Limited Nature Research Articles

Towards the Integrative Theory of Alzheimer's Disease: Linking Molecular Mechanisms of Neurotoxicity, Beta-amyloid Biomarkers, and the Diagnosis.

A major gap in amyloid-centric theories of Alzheimer's disease (AD) is that even though amyloid fibrils per se are not toxic in vitro, the diagnosis of AD clearly correlates with the density of beta-amyloid (Aβ) deposits. Based on our proposed amyloid degradation toxicity hypothesis, we developed a mathematical model explaining this discrepancy. It suggests that cytotoxicity depends on the cellular uptake of soluble Aβ rather than on the presence of amyloid aggregates. The dynamics of soluble beta-amyloid in the cerebrospinal fluid (CSF) and the density of Aβ deposits is described using a system of differential equations. In the model, cytotoxic damage is proportional to the cellular uptake of Aβ, while the probability of an AD diagnosis is defined by the Aβ cytotoxicity accumulated over the duration of the disease. After uptake, Aβ is concentrated intralysosomally, promoting the formation of fibrillation seeds inside cells. These seeds cannot be digested and are either accumulated intracellularly or exocytosed. Aβ starts aggregating on the extracellular seeds and, therefore, decreases in concentration in the interstitial fluid. The dependence of both Aβ toxicity and aggregation on the same process-cellular uptake of Aβ-explains the correlation between AD diagnosis and the density of amyloid aggregates in the brain. We tested the model using clinical data obtained from the Alzheimer's Disease Neuroimaging Initiative (ADNI), which included records of beta-amyloid concentration in the cerebrospinal fluid (CSF-Aβ42) and the density of beta-amyloid deposits measured using positron emission tomography (PET). The model predicts the probability of AD diagnosis as a function of CSF-Aβ42 and PET and fits the experimental data at the 95% confidence level. Our study shows that existing clinical data allows for the inference of kinetic parameters describing beta-amyloid turnover and disease progression. Each combination of CSF-Aβ42 and PET values can be used to calculate the individual's cellular uptake rate, the effective disease duration, and the accumulated toxicity. We show that natural limitations on these parameters explain the characteristic distribution of the clinical dataset for these two biomarkers in the population. The resulting mathematical model interprets the positive correlation between the density of Aβ deposits and the probability of an AD diagnosis without assuming any cytotoxicity of the aggregated beta-amyloid. To the best of our knowledge, this model is the first to mechanistically explain the negative correlation between the concentration of Aβ42 in the CSF and the probability of an AD diagnosis. Finally, based on the amyloid degradation toxicity hypothesis and the insights provided by mathematical modeling, we propose new pathophysiology-relevant biomarkers to diagnose and predict AD.

