Early State Research Articles

National security and information in the early modern state: the case of Ukraine

The system of information support of the authorities of the Ukrainian early modern state, as well as implementing internal and external policies, contributed to protecting Ukrainian lands from external aggression and the expansion of Ukrainian interests in the world. The main purpose of the study is to analyze this statement. The methodological basis of the research is a comprehensive analysis of archival sources and historiography, which is based on the main principles of historicism and scientific objectivity. The scientific novelty of this publication is to prove the hypothesis that thoughtful information activity in its various segments was an important component of the policy of the Ukrainian early-modern state and contributed to protecting its lands and interests from foreign encroachments. Conclusions. Information activity was an important component of the security activities of the Ukrainian Cossacks and a means of implementing power policy. The principles and approaches developed in working with information will help reveal the secrets of the Cossacks' information skills and will contribute to the deepening of interest in the study and revival of Cossack traditions, which is necessary both for filling research gaps and for training specialists in the field.

Pre-Modernite, Devlet ve Kamu Yönetimi Teşkilatlanması: Antik Roma’da Augustus Octavianus Dönemi Bürokrasisi Örneği (M.Ö. 27-M.S. 14)

The concept of pre-modernity refers to the process in the political, social and economic fields in Western Europe before the 17th century. As a matter of fact, during this period, states and public administrations were organized within the framework of this system. Because the expression of pre-modernity, which is associated with concepts such as tradition, theocracy and patrimonial bureaucracy, dates back to a very long period in human history. As tribes began to evolve into states throughout history, early states also emerged. Communities reaching state structures led to division of labor, specialization and classes. The Roman state can also be seen as one of the important examples of the early state in history. Because Ancient Rome, with its political, administrative, economic and cultural structure, overlapped with the characteristic features of the early states in certain areas. As a matter of fact, the bureaucratic Roman state of the Augustus Octavianus period, which is the main subject of this study, also shows the characteristics of the early states and carries the advanced developments and features of the institutionalized structure. The aim of this study is to analyze how political developments and especially bureaucracy during the Augustus Octavianus period can serve as an example in tracing the historical course of the early state. For this, Claessen and Skalnik's (1993) work titled "Early State" will be greatly benefited from. The method of the study is literature review. Key Words: Pre-Modernity, Early State, Bureaucracy, Rome, Augustus Octavianus Jel Codes: D73, B15

WNT-dependent interaction between inflammatory fibroblasts and FOLR2+ macrophages promotes fibrosis in chronic kidney disease

Chronic kidney disease (CKD) is a public health problem driven by myofibroblast accumulation, leading to interstitial fibrosis. Heterogeneity is a recently recognized characteristic in kidney fibroblasts in CKD, but the role of different populations is still unclear. Here, we characterize a proinflammatory fibroblast population (named CXCL-iFibro), which corresponds to an early state of myofibroblast differentiation in CKD. We demonstrate that CXCL-iFibro co-localize with macrophages in the kidney and participate in their attraction, accumulation, and switch into FOLR2+ macrophages from early CKD stages on. In vitro, macrophages promote the switch of CXCL-iFibro into ECM-secreting myofibroblasts through a WNT/β-catenin-dependent pathway, thereby suggesting a reciprocal crosstalk between these populations of fibroblasts and macrophages. Finally, the detection of CXCL-iFibro at early stages of CKD is predictive of poor patient prognosis, which shows that the CXCL-iFibro population is an early player in CKD progression and demonstrates the clinical relevance of our findings.

The politics of commerce in eighteenth-century Bengal: A reappraisal

This article broaches a simple question: Was there a politics of commerce within Bengali society in the eighteenth century, or was such politics limited to disputes between the British East India Company (EIC) and the Bengal nawabs? I begin by discussing the literature on markets in eighteenth-century Bengal and argue that the relationship between commerce and politics has been too narrowly defined in this body of work. A one-sided focus on determining the impact of the early colonial state, coupled with an uncritical acceptance of Peter Marshall’s Namierite story about the origins of the British empire, has led historians to downplay ideological conflicts within the EIC and British society. To show why these divisions matter, I build on the recent work of James Vaughn and Spencer Leonard, who have shown that between 1750 and 1770, political and ideological conflicts in both Britain and Bengal had far-reaching effects on the character of the British empire. Through an extended discussion of a dispute over market access in 1778 in the city of Calcutta, I show that petty merchants and shopkeepers often opposed arbitrary impositions by regional elites. To fully understand the motivations behind such challenges, I argue that we need to seriously consider divisions within Bengali society as well: namely, the reproduction of caste hierarchies through differential access to markets (and land).

