Large-scale Expansion Research Articles

Synergy between pluripotent stem cell-derived macrophages and self-renewing macrophages: Envisioning a promising avenue for the modelling and cell therapy of infectious diseases.

As crucial phagocytes of the innate immune system, macrophages (Mϕs) protect mammalian hosts, maintain tissue homeostasis and influence disease pathogenesis. Nonetheless, Mϕs are susceptible to various pathogens, including bacteria, viruses and parasites, which cause various infectious diseases, necessitating a deeper understanding of pathogen-Mϕ interactions and therapeutic insights. Pluripotent stem cells (PSCs) have been efficiently differentiated into PSC-derived Mϕs (PSCdMϕs) resembling primary Mϕs, advancing the modelling and cell therapy of infectious diseases. However, the mass production of PSCdMϕs, which lack proliferative capacity, relies on large-scale expansions of PSCs, thereby increasing both costs and culture cycles. Notably, Mϕs deficient in the MafB/c-Maf genes have been reported to re-enter the cell cycle with the stimulation of specific growth factor cocktails, turning into self-renewing Mϕs (SRMϕs). This review summarizes the applications of PSCdMϕs in the modelling and cell therapy of infectious diseases and strategies for establishing SRMϕs. Most importantly, we innovatively propose that PSCs can serve as a gene editing platform to creating PSC-derived SRMϕs (termed PSRMϕs), addressing the resistance of Mϕs against genetic manipulation. We discuss the challenges and possible solutions in creating PSRMϕs. In conclusion, this review provides novel insights into the development of physiologically relevant and expandable Mϕ models, highlighting the enormous potential of PSRMϕs as a promising avenue for the modelling and cell therapy of infectious diseases.

The Giant Leap in the Development of Higher Engineering Education in China

Purpose This study discusses the development of higher engineering education and its future direction following the increased enrollment in higher education institutions in China. Design/Approach/Methods By compiling and analyzing corresponding policies and historical and statistical data, the large-scale expansion process and quality enhancement pathways of China's higher engineering education are summarized. Additionally, probable future development scenarios are identified based on the current situation. Findings Ever since the expansion of higher education enrollment in China, higher engineering education has experienced rapid expansion in scale and quality, leading China toward becoming a prolific global leader in this aspect. Through a series of national engineering educational reforms, such as “Engineering Program Accreditation,” “Outstanding Engineer Plan,” and “New Engineering Construction,” China has sought to improve the quality of engineering talent to “transition from a large state to a powerful state” in higher engineering education. Therefore, this development process can be considered a “golden age” of higher engineering education development in China. Going forward, China's higher engineering education should focus on continuous quality improvement, strengthen international exchanges and collaboration, and expansion into new engineering fields. Originality/Value This study systematically analyzes the large-scale expansion and quality enhancement routes of China's higher engineering education. By enhancing the understanding of such education, this study can serve as a reference for domestic and foreign engineering education researchers.

Experimental study on the operating characteristics of multiple collector direct expansion solar-assisted heat pump

Solar thermal application is one of the most important ways to replace fossil energy. The discontinuous heating character and low heating efficiency are two key factors that limit the large-scale promotion of solar thermal application. Large-scale direct expansion solar heat pump systems (DX-SAHP) can provide high efficiency and low-cost continuous heating. However, the characteristics of multiple collector arrays and the system's performance still need more research and exploration. In this paper, a DX-SAHP system with multiple solar collectors was constructed and the work process of the system under different operation conditions was expressed. An experimental platform with two DX-SAHP system was built and studied, and each system contained a 10HP compressor, 16 set solar collectors and one fin evaporator in parallel. The results show that the coefficient of performance (COP) of the system running with solar collectors was nearly 30 % higher than that with the fin evaporator under constant frequency mode, and nearly 45 % under variable frequency mode, indicating that such a system has better performance under variable frequency operation mode. The refrigerant in the collector/evaporators were distributed uniformly in equal-path connection mode, which was beneficial in promoting the system's performance. The heating performance of the system under sunny and cloudy weather conditions was analyzed and discussed, respectively. The test results indicated that the COP of the system on sunny or cloudy days was higher than 4.0, and the maximum hourly COP can reach 11.3 and the maximum hourly heating capacity was 27 kW.

