CiADS facility, an intense external neutron source provided by a proton accelerator coupled to a spallation target is used to drive a sub-critical reactor. Without any control rod inside the sub-critical reactor, the core power is controlled by adjusting the proton beam intensity. In order to continuously change the beam intensity, an adjustable aperture is considered to be used at the Low Energy Beam Transport (LEBT) line of the accelerator. The aperture size is adjusted based on the Proportional Integral Derivative (PID) controllers, by comparing either the setting beam intensity or the setting core power with the measured value. To evaluate the proposed control method, a CiADS core model is built based on the point reactor kinetics model with six delayed neutron groups. The simulations based on the CiADS core model have indicated that the core power can be controlled stably by adjusting the aperture size. The response time in the adjustment of the core power depends mainly on the adjustment time of the beam intensity.

Implementing computational methods for preservation, inheritance, and promotion of Cultural Heritage (CH) has become a research trend across the world since the 1990s. In China, generations of scholars have dedicated themselves to studying the country’s rich CH resources; there are great potential and opportunities in the field of computational research on specific cultural artefacts or artforms. Based on previous works, this paper proposes a systematic framework for Chinese Cultural Heritage Computing that consists of three conceptual levels which are Chinese CH protection and development strategy, computing process, and computable cultural ecosystem. The computing process includes three modules: (1) data acquisition and processing, (2) digital modeling and database construction, and (3) data application and promotion. The modules demonstrate the computing approaches corresponding to different phases of Chinese CH protection and development, from digital preservation and inheritance to presentation and promotion. The computing results can become the basis for the generation of cultural genes and eventually the formation of computable cultural ecosystem Case studies on the Mogao caves in Dunhuang and the art of Guqin, recognized as world’s important tangible and intangible cultural heritage, are carried out to elaborate the computing process and methods within the framework. With continuous advances in data collection, processing, and display technologies, the framework can provide constructive reference for building up future research roadmaps in Chinese CH computing and related fields, for sustainable protection and development of Chinese CH in the digital age.

Leptin is the pivotal modulator in the onset and progression of breast cancer and obesity. Celastrol, which is extracted from the roots of Tripterygium wilfordi plants, exerts various anticancer bioactivities and has recently emerged as a candidate to treat obesity by improving leptin sensitivity. However, the relationship between leptin and celastrol in the treatment of breast cancer is unknown. Here, the growth and migration of MCF-7 cells induced by leptin were tested to demonstrate the antineoplastic activity of celastrol. Transcriptomic analysis and western blotting were conducted to explore the biological roles of leptin in treating breast cancer with celastrol. The present findings showed that celastrol remarkably reversed leptin-triggered cell proliferation and migration in MCF-7 cells. Fifty-two mRNAs with fivefold higher counts and 149 mRNAs with fivefold lower counts were identified in the celastrol-treated MCF-7 cells. According to the GO and KEGG analyses, the effects of celastrol on MCF-7 cells forced lipid metabolism and the endocrine system. Moreover, leptin treatment induced phosphorylation of leptin receptor and PI3K/AKT in MCF-7 cells, whereas pretreatment with celastrol partly abrogated leptin activation. The binding of celastrol to the leptin receptor was also confirmed by molecular docking. The antitumor effect of celastrol is proposed to be mediated by its binding to the leptin receptor and controlled downregulation of the PI3K/AKT pathway.

Ginseng is an international herb that has been used for thousands of years. Two species most commonly applied and investigated in the ginseng family are Asian ginseng and American ginseng. The number of randomized controlled clinical trials (RCTs) has conspicuously increased, driven by the rapid development of ginseng. However, the reporting of RCT items of ginseng is deficient because of different trial designs and reporting formats, which is a challenge for researchers who are looking for the data with high quality and reliability. Thus, this study focused on providing an extensive analysis of these two species and examined the quality of the RCTs, based on the Consolidated Standards of Reporting Trials (CONSORT) guideline. Ninety-one RCTs conducted from 1980 to 2019 that were related to Asian ginseng and American ginseng used singly met our inclusion criteria. We found that the reporting quality of the two species has improved during the past 40 years. Publication date and sample size were significantly associated with the reporting quality. Rigorous RCTs designed for the species of ginseng are warranted, which can shed light on product research and development of ginseng in the future.

Gangue-cemented paste backfill is one kind of paste backfill that is composed of cement, fly ash, and gangue, which is widely used in mining operation for controlling the strata movement and guaranteeing the safety of workplace. The knowledge of thermal conductivity of mine backfill is vital for understanding the thermal interaction of backfill with surrounding rock mass and therefore contributing to geothermal energy extraction with backfill technology in deep mines. Thermal conductivity of gangue-cemented paste backfill is investigated through laboratory tests in this article. The influences of mix proportion parameters and water saturation degree on the thermal conductivity of gangue-cemented paste backfill were analyzed. The results showed that thermal conductivity of gangue-cemented paste backfill markedly increased with the water/binder ratio from 0.35 to 0.55, while cement amount ranging from 4% to 12% had nearly no influence on the thermal conductivity. Meanwhile, the linear positive correlation was notable between thermal conductivity and water saturation degree of gangue-cemented paste backfill, which was interpreted from the perspective of component. The series model was found more reliable for predicting thermal conductivity of gangue-cemented paste backfill by importing the thermal conductivity and volume fraction of continuous paste and dispersed gangue separately. This study would provide a new insight into the design of backfill considering the thermal conductivity and lay a foundation for the efficient geothermal energy extraction in deep mines.