Clinical and hematological analysis of testicular torsion in children.

Analyze the clinical manifestations, laboratory tests, and imaging data of testicular torsion to provide clinical insights for timely and accurate diagnosis and treatment of testicular torsion. A retrospective analysis was conducted on the clinical data of 67 pediatric patients suspected of testicular torsion, admitted and subjected to surgical exploration from June 2018 to June 2023. Based on whether the torsed testicle was excised during surgery, the patients were divided into orchiectomy group (40 cases) and orchidopexy group (27 cases). Combining clinical symptoms, signs, ultrasound examinations, and laboratory tests, the study aimed to summarize the influencing factors on the onset, diagnosis, and treatment of testicular torsion. The clinical manifestations of all 67 pediatric patients were generally typical. Color Doppler Flow Imaging (CDFI) and surgical exploration were performed for all cases, and the results were consistent. Testicular color doppler ultrasound suggested reduced or absent blood flow, leading to surgical treatment in all cases. All patients had unilateral testicular torsion, with 46 cases (68.66%) on the left side and 21 cases (31.34%) on the right side. Intrafunicular torsion occurred in 60 cases (89.55%), while extrafunicular torsion occurred in 7 cases (10.45%). The onset distribution was as follows: 20 cases in spring, 16 cases in summer, 16 cases in autumn, and 15 cases in winter. Univariate analysis indicated significant statistical differences in age, degree of testicular torsion, duration of symptoms, NEUT, NLR, and occurrence of tunica fluid between the two groups of patients. Multivariate logistic regression analysis showed that the duration of symptoms and the occurrence of hydrocele were independent risk factors for determining testicular viability. Testicular torsion is more common in children and adolescents, with clinical manifestations including scrotal pain, scrotal redness and swelling, abdominal pain, nausea, and vomiting. In the early stages of testicular torsion, inflammatory markers in the blood increase, and preoperative ultrasound indicates hydrocele. This suggests that the testicle is in an early twisted state, with good viability and potential for preservation.

The Witch and the Devil in the Well: Women and Magic in Venetian Politics

Abstract: In early modern Venice, men and women regularly visited wells and remote islands to summon the Devil. This practice, rooted in traditions established in the Middle Ages, continued into the eighteenth century. One popular form of this tradition involved witches opening up a portal to Hell in the deserted wells of the city. Witnesses to these conjurations testified that they could smell sulfur, see hellfire and smoke, and hear the groaning of the damned when the witches performed their magical rites. The Devil himself appeared to talk to the witch who summoned him, usually to give her advice on elections to the Great Council or the location of hidden treasures. Using trials from the Venetian Inquisition, this essay examines women's involvement in the political life of the city, maintaining that through their expertise in magic and knowledge of rumor, they played a larger role in the early modern state and knew more of its secrets than we have credited them with having.

Борьба с беспризорностью несовершеннолетних в Енисейской губернии в контексте деятельности Комиссии по улучшению жизни детей. 1921 г.

Early years of the Soviet regime were a period of implementation of the ideological doctrine that stated that children welfare should be the exclusive remit of the State. The study of the entire range of solutions for the so called children’s problem in early Soviet state requires involvement of multiple kinds of sources. The object of our interest was the report of Robert Krishyanovich Lepsis (1896–1942), a representative of Yenisseyskii Provincial Executive Committee on the Improvement of Children’s Lives, about the condition of childcare facilities by July 1921. The report was prepared for the Commission for the Improvement of Children’s Lives under the All-Russian Central Executive Committee. The document included into the publication was identified as part of Fund P-93 “Department of National Education of the Yenisseyskii Provincial Executive Committee” in State Archive of Krasnoyarsk Territory. The document is reliable and informative; it provides details of geographical location and regional aspects of formation and activities of Soviet machinery during its establishment. The document also gives an idea of searching for humane mechanisms to eliminate juvenile homelessness. We failed to find papers that would highlight organization and initial steps of the Commission for the Improvement of Children’s Lives in Yenisseyskaya Province. The published document the data on the condition and supply of orphanages and shelters in Yenisseyskaya Province; it evaluates the activities of the representatives for the improvement of children’s lives and mechanisms of solution for the problem of juvenile homelessness. The author of the report does not hide the fact that the problems of homeless and neglected children are not a priority in the activities of all the Soviet institutions or administrative organizations. However, due to his being at the same time a Chairman of the Provincial Extraordinary Commission, he manages to solve some urgent issues of childcare facilities. We applied diachronic method to analyze information from the source. As a result we came to a conclusion that they did not manage to change the situation with children’s homelessness in Yenisseyskaya Province radically by July 1921. But a process of introduction of newly formed Soviet institutions into the solution of the above mentioned problem started. Due to the lack of financial and material resources, as well as poor staffing, orphanages and shelters were in poverty. They did not properly solve the educational tasks assigned to them, but at least they served as feeding stations where one could survive in the midst of destruction and famine. The information from the source may be of interest to those who study Soviet society, forms and practical activities of addressing the problems of children’s homelessness.