Southeast Asian rainforest lost biodiversity during the range expansion to ice-age Sunda Shelf

The capability of tropical forest to recover from extensive land-use remains a matter of debate, despite its importance for guiding conservation and restoration policies. This is especially the case for Southeast Asia. Fortunately, the Sunda Shelf was extensively exposed during the Last Glacial Maximum sea-level lowstand, providing a unique window to study the long-term and landscape-scale development of tropical forest in new accommodation spaces that may be analogous to those emerge after the cessation of human activities. Here we conduct pollen analyses on three sediment cores from the southern South China Sea – two located in front of the Sunda Shelf paleo-river mouths and one close to the northern Borneo – in order to evaluate the similarity/difference between the “primary” and “secondary” tropical forest of Southeast Asia. The assemblages of major pollen taxa and the life-form composition of identified plant types are found to be quite similar among the sites, indicating that well-structured rainforest should have expanded to the Sunda Shelf despite the sandy and potentially saline, nutrient-poor soils. The plant biodiversity, however, was obviously lower on the Sunda Shelf than on Borneo as inferred from the pollen richness. This indicates a loss of biodiversity during large-scale range expansions. Our findings suggest the potential of reforestation in the lowlands of Southeast Asia, but unfortunately the incapability of restoring biodiversity to pre-disturbance levels through natural regeneration alone. Moreover, the old forests in the mountainous northern Borneo appears to be irreplaceable and thus a priority of conservation efforts.

What you do (not) get when expanding the net-evidence from forced taxpayer registrations in South Africa

A significant share of firms in developing countries is not registered for income taxation. Expanding the tax net is a priority for many governments, but most formalization policies proved relatively ineffective in bringing firms into the tax net. Drawing on rich tax administrative data, we document that snapshot-synchronizations of the business tax and the commercial registry in South Africa led to a large-scale expansion of the South African business taxpayer net. While the targeted firms are a valuable segment within the non-formal sector, we show that their post-registration tax compliance is weak and few of them pay taxes. Owing to the large scope of the tax net expansion, the aggregate revenue gains are, nevertheless, non-negligible and the interventions are fiscally cost-effective. In additional analyses, we provide evidence for enforcement spillovers: In areas where many firms were drawn into the tax net, tax registration timing compliance significantly improved after the snapshot synchronizations. We find no indication of a drop in registration numbers at the commercial registry.

Topical issues of the development of integration in EU

The article examines the current trends in the development of international integration processes. The key point in the development of the global economy is the growth of interdependence and the intensification of fierce competition among participants in the global economic system. The last decades of the existence of the European Union, which have passed since its last large-scale expansion, allow us to conclude that since 2004 the era of rapid development and unprecedented successes of European integration has ended, and a new era of its development has begun. Therefore, it seems appropriate to study the processes of market transformation, integration priorities and the results of integration adaptation of the economies of the countries of Central and Eastern Europe, for which aspirations and hopes for entering the mainstream of modern civilization are associated with the European Union. The purpose of the study is to study the issues of European integration, taking into account an analytical assessment of the economic transformations taking place in the EU countries during the pandemic period. In this regard, the authors of the article explore the economic development of Poland, which is the sixth largest in the European Union. Keywords: integration, integration process, Eurasian Union, economy, export, import.

Expandable hESC-derived cardiovascular progenitor cells generate functional cardiac lineage cells for microtissue construction

BackgroundCardiovascular progenitor cells (CPCs) derived from human embryonic stem cells (hESCs) are considered valuable cell sources for investigating cardiovascular physiology in vitro. Meeting the diverse needs of this application requires the large-scale production of CPCs in an in vitro environment. This study aimed to use an effective culture system utilizing signaling factors for the large-scale expansion of hESC-derived CPCs with the potential to differentiate into functional cardiac lineage cells.Methods and resultsInitially, CPCs were generated from hESCs using a 4-day differentiation protocol with a combination of four small molecules (CHIR99021, IWP2, SB-431542, and purmorphamine). These CPCs were then expanded and maintained in a medium containing three factors (bFGF, CHIR, and A83-01), resulting in a > 6,000-fold increase after 8 passages. These CPCs were successfully cryopreserved for an extended period in late passages. The expanded CPCs maintained their gene and protein expression signatures as well as their differentiation capacity through eight passages. Additionally, these CPCs could differentiate into four types of cardiac lineage cells: cardiomyocytes, endothelial cells, smooth muscle cells, and fibroblasts, demonstrating appropriate functionality. Furthermore, the coculture of these CPC-derived cardiovascular lineage cells in rat tail collagen resulted in cardiac microtissue formation, highlighting the potential of this 3D platform for studying cardiovascular physiology in vitro.ConclusionIn conclusion, expandable hESC-derived CPCs demonstrated the ability to self-renewal and differentiation into functional cardiovascular lineage cells consistently across passages, which may apply as potential cell sources for in vitro cardiovascular studies.Graphical

