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Bioactive cations, including calcium, copper and magnesium, have shown the potential to become the alternative to protein growth factor-based therapeutics for bone healing. Ion substitutions are less costly, more stable, and more effective at low concentrations. Although they have been shown to be effective in providing bone grafts with more biological functions, the precise control of ion release kinetics is still a challenge. Moreover, the synergistic effect of three or more metal ions on bone regeneration has rarely been studied. In this study, vaterite-calcite CaCO3 particles were loaded with copper (Cu2+) and magnesium (Mg2+). The polyelectrolyte multilayer (PEM) was deposited on CaCuMg-CO3 particles via layer-by-layer technique to further improve the stability and biocompatibility of the particles and to enable controlled release of multiple metal ions. The PEM coated microcapsules were successfully combined with collagen at the outmost layer, providing a further stimulating microenvironment for bone regeneration. The in vitro release studies showed remarkably stable release of Cu2+ in 2 months without initial burst release. Mg2+ was released in relatively low concentration in the first 7 days. Cell culture studies showed that CaCuMg-PEM-Col microcapsules stimulated cell proliferation, extracellular maturation and mineralization more effectively than blank control and other microcapsules without collagen adsorption (Ca-PEM, CaCu-PEM, CaMg-PEM, CaCuMg-PEM). In addition, the CaCuMg-PEM-Col microcapsules showed positive effects on osteogenesis and angiogenesis in gene expression studies. The results indicate that such a functional and controllable delivery system of multiple bioactive ions might be a safer, simpler and more efficient alternative of protein growth factor-based therapeutics for bone regeneration. It also provides an effective method for functionalizing bone grafts for bone tissue engineering.

Legal consciousness is the individual consciousness which reflects legal phenomena. Well-developed legal consciousness plays a crucial role in informing citizens of his legal right and ability to exercise these rights, therefore forms certain connections of individuals and society, and its development is a key part of individual’s socialization process. Here, we investigated the emotion aspect of legal consciousness (henceforth legal emotion) and tried to identify several factors affecting the development of legal emotion and several factors affected by legal emotion. A large sample of Chinese junior middle school students (N = 967) completed a battery of self-reported questionnaires regarding legal emotion, peer attachment, self-esteem, prosocial tendencies, and interpersonal trust. The results indicated that for early adolescents, peer attachment predicts both positive and negative legal emotion. Importantly, peer attachment affects legal emotion partially through self-esteem. We also showed that negative legal emotion acted as a mediator on the relationship between interpersonal trust and prosocial tendencies. The results provided important insights into the role of legal emotion, the emotion aspect of legal consciousness, in the social interactions and its potential psychological mechanism.

The process of storing oil depots and combined station tanks is affected by factors such as process technology, equipment, and management methods. Inevitably, some heavy hydrocarbon components will condense. According to the available literature, the existing detection methods are not enough to accurately measure the component composition so that the proportion of heavy hydrocarbon substances in the lost gas is reduced. In this paper, by inventing a homogeneous reduction device, the lost gas in the entire laboratory process was kept in a homogeneous state so that the gas components were well-retained. Using the homogeneous reduction method and a traditional inspection method, gas chromatography was performed on a standard gas and the on-site lost gas, respectively. The standard gas measurement results show that the mean deviations of the homogeneous reduction method and the traditional test method were −3.45% and −11.62%, respectively, and the reduction degree reached 96.55% with the homogeneous reduction method. The results of the on-site gas loss measurements show that the proportions of most hydrocarbon substances in each lost gas increase to varying degrees after using the homogeneous reduction technology. Therefore, it is proved that these components can be better preserved using the homogeneous reduction method. It can effectively avoid the condensation of components, which is of great significance to the study of oil and gas loss.