Chronic copper exposure could cause potential nephrotoxicity and effective therapy strategies are limited. This study investigated the protective effects of curcumin on copper sulfate (CuSO4)-induced renal damage in a mouse model and the underlying molecular mechanisms. Mice were administrated orally with CuSO4 (100 mg/kg per day) in combination with or without curcumin (50, 100 or 200 mg/kg per day, orally) for 28 days. Results showed that curcumin supplementation significantly reduce the Cu accumulation in the kidney tissues of mice and improved CuSO4-induced renal dysfunction. Furthermore, curcumin supplantation also significantly ameliorated Cu exposure-induced oxidative stress and tubular necrosis in the kidneys of mice. Moreover, compared to the CuSO4 alone group, curcumin supplementation at 200 mg/kg per day significantly decreased CuSO4-induced the expression of p53, Bax, IL-1β, IL-6, and TNF-α proteins, levels of NF-κB mRNA, levels of caspases-9 and − 3 activities, and cell apoptosis, and significantly increased the levels of Nrf2 and HO-1 mRNAs in the kidney tissues. In conclusion, for the first time, our results reveal that curcumin could trigger the inhibition of oxidative stress, mitochondrial apoptotic, p53, and NF-κB pathways and the activation of Nrf2/HO-1 pathway to ameliorate Cu overload-induced nephrotoxicity in a mouse model. Our study highlights that curcumin supplementation may be a promising treatment strategy for treating copper overload-caused nephrotoxicity.

Summary: Here, we present a detailed protocol for the identification of potential oncofetal targets for hepatocellular carcinoma (HCC) patients through a hepatocyte differentiation model and a sorafenib refractory cell-line-derived xenograft model. We describe the procedures of tumor sphere formation, organoid generation, and subcutaneous tumor formation for functional studies. We then detail the procedures of immunohistochemistry and immunofluorescence for examination of changes in lineage-specific markers. Finally, we describe the development of antibody-based therapeutics targeting tumor lineage plasticity in HCC.For complete details on the use and execution of this protocol, please refer to Kong et al. (2021).1 : Publisher’s note: Undertaking any experimental protocol requires adherence to local institutional guidelines for laboratory safety and ethics.

Background: Several studies have evaluated whether depressed persons have older appearing brains than their nondepressed peers. However, the estimated neuroimaging-derived “brain age gap” has varied from study to study, likely driven by differences in training and testing sample (size), age range, and used modality/features. To validate our previously developed ENIGMA brain age model and the identified brain age gap, we aim to replicate the presence and effect size estimate previously found in the largest study in depression to date (N = 2126 controls & N = 2675 cases; +1.08 years [SE 0.22], Cohen's d = 0.14, 95% CI: 0.08–0.20), in independent cohorts that were not part of the original study. Methods: A previously trained brain age model (www.photon-ai.com/enigma_brainage) based on 77 FreeSurfer brain regions of interest was used to obtain unbiased brain age predictions in 751 controls and 766 persons with depression (18–75 years) from 13 new cohorts collected from 20 different scanners. Meta-regressions were used to examine potential moderating effects of basic cohort characteristics (e.g., clinical and scan technical) on the brain age gap. Results: Our ENIGMA MDD brain age model generalized reasonably well to controls from the new cohorts (predicted age vs. age: r = 0.73, R2 = 0.47, MAE = 7.50 years), although the performance varied from cohort to cohort. In these new cohorts, on average, depressed persons showed a significantly higher brain age gap of +1 year (SE 0.35) (Cohen's d = 0.15, 95% CI: 0.05–0.25) compared with controls, highly similar to our previous finding. Significant moderating effects of FreeSurfer version 6.0 (d = 0.41, p = 0.007) and Philips scanner vendor (d = 0.50, p 3400 patients and >2800 controls worldwide show reliable but subtle effects of brain aging in adult depression. Future studies are needed to identify factors that may further explain the brain age gap variance between cohorts.

Crack detection plays an important role in disease assessment of concrete buildings. However, factors such as complex background, irregular edge, and the real-time and accuracy requirement also make crack detection a challenging task. Aiming at the above challenges, an improved U-Net model for concrete crack detection is proposed, which has strong capability to extract the linear object, improving the performance in crack detection. The model is named Residual Linear Attention U-Net (RLAU-Net). There are three key measures in this paper. First, mirror padding the source image before convolution. Second, the multi-level features are obtained by aggregating the multi-scale features level by level. Third, strip pooling kernels are used to extract global contextual information, reducing information interference from the background. We tested the performance of RLAU-Net on our crack dataset, and the experimental results exhibited that it can improve the quantitative results of mean Intersection Over Union to 81.69%. In addition, F1 score has increased to, 78.21%, the Intersection Over Union of crack increased to 64.47%. We also compared the detect time-consuming of RLAU-Net and that of the original U-Net. Results demonstrate that the proposed model has a short processing time while maintaining a high detection accuracy for crack detection.

Nanomedicines have shown a promising strategy for cancer therapy because of their higher safety and efficiency relative to small-molecule drugs, while the dense extracellular matrix (ECM) in tumors often acts as a physical barrier to hamper the accumulation and diffusion of nanoparticles, thus compromising the anticancer efficacy. To address this issue, two major strategies including degrading ECM components and inhibiting ECM formation have been adopted to enhance the therapeutic efficacies of nanomedicines. In this review, we summarize the recent progresses of tumor ECM modulating strategies for enhanced antitumor therapy of nanomedicines. Through degrading ECM components or inhibiting ECM formation, the accumulation and diffusion of nanoparticles in tumors can be facilitated, leading to enhanced efficacies of chemotherapy and phototherapy. Moreover, the ECM degradation can improve the infiltration of immune cells into tumor tissues, thus achieving strong immune response to reject tumors. The adoptions of these two ECM modulating strategies to improve the efficacies of chemotherapy, phototherapy, and immunotherapy are discussed in detail. A conclusion, current challenges and outlook are then given.

Propellant materials are occasionally experiencing severe dynamic loading during transporting and service process, thus their mechanical characteristics and potential mechanisms under transient loading are needed thoroughly understanding for its integrity designing and reliable service. The paper focuses on the mechanical behaviors of propellant CMDB, along with its potential mechanism and constitutive characterizations. Mechanical behaviors are firstly studied experimentally under strain rates from 0.0001 s−1 to 3800 s−1 using Instron mechanical device and Hopkinson bar apparatus. Strain-controlled experiments are also performed for specific focus on severe multiple loadings. It is found that CMDB presents high rate-dependence, and shares parallel mechanical behaviors under wide strain rates. So does the strain hardening ratio. The microstructural observation on crack maps demonstrates that the crack is rate-dependent too, which presents the increasing dimension and decreasing quantity with increasing strain rate. The mechanisms are accordingly proposed based on microstructures, which can explain reasonably the rate dependences. Finally, a constitutive equation is succinctly deduced to well capture the mechanic characteristics at large deformation under wide strain rate range, and the involved less parameters own the overwhelming merit in engineering simulation and applications.