Efficacy of omental graft to facilitate canine radial fracture repair

PICO Question In dogs with a displaced radial fracture, does the use of a free autologous greater omental graft, combined with other standard fracture repair methods, compared to not using a greater omental graft, reduce fracture healing time? Clinical bottom line Category of research Treatment. Number and type of study designs reviewed Three papers were critically reviewed: one retrospective clinical study and two experimental case control studies. All three papers answered the PICO question. Each of the three papers had a very small sample size, with two having a sample size of 16 (n = 4 in the relevant experimental group, and n = 4 for the control). The third had an initial sample of 25 that was later reduced to 19, as six dogs were excluded from the study. Strength of evidence Weak. Outcomes reported Two papers were experimental case control studies, which looked at radial fracture healing of dogs that had undergone an osteotomy, followed by bone plate and screw fixation, as well as either with a free autologous greater omental graft (OG) or without. Healing was measured in both studies via radiographical analysis using a modified Lane and Sandhu scoring system, and histopathological analysis post euthanasia with Heiple’s histopathological scoring system. Both studies found higher radiographic and higher histopathological scores in the OG group, though there was a large overlap between group scores. There was no mention of randomisation or power analysis in either of these studies, and blinding was only mentioned regarding histopathological analysis. The other was a retrospective study, looking at the outcomes of radial and ulna fractures in small breed dogs, after being surgically treated with a plate and screw, and either with or without OG. They found that dogs with omental grafts healed faster than those without, and had no major complications (whereas the non-OG group did). Note that this study was not (and could not) be randomised due to its nature, and it made no mention of blinding. Conclusion All three studies concluded that the use of OG assisted healing in canine radial fractures. However, care must be taken when applying these results to practice, as the studies lack robustness. While two of the studies had a good study design, both had very small sample sizes and neither mentioned randomisation. Blinding was only mentioned in the histopathological analysis, not radiographical analysis, and while both studies reported significant differences between their respective OG and control groups, they failed to account for multiple comparisons in statistical analysis, which likely skewed the results. The third study also represents a weak level of evidence, due to its retrospective nature and other limitations. Its small sample size, and the fact that 4/8 control (non-OG) dogs received a different type of graft, contributed to this. Due to the small number of animals in each study and the poor-quality design, it is concluded that there is weak evidence to support the PICO question. Further randomised blinded clinical trials with larger samples sizes are recommended, to increase the strength of the evidence before the routine clinical use of greater omentum grafts for aiding fracture repair can be recommended, considering that this means an additional abdominal surgical procedure. How to apply this evidence in practice The application of evidence into practice should take into account multiple factors, not limited to: individual clinical expertise, patient’s circumstances and owners’ values, country, location or clinic where you work, the individual case in front of you, the availability of therapies and resources. Knowledge Summaries are a resource to help reinforce or inform decision making. They do not override the responsibility or judgement of the practitioner to do what is best for the animal in their care.

Coupling of island tourism carbon emission and sustainable resource development – taking Hainan Fenjie Island as an example

ABSTRACT Fenjie Island, as an isolated island, has evolved into a 5A-rated tourist destination. However, in recent years, due to the one-sided pursuit of economic gains, the island has continuously developed its tourism resources, resulting in over-exploitation of resources and significant ecological impacts. This study meticulously scrutinizes tourism-related carbon emissions in comparison to the island's natural capacities. Comprehensive research spans ships, accommodations, dining, and various activities, revealing emissions surpassing nature's limits. The study delves into intricate emission models, emphasizing energy-intensive sectors.Empirical findings underscore a pressing disparity: daily emissions far exceed the island's absorption and purification capacities, underscoring the urgency for intervention. To restore equilibrium, the study proposes recalibrating tourism by aligning it with the island's natural resources. Forest and seawater capacities emerge as vital benchmarks for sustainable tourist numbers. Proposed strategies emphasize rigorous energy conservation and emissions reduction, offering a roadmap for sustainable development.These robust findings provide an essential scientific basis for Fenjie Island's future. They illuminate a path toward balanced growth, crucial for harmonizing economic prosperity and environmental preservation. Informed by this research, policymakers can steer the island's trajectory, ensuring a sustainable, thriving future amidst the challenges of modern tourism..

Overall Survival and Erythroid Response in Patients with Low-Risk Myelodysplastic Neoplasms after First-Line Treatment in a Low-Middle Income Country