Since the Industrial Revolution, methane has become the second most important greenhouse gas component after CO2 and the second most important culprit of global warming, leading to serious climate change problems such as droughts, fires, floods, and glacial melting. While most of the methane in the atmosphere comes from emissions from energy activities such as petroleum refining, storage tanks are an important source of methane emissions during the extraction and processing of crude oil and natural gas. Therefore, the use of high-resolution remote sensing image data for oil and gas production sites to achieve efficient and accurate statistics for storage tanks is important to promote the strategic goals of “carbon neutrality and carbon peaking”. Compared with traditional statistical methods for studying oil storage tanks, deep learning-based target detection algorithms are more powerful for multi-scale targets and complex background conditions. In this paper, five deep learning detection algorithms, Faster RCNN, YOLOv5, YOLOv7, RetinaNet and SSD, were selected to conduct experiments on 3568 remote sensing images from five different datasets. The results show that the average accuracy of the Faster RCNN, YOLOv5, YOLOv7 and SSD algorithms is above 0.84, and the F1 scores of YOLOv5, YOLOv7 and SSD algorithms are above 0.80, among which the highest detection accuracy is shown by the SSD algorithm at 0.897 with a high F1 score, while the lowest average accuracy is shown by RetinaNet at only 0.639. The training results of the five algorithms were validated on three images containing differently sized oil storage tanks in complex backgrounds, and the validation results obtained were better, providing more accurate references for practical detection applications in remote sensing of oil storage tank targets in the future.

Abstract Wound dressing with the capacities of antioxidation, antiinflammation, and efficient angiogenesis induction is expected for effectively promoting wound healing. Herein, a novel core‐shell hyaluronic acid (HA) microneedle (MN) patch with ferrum‐mesenchymal stem cell‐derived artificial nanovesicles (Fe‐MSC‐NVs) and polydopamine nanoparticles (PDA NPs) encapsulated in the needle tips is presented for wound healing. Fe‐MSC‐NVs containing multifunctional therapeutic cytokines are encapsulated in the inner HA core of the MN tips for accelerating angiogenesis. The PDA NPs are encapsulated in the outer methacrylated hyaluronic acid (HAMA) shell of the MN tips to overcome the adverse impacts from reactive oxygen species (ROS)‐derived oxidative stress. With the gradual degradation of HAMA patch tips in the skin, the PDA NPs are sustainably released at the lesion to suppress the ROS‐induced inflammation reaction, while the Fe‐MSC‐NVs significantly increase the migration, proliferation, and tube formation of human umbilical vein endothelial cells (HUVEC). More attractively, the combination of PDA NPs and Fe‐MSC‐NVs further promotes M2 macrophage polarization, thereby suppressing wound inflammation. Through in vivo experiment, the Fe‐MSC‐NVs/PDA MN patch shows an excellent effect for diabetic wound healing. These features of antioxidation, antiinflammation, and pro‐angiogenesis indicate the proposed composite core‐shell MN patch is valuable for clinical wound healing applications.

Abstract Biomedical patches are considered as a promising strategy to help tissue repair and regeneration, prevent tissue adhesion, and reduce neighboring friction. Here, novel arrowhead composite microneedle patches (MNPs) are presented with anisotropic surface adhesion and growth factor encapsulation using a heterogeneous template replication approach for endometrium repair and intrauterine adhesions (IUAs) prevention. The arrowhead structures bring about interlocking between the microneedle (MN) tips and tissues, allowing these MNPs to steadily adhere to the tissues. Besides, benefitting from the cytoadhesive needle‐tip material and the antiadhesive base material, these MNPs possess anisotropic surface adhesion and can facilitate cell adhesion on one surface to repair damaged tissues while restrain tissue contact on the other to prevent adverse adhesion. In the meanwhile, the encapsulated growth factor can be delivered through the MNs to the deep tissue, further accelerating tissue repair. Additionally, as the bases are soft and their patterns are highly tunable, the MNPs can change their shapes flexibly to adjust to the irregular morphology of uteri. It is demonstrated that these MNPs show good performances in treating injured endometrium and preventing IUAs of a rat model, indicating their great potential in versatile postoperative adhesion prevention and other clinical applications.