Does school climate affect student well-being? Anxiety in school situations as a predictor of stress in high-school students.

When the school climate is not ideal and coping skills for school situations are not strengthened in adolescents, school anxiety and stress may be manifested, potentially harming development and mental health during adulthood. This study aimed to analyze the predictive ability of school anxiety on elevated levels of stress in high-school students. This cross-sectional predictive study was conducted with 1588 students aged 12-18 (M = 14.82; SD = 1.86) years in 2023. The School Anxiety Inventory (SAI) and the Depression, Anxiety, and Stress Scale (DASS-21) were administered to the participants. An inferential data analysis method was applied. Specifically, binary logistic regression was used for data analysis. The influence of school anxiety on stress was examined using the odds ratio statistic. The total score on school anxiety (OR = 1.02), the situational factors: anxiety about aggression (OR = 1.03), anxiety regarding social evaluation (OR = 1.02), anxiety about failure and school punishment (OR = 1.03), and anxiety about school evaluation (OR = 1.04), as well as the response systems: cognitive (OR = 1.04), behavioral (OR = 1.08), and psychophysiological (OR = 1.04), positively and significantly (P = 0.000) influenced the high scores on stress. The results demonstrate the need to detect school anxiety in adolescents at an early state to intervene in both anxiety-provoking situations and responses and in the resulting high stress. Similarly, schools should promote mental health work and self-regulation to prepare students for adult life.

In situ aggregation and early states of gelation of gold nanoparticle dispersions.

The aggregation and onset of gelation of PEGylated gold nanoparticles dispersed in a glycerol-water mixture is studied by small-angle X-ray scattering and X-ray photon correlation spectroscopy. Tracking structural dynamics with sub-ms time resolution over a total experimental time of 8 hours corresponding to a time windows larger than 108 Brownian times and varying the temperature between 298 K and 266 K we can identify three regimes. First, while cooling to 275 K the particles show Brownian motion that slows down due to the increasing viscosity. Second, upon further cooling the static structure changes significantly, indicated by a broad structure factor peak. We attribute this to the formation of aggregates while the dynamics are still dominated by single-particle diffusion. Finally, the relaxation functions become more and more stretched accompanied by an increased slow down of the dynamics. At the same time the structure changes continuously indicating the onset of gelation. Our observations further suggest that the colloidal aggregation and gelation is characterized first by structural changes with a subsequent slowing down of the systems dynamics. The analysis also reveals that the details of the gelation process and the gel structure strongly depend on the thickness of the PEG-coating of the gold nanoparticles.

Connexin43 overexpression promoted ferroptosis and increased myocardial vulnerability to ischemia-reperfusion injury in type 1 diabetic mice.