Implementation of Nanosilica particles in chemical flooding processes would be of interest for petroleum industries as nanoparticles can improve the polymer performances during oil recovery processes. In this paper, three different injectivity scenario of polymer–Nanosilica, Polymer solution, and water flooding were experimentally investigated to measure oil recovery factor, contact angle, and interfacial tension. Oil recovery factor for polymer–Nanosilica, polymer, and water flooding is 65%, 55%, and 50% respectively. Water flooding was performed until 2 PV and it did not continue as there is no progress in recovery factor in this scenario. After that, polymer solution was injected until 5 PV to reach a plateau. Krwhas witnessed its minimum value of 0.3 and 0.15 for water–polymer–Nanosilica and polymer–Nanosilica respectively. This issue has a capillary forces decrease, which would be a proper reason for oil recovery enhancement. Secondary water drive mechanism would be an increasing point on the Krwfor both scenarios. Regarding the increase of surface hydrophilicity in the presence of Nanosilica–polymer, contact angle has been decreased dramatically in the low concentration of Nanosilica. Nanosilica addition into water and polymer has caused to reduce the IFT by the increase of Nanosilica concentration. This reduction corresponds to the decrease of Gibbs energy in the presence of Nanosilica particles.

Industrial development, increased demand for energy, limited fossil fuels, and the prevention of environmental damage have led to the use of renewable energy to produce power. The combined system includes renewable wind and solar energy systems or other renewable energy. The hybrid system has been widely used in recent decades to provide energy. In this research, an optimal integrated system has been used to generate electricity. The proposed system includes wind, hydropower, and photovoltaic systems. to estimate the maximum power generation and reduce fluctuations in electricity generation, three proposed algorithms have been used and three common solutions have been applied to solve the optimization problem. The performance of the combined system in different weather conditions has also been assessed. The results showed that among the three proposed algorithms, the model improved the Barnacles Mating Optimizer Algorithm (IBMO) has the best distribution and convergence. Among the three common solutions, a common solution has the most logical solution to the optimization problem. And among the different hydrological conditions, the highest electricity generation is related to the wet season. the most important role in the hybrid system related the hydropower so that despite the reduction of electricity produced in the wind and photovoltaic power plants, the hydropower plant compensates for the drop in production of these systems and causes the production flow to continue.

Acid mine drainage commonly occupies some pore space after underground coal mining, and this severely depreciates coal pillars, thereby posing a significant risk to mine stability. Considering that such depreciation is reflected in the microstructures of these pillars, in the present study, we propose a static immersion method suitable for coal seam samples immersion in the laboratory. We immersed the No. 2–2 coal seam samples from the Ningtiao Tower Coal Mine in Yulin, Shaanxi Province, in different acid mine drainage solutions and monitored the pH, oxidation–reduction potential (ORP), electrical conductivity (EC), total dissolved solids (TDS) among other water quality parameters for 300 h. After the immersion tests, samples were examined using scanning electron microscopy (SEM). The pH, ORP, EC, and TDS of the prepared acid mine drainage solutions increased significantly as the immersion time increased. Changes in water quality parameters are attributed to the absorption of hydrogen ions by insoluble clay minerals in the coal, which reduced the acidity, increased the pH value, and enhanced the electrical conductivity of the acid mine drainage solutions. SEM analysis reveals differences in the pore characteristics of (pore throat size and orientation) of the coal samples, and these are caused by erosive effects of the acid mine drainage solutions. Pores with throat sizes greater than 10μmincreased by 95% as the pH of the acid mine drainage solutions decreased, while the dominant pore orientation (60–90°) decreased to the 0–30° or increased to the 150–180° range, thereby increasing their randomness.

In room-and-pillar mining (RPM), the roof of a coal seam is supported by coal pillars; however, the roof is non-uniformly deformed with time. Moreover, coal pillars at different positions are subjected to different stresses and some coal pillars are prone to the effects of eccentric load, thus influencing their stability. Therefore, by taking Bandingliang Coal Mine, Shaanxi Province, China, as the engineering background, the non-uniform deformation characteristics of the roof of a room-and-pillar mining goaf (RPMG) were first analysed by using numerical simulation and theoretical analysis. The residual pillars in the RPMG were partitioned into a uniform deformation zone, a transition zone, and a sub-uniform deformation zone; thereafter, the stress distribution in coal pillars under non-uniform deformation was revealed to show that coal pillars were subjected to non-uniform stresses; subsequently, the distributed force under the eccentric load was concentrated to attain the changes in stress state of coal pillars under eccentric load, including behaviour such as a non-uniformly compressed state, critical state, and a tensile stress state; finally, the pillar stability under the eccentric load was judged by taking the No. 19 coal pillar as an example. The result showed that the shear stress generated by the coal pillar was 0.58 MPa, which was lower than the allowable shear stress (1.51 MPa). As a result, the pillar did not collapse, consistent with actual conditions on site. The result is expected to provide a theoretical basis for controlling pillar stability in the RPMG. The theory of the stability of the residual pillars in the RPMG provided in this paper provides a new direction for determining the stability of pillars, and the study findings have been applied in specific mines and verified.

Integrins are transmembrane receptors that have been implicated in the biology of various human physiological and pathological processes. These molecules facilitate cell–extracellular matrix and cell–cell interactions, and they have been implicated in fibrosis, inflammation, thrombosis, and tumor metastasis. The role of integrins in tumor progression makes them promising targets for cancer treatment, and certain integrin antagonists, such as antibodies and synthetic peptides, have been effectively utilized in the clinic for cancer therapy. Here, we discuss the evidence and knowledge on the contribution of integrins to cancer biology. Furthermore, we summarize the clinical attempts targeting this family in anti-cancer therapy development.