BackgroundParkinson’s disease (PD) is a multifactorial degenerative disease of the central nervous system, which affects mostly older adults. To date, research has focused on the progression of PD. Simultaneously, it was confirmed that the imbalances in gut microbiota are associated with the onset and progression of PD. Accurate diagnosis and precise treatment of PD are currently deficient due to the absence of effective biomarkers.MethodsIn this study, the pharmacodynamic study of cyanidin-3-O-glucoside in PD mice was used. It intends to use the “imbalance” and “balance” of intestinal microecology as the starting point to investigate the “gut-to-brain” hypothesis using metabolomic-combined 16S rRNA gene sequencing methods. Simultaneously, metabolomic analysis was implemented to acquire differential metabolites, and microbiome analysis was performed to analyze the composition and filter the remarkably altered gut microbiota at the phylum/genera level. Afterward, metabolic pathway and functional prediction analysis of the screened differential metabolites and gut microbiota were applied using the MetaboAnalyst database. In addition, Pearson’s correlation analysis was used for the differential metabolites and gut microbiota. We found that cyanidin-3-O-glucoside could protect 1-methyl-4-phenyl-1,2,3,6− tetrahydropy ridine (MPTP)-induced PD mice.ResultsMetabolomic analysis showed that MPTP-induced dysbiosis of the gut microbiota significantly altered sixty-seven metabolites. The present studies have also shown that MPTP-induced PD is related to lipid metabolism, amino acid metabolism, and so on. The 16S rRNA sequencing analysis indicated that 5 phyla and 22 genera were significantly altered. Furthermore, the differential gut microbiota was interrelated with amino acid metabolism, and so on. The metabolites and gut microbiota network diagram revealed significant correlations between 11 genera and 8 differential metabolites.ConclusionIn combination, this study offers potential molecular biomarkers that should be validated for future translation into clinical applications for more accurately diagnosing PD. Simultaneously, the results of this study lay a basis for further study of the association between host metabolisms, gut microbiota, and PD.

Older people are more likely to develop insulin resistance and lipid metabolism disorders. Purendan (PRD) is a clinically verified traditional Chinese medicine compound, which plays an obvious role in regulating lipid metabolism disorder and improving insulin sensitivity. Our study aimed to investigate the efficacy and mechanism of PRD on aged type 2 diabetes mellitus (T2DM) complicated with non-alcoholic fatty liver disease (NAFLD) rats. Sprague-Dawley rats (13 months) were fed with high-fat diet (HFD) and injected with low-dose STZ to replicate T2DM model. PRD was treated at three concentrations with metformin as a positive control. After administration, blood and liver tissue samples were collected to measure glucose metabolism indexes such as serum glucose and insulin, as well as lipid metabolism indexes such as TC, TG, LDL, HDL and FFA. Liver fat accumulation was observed by HE staining and oil red O staining. And protein expression levels of mTOR, p-mTOR, S6K1, p-S6K1 and SREBP-1c were detected by western blot. After PRD treatment, not only the insulin sensitivity and insulin resistance were significantly improved, but also the TC, TG, LDL, FFA, AST and ALT in serum and the lipid accumulation in liver tissue were significantly decreased. Moreover, PRD significantly down-regulated the expression of p-mTOR, p-S6K1 and SREBP-1c in liver tissues. In conclusion, PRD can alleviate NAFLD in aged T2DM rats by inhibiting the mTOR /S6K1/ SREBP-1c pathway.

Pancreatic cancer remains one of the cancers with the poorest prognosis bearing an overall 5-year survival rate of about 5%. Efficient new chemotherapic drugs are still highly desired. Here, bruceine A, a quassinoid identified from the dried fruits of Brucea javanica (L.) Merr., displayed the most potent anti-proliferation activity against pancreatic cancer in vitro and in vivo. Phosphoproteomic analysis revealed p38α MAPK phosphorylation was involved in bruceine A’s action in MIA PaCa-2 cells. Utilizing fortebio octet system and microscale thermophoresis, we found p38α MAPK had high affinity for bruceine A. Molecular docking and molecular dynamic simulations showed that bruceine A widely bound to residues (Leu171, Ala172, Met179, Thr180, Val183) in P-loop of p38α MAPK. Key determinants of bruceine A binding with P-loop of p38α MAPK were 19-CO, 22-CH3, 32-CH3, and 34-CH3. Taken together, our findings demonstrate that bruceine A binds directly to p38α MAPK, which can be used to probe the role of p38α MAPK phosphorylation in pancreatic cancer progression, and as a novel lead compound for pancreatic cancer therapy.