Enhancement of Connexin43 (Cx43) and ferroptosis are respectively associated with the exacerbation of myocardial ischemia-reperfusion injury (MIRI) in diabetes. Myocardial vulnerability to ischemic insult has been shown to vary during early and later phases of diabetes in experimental settings. Whether or not Connexin43 (Cx43) and ferroptosis interplay during MIRI in diabetes is unknown. We, thus, aimed to investigate whether or not the content of myocardial Cx43 may be attributable to myocardial vulnerability to MIRI at different stages of diabetes and also to explore the potential interplay between Cx43 and ferroptosis in this pathology. Age-matched control and subgroups of Streptozotocin-induced diabetic mice were subjected to MIRI induced by 30 minutes coronary artery occlusion and 2 hours reperfusion respectively at 1, 2 and 5 weeks of diabetes. Rat cardiac H9C2 cells were exposed to high glucose (HG) for 48h in the absence or presence of Cx43 gene knockdown followed by hypoxia/reoxygenation (HR) respectively for 6 and 12 hours. Post-ischemic myocardial infarct size was reduced in 1 and 2 weeks DM mice concomitant with enhanced GPX4 and reduced cardiac Cx43 and ferroptosis as compared to control. By contrast, cardiac GPX4 was significantly reduced while Cx43 increased at DM 5 weeks (D5w) which was correspondent to significant increases in ferroptosis and myocardial infarction. Post-ischemic cardiac function was improved in 1 and 2 weeks but worsened in 5w DM mice as compared with non-diabetic control. GAP19 (Cx43 inhibitor) significantly attenuated ferroptosis and reduced myocardial infarction in D5w mice. Erastin (ferroptosis activator) reversed the cardioprotective effect of GAP19. In vitro, HR significantly reduced cell viability accompanied with reduced GPX4 but elevated Cx43 expression, MDA production and ferroptosis. Cx43 gene knockdown in H9C2 resulted in a significant increase in GPX4, reduction in MDA and ferroptosis, and subsequently reduced post-hypoxic cell viability. The beneficial effects of Cx43 gene knock-down was minified or eliminated by Erastin. It is concluded that Cx43 overexpression exacerbates MIRI under diabetic conditions via promoting ferroptosis, while its down-regulation at early state of diabetes is attributable to enhanced myocardial tolerance to MIRI.

Еволюційна система біосфери: діалектичний підхід

The dialectics of evolution is that the development of various systems, complication is determined by several principles, which themselves are similar to emergent systems based on opposite but dialectically complementary categories and concepts. A new concept of evolution of the biosphere as an integral system of its successive states united by development trends is proposed. The structure of the biosphere is considered as a fractal system with the ecosystem as its elementary unit. The next fractal levels are biogeomes and biospheromerons. The fractal structure corresponds to the principle of emergence. The proposed concept of biosphere evolution is based on general naturalistic principles and categories of dialectics, such as states and interstates, continuity and discreteness, reproducibility and uniqueness, the hypothesis of information channels or trends, the concept of biosphere organisation in a specific evolutionary space-time. In general, the evolutionary history of the biosphere is a metameric picture of changing states and interstates. A complex system of continuums is the most important feature of the biosphere’s organisation in space-time. Continuity of the first kind can be observed when there is a continuum of indistinguishability within a continuing state: during a long geological time, there were no cardinal changes in the structure of biosphere elements and connections between them. At the same time, the development of an integral biosphere system occurs in a continuum of the second kind: given the continuity of life, the differences between the early and subsequent states are very significant and obvious in the biosphere. Moreover, these differences are associated with complication, development, which is, in fact, evolution. The states of the biosphere in certain periods are connected by trends, which form an evolutionary system. Continuing states, when the system remains self-identical for a long period, are replaced by new states through interstates. Thus, a specific type of continuum, the metameric continuum, is formed. The taxonomic, ecomorphic, symbiotic, and ecosystem trends are identified and considered as the main ones in the evolution of the biosphere. The Vernadsky–Margalef hypothesis of the origin of life and biosphere in the form of protoecosystems is considered and supported.

AN OVERVIEW OF THE INTERESTS AND PERCEPTIONS OF EARLY-STAGE RESIDENT DOCTORS TOWARDS ETHICS AND MEDICO-LEGAL TEACHING METHODS IN A FACULTY OF MEDICINE

Background: Ethics and medico-legal (EM) teaching must be carried out in a fun way so that resident doctors can more easily understand the material being taught. Conventional lecture methods are considered monotonous, so efforts are needed to find the best method that is most in demand by early-stage resident doctors so that learning objectives are achieved optimally. This study aims to describe the interests and perceptions of early-stage resident doctors toward EM teaching methods at the Faculty of Medicine, Universitas Syiah Kuala.Methods: This was an interventional study with a cross-sectional design conducted among early state resident doctors (n=54) with a self-administered online questionnaire. The participants of this study were early-stage resident doctors who had passed the EM courses. The participants were collected using the total sampling method. The participants were tested for seven teaching methods for seven EM materials. After all teaching methods were carried out, participants were asked to fill out a questionnaire.Results: A total of 54 participants were involved in this study. All resident doctors have a high interest and positive perception of all EM teaching methods. The respondent chose the film/video clipping method as the most interesting, followed by CBL, role play, MCD, jigsaw technique, conventional lecture, and narrative writing. The resident doctor's perception of the CBL teaching method was considered the most positive, followed by the film/video clip method, moral case deliberation, role play, jigsaw technique, conventional lecture, and finally narrative writing.Conclusion: The CBL method is most in demand by resident doctors because it directly discusses cases in educational settings, but the resident doctor considers the film/video clipping method to be the most enjoyable. The most favorite teaching method is expected to produce a better understanding of the material than others.