Introduction Myelodysplastic neoplasms/syndromes (MDS) are a heterogeneous group of clonal disorders characterized by ineffective hematopoiesis and an increased risk of transformation to acute myeloid leukemia (AML). Current standard risk stratification model, the Revised International Prognostic Scoring System (IPSS-R), classifies patients into lower (≤3.5 points) or higher risk MDS. Lower-risk MDS (LR-MDS) treatment is based on the prevailing cytopenia and intends to improve symptomatic burden and minimize transfusion dependency. Anemia is present in 80-90% of patients with MDS. Throughout most of the course of the disease, patients with MDS have a hemoglobin < 10 g/dL, which leads to a decreased quality of life. Also, 50% of patients with MDS will eventually need red blood cell transfusions. Current options for the active treatment of anemia in LR-MDS are limited and vary among countries. Although erythropoiesis stimulating agents (ESAs) are considered standard of care in the absence of del5q, immunosuppressive therapy (IST) and androgens are still used in low income countries. The present study aims to evaluate whether erythroid responses and overall survival differ in patients with LR-MDS, based on their first-line treatment. Methods This is a retrospective study in patients with LR-MDS at Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran, a tertiary care center in Mexico City. Eligible patients were diagnosed between January 2002 and December 2022 according to World Health Organization (WHO) 2016 criteria. Response was assessed according to International Working Group (IWG) 2018 criteria. We defined erythroid response (HI-E) as the sum of the responses achieved within different transfusion burden categories. First line therapy included ESAs, IST (cyclosporine ± eltrombopag), and androgens (mesterolone, danazol). These were compared through bivariate analysis, Kaplan-Meier curves and log-rank test. Results Until December 2022, 109 LR-MDS patients were considered for inclusion. Among them, 29 patients were lost to follow-up, and 25 patients were solely observed without any further therapy. Also, 7 patients who received other therapies were excluded. Ultimately, 48 patients were included in this analysis, 56.3% (n=27) were female, mean age was 62.8 (±15.9) years. Based on WHO 2016 classification, MDS with uni- and multilineage dysplasia was present in 58.3% (n=28) of the patients, while 29.2% (n=14) had hypoplastic MDS. Anemia was present in 89.6% (n=43) of the patients. When evaluating transfusion burden, 37.5% (n=18) of patients were non-transfusion dependent (NTD), 31.3% (n=15) low-transfusion burden (LTB), and another 31.3% (n=15) high-transfusion burden (HTB). ESAs and IST were the most frequently used frontline therapies, each accounting for 41.7% (n=20) of the patients; the remaining 16% (n= 8) received androgens. When comparing baseline characteristics between treatment arms, we found lower hemoglobin values and a greater proportion of severe anemia in ESA-treated patients (p= 0.039, p= 0.036), however, no differences in transfusion burden was observed (p= 0.212). Erythroid response rates were 25% (n=5), 20% (n=4) and 62.5% (n=5) among those treated with ESAs, IST and androgens, respectively (p= 0.071). When assessing HI-E by transfusion burden, no differences were observed between treatment arms except in HTB patients (p= 0.023). Neither time to response, nor duration of response were significantly different between treatment groups ( Table 1). Importantly, 3 of the 4 responders in the IST group received cyclosporine monotherapy, also 50% were hypoplastic MDS. After a median follow up of 47 months (IQR:22.5-85.5), the median overall survival(OS) for the entire cohort was not reached. The 3-year-OS rates for IST, ESA and androgens were 94%, 54% and 50%, respectively (p= 0.018) ( Figure 1). Conclusions In spite of the bias and limitations in the retrospective nature of this study, IST seems to be a valid option in frontline therapy for LR-MDS, since HI-E rates are similar to those observed with ESAs. Additionally, IST group showed a better OS. Results obtained with androgens merit further study and should be interpreted with caution because of the sample size.

Prediction of the MammaPrint Risk Group Using MRI Features in Women With Estrogen Receptor-Positive, HER2-Negative, and 1 to 3 Node-Positive Invasive Breast Cancer