Background & aims: Excessive inflammatory responses and oxidative stress are considered the main characteristics of inflammatory bowel disease (IBD). Endogenous hydrogen sulfide (H2S) has been reported to show anti-inflammatory activity in IBD. The main aim of this study was to explore the role of 3-mercaptopyruvate sulfurtransferase (MPST), a key enzyme that regulates endogenous H2S biosynthesis, in IBD. Methods: Colonic MPST expression was evaluated in mice and patients with IBD. Various approaches were used to explore the concrete mechanism underlying MPST regulation of the progression of colitis through in vivo and in vitro models. Results: MPST expression was markedly decreased in colonic samples from patients with ulcerative colitis (UC) or Crohn's disease (CD) and from mice treated with DSS. MPST deficiency significantly aggravated the symptoms of murine colitis, exacerbated inflammatory responses and apoptosis, and inhibited epithelium stem cell-derived organoid formation in an H2S-independent manner. Consistently, when HT29 cells were treated with TNF-α, inhibition of MPST significantly increased the expression of proinflammatory cytokines, the amount of ROS and the prevalence of apoptosis, whereas overexpression of MPST markedly improved these effects. RNA-seq analysis showed that MPST might play a role in regulating apoptosis through AKT signaling. Mechanistically, MPST directly interacted with AKT and reduced the phosphorylation of AKT. Additionally, MPST expression was positively correlated with AKT expression in human IBD samples. In addition, overexpression of AKT rescued IEC apoptosis caused by MPST deficiency, while inhibition of AKT significantly aggravated it. Conclusions: MPST protects the intestines from inflammation most likely by regulating the AKT/apoptosis axis in IECs. Our results may provide a novel therapeutic strategy for the treatment of colitis.

Lactobacillus kefiri is a beneficial bacteria that is often used to make yogurt only, and is beneficial to human health when it is used in food fermentation. In this article, a fermentation supernatant (LAF) is prepared by culturing Lactobacillus kefiri, and the anti-aging effects of LAF are evaluated at the biochemical, cellular, and molecular biology levels. The antioxidant activity of LAF is comprehensively evaluated by three free radical scavenging tests and the total antioxidant capacity (ABTS method) test. The toxicity of LAF on human skin fibroblasts (HSF) is detected using the MTT method, and the effects of LAF on H2O2-induced oxidative stress in terms of intracellular reactive oxygen species (ROS), Malondialdehyde (MDA) content, antioxidant enzyme activity are evaluated. The gene expression levels of LC3 and Beclin-1 are detected using the real-time reverse transcription-polymerase chain reaction (qRT-PCR) method, and the protein expression levels of LC3 are detected using the Western blot method to evaluate the effects of LAF on HSF autophagy. The expression of type I collagen (COL-1), Matrix metalloproteinase-1(MMP-1), AKT pathway, MAPK pathway, and other genes are detected by qRT-PCR to study the anti-aging effects of LAF. From the experimental results, it is found that LAF can delay the aging of HSF at the biochemical, cellular, and molecular biology levels, and can be utilized as a functional food ingredient.

We developed a Dual-PPACs detector for fast neutron measurements that consists of two sets of PPAC: conventional PPAC and fission PPAC. A238U(U3O8) coating is placed in the fission PPAC’s anode, which is used as the neutrons conversion layer. An experiment was performed to measure neutron time-of-flight (TOF) in which 252Cf spontaneous fission source was used. An excellent time resolution of 164ps has been observed at 6 mbar in isobutene gas. With the excellent time resolution of Dual-PPACs detector, exact neutron energy can be extracted from the timing measurement. The experimental detection efficiency was 1.9 × 10−7, consistent with the efficiency of 2.5 × 10−7 given by a Geant4 simulation. Ultimately, the results show that the Dual-PPACs detector is a suitable candidate for measuring fast neutrons in the future CiADS system.

Rapid industrialization and urbanization trends have brought many challenges, one of the most acute of which is air pollution. Until recently, scholars have primarily focused on the toll that air pollution exacts through its health effects while ignoring air pollution's impact on consumer behavior. The scattered research in the recent year reveals that air pollution might influence consumers' decision-making process before, during, and after consumptions in both online and offline contexts. However, no research to our knowledge has reviewed the influence effect of air quality on consumer behaviors, which impedes the scholars and practitioners from acquiring knowledge from this emerging field. This informative review aims to collect and analyze the existing scattered research for air pollution effects on consumer decision-making behavior. This review illustrates that the impact of air pollution on consumer behavior is rather extensive, ranging from health risks to emotional changes, from changes in daily habits to individual and group consumption behaviors. We propose that future research can potentially explore the impact of air pollution on consumers' consumption experience and evaluation behavior and examine the differential impacts of air pollution on consumers' individual and group consumption decisions.

Background: Apoptosis played vital roles in the formation and progression of osteosarcoma. However, no studies elucidated the prognostic relationships between apoptosis-associated genes (AAGs) and osteosarcoma. Methods: The differentially expressed genes associated with osteosarcoma metastasis and apoptosis were identified from GEO and MSigDB databases. The apoptosis-associated prognostic signature was established through univariate and multivariate cox regression analyses. The Kaplan–Meier (KM) survival curve, ROC curve and nomogram were constructed to investigate the predictive value of this signature. CIBERSORT algorithm and ssGSEA were used to explore the relationships between immune infiltration and AAG signature. The above results were validated in another GEO dataset and the expression of AAGs was also validated in osteosarcoma patient samples by immunohistochemistry. Results: HSPB1 and IER3 were involved in AAG signature. In training and validation datasets, apoptosis-associated risk scores were negatively related to patient survival rates and the AAG signature was regarded as the independent prognostic factor. ROC and calibration curves demonstrated the signature and nomogram were reliable. GSEA revealed the signature related to immune-associated pathways. ssGSEA indicated that one immune cell and three immune functions were significantly dysregulated. The immunohistochemistry analyses of patients’ samples revealed that AAGs were significantly differently expressed between metastasis and non-metastasis osteosarcomas. Conclusions: The present study identified and validated a novel apoptosis-associated prognostic signature related to osteosarcoma metastasis. It could serve as the potential biomarker and therapeutic targets for osteosarcoma in the future.