Africa’s Contribution to the Discourse on Environment, Renewable Energy and Sustainable Development

Renewable energy and sustainability are vital for the development of Africa. Social welfare and economic growth are contingent on meeting the consumption needs and production targets using modern, sustainable energy sources. This is particularly crucial to Africans, given that the continent is home to the least developed countries globally, and the population with access to electricity is less than half. Colonialism has undoubtedly impacted and shaped our energy and, consequently, environmental transitions by allowing the traumatic exploitation of natural habitats and plundering of minerals, all at the service of the formation of their early modern states and the growth of capitalism. This status has been greased and maintained using neo-colonial and imperial tools such as the illusion of ‘free trade’, structural adjustment programs and crippling debt. All these are aimed at staging a stagnation of economic development that translates to underdeveloped industries and inefficient energy production levels. The domino effect of this is also seen in the current environmental crisis, which is essentially the biological destruction of wildlife and marine life while posing grave dangers to the continuation of African civilisation. This article explores the impact of imperialism and traces of neo-colonialism on the energy sector in Africa and how Africa can push for renewable energy by building its own industries and utilising abundant resources to chart a path towards sustainability. It dives into the depths of already established renewable energy programs that the states ought to accelerate to enable them to reach wider populations, as well as the mutually beneficial relationship we have between renewable energy and the environment.

About the First Koguryo Capital

The article presents the formation problem of the early Koguryo state’s capital in the early medieval time. This subject has not been a particularly hot issue in Russian historiography. The main Korean and Chinese written and epigraphic sources were considered to resolve this background about the early capital. It categorically said, that in the 1st century BC, Koguryo developed as an established real state with an obligatory element as the capital. At the same time, information about the localization and structure of the early capital is uninformative and convoluted. Therefore, written sources were supplemented by archaeological data on the Wunu mountain city located in the Liaoning province, since in historiography, this site is correlated with the location of the first Koguryo capital. According to its characteristics, it represents a sparsely populated fortified settlement located in a hard-to-reach mountain valley on top of a high mountain. Different locations of the surrounding area are considered as the location of the valley settlement (including Xiàgǔchéngzi plain city). Several early Koguryo cemeteries were located in the neighbourhood. The Koguryo state system was finally organized only after several centuries, thus, the location indicated in written resources as the early capital, should be attributed as the leaders' military centre of the early Koguryo population group.

Salt in Late Iron Age Italy. A multidisciplinary approach to the exploration of Italy’s coastal exploitation sites: Piscina Torta (Ostia, Rome) case study

During the Copper Age and onwards, unique archaeological sites emerged throughout Europe. These sites exhibit distinct features such as the absence of typical household pottery, the presence of kilns, and extensive layers composed solely of fragments of reddish-brown jars. Scholars generally interpret these sites as specialized locations for salt production through the technique of boiling saltwater, known as briquetage. In Italy, many of these sites are found along the Tyrrhenian coast and span from the Middle Bronze Age to the Roman era, with a particular concentration during the early Iron Age. However, the archaeological evidence in Italy differs from that of other European sites, suggesting that these Italian sites were not solely dedicated to salt production but also involved other economic activities. To delve deeper into the understanding of these sites and their socio-economic context, the University of Groningen initiated the Salt & Power: Early States, Rome and Resource Control project in 2021. The project aims to comprehensively analyze these sites and shed light on the production of salt within their broader societal and economic framework.In this contribution, we present preliminary findings derived from intensive surveys, coring campaigns, and geophysical investigations conducted at one such site, Piscina Torta. This site is believed to be connected to the city of Rome and dates back to the 7th and 6th centuries BCE. Furthermore, we propose a multidisciplinary workflow for studying specialized sites, incorporating various research methodologies and disciplines.