BackgroundMammaPrint assigns chemotherapeutic benefits to patients with estrogen receptor (ER)-positive, human epidermal growth factor receptor 2 (HER2)-negative, and 1 to 3 node-positive invasive breast cancer. However, its cost and time-consuming nature limit its use in certain clinical settings. We aimed to develop and validate the prediction models for the low MammaPrint risk group using clinicopathologic and MRI features. Patients and MethodsOverall, 352 women with ER-positive, HER2-negative, and 1 to 3 node-positive invasive breast cancer were retrospectively reviewed and assigned to development (n = 235) and validation sets (n = 117). Univariate and multivariate analyses identified features associated with the low MammaPrint risk group. The area under the receiver operating characteristic curves (AUROCs) of models based on clinicopathologic, MRI, and combined features were evaluated. ResultsDevelopment set multivariate analysis showed that clinicopathologic features including low histologic grade (odds ratio [OR], 5.29; P = .02), progesterone receptor-positivity (OR, 3.23; P = .01), and low Ki-67 (OR, 6.05; P < .001) and MRI features, including peritumoral edema absence (OR, 2.24; P = .04) and a high proportion of persistent components (OR, 1.15; P = .004) were significantly associated with the low MammaPrint risk group. The AUROCs of models based on clinicopathologic, MRI, and combined features were 0.77, 0.64, and 0.80 in the development and 0.66, 0.60, and 0.70 in the validation sets, respectively. ConclusionThe combined model incorporating clinicopathologic and MRI features showed potential in predicting the low MammaPrint risk group, and may support decision-making in clinical settings with limited access to MammaPrint.

Action Strategies of Start-ups

There are quite a lot of opinions and little knowledge about the strategies of start-ups. The notions on this topic are inconsistent and with little agreement. Hypothetical works predominate and, although logically consistent, there is no empirical research that would provide verified scientific knowledge. Business strategies of start-ups should be a systematic object of research because start-ups have to compensate for a number of their natural limitations (weaknesses) with practical conduct that has the nature of an action strategy. The goal of the research is to identify a typology of start-up strategies that would clarify and specify the strategizing of start-ups based on their actual action. The research was conducted on a sample of 147 start-ups. Methods of descriptive statistics, factor analysis, hierarchical clustering, and ANOVA were used to analyse the research sample. The criteria describing the action of start-ups were divided (reduced) into two strategic dimensions using factor analysis, the combination of which, using clustering by the Ward method, there were identified four types of action strategies of start-ups: proactive leader, waiting leader, proactive follower, waiting follower. The main knowledge contribution of the research lies in the fact that the seemingly disorganized, spontaneous, and even chaotic action got clear contours that will allow a better understanding of the behaviour of start-ups. The research also included an assessment of the performance of the identified types of strategies.

Microwave Reactor with Combined Rigid and Flexible Stirring Paddles for Improving Fluid Heating Uniformity in Soft Manganese Ore Leaching Processes.

In order to overcome the apparent limitations of the inhomogeneous nature of large-scale microwave heating of fluids, a microwave reactor with a rigid-flexible combined stirring paddle is used to heat fluids, destabilizing the hot spots present in the microwave heating of fluids process. An integrated multiphysics field simulation model for calculating the microwave heating process with fluid was created for the purpose of clarifying the temperature field dispersion and fluid flow patterns in the reactor. By using the proposed model, the rigid-flexible combined stirring paddle is compared with the conventional single- and double-layer stirring paddle to highlight the benefits of the rigid-flexible combined stirring paddle in improving fluid heating uniformity. It was found experimentally that the leaching rate of soft manganese ore was increased by 7.08 and 5.22% compared to conventional single and double stirred paddles, respectively. In addition, the optimal stirrer parameters were investigated by the response surface method.

Recognition of motor intentions from EEGs of the same upper limb by signal traceability and Riemannian geometry features.