Industrial land is a prerequisite for industrial development and a crucial factor in promoting local economic growth. However, while promoting industrial development, industrial land expansion has produced much environmental pollution, but its impact has not been effectively evaluated. Based on the balanced panel data of 324 cities in China from 2007 to 2016, the effect of industrial land expansion on PM2.5 concentrations is studied using a spatial econometric model. The results show the evident regional heterogeneity of industrial land expansion. The eastern region has the largest expansion scale. Additionally, since 2013, the scale of industrial land expansion has decreased. The vast cities in the central and eastern regions have relatively high PM2.5 concentrations, especially in the North China Plain. Furthermore, the overall PM2.5 concentrations show a downward trend; however, a noticeable interannual fluctuation has been observed. Besides, the industrial land expansion has significantly promoted increased PM2.5 concentrations, both nationally and regionally. The most significant impact is in the eastern region, and the smallest impact is in the central region. Population density (POPD), road density (RORD), and temperature (TEM) positively correlate with PM2.5 concentrations, whereas economic development levels (EDL), industrial structure upgrading (ISU), vegetation coverage (NDVI), and precipitation (PRE) have varying effects on PM2.5 concentrations in each region.

A growing body of evidence has demonstrated the significance of the gut microbiota in host health, while the association between gut microbiota dysbiosis and multiple diseases is yet elusive in the scenario of exposure to widely used pesticides. Here, we show that gut microbiota dysbiosis involves in host's abnormal lipid metabolism and consequently the non-alcoholic fatty liver disease in Xenopus laevis upon exposure to cis-bifenthrin, one of the most prevalent pyrethroid insecticides in the world. With the guidance of gut microbiota analysis, we found that cis-bifenthrin exposure significantly perturbed the gut microbial community, and the specific taxa that served as biomarkers were identified. Metabolomics profiling and association analysis further showed that a significant change of intestinal metabolites involved in lipid metabolic pathways were induced along with the microbiota dysbiosis upon exposure to cis-bifenthrin. Detailed investigation showed an altered functional regulation of lipids in the liver after cis-bifenthrin exposure and the accumulation of lipid droplets in hepatocytes. Specifically, a change in deoxycholic acid alters bile acid hepatoenteral circulation, which affects lipid metabolism in the liver and ultimately causes the development of fatty liver disease. Collectively, these findings provide novel insight into the gut microbiota dysbiosis upon pesticide exposure and their potential implication in the development of chronic host diseases related to liver metabolic syndrome.

Flexible piezoelectric pressure sensors have been paid great attention in wearable electronic devices, obtaining mechanical energy and driving portable devices. Presently, membranes based on piezoelectric ceramic/polymer composite materials encounter problems such as filler agglomeration and surface defects, which affects the energy conversion performance of piezoelectric devices. Herein, the surface of lead zirconate titanate (Pb(Zr0.52Ti0.48)O3, PZT),was modified by coupling agent-polydopamine (Pdop), and combined with the polyimide (PI) matrix by in-situ polymerization to form a uniform Pdop@PZT/PI composite. This polydopamine modification method increases the compatibility between the two components, and promotes the dispersion of PZT in the polyimide matrix more uniform. Under the external force of 10 N, the maximum open circuit voltage of Pdop@PZT/PI-based piezoelectric pressure sensor (PPS) can reach 12.8 V. In addition, the sensitivity of the sensor is 1.4 V/N (0.24 V/kPa), which can maintain a stable output voltage under different frequencies of external force. After 10,000 cycles of periodic impacting/releasing, the open circuit voltage of PPS remained stable, indicating that the device has excellent stability and durability. It has the potential to be used as self-powered wearable sensors and detect human motion in daily life.

Excessive arsenic in soil and groundwater will not only seriously affect the growth of plants, but also endanger human health through the food chain. However, there are few studies on the effects of metalloid speciation and anion competition on the toxicity of arsenate [As(Ⅴ)]. To investigate the effects of accompanying anions and pH on the toxicity of As(Ⅴ) on wheat root elongation, wheat roots were exposed to the concentrations of As(Ⅴ) in the solution ranged from 0 to 500 mM and different levels of pH (4.5–8.0) and different accompanying anions (H2PO4-, SO42-, NO3- and Cl-) for five days. The root length of wheat was measured and the biotic ligand model (BLM) was developed to predict the potential toxicity of As(V) speciation to wheat roots. The results illustrated that EC50 of total As(V) (EC50{As(Ⅴ)T}) values increased from 6.88 to 33.9 μM with increasing pH values from 4.5 to 8.0, suggesting that increasing pH alleviated As(Ⅴ) toxicity. The EC50{AsO43-} and EC50{HAsO42-} values increased from 0.001 to 4342 μM and from 0.0214 to 27.4 μM, respectively, while the EC50{H2AsO4-} and EC50{H3AsO4} values sharply decreased from 6.62 to 2.68 μM and from 41.8 μM to 5.34 nm, respectively, when pH increased from 4.5 to 8.0. The toxicity of As(Ⅴ) decreased as the H2PO4- and SO42- activities increased but not when the activities of NO3- and Cl- increased, indicating that SO42- and H2PO4- showed competitive effects with As(Ⅴ) on the binding sites. Based on BLM theory, the stability constants were obtained: logKAsO4BL= 3.70; logKHAsO4BL= 4.08; logKH2AsO4BL= 4.77; logKH3AsO4BL= 6.50; logKH2PO4BL= 2.09 and logKSO4BL= 1.86, with fAsBL50%= 0.30 and β = 1.73. Results implied that BLM performed well in As(Ⅴ) toxicity prediction when coupling toxic species AsO43-, HAsO42-, H2AsO4-, and H3AsO4, and the competition of SO42- and H2PO4- for binding sites. The current study provides a useful tool to accurately predict As(V) toxicity to wheat roots.

Limnocythere inopinata (Baird, 1843) is a widely distributed ostracod in modern non-marine waters and Quaternary sediments. Based on its morphological variation (the number and position of its nodes), different phenotypes have been identified. However, the factors controlling its morphological variation are currently open to debate, which hinders palaeoecological reconstructions based on this species. In this study, ostracod distribution and hydrochemical analyses of the ambient environment of 21 lakes in the Badain Jaran Desert were carried out. Three ostracod species belonging to two genera are identified as Limnocyhtere inopinata, Cypris cf. granulate and Cypris sp. with the dominant species L. inopinata represented by six phenotypes. The distribution features of these ostracods in the lakes and related ecological information are reported. In addition, the factors controlling the morphological variations of L. inopinata were analysed. Our data indicate that the noded individuals of L. inopinata prefer water with appropriate Ca2+ content (30–40 mg L−1) and low salinities (below 4.60 g L−1). The percentage of noded individuals of L. inopinata increases with increasing salinity only within a certain salinity range. Hence, caution should be exercised in reconstructions of palaeosalinity based on the morphological variability of L. inopinata.