An efficient serum-free medium for ex vivo expansion of myoblasts from Larimichthys crocea for cultured meat production

The large-scale production of cultured meat has been restricted by high cost of serum, batch difference and unclear composition, thus it is important to develop serum-free media for cell growth. Here we obtained a serum-free medium (SFM), which was suitable for ex vivo culturing of myoblasts from larimichthys crocea. It offered simple composition and high effectiveness that supporting myoblast attachment, expansion and differentiation. Our findings revealed that the optimal SFM consisted of DMEM/F12 base medium, 5 mg/mL bovine serum albumin (BSA), 20 mmol HEPES, 1 % penicillin/streptomycin mixture (PS) and the exogenous additive hydrocortisone. The living cells of SFM could occupy about 65 % of the serum-containing medium (SM). Additionally, differentiation assays showed that myoblasts cultured without serum still differentiated into more muscle tubes, with a higher fusion index than those cultured with serum. Finally, transcriptome sequencing was conducted to demonstrate that hydrocortisone might act as a ligand binding to G protein-coupled receptors, triggering the downstream PI3K/AKT signaling pathway and leading to cell proliferation. Our findings will provide a basis for large-scale cell expansion and cell culture meat production in the future.

Położenie polityczno-wojskowe Rzeszy Niemieckiej u progu II wojny światowej w świetle wykładu szefa wywiadu wojskowego pułkownika dyplomowanego Tadeusza Pełczyńskiego

After Adolf Hitler took power in Germany, the country was quickly remilitarised. Large-scale rearmament and expansion of the armed forces were closely monitored by the Polish military intelligence, which kept the supreme military authorities of the Second Polish Republic informed about the Third Reich’s preparations for war. The main task of the Second Department was to determine the probable date of the attack from this country. Already at the end of 1934, it was estimated that Germany would be ready for war within 6-8 years. The information reaching the headquarters of the “two” showed that at the turn of 1937 and 1938, the Third Reich’s preparations for a future armed conflict were intensified. At the end of the 1930s, the Second Department organized special lectures for senior commanders of the Polish army, presenting the military, political, economic and social situation of the Third Reich and the Soviet Union, i.e. the countries from which Poland faced the greatest danger. The idea was to make the senior command staff of the Polish Army acquainted with the current military and political situation of the Second Polish Republic and the scale of the threat from the two most dangerous neighbours. The presented lecture was delivered by the head of Polish military intelligence on November 29, 1937 in Rembertów and concerned Germany. It has great cognitive value because it allows us to understand the assessments of the Second Division regarding the military potential of the Third Reich and the expansion of the German armed forces. It is, in fact, a synthesis of the knowledge that the military intelligence of the Second Polish Republic had in 1937 about the German state ruled by the National Socialists.

Refined home-brew media for cost-effective, weekend-free hiPSC culture and genetic engineering