HSP90α is one of the most common stress proteins in cells; hence, it is a good target for developing drugs and testing systems for cancer or physical stress levels in humans. Streptavidin conjugated quantum dots (Sav-QDs) are widely used as fluorophores for biosensing to overcome chemical labelling problems. In this work, we have attempted to develop a multifunctional and robust assay for HSP90α. The detection technique was based on the masking of the fluorescence of spotted Sav-QDs on nitrocellulose chips (NC). Biotinylated ligand/antibody attaches to the spotted Sav-QD and then HSP90α is attached, which causes the masking of fluorescence. The masking of fluorescence was used to detect protein–ligand interactions, the effect of inhibitors, protein–protein interactions, and the presence of protein in the biological sample. The load of detection (LoD) of the assay lies in the nano molar range, making it a sensitive assay. The results from the experiments suggest that the used approach is promising for developing a multifunctional, robust, and sensitive assay for proteins that can be used for point-of-care detection in complex biological samples.

Synthetic bone substitute materials (BSMs) are becoming the general trend, replacing autologous grafting for bone tissue engineering (BTE) in orthopedic research and clinical practice. As the main component of bone matrix, collagen type I has played a critical role in the construction of ideal synthetic BSMs for decades. Significant strides have been made in the field of collagen research, including the exploration of various collagen types, structures, and sources, the optimization of preparation techniques, modification technologies, and the manufacture of various collagen-based materials. However, the poor mechanical properties, fast degradation, and lack of osteoconductive activity of collagen-based materials caused inefficient bone replacement and limited their translation into clinical reality. In the area of BTE, so far, attempts have focused on the preparation of collagen-based biomimetic BSMs, along with other inorganic materials and bioactive substances. By reviewing the approved products on the market, this manuscript updates the latest applications of collagen-based materials in bone regeneration and highlights the potential for further development in the field of BTE over the next ten years.

Due to policy changes in the context of COVID-19 pandemic, online teaching has become the main form of class in many Chinese universities. Flipped classroom has been widely used in other disciplines, but there is a dearth of evidence available about the use in online teaching of emergency medicine. This study aimed to develop a flipped classroom for online emergency medicine teaching and evaluate its effectiveness by comparing it with traditional lecture-based online teaching. A total of 62 clinical medical undergraduates from Jinan University participated in this study from September to December in 2022. An online flipped classroom approach was developed (FC group, n = 31). Traditional lecture-based online teaching was applied as a contrast (LBT group, n = 31). The undergraduates completed examinations and questionnaires at the end of the course. A course experience questionnaire and course examination score were used to evaluate the effectiveness of the flipped classroom approach. Regarding the five dimensions of the course experience questionnaire, the scores for good teaching (3.47 ± 0.50 vs. 2.34 ± 0.48, p <.001), appropriate assessment (3.31 ± 0.68 vs. 2.95 ± 0.71, p =.043) and generic skills (3.16 ± 0.60 vs. 2.72 ± 0.39, p <.001) were higher for the FC group than for the LBT group. There was no significant difference between the two groups in clear goals and standards, and appropriate workload. The undergraduates in the FC group showed significantly higher overall satisfaction than those in the LBT group (3.52 ± 0.1.03 vs. 2.87 ± 0.92, p =.012). The examination scores (77.936 ± 11.573 vs. 70.484 ± 7.434, p <.001), especially the scores for questions related to case analysis (33.032 ± 5.363 vs. 26.968 ± 7.657, p <.001), were significantly higher in the FC group than in the LBT group. The flipped classroom for online teaching was efficient in improving undergraduates' emergency medical academic performance and promoting the development of clinical case analysis ability. These findings provide an alternative flipped classroom approach for online teaching of emergency medicine. [ABSTRACT FROM AUTHOR]