A novel, three-dimensional filter based on corn stalk (CS) was prepared by in-suit growing ZnO nanoparticles (NPs) for potential water sterilization. The hierarchical mesostructure consisting of vessels and parenchymas facilitated the diffusion of Zn2+ and immobilization of ZnO NPs. The different zinc sources influenced various morphology and chemical characteristics of ZnO loaded in CS, leading to a variety of antibacterial activities. The nanocomposites from Zn(NO3)2, exhibited high rates for killing both Escherichia coli (>99.2%) and Staphylococcus aureus (>95.4%) through the short-time filtration. The antimicrobial mechanism of CS/ZnO was owed to interception of the bacteria by a porous architecture of CS. Thus, it enhanced the bactericidal efficiency of nano ZnO through physical friction, chemical reactions with reactive oxygen species (ROS) and penetration of zinc-hydrated ions. Consequently, deformation of the cell membranes, leakage or damage of intercellular components caused the death of bacteria.

Solid backfill mining (SBM) is a form of green mining, the core of which is to control and minimize the deformation and movement of strata above longwall coal mines. Establishing a mechanical model that can reliably describe roof deformation by considering the viscoelastic properties of waste gangue is important as it assists in improving mine designs and reducing the environmental impact on the surface. In this paper, the time-dependent deformation characteristics of gangue under different stress levels were obtained by using lateral confinement compression, that reliably represents the compaction of goaf. The viscoelastic foundation model for gangue mechanical response is different from the traditionally used elastic foundation model, as it considers the time factor and viscoelasticity. A mechanical model using a thin plate on a fractional viscoelastic foundation was established, and the roof deflection, bending moment, time-dependent, viscous and other characteristics of SBM were included and analyzed. Compared with the existing elastic foundation model, the proposed fractional order viscoelastic foundation model has higher accuracy with laboratory data. The plate deflection increases by 50.9% and the bending moment increases by 37.9% after 100 days, which the elastic model would not have been able to predict.

The objective of this study is to evaluate the performance of three models for estimating daily evapotranspiration (ET) by employing flux observation data from three years (2007, 2008 and 2009) during the growing seasons of winter wheat and rice crops cultivated in a farmland ecosystem (Shouxian County) located in the Huai River Basin (HRB), China. The first model is a two-step model (PM–Kc); the other two are one-step models (e.g., Rana–Katerji (R–K) and advection-aridity (AA)). The results showed that the energy closure degrees of eddy covariance (EC) data during winter wheat and rice-growing seasons were reasonable in the HRB, with values ranging from 0.84 to 0.91 and R2 of approximately 0.80. Daily ET of winter wheat showed a slow decreasing trend followed by a rapid increase, while that of rice presented a decreasing trend after an increase. After calibrating the crop coefficient (Kc), the PM–Kc model performed better than the model using the Kc recommended by the Food and Agricultural Organization (FAO). The calibrated key parameters of the R–K model and AA model showed better universality. After calibration, the simulation performance of the PM–Kc model was satisfactory. Both the R–K model and AA model underestimated the daily ET of winter wheat and rice. Compared with that of the R–K model, the simulation result of the AA model was better, especially in the simulation of daily ET of rice. Overall, this research highlighted the consistency of the PM–Kc model to estimate the water demand for rice and wheat crops in the HRB and in similar climatic regions in the world.

For solving the problems such as high energy consumption of cooling system of big DC and utilization of abandoned wells, this paper proposed Libr/H2O absorption cooling system based on enhanced geothermal system (EGS) using abandoned wells for DC, which can realize the cascade utilization of geothermal energy, meet the cooling needs of the big DC. Firstly, a model of Libr/H2O absorption cooling system based on enhanced geothermal system using concentric circles wells for of DC was established and verified in this paper, then the influence of key parameters such as well depth, injection rate on the refrigeration system was analyzed. The results showed that the driven temperature of hot water from EGS can reach above 150 °C steadily for 20 years to meet the requirements of two-effect Libr/H2O refrigeration. The cooling capacity of this system can reach above 9 MkW with COP above 1.0 for providing cold water for DC, and cooling capacity increases with well depth and injection rate increasing while there is best injection rate with highest COP of system.

There are lots of emission gas and hot water generating from power generation system, which can be been utilization again to improve energy efficiency and reduce gas emission. For utilization of emission gas and hot water from power plant of oil flied, this paper analyzed and compared combination emission gas including CO2, flue gas, N2and Air co-injected with hot water flooding for heavy oil recovery. The experiments results indicate that different gases including CO2, N2, Air and Flue gas co-injected with hot water can significantly improve recovery of reservoir, and CO2 co-injected with hot water has the beat recovery factor compared to the other gas co-injected for enhanced heavy oil recovery. By measuring the temperature field of reservoir, it finds that co-injected CO2 does not affect the heat effect of hot water.

Vitamin D deficiency is a common phenomenon in non-alcoholic fatty liver disease (NAFLD) and the progressive non-alcoholic steatohepatitis (NASH). Jiangzhi Granule (JZG) formula is a Traditional Chinese medicine prescription, and has been found effective against NAFLD/NASH. Here we showed that vitamin D deficiency could accelerate NASH development, and reduce vitamin D receptor (VDR) expression. JZG treatment alleviated high-fat vitamin D deficient (HF-VDD) diet-induced NASH in C57BL/6 J mice, and up-regulated both the liver and intestinal VDR expression independent of 1,25-dihydroxy-vitamin D3 level. We analyzed the fecal BA profile using liquid chromatography coupled with triple quadrupole mass spectrometry (UPLC-TQMS) -based metabolomics, and found that JZG modulated fecal BA profile, predominantly increased the ratio of secondary BA species, as well as the expression of tight junction proteins Zona occludens 1(ZO-1) and occludin in the colon. In vitro experiment further confirmed the representative secondary BA species lithocholic acid (LCA) and keto-LCA upregulated the expression of and ZO-1 through VDR in LPS-stressed Caco-2 cells. Our results identified the endogenous VDR activation by JZG through modulating BA species in vitamin D deficiency-related NASH mice, thus providing evidence for the clinical application of JZG in treating NASH.