The electroencephalographic (EEG) based on the motor imagery task is derived from the physiological electrical signal caused by the autonomous activity of the brain. Its weak potential difference changes make it easy to be overwhelmed by noise, and the EEG acquisition method has a natural limitation of low spatial resolution. These have brought significant obstacles to high-precision recognition, especially the recognition of the motion intention of the same upper limb. This research proposes a method that combines signal traceability and Riemannian geometric features to identify six motor intentions of the same upper limb, including grasping/holding of the palm, flexion/extension of the elbow, and abduction/adduction of the shoulder. First, the EEG data of electrodes irrelevant to the task were screened out by low-resolution brain electromagnetic tomography. Subsequently, tangential spatial features are extracted by the Riemannian geometry framework in the covariance matrix estimated from the reconstructed EEG signals. The learned Riemannian geometric features are used for pattern recognition by a support vector machine with a linear kernel function. The average accuracy of the six classifications on the data set of 15 participants is 22.47%, the accuracy is 19.34% without signal traceability, the accuracy is 18.07% when the features are the filter bank common spatial pattern (FBCSP), and the accuracy is 16.7% without signal traceability and characterized by FBCSP. The results show that the proposed method can significantly improve the accuracy of intent recognition. In addressing the issue of temporal variability in EEG data for active Brain-Machine Interfaces, our method achieved an average standard deviation of 2.98 through model transfer on different days' data.

Carrying capacity and cumulative effects management: A case study using bighorn sheep

AbstractSuccessful cumulative effects management is fundamental for conservation policy and practice. We investigated the application of a carrying capacity (CC) model as a cumulative effects management tool for bighorn sheep (Ovis canadensis canadensis) in British Columbia, Canada, where CC is defined as the natural limit of a sustainable population that is set by the availability of resources in the environment. We estimated winter CC using forage availability across winter ranges, weighted by relative selection by sheep and a safe use factor, and divided by overwinter forage requirements to determine how many sheep the landscape can support. We explored application of our model to decision‐making about new industrial projects or conservation activities in a cumulative effects context. Cumulative effects include both positive and negative contributions to animal populations and we simulated the potential positive outcomes of burning to increase bighorn sheep carrying capacity in our study area. Our results show that carefully planned conservation actions could generate a 5% increase in CC (i.e., from 493 to 519 sheep). Robust tools and scientific techniques that are capable of quantifying multiple impacts and conservation actions and that consider spatial processes over long temporal scales, such as the CC model presented, should be applied to help inform decisions about how to better manage cumulative habitat change and achieve conservation objectives.

Actions of 𝐴𝑙𝑡(𝑛) on groups of finite Morley rank without involutions

We investigate faithful representations of Alt ⁡ ( n ) \operatorname {Alt}(n) as automorphisms of a connected group G G of finite Morley rank. We target a lower bound of n n on the rank of such a nonsolvable G G , and our main result achieves this in the case when G G is without involutions. In the course of our analysis, we also prove a corresponding bound for solvable G G by leveraging recent results on the abelian case. We conclude with an application towards establishing natural limits to the degree of generic transitivity for permutation groups of finite Morley rank.

Shrinking labour geographies: Transport access for paid work in later ages

Background and objectivesIn developing countries, a substantial share of the older population is employed (WHO, 2007), which is anticipated to triple between 2020 and 2050, bolstered by the rise of bridge employment in later life. Bridge jobs are part-time, informal work arrangements that serve as a transitional phase between full-time employment and retirement. While transport access for older adults is a primary policy concern in the age-friendly cities framework, their experiences of encountering and negotiating labour geographies, particularly transport systems to access bridge employment, are understudied. Research design and methodsThis paper used a qualitative and interpretative approach to analyse how older adults engage in nonlinear work patterns and commute to workspaces. We use a combination of visual mapping, observations, and in-depth interviews with older adults in Bengaluru, an urban metropolis in southern India. ResultsOlder workers engage in regular mobility routines to access informal bridge jobs. Our results suggest that the precarity of their bridge jobs permeates into their mobilities. Class, gender, and spatialities create additional layers of barriers to their already constrained transport resources. Economically disadvantaged older individuals encountered shrinking labour geographies due to unaffordable public transportation and first-and-last-mile journeys. For reasons of safety, older women were forced to depend on shared and public transport options, which were often unreliable. Lastly, older workers residing in geographically marginalised areas find more difficulty in organising transport to bridge jobs. Discussion and implicationsBridge jobs in informal arrangements are important means of livelihood for older persons in countries like India. Apart from the already precarious working conditions, the weak systemic transport support induces strain on the working conditions of older workers. From the purview of labour geography, adding to the natural limits of ageing, induced limits such as ageism and precarity at workplaces and non-age-friendly transport infrastructure create situations of vulnerable employment among older adults in the cities of the Global South.