Background Cost-effective, practical, and reproducible culture of human induced pluripotent stem cells (hiPSCs) is required for both basic and translational research. This is especially crucial for large-scale expansion of hiPSCs for cell therapy, which should be made accessible to many patients regardless of their socioeconomic background. Basal 8 (B8) has emerged as a cost-effective solution for weekend-free and chemically-defined hiPSC culture. However, homebrewing of some recombinant growth factors for B8 can be a bottleneck towards both access and reproducibility of this technology. Moreover, we found the published B8 formulation to be suboptimal in normoxic hiPSC culture, which is widely used. Lastly, the suitability of B8 for applications such as genome editing or organoid differentiation remains to be assessed. Methods We formulated B8 with commercially available, animal-free growth factors, refined its composition to support normoxic culture of the widely-used WTC11 hiPSC line, and compared it to commercial Essential 8 (E8) and a home-made, weekend-free E8 formulation (hE8). We measured pluripotency marker expression and cell cycle with flow cytometry, and investigated the transcriptional profiles by bulk RNA sequencing. We also assessed the efficiency of gene editing, single-cell sorting, and cardiac differentiation in both monolayer and organoids. Results hE8 performed similarly to commercial E8 in all the assays. Despite morphological changes, cells in B8+, our optimised variant of B8, expressed the pluripotency marker NANOG at the highest level. At the same time, cells grown in B8+ were primed towards a mesendodermal fate. B8+ outperformed other media with regard to genome editing via homology directed recombination, and was on par with other media in other assays. Conclusions Overall, optimised weekend-free media formulations promise to democratise the generation of engineered cells for a wide range of applications.

Late Holocene rapid paleoenvironmental changes and anthropogenic impacts in central Yunnan, southwest China

Understanding long-term anthropogenic impact on the Earth's surface system is crucial for establishing reference conditions and potentially allowing future trajectories to be more rigorous and tightly constrained. In this study, the evolution of catchment erosion, chemical weathering and bottom-water hypoxia during the late Holocene are investigated using multi-proxy records from an accurately-dated sediment core from Lake Qilu in central Yunnan, southwest China. Through the comparison of our results with other paleoenvironmental records from the study region, we are able to see that the increase in anthropogenic impact on the catchment of Lake Qilu began in 780 CE, which is associated with the large scale expansion of agriculture in China. In the early stages of vegetation disturbance and agricultural land use, soil erosion and chemical weathering within in the catchment was significantly intensified, while the lake gradually changed to a state of anoxia until the period of accelerating eutrophication in 1945 CE. However, the extremely high rate of soil erosion and weak chemical weathering suggest the beginning of a new phase in terms of anthropogenic impact on the landscape. Furthermore, the late Holocene intensification of chemical weathering in monsoonal China can also be linked to increased anthropogenic activities rather than spatial differences in hydroclimate changes. This study highlights the fact that humans have been shaping the Earth's surface for millennia, which means that it is essential to place present environmental concerns into a long-term context.

Attainment and Gender Equality in Higher Education: Evidence from a Large-Scale Expansion

Attainment and Gender Equality in Higher Education: Evidence from a Large-Scale Expansion

Potential distribution prediction of Pomacea canaliculata in China based on the Biomod2.

Pomacea canaliculata is a globally significant invasive species that poses substantial threats to agricultural production, ecosystems, and human health in China. To evaluate its habitat suitability in China, we collected and collated 741 county-level occurrence points of P. canaliculata in China through database query, literature search and news reports, and obtained the five most important climatic factors by variance inflation factor and Pearson correlation coefficient from 19 bioclimatic factors. We investigated the potential suitable distribution areas of P. canaliculata under current and future climate scenarios using the Biomod2 ensemble model, and identified the primary environmental variables influencing their distributions. The results showed that under the current climate, the suitable habitat areas were concentrated in southern provinces or municipalities, such as Zhejiang, Shanghai, Fujian, Jiangxi, Guangdong, Guangxi, Hainan, and Yunnan. Under different climate scenarios in the future, the suitable habitat area would show large-scale expansion in the southern provinces or municipalities, and spread to the northern region. The most two important environmental factors affecting the distribution of suitable habitat areas were precipitation of wettest month and mean temperature of wettest quarter. A combination model to predict the potential distribution of P. canaliculata under current and future climate conditions would help manage the risk of its invasion and spread, and provide a reference for relevant regions and departments to take active measures in advance to prevent the spread, monitor and mitigate its invasion.

Three-dimensional cultured human umbilical cord mesenchymal stem cells attenuate pulmonary fibrosis by improving the balance of mitochondrial fusion and fission.

