Transition Process Research Articles

On the Structure of Early Neolithic Societies of the Forest Tobol-Ishim Area: morphology and ornamentation of the pottery

The Early Neolithic complexes located in Western Siberia are characterized by the following common determinant features: chronological position within the end of 7,000 – turn of 6,000 cal BC, flat-bottomed vessels, design layouts of vessel necks (lips, rims, collars), and geometric and tree-like ornamental elements. The ceramic complexes are distinguished by different qualitative and quantitative ratios of the types of pottery (Boborykino, Koshkino, Satyga (with rims), comb ceramics, etc.) identified by researchers. When found in the same occupation layer, such a variety of ceramics might be evidence of an unequal sociocultural structure of the Neolithic population groups. The author stand for the concept that ceramic production and new stone processing skills and technologies were introduced (Zach, 2018, 2020) to the indigenous groups with Mesolithic traditions. It resulted in the interaction of autochthonous groups and newcomers and the subsequent merging of their structures, which ran differently in different territories. The author tend to consider the development of “syncretistic” societies in the first stages of such interaction in the Tobol-Ishim Rivers area as a process of transition from the Mesolithic to the Neolithic. Various types of pottery have been recorded at Boborykino complexes. The variety increases at Koshkino complexes, in different settlements and different proportions, which apparently reflects the formation of a new stable cultural tradition. The Kozlovo ceramics became such a tradition, being characterized by round-bottomed vessels with sags in the interior of the rim and a combination of ornaments in mainly incised-receding and comb techniques.

Transition of care from pediatric to adult nephrology post-renal transplant: a review.

Pediatric renal transplant recipients (RTRs) face heightened risks when they transition from a childhood nephrologist to an adult-centered one. The transition of care usually occurs when an individual is between ages 18 and 21 years, although some change providers earlier or later depending on varying circumstances. Turbulence during this shift can significantly impact daily life and, in severe cases, lead to graft loss. Several modern studies have explored the transition from pediatric to adult-centered nephrology care post-renal transplant. In this review, we first provide an overview of the differences between pediatric and adult renal transplant, highlighting unique challenges faced by pediatric patients such as donor-recipient size disparity, growth impairment, and need for additional immunizations. We then emphasize the criticality of a well-planned transition process, identifying factors that can hinder a smooth transition-such as medical and medication nonadherence, lack of health literacy, patient psychosocial challenges, and systemic shortcomings in coordination between care teams. Furthermore, this review outlines existing protocols and risk assessment tools, in addition to highlighting recent advancements aimed at facilitating smoother transitions such as the RISE protocol, readiness assessment, and the use of multidisciplinary teams. Proper implementation of coordinated, evidence-based transition protocols can improve patient outcomes, promote medication and appointment adherence, and reduce graft rejection rates. Efforts from multidisciplinary teams utilizing technology, risk stratification tools, and open communication between providers and patients are key to optimizing the transition process for pediatric RTRs as they transfer to adult-centered care.

CO2 Dynamics in a Flexible Metal-Organic Framework with Gate-Opening Phenomenon.

As a promising porous material for CO2adsorption and storage, elastic layer-structured metal-organic framework-11 (ELM-11) has attracted significant attention owing to its distinct gate-opening phenomenon. There is a sharp increase in CO2uptake once reaching the gate-opening threshold pressure. To better understand this gate-opening mechanism, we investigated its transition process from the perspective of CO2dynamics and its interaction with the framework via variable-temperature13C solid-state nuclear magnetic resonance spectroscopy.Our findings revealed that during the gate-opening process, CO2is initially strongly adsorbed at one site when the gate only slightly opens,while two distinct types of CO2molecules exist when the gate fully opens.11B,13C, and19F magic-angle spinning NMR, in conjunction with in-situ XANES experiments, were also conducted to probethe location of adsorption sites.