Epigenetics refers to alterations in gene expressions that are reversible and stable, but do not involve changes in DNA sequences. In recent years, an increasing number of studies have shown that epigenetics plays a critical role in autophagy, which can be schematized as a biological process comprising of the following steps: autophagy signal activation, autophagic vesicle elongation, autophagosome maturation and autophagosome-lysosome fusion. As previously reported, autophagy can maintain intracellular homeostasis and autophagy dysfunction will lead to various diseases. For instance, the abnormal expression of genes involved in autophagy can result in the occurrence of many cancers and atherosclerosis. It is also well known that epigenetic modifications can affect autophagy related genes expressions and modulate other signaling molecular involved in autophagy. As an important epigenetic enzyme, LSD1 (lysine specific demethylase 1) plays an essential role in modulating autophagy. On one hand, LSD1 directly regulates autophagy-related genes expressions, including ATGs, Beclin-1, LC3 and SQSTM1/p62. On the other hand, inhibition of LSD1 can activate autophagy through regulating the activities of some other proteins such as p53, SESN2, mTORC1 and PTEN. Since autophagy activation is tightly related to the occurrence of various diseases and can be induced by LSD1 inhibition, development of LSD1 inhibitors will provide a new direction to treat such diseases. In this review, we described the mechanisms by which LSD1 regulates autophagy in different manners and how autophagic dysfunction leads to diseases occurrence. In addition, some LSD1 inhibitors used to treat diseases through modulating autophagy are also summarized in our review.

Pulmonary fibrosis induced by silica particles is defined as silicosis, which is an incurable disease. The pathogenesis of silicosis is not completely clear, but it’s certain that immune system dysfunction is closely related to it. Immune checkpoint inhibitors (ICIs) are emerging immunotherapeutic agents that mainly target adaptive immune cells, and there is abundant evidence that ICIs are of great value in cancer treatment. However, whether these attractive agents can be implemented in silicosis treatment is unclear. In this study, we explored the efficacy of small molecule inhibitors targeted PD-1/PD-L1 and CTLA-4 on silica-induced pulmonary fibrosis in mice. ICIs were injected intraperitoneally into mice that received silica instillation twice a week. The mice were sacrificed 7 and 28 days after the injection. The lungs, spleen, hilar lymph nodes, thymus, and peripheral blood of mice were collected and subjected to histological examination, flow cytometry analysis, and mRNA and protein quantification. Our results demonstrated that silica exposure caused damage to multiple immune organs in mice, leading to an imbalance in systemic immune homeostasis. Specifically, proportions and subtypes of T and B cells were significantly altered, and the expressions of PD-1, PD-L1 and CTLA-4 were abnormal on these cells. Both PD-1/PD-L1 and CTLA-4 inhibitor administration modulated silica-induced immune system disruption, however, only PD-1/PD-L1 signaling inhibition showed significant amelioration of silicosis. Our findings confirmed for the first time the potential value of ICIs for the treatment of silica-induced pulmonary fibrosis, and this may provide new ideas for the treatment of other fibrosis-related diseases.

Thermosensitive Hydrogel System (THS) is a suitable candidate for targeted drug delivery, because of its intelligent response and controlled release. In this work, combination of guanidine-chitosan (GCS), β-glycerol phosphate disodium salt (β-GP) and hydroxypropyl-β-cyclodextrin (HP-β-CD) can successfully result in a novel THS by single factor and response surface method. The characterization of THS is detected with gelation temperature, FT-IR, SEM, in vitro release, rheology and biocompatibility. Resveratrol (Res) is selected as a model drug to evaluate the anti-depressant effects of THS loaded Res (Res-THS) via intranasal administration of chronic unpredictable mild stress (CUMS) rats. The results display that the Res-THS can increase concentration of neurotransmitter in rats’ brain tissue via intranasal administration, indicating the anti-depressant effect.

Hemostasis is achieved through the comprehensive effect of multiple pathways. A composite porous material was designed consisting of silk fibroin (SF), gelatin (GA) and calcium alginate (CA), integrating the good biocompatibility of SF, swelling property of GA and hemostatic factor Ca2+ of CA. Water absorption, platelet adhesion, fibrinogen adsorption, blood coagulation activity, and cytotoxicity were investigated. Pore size in SF/GA porous materials increased with increasing content of GA in SF but decreased significantly in SF/CA porous materials after incorporating CA in SF. Based on the water binding capacity of materials and capillary effect of pores, the binary composites SF/GA1:1 and SF/CA3:1 displayed the best water absorption. Although GA and CA were more favorable for fibrinogen adsorption, SF/GA1:1 and SF/CA1:1 exhibited greater numbers of adhered platelets, shorter clotting times, and greater whole blood coagulation ability. Human skin fibroblasts spread well on the pure SF and GA and all the composites of SF/GA and SF/CA, and they showed high proliferative activity. Pure CA inhibited cell proliferation. For ternary composite materials, the comprehensive hemostatic ability of SF/GA/CA1:1:1 was greater than that of SF/GA/CA1:1:3.

The surface of the female lower genital tract is covered with squamous epithelium, and some bacteria and fungi reside in the cavity. Among them, the dominant Lactobacillus maintain the acidic environment of the vagina. The acidic environment, squamous epithelium barrier, mucus and innate immune response together resist the invasion of pathogens and local homeostasis. Bacterial vaginosis (BV) is a disorder of the vaginal microbiota, which is characterized by a shift in the vaginal flora from the dominant Lactobacillus to a polymicrobial anaerobic flora accompanied by an increase in pH ​> ​4.5. Its high recurrence rate, obvious clinical symptoms, and possible adverse pregnancy outcome seriously disturb women's healthy life. However, its pathogenesis is still elusive. The vaginal microenvironment includes not only microbiota, but also microbially and host-produced metabolites, and vaginal local immunity. Given the inseparable relationship between the microbiota and its metabolites and the immune response, it is important to study how these interactions regulate vaginal local immunity to resist pathogens. In this review, we will discuss the main theories of BV etiology, which eventually involves the interaction between BV-related pathogens, small molecular metabolites, and host immune responses in the vagina.

Summary: Background: Safe and effective vaccines are urgently needed to end the COVID-19 pandemic caused by SARS-CoV-2 infection. We aimed to assess the preliminary safety, tolerability, and immunogenicity of an mRNA vaccine ARCoV, which encodes the SARS-CoV-2 spike protein receptor-binding domain (RBD). Methods: This single centre, double-blind, randomised, placebo-controlled, dose-escalation, phase 1 trial of ARCoV was conducted at Shulan (Hangzhou) hospital in Hangzhou, Zhejiang province, China. Healthy adults aged 18–59 years negative for SARS-CoV-2 infection were enrolled and randomly assigned using block randomisation to receive an intramuscular injection of vaccine or placebo. Vaccine doses were 5 μg, 10 μg, 15 μg, 20 μg, and 25 μg. The first six participants in each block were sentinels and along with the remaining 18 participants, were randomly assigned to groups (5:1). In block 1 sentinels were given the lowest vaccine dose and after a 4-day observation with confirmed safety analyses, the remaining 18 participants in the same dose group proceeded and sentinels in block 2 were given their first administration on a two-dose schedule, 28 days apart. All participants, investigators, and staff doing laboratory analyses were masked to treatment allocation. Humoral responses were assessed by measuring anti-SARS-CoV-2 RBD IgG using a standardised ELISA and neutralising antibodies using pseudovirus-based and live SARS-CoV-2 neutralisation assays. SARS-CoV-2 RBD-specific T-cell responses, including IFN-γ and IL-2 production, were assessed using an enzyme-linked immunospot (ELISpot) assay. The primary outcome for safety was incidence of adverse events or adverse reactions within 60 min, and at days 7, 14, and 28 after each vaccine dose. The secondary safety outcome was abnormal changes detected by laboratory tests at days 1, 4, 7, and 28 after each vaccine dose. For immunogenicity, the secondary outcome was humoral immune responses: titres of neutralising antibodies to live SARS-CoV-2, neutralising antibodies to pseudovirus, and RBD-specific IgG at baseline and 28 days after first vaccination and at days 7, 15, and 28 after second vaccination. The exploratory outcome was SARS-CoV-2-specific T-cell responses at 7 days after the first vaccination and at days 7 and 15 after the second vaccination. This trial is registered with www.chictr.org.cn (ChiCTR2000039212). Findings: Between Oct 30 and Dec 2, 2020, 230 individuals were screened and 120 eligible participants were randomly assigned to receive five-dose levels of ARCoV or a placebo (20 per group). All participants received the first vaccination and 118 received the second dose. No serious adverse events were reported within 56 days after vaccination and the majority of adverse events were mild or moderate. Fever was the most common systemic adverse reaction (one [5%] of 20 in the 5 μg group, 13 [65%] of 20 in the 10 μg group, 17 [85%] of 20 in the 15 μg group, 19 [95%] of 20 in the 20 μg group, 16 [100%] of 16 in the 25 μg group; p

Due to the applicability of hot water injection in the heavy oil production, it has considered as one of the efficient methods in recovery performances. However, its low viscosity has caused to produce lower oil in shale formations. Therefore, hybrid chemical enhanced oil recovery techniques such as foam injection with sequential carbon dioxide injection would be of important in the heavy oil production. In this paper, we aimed to consider induced hot carbon dioxide–foam enhanced oil recovery technique after water flooding at different temperatures. First, we investigated temperature impact on the resistance factor at different gas–oil ratios (henceforth; GOR). Then, polyacrylamide additive (PAM) at different concentrations were added to the foaming agent to increase the foam stability. Oil recovery factor and water cut were measured for each scenario. According to the results of these experiments, temperature increase would cause to resistance factor increase in which the temperature of 180 °Chas the highest resistance factor. It is about 93%. Moreover, increase of GORs has caused to enhance the resistance factor. Polymer concentration increase has caused to resistance factor increase that is related to the polymer property to enhance the foam stabilization. Consequently, by the increase of temperature, water changes from liquid phase to gas or vapor and this is why it has decreased in the first steps of pore volume injection. Therefore, in the temperature of 180 °C, there is not any water cut in the first period of injection. Furthermore, higher polymer concentration would have an important role on the oil recovery increase.

This study examines the impact of cash crop cultivation on household income and migration decisions, using survey data collected from low-income regions in China. Given farmers decide themselves whether to cultivate cash crops, an endogenous treatment regression model that accounts for potential selection bias issue is used to analyze the data. The empirical results show that cash crop cultivation exerts a positive and statistically significant impact on household income, but it does not affect household migration decisions significantly. The disaggregated analyses reveal that cash crop cultivation significantly increases farm income but decreases off-farm income.

In the current study, a porous 3D scaffold using Gallium-Apatite/chitin/pectin (Ga-HA/C/P) nanocomposites scaffolds (NCS) were fabricated by freeze-drying process with applications in orthopedics (bone tissue engineering). Various NCSs (0%, 30%, 50 and 70%) were prepared and characterized for its chemical structure, crystalline phase, surface texture by using various techniques such as FT-IR, XRD and SEM-EDX, respectively. The analyses of physicochemical properties proved that the formulated scaffolds were highly porous, and mechanically stable with superior density. The nanocomposite scaffolds also presented with increased swelling ability, lower biodegradation rate and higher mechanical strength. Further, biocompatibility and cytotoxicity of Ga-HA/C/P nanocomposite scaffolds were studied using NIH3T3 cells and MG-63 cells revealed no toxicity and cells attached and proliferated on scaffolds. Further implantation of prepared NCS showed mature bone formation through formation of new bone cells and osteoblast differentiation. Also, Ga-HA/C/P nanocomposites scaffolds proved to be more effective than chitin-pectin composite scaffolds. Taking results together it can be inferred that the prepared nanocomposite scaffolds possesses the prerequisites and showed great potential for treating orthopedic applications.