Pulmonary fibrosis is a kind of fibrotic interstitial pneumonia with poor prognosis. Aging, environmental pollution, and coronavirus disease 2019 are considered as independent risk factors for pulmonary fibrogenesis. Consequently, the morbidity and mortality striking continues to rise in recent years. However, the clinical therapeutic efficacy is very limited and unsatisfactory. So it is necessary to develop a new effective therapeutic approach for pulmonary fibrosis. Human umbilical cord mesenchymal stem cells (hucMSCs) are considered as a promising treatment for various diseases because of their multiple differentiation and immunomodulatory function. The key bottleneck in the clinical application of hucMSCs therapy is the high-quality and large-scale production. This study used FloTrix miniSpin bioreactor, a three-dimensional (3D) cell culture system, for large-scale expansion of hucMSCs in vitro, and proved 3D cultured hucMSCs inhibited the differentiation of fibroblasts into myofibroblasts and myofibroblasts proliferation and migration, leading to slow down the development of pulmonary fibrosis. Further mechanistic studies clarified that hucMSCs reduced the amount of binding between circELP2 and miR-630, resulting in blocking YAP/TAZ translocation from cytoplasm to nucleus. This condition inhibited mitochondrial fusion and promoted mitochondrial fission, and ultimately improved fusion/fission balance and cellular homeostasis. To sum up, this work clarified the anti-fibrosis and mechanism of hucMSCs cultured from the 3D FloTrix miniSpin bioreactor. We hope to provide new ideas and new methods for the clinical transformation and industrialization of hucMSCs therapy.

A Comparison of the Validity of Online Courses Quality Evaluation Models

The large scale expansion of online courses has led to the crisis of course quality issues. In this study, we first established an evaluation index system for online courses using factor analysis, encompassing three key constructs: course resource construction, course implementation, and teaching effectiveness. Subsequently, we employed factor analysis and entropy weight TOPSIS multi-attribute decision analysis methods to comprehensively evaluate 541 courses. Later on, we conducted correlation and regression analyses between the evaluation results of these two methods and that of experts. The results reveal that the comprehensive evaluation scores derived from both factor analysis and entropy weight TOPSIS models exhibit a significant positive correlation with the experts'. Furthermore, the factor analysis model outperforms the entropy weight TOPSIS model in predicting experts' evaluation scores. The application of this model will help achieve timely and accurate course evaluation, and provide novel idea and approach for real-time monitoring of online courses quality.

Scalable process development of NK and CAR-NK expansion in a closed bioreactor.

Production of large amounts of functional NK and CAR-NK cells represents one of the bottlenecks for NK-based immunotherapy. In this study, we developed a large-scale, reliable, and practicable NK and CAR-NK production using G-Rex 100M bioreactors, which depend on a gas-permeable membrane technology. This system holds large volumes of medium with enhanced oxygen delivery, creating conditions conducive to large-scale PBNK and CAR-NK expansions for cancer therapy. Both peripheral blood NK cells (PBNKs) and CAR-NKs expanded in these bioreactors retained similar immunophenotypes and exhibited comparable cytotoxicity towards hepatocellular carcinoma (HCC) cells akin to that of NK and CAR-NK cells expanded in G-Rex 6 well bioreactors. Importantly, cryopreservation minimally affected the cytotoxicity of NK cells expanded using the G-Rex 100M bioreactors, establishing a robust platform for scaled-up NK and CAR-NK cell production. This method is promising for the development of "off-the-shelf" NK cells, supporting the future clinical implementation of NK cell immunotherapy.

Development Pathways and the Political Economy of Maladaptation: The Case of Bioenergy as a Climate Strategy in Brazil

AbstractAlthough it is well known that large-scale bioenergy expansion erodes different environmental, social, and economic dimensions of sustainable development, in countries like Brazil, bioenergy is institutionalized as a flagship climate strategy aimed to cut down CO2 emissions in transport. These trade-offs have serious implications for climate change governance and sustainable development; however, conventional approaches have not yet properly explained this seeming paradox. This article addresses this gap from a critical development pathways approach to bioenergy as a maladaptive strategy in Brazil. I propose an analytical framework to observe how different ideas, interests, and institutions interplay in the historical institutionalization of bioenergy as a climate strategy. The analysis shows that bioenergy institutionalization has been driven by the endemic economic crisis in the sugar sector and governmental interests associated with security and developmental imperatives. The unsustainable co-evolution of development pathways and bioenergy, marked by deforestation, land colonization, and agricultural expansion, has narrowed the adaptation space in agriculture, gearing current climate policy towards path-dependent maladaptive strategies like bioenergy. Paradoxically, framing bioenergy as a climate strategy has been useful to justify more expansive policies in favor of the sugarcane industry, and to greenwash the Brazilian climate policy in the international arena of climate governance.

Interaction between dislocation and heterogeneous interface in Cu/Fe laminated composites based on discrete dislocation dynamics

Bimetal laminated composites (BLCs) exhibit more outstanding mechanical properties than traditional alloys due to the interaction between heterogeneous interface boundary (HIB) and dislocation. However, the underlying physics of the dislocation motion and the strengthening effect has not been uncovered at mesoscopic scale. In this study, the detailed microstructure of the Cu/Fe HIB was obtained by transmission electron microscope (TEM) observation. The dislocation model was established using discrete dislocation dynamics (DDD), and several interactions between the dislocation and HIB were focused on, as well as the intrinsic strengthening mechanisms of the HIB. The results show that different HIB characteristics induce different interaction mechanisms such as absorption, slip transmission, slip on the HIB, emission from HIB and reflection by HIB, resulting in different strengthening effect on the BLCs. The HIB promotes slip of the dislocation emitted from the Fe, while prevents movement of the dislocation emitted from Cu. Since dislocation slip is more difficult in Fe, greater elastic deformation occurs before large-scale expansion of the dislocation, resulting in larger nominal yield strength. The presence of HIB increases the difficulty of dislocation movement compared to the single crystal structure, which in turn improves the overall strength of BLCs. Due to the different dislocation motion and strain gradient, the mechanism of that dislocation slip absorption by the HIB has optimal strengthening effect relative to other interaction mechanisms. The strengthening effect of other interaction mechanisms is influenced by the position of the dislocation emission, the type of interaction mechanism, and the angle between adjacent slip planes, etc. The outcome of present research sheds important insights into the design of HIB strengthening materials, such as multi- and nano- laminated composites.

A two-stage distributed stochastic planning method for source-grid-load-storage flexibility resources considering flexible ramp capacity

With rapidly increasing levels of renewable energy penetration, flexibility resources play an ever more critical role in the future power system. This paper describes a two-stage stochastic mixed integer second order cone (MISOC) method for flexibility resource planning (VFRP) considering source-grid-load-storage interactions. Considering renewable energy penetration levels and flexibility resource characteristics, this study quantifies the extent to which the share of renewable energy generation affects cost performance, and assesses the priority and potential of investing in flexibility resources. Moreover, the multi-type flexibility resource portfolio allocation method and energy storage only approach are compared in terms of socio-economic benefits. A multi-cut Benders-based approach is used for decomposing large-scale stochastic expansion planning problems to reduce the computational burden. Numerical simulation tests on the modified energy test systems I39G20 and F213G20 verified the correctness and effectiveness of the proposed flexible resource planning models and solution algorithms. The simulation results show that retrofit of coal-fired units for better flexibility has a higher investment return. Still, energy storage presents a tremendous investment prospect and potential. Finally, the multi-type flexibility resource portfolio allocation method is more cost-effective than an energy storage only approach.

Potential of agrivoltaics in ASEAN considering a scenario where agroforestry expansion is also pursued

Integration of solar photovoltaics on croplands (“agrivoltaics”) has been promoted as an environmentally-friendly approach for solar energy deployment. Past studies, however, have not considered that these croplands could alternatively be used as sites for expanding agroforestry, a practice which provides important ecosystem services to the neighbouring environment. We assessed the potential of agrivoltaics on herbaceous croplands in ASEAN, considering potential trade-offs with agroforestry. We assumed that croplands located in environmentally sensitive areas (ESAs) – including protected areas, key biodiversity areas, forests, wetlands/inland water bodies, their buffer zones, and areas with steep slopes – were better suited for agroforestry than agrivoltaics. We found that even if agrivoltaics are prohibited on all croplands located in ESAs, using just 10 % of the remaining land for agrivoltaics can still allow it to provide most of ASEAN's electricity generation needs. Thus, large-scale expansion of agrivoltaics need not conflict with regional efforts to enhance biodiversity/ecosystem services through agroforestry.