"Frivolous" Believers and "Non-Modern" Rules: on the Issue of Traditional Orthodox Practices Deformation in the late Soviet Period

The relevance of the research topic is connected with the importance of historiographical understanding of the patterns of traditional confessional culture development in the conditions of Soviet modernization, as well as the need to clarify the place of Orthodoxy in the life of Soviet society of the late Soviet period.The purpose of the study: to analyze the changes that occurred in the rites of the Russian Orthodox Church in the late Soviet period.Objectives: to consider the socio-cultural prerequisites for the deformation of the Orthodox community cult life, to identify the features of changes in the most common Orthodox practices, to characterize the causes of these changes.Methodology. In the process of forming the factual base of the paper the author used traditional methods of archival work, as well as methods of field research questioning, interviewing. Methods of description and historical induction, historical-statistical, historical-genetic methods were used to systematize the data.Results. The paper examines the socio-cultural consequences of the socialist project of the renewal of society implementation in the late Soviet period, which determined the changes in the attitude of Orthodox-oriented citizens to religious life, analyzes the changes in the organization of the most common Orthodox rites – baptism, church burial, confession, investigates the causes of changes in their traditional forms.Conclusions. The author concludes that the main vectors of deformation of Orthodox rites in the late Soviet period were associated with giving them a secret or correspondence character, reduction, as well as profanation. The corresponding changes were caused not only by the artificial and natural limitations with which church life was connected, but also by the lack of systematic knowledge about the mysteries and dogmatics of the overwhelming majority of parishioners.

Validation of the Digital Transformation Model of the Universidad Autónoma de Chile

The emergence and massification of digital technologies are having such an impact on educational systems that universities are being forced to design transformation processes that make it possible to ensure the gradual incorporation of technologies into academic-administrative processes with a view to achieving greater student-centered educational quality. In response to this need and for the specific case of the Autonomous University of Chile, a digital transformation model composed of nine dimensions and 54 indicators was designed, which was subjected to an analysis process through structural equation modeling to check its consistency, reliability, and validity. With the data resulting from the application of surveys to 97 undergraduate students from that university, it was possible to demonstrate that the variables considered, and their corresponding dimensions form a solid construct that can explain the preliminary model of the digital transformation process at the university. Therefore, even recognizing limitations of a methodological nature, the model was intrinsically validated by the data. The findings represent a first approximation for the construction of a new academic-administrative scenario at the Autonomous University of Chile, which is based on the proper use of scientific-technological advances that have occurred in the global context.

The forbidden region for random zeros: Appearance of quadrature domains

AbstractOur main discovery is a surprising interplay between quadrature domains on the one hand, and the zeros of the Gaussian Entire Function (GEF) on the other. Specifically, consider the GEF conditioned on the rare hole event that there are no zeros in a given large Jordan domain. We show that in the natural scaling limit, a quadrature domain enclosing the hole emerges as a forbidden region, where the zero density vanishes. Moreover, we give a description of the class of holes for which the forbidden region is a disk. The connecting link between random zeros and potential theory is supplied by a constrained extremal problem for the Zeitouni‐Zelditch functional. To solve this problem, we recast it in terms of a seemingly novel obstacle problem, where the solution is forced to be harmonic inside the hole.