Circular economy and the separated yet inseparable social dimension: Views from European circular city experts

Circular economy has received significant attention worldwide for its potential to reconcile ecological limits and economic development. Europe, in particular, has made it a policy focus for achieving its climate ambitions. However, to date, the circular economy remains a loosely defined concept with competing discourses of technocentrism and holistic societal transformation. As the former prevails, its neglect of the social dimension raises concerns about the circular economy's social sustainability and feasibility. Therefore, this study explores how the relationship between the circular economy and the social dimension is perceived by experts directly engaged in the current circular transition process. By uncovering their experiences and perceptions, this study aims to offer empirical insights for the future development of the circular economy. Through qualitatively exploring the views of 14 experts across 11 European cities with a clear circular vision, this study found that although the social dimension is not a primary focus or fundamentally connected with the circular economy, it plays a fundamental role in the transition process and is simultaneously an impacted area. However, there is a significant gap between the ideal social environment required for circular transition and what the current transition can facilitate. As such, the future of the circular economy may be precarious unless it shifts from a technocentric tendency to more holistic, transformational approaches.

STUDY OF THE BEHAVIOR OF ARSENIC IN COPPER ELECTROLYTE

Abstract. In industrial wastewater, arsenic is most often present in the trivalent state. An analysis of existing purification methods shows that in all cases, with a few exceptions, the most complete removal of arsenic is observed from solutions in which it is in the pentavalent state. This is explained by the significantly lower solubility of arsenates of heavy and alkaline earth metals compared to the corresponding arsenites. The chemical oxidation of As(III) in the following systems was studied: As(III)-H2SO4-H2O, As(III)-MeSO4-H2O, As(III)–H2SO4–MeSO4–H2O (where Me is Cu, Ni, Co, Mn, Zn). The influence of temperature, the amount of transition metal ions, the duration of the experiment, and the concentration of sulfuric acid on the degree of transition of As(III) to As(V) was studied. The effect of catalytic oxidation of As(III) in sulfuric acid solutions was discovered. The maximum degree of oxidation of trivalent arsenic (55-60%) is observed when transition metal salts are introduced into an arsenic solution in the presence of a platinum plate. It has been established that the nature of the studied transition metal salts (Cu2+, Ni2+, Co2+, Mn2+, Zn2+), process duration and temperature do not have a significant effect on the degree of As(III) conversion. The results obtained largely explain the predominance of pentavalent forms of arsenic in production solutions of non-ferrous metallurgy. Key words: copper electrolyte, arsenic, transition metals, catalytic role, instant oxidation effect, activated oxygen.

Exogenous Reactive Oxygen Species Augments SMAD4 Expression And TGF-β Paradox in Human Breast Cancer

Background: The Transforming growth factor-β (TGF-β) functions to induce apoptosis, cell cycle arrest, and differentiation is central to sustaining tissue homeostasis and maintaining genomic stability. TGF-β normally, an effective tumor-suppressor that restricts the uncontrolled division of cells augments the development and progression of human malignancies when cytostatic activities of TGF-β are resisted by genetic and epigenetic events caused by tumorigenesis. This dichotomic nature of TGF-β during oncogenesis termed as “TGF-β Paradox,” persists to be the most crucial and puzzling query regarding its physio-pathological function and the role of cellular antioxidant status is highly interrelated which warrants more studies on the role of endogenous reactive oxygen species (ROS) in deciding epithelial-mesenchymal transition (EMT) process. The objective of the study was to check whether enhanced ROS augments the TGF-β pathway facilitating EMT. Methods: In vitro toxicity assay was performed to assess the appropriate concentration of hydrogen peroxide (H2O2) imparting oxidative stress. Comet assay and 8-OHdG (8-hydroxy-2’-deoxyguanosine) enzyme-linked immunosorbent assay (ELISA) were performed to check the extent of DNA damage and adduct production respectively. Mitogen-activated protein kinase (MAPK) p38 ELISA and mRNA gene expression analysis of TGF-β and SMAD were done to verify the effect of H2O2 on these signaling. Results: The objective of the study was to check whether enhanced ROS augments the TGF-β pathway facilitating EMT. Along with morphological alterations, a dose-dependent decrease in cell viability was seen at 300µM of H2O2 compared to 75µM. DCFDA labeling discovered the dose-dependent gradation of intracellular ROS generation and this was correlated to increased cellular DNA damage and DNA adduct