The defender of orphans

In the middle of the 17th century a transformation of states can be observed. The strives of early absolutist states were aimed at the increase of their economic and, in turn, their military potential. These goals were served by social policy measures aimed at increasing economic effi ciency and increasing state revenues. The development of central administration and regulations for orphan aff airs also served to maintain labour force and economic potential. The preservation of orphans’ property was intended to keep the economy going, and in the case of destitutes, orphanages intended to concentrate the workforce. The measures introduced in the German principalities soon appeared in the provinces of the Habsburg Monarchy. In the first quarter of the 17th century, the first theoretical work on orphan aff airs was written, and in the second half of the century it was followed by the first royal decree based on the principles set out in this volume. The aim of these provisions was to ensure the preservation and the control of the assets of the orphans by state means. Similar provisions to the Monarchy’s provinces were enacted in the Hungarian Kingdom in the last third of the 17th century. The offices introduced in the Austrian provinces, the separate Orphan’s Court (árvaszámvevőszék), the keeping of register on orphans (árvakönyv), and the continuous scrutiny of guardians were introduced in the free royal towns in the first third of the 18th century. All of this went parallel with the administrative reforms ordered in towns. The reform measures introduced regarding orphan affairs were realized at a varying pace one town to another, but by the end of the first third of the 18th century, the orphan regulations developed in the Austrian provinces had become established in all the free royal towns.

Performance Comparison of Directed Acyclic Graph-Based Distributed Ledgers and Blockchain Platforms

Since the introduction of the first cryptocurrency, Bitcoin, in 2008, the gain in popularity of distributed ledger technologies (DLTs) has led to an increasing demand and, consequently, a larger number of network participants in general. Scaling blockchain-based solutions to cope with several thousand transactions per second or with a growing number of nodes has always been a desirable goal for most developers. Enabling these performance metrics can lead to further acceptance of DLTs and even faster systems in general. With the introduction of directed acyclic graphs (DAGs) as the underlying data structure to store the transactions within the distributed ledger, major performance gains have been achieved. In this article, we review the most prominent directed acyclic graph platforms and evaluate their key performance indicators in terms of transaction throughput and network latency. The evaluation aims to show whether the theoretically improved scalability of DAGs also applies in practice. For this, we set up multiple test networks for each DAG and blockchain framework and conducted broad performance measurements to have a mutual basis for comparison between the different solutions. Using the transactions per second numbers of each technology, we created a side-by-side evaluation that allows for a direct scalability estimation of the systems. Our findings support the fact that, due to their internal, more parallelly oriented data structure, DAG-based solutions offer significantly higher transaction throughput in comparison to blockchain-based platforms. Although, due to their relatively early maturity state, fully DAG-based platforms need to further evolve in their feature set to reach the same level of programmability and spread as modern blockchain platforms. With our findings at hand, developers of modern digital storage systems are able to reasonably determine whether to use a DAG-based distributed ledger technology solution in their production environment, i.e., replacing a database system with a DAG platform. Furthermore, we provide two real-world application scenarios, one being smart grid communication and the other originating from trusted supply chain management, that benefit from the introduction of DAG-based technologies.

Short-interval, high-severity wildfires cause declines in soil seed bank diversity in montane forests of south-eastern Australia

Wildfires in forested ecosystems are increasing in severity and extent. The adaptations many plants have acquired in response to their natural fire regime may not be sufficient to allow some species to persist. This could impact the forest understorey and its seed bank, which are vital reservoirs of biodiversity, and forest resilience in the face of global change. We present a case study of the montane forests of south-eastern Australia, an area subjected to an increase in frequency and severity of fires. We utilise field surveys and a soil seed bank germination study to investigate if short-interval, high-severity wildfires affect the understorey diversity in montane forests, and if the extant vegetation and the soil seed bank exhibit contrasting responses. We consider species diversity and plant functional traits to explore plant diversity in long unburned sites, and sites with one, two or three short-interval, high-severity fires in the past 25 years. With increasing fire frequency, we found a decrease in total species richness, Shannon’s diversity, and the richness of resprouters in the soil seed bank, contrasting a lack of response in the extant vegetation. Increased fire frequency shifted the species composition and the frequency of plant functional groups of both extant vegetation and soil seed bank towards a decrease in clonal resprouters and increase in grasses and other upright herbs. The frequency of wind-dispersed perennials and short-lived seeders and exotics increased sharply following single high severity burn, particularly in the soil seed bank, and remained elevated relative to long unburnt with subsequent fire. The combined species (extant vegetation plus soil seed bank) pool mirrored shifts in the frequency of functional groups in extant vegetation and soil seed bank. These findings highlight the importance of considering the soil seed bank when examining the effects of fire on fire-prone forests. Although a lack of response in the extant vegetation may be a buffering effect of the soil seed bank, the shift in the frequency of plant functional groups in the combined species pool suggests this cannot be maintained indefinitely. The increase in frequency and abundance of species characteristic of early successional states has implications for increased flammability and potential positive feedbacks between past fire and future fire, especially in a warming and drying climate. These shifts were independent of the fire response strategy of eucalypt canopy species raising significant questions of whether artificial re-seeding programs should extend beyond the current focus on obligate seeding forests and an obligate seeding tree.