Charge ordering at a dielectric gate in itinerant metallic states with low-field memristor properties in VO2 thin films

Vanadium dioxide (VO2) − a non-stoichiometric oxide semiconductor (SC) offers exotic properties at a self-confined structure of correlated 3d1-electrons (spins) useful for non-volatile memory devices, smart switches, and human brain-inspired neuromorphic devices. Poor chemical stability and fragile nature limit its technologies of thin films. In view of resolving some of these issues, we developed polymer stabilized VO2 films (thickness t ≤ 100 nm), using VO2 nanocolloids in poly(vinylpyrrolidone) (PVP) (as a VO2 dispersoid, a molecular template, and a film former) in water, at a (100) Si(p++) substrate. Using a nano SiO2/TiO2 gate (t ≤ 10 nm), VO2 is grown (011) preferentially in a confined shape of nanoplates (nanocrystals) along the films, mostly of 15 to 40 nm widths at 20–30 nm crystallite size. The results are described with X-ray diffraction, surface topologies, lattice images, and X-ray photoelectron spectroscopy (XPS) of films in the variable charges 2V4+ → V3+ + V5+ order at the itinerant metallic states. A significant V5+-3d0, ≤ 33 at%, is shown in the XPS bands, which induces metallic states at conducting ‘V4+ → V5+ + e−’ channels. So, a charge-regulated SC → metal transition incurs via an induced M1 → R-VO2 metallic state near room temperature. A memristor VO2@TiO2/Si so made renders a wide current-voltage (I-V) loop at room temperature, with a leakage current that is well controlled at a high-k TiO2 gate. It exhibits a reversible switching at a duly small threshold field, Vt ≤ 0.2 V. This is the smallest Vt tuned so far beneficial for the low field, ≤ 1.0 V, devices. The charge models corroborate the effect of field-induced charge order at the interfaces of ‘conducting through channels’, regulating a reversible I-V hysteresis in an on-off cycle.

Woman as the call of being according to Eastern theology and the example of Jadwiga Zamoyska

Man understood as the image of God has an inalienable right and the ability to express his identity as a woman or as a man. This proves the ontological equality of a man and a woman, equally called to overcome the limitations of individual nature. The modern movements of women’s liberation efforts in the pursuit of freedom often lose sight of the basic sense of humanity. The result is sometimes their highly confrontational style of struggle for their own separateness and autonomy, leading to the achievement of an exclusive position and total opposition to the male form of leadership in community life. This seems absolutely strange to Jadwiga Zamoyska’s attitude. Meanwhile, today a woman, like a man, needs to rediscover the lost aspects of Christianity in herself, which would allow her to constantly remain in harmony with herself.

Recent advances in multi‐metallic‐based nanozymes for enhanced catalytic cancer therapy

AbstractNanozymes have emerged as a promising alternative to natural enzymes, effectively addressing natural enzymes' inherent limitation. Versatility and potential applications of nanozyme span across various fields, with catalytic tumor therapy being one prominent area. This has sparked significant interest and exploration in the utilization of nanozymes for targeted cancer treatment. Recent advancements in interdisciplinary research, nanotechnology, biotechnology, and catalytic technology have led to the emergence of multi‐metallic‐based nanozymes, which exhibit tremendous potential for further development. This review focuses on investigating the synergistic effects of multi‐metallic‐based nanozymes, aiming to enhance our understanding of their catalytic activities and facilitate their broader applications. We comprehensively survey the remarkable achievements in the synthesis, catalytic mechanisms, and the latest applications of multi‐metallic‐based nanozymes in cancer catalytic therapy. Furthermore, we identify the current limitations and prospects of multi‐metallic‐based nanozymes in the development of new materials and the application of novel technologies, along with the potential challenges associated with catalytic cancer therapy. This review underscores the significance of multi‐metallic‐based nanozymes and emphasizes the need for continued exploration as well as their potential impact on the development of novel materials and the realization of breakthroughs in catalytic tumor therapy.

Deep-sea mining: using hyperbaric conditions to study the impact of sediment plumes in the subtidal clam Spisula solida.