China stands out as a major contributor to anthropogenic methane (CH 4) emissions, with coal mine methane (CMM) playing a crucial role. To control and reduce CH 4 emissions, China has made a dedicated commitment and formulated an ambitious mitigation plan. To verify the progress made, the consistent acquisition of independent CH 4 emission data is required. This paper aims to implement a wind-assigned anomaly method for the precise determination of regional-scale CMM emissions within the coal-rich Shanxi province. We use the TROPOspheric Monitoring Instrument (TROPOMI) CH 4 observations from May 2018 to May 2023, coupled with ERA5 wind and a bottom-up inventory dataset based on the IPCC (Intergovernmental Panel on Climate Change) Tier 2 approach covering the Changzhi, Jincheng, and Yangquan regions of the Shanxi province. The derived emission strengths are 8.4 × 10 26 molec. s -1 (0.706 Tg yr -1 , ± 25 %), 1.4 × 10 27 molec. s -1 (1.176 Tg yr -1 , ± 20 %), and 4.9 × 10 26 molec. s -1 (0.412 Tg yr -1 , ± 21 %), respectively. Our results exhibit biases of - 18 %, 8 %, and 14 %, respectively, when compared to the IPCC Tier 2 bottom-up inventory. Larger discrepancies are found when comparing the estimates to the Copernicus Atmosphere Monitoring Service global anthropogenic emissions (CAMS-GLOB-ANT) and Emissions Database for Global Atmospheric Research (EDGARv7.0) inventories (64 %–176 %), suggesting that the two inventories may be overestimating CH 4 emissions from the studied coal mining regions. Our estimates provide a comprehensive characterization of the regions within the Shanxi province, contribute to the validation of emission inventories, and provide additional insights into CMM emission mitigation. [ABSTRACT FROM AUTHOR]

Actual evapotranspiration constitutes a vital component of the exchange of energy and water vapour between the soil‐vegetation and atmospheric systems on terrestrial terrain. Nevertheless, the Tibetan Plateau, owing to its austere environmental conditions, harbours a scarcity of terrestrial monitoring stations. This circumstance presents a formidable challenge in attaining precise estimations of actual evapotranspiration. The complementary relationship method is a potential approach because it requires only routine meteorological data to estimate actual evapotranspiration on a regional or global scale. However, the suitability of the complementary relationship model across diverse ecosystems on the Tibetan Plateau necessitates further investigation. In this study, we scrutinized the simulation of daily and monthly actual evapotranspiration across 18 observation sites spanning eight distinct land use categories on the Tibetan Plateau. We employed the polynomial generalized complementary function introduced by Brutsaert (B2015), alongside its enhanced rendition proposed by Szilagyi (S2017) and Crago (C2018). The outcomes reveal that all three models adeptly replicate the fluctuations in actual evapotranspiration, irrespective of land use category or temporal scale—whether daily or monthly. This is true regardless of whether original or calibrated parameter values are applied. However, there exist significant variations in the performance of these models. In general, the C2018 model demonstrates superior performance across most ecosystems when original parameters are employed. Following parameter calibration, the simulation efficacy of the models experienced marked enhancement. Post parameter calibration, the B2015 model outperforms the other two models notably in desert and wetland environments. Furthermore, the simulation outputs from all three models display heightened sensitivity to parameter α, particularly in the context of the C2018 and S2017 models. These findings suggest that accurate estimation of parameter values is critical to improving the accuracy of estimating actual evapotranspiration. Calibrated parameter values, contingent on a fusion of vegetation, meteorology and surface roughness, exhibit variability across diverse ecosystems. [ABSTRACT FROM AUTHOR]