ROS-Scavenging Lignin-Based Tolerogenic Nanoparticle Vaccine for Treatment of Multiple Sclerosis.

Multiple sclerosis (MS) is a demyelinating autoimmune disease, in which the immune system attacks myelin. Although systemic immunosuppressive agents have been used to treat MS, long-term treatment with these drugs causes undesirable side effects such as altered glucose metabolism, insomnia, and hypertension. Herein, we propose a tolerogenic therapeutic vaccine to treat MS based on lignin nanoparticles (LNP) with intrinsic reactive oxygen species (ROS)-scavenging capacity derived from their phenolic moieties. The LNP loaded with autoantigens of MS allowed for inducing tolerogenic DCs with low-level expression of costimulatory molecules while presenting antigenic peptides. Intravenous injection of an LNP-based tolerogenic vaccine into an experimental autoimmune encephalomyelitis (EAE) model led to durable antigen-specific immune tolerance via inducing regulatory T cells (Tregs). Autoreactive T helper type 1 cells, T helper type 17 cells, and inflammatory antigen presentation cells (APCs) were suppressed in the central nervous system (CNS), ameliorating ongoing MS in early and late disease states. Additionally, the incorporation of dexamethasone into an LNP-based tolerogenic nanovaccine could further improve the recovery of EAE mice in the severe chronic stage. As lignin is the most abundant biomass and waste byproduct in the pulping industry, a lignin-based tolerogenic vaccine could be a novel, cost-effective, high-value vaccine platform with potent therapeutic efficiency in treating autoimmune diseases.

The effect of microglia activation on cerebral injury induced by conditional Tpk knockout in brain neurons of adult mice and the mechanism exploration

AbstractBackgroundWe previously designed and constructed the neuronal Tpk conditional knockout mouse model, which can simulate various pathophysiological changes of Alzheimer’s disease (AD). The objective of this study was to explore the effect and mechanism of microglia activation induced by the conditioned neuronal Tpk knockout on neuronal injury.MethodWe selected the 3‐month‐old CaMKII‐CreERT2/+ ; Tpkfl/fl (Tpk‐cKO) and negative control mice Tpkfl/f (Control) from the same nest. The mice were given CSF1R inhibitor (PLX3397)respectively during the whole stage (the 2nd∼10th weeks after induction), the late stage (the 6th∼10th weeks after induction), and the early stage (the 2nd∼6th weeks after induction) to eliminate microglia during whole/early/late stage. Besides, the single‐cell RNA sequencing (scRNA‐seq) analysis was performed at different time courses.ResultAccording to scRNA‐seq analysis, Microglia can be divided into different subgroups, which have different functions and proportions, and their pseudotime states were quite distinct. Among them, microglia subgroup 5 was highly distributed in the early pseudotime state playing the role of immune regulation and neuroprotection, while subgroup 6 was mainly distributed in the late pseudotime state contributing to phagocytosis damage. Therefore, when microglia were eliminated for the whole period, the protective effect of microglia was completely lost leading to more cerebral injury. Eliminating microglia at the early stage, the cerebral injury was alleviated because the repopulated microglia was still in the early pseudotime state performing immunomodulatory and neuroprotective functions. Eliminating microglia at late stage can also mitigate the cerebral injury, mainly because it not only has received the immunomodulatory and neuroprotective effects in the early stage, but also reduce the phagocytic damage in the late stage.ConclusionThe overall effect and mechanism of microglia activation induced by neuronal Tpk conditional knockout on cerebral injury are distinct in different stages, which is associated with the function and proportion of microglia clusters. The major effect of microglia at the early stage was immunoregulation and neuroprotection induced by cluster 5, and the general effect of the late stage was phagocytic damage mainly provided by cluster 6.