With the growing interest to exploit mineral resources in the deep-sea, there is the need to establish guidelines and frameworks to support hazard and risk assessment schemes. The present study used a subtidal species of filter-feeding bivalve, the clam Spisula solida, as a proxy to better understand the impacts of sediment plumes in marine organisms under hyperbaric conditions. Four concentrations of suspended sediments (0g/L, 1g/L, 2g/L, and 4g/L) were used in a mixture with different grain sizes at 4 Bar for 96h. Functional (filtration rate-FR) and biochemical endpoints (catalase-CAT, glutathione s-transferase-GST, and lipid peroxidation-LPO) were analyzed in the gonads, digestive gland, and gills of S. solida after a 96-h exposure at 4 Bar (the natural limit of the species vertical distribution). The FR showed a decreasing trend with the increasing sediment concentrations (significant effects at 2 and 4g/L). Additionally, significant changes were observed for some of the tested oxidative stress biomarkers, which were concentration and tissue-dependent, i.e., CAT activity was significantly elevated in gills (1g/L treatment), and GST was decreased in digestive gland (1g/L treatment). Overall, the results show that suspended sediments, at 2 and 4g/L, have negative functional impacts in the bivalve S. solida providing additional insights to improve hazard assessment of deep-sea mining. These findings represent a step forward to ensure the mitigation of the potential negative effects of deep-sea resource exploitation.

НЕКОММЕРЧЕСКИЕ ОРГАНИЗАЦИИ В СИСТЕМЕ МЕЖНАЦИОНАЛЬНЫХ ОТНОШЕНИЙ: ИСТОРИЯ И СОВРЕМЕННОСТЬ

To understand the modern role of nonprofi t organizations in the system of interethnic relations, it is important to analyze the historical experi-ence of public participation in the formation of ethnic policies in Russia. The goal of this article is to identify the potential of civil society organizations in the field of harmonization of interethnic relations, and to consider the possibilities and limitations of the potential of national-cultural autonomies based on reference to historical experience and its comparison with modern phenomena. To achieve research goals, the article uses a historical-genetic method that allows us to identify cause-and-eff ect relationships of historical processes and phenomena, as well as classifi cation methods that allow to systematically analyze the mechanisms of cross-sector partnership. Th e idea of national-cultural autonomy as a tool for maintaining and harmonious development of the cultural identity of “non-dominant” ethnic groups gained particular popularity in Austria-Hungary and Russia at the beginning of the twentieth century. The revival of this concept in our time is due to the fact that NCA is a historically established and theoretically substantiated “classical” principle for implementing ethnocultural development that does not violate the political structure and territorial-administrative composition of multinational states. However, the national-cultural autonomies created in accordance with the 1996 law are heterogeneous both in size and development potential. Due to this inconsistency, the possibilities of civil society in the ethnocultural and ethnopolitical sphere are realized not only in the form of creating national and cultural autonomies, but also using other organizational and legal forms. Th e nonprofi t sector is the organizational and economic basis of civil society, and it is in this capacity that it reflects the diversity of public interests. Th e role of the nonprofi t sector is not limited to representing the interests of diverse groups, including national and religious groups, in the public political space. Nonprofi t organizations are called upon to solve specifi c problems of society, provide social assistance, prevent crises and help resolve them. It is in this capacity that they are most useful as a tool for harmonizing interethnic relations. Civil society organizations, due to natural resource limitations, cannot eff ectively solve the problems of harmonizing interethnic relations without cooperation with the state and business. The issues of development of national culture and national heritage, social assistance and support for representatives of various ethnic groups, public participation in the activities of government bodies on issues of interethnic relations become the responsibility of various civil structures involved in the system of intersectoral social partnership

Defining Nature's Limits: The Roman Inquisition and the Boundaries of Science. By Neil Tarrant. Chicago: The University of Chicago Press, 2022.

Defining Nature's Limits: The Roman Inquisition and the Boundaries of Science. By Neil Tarrant. Chicago: The University of Chicago Press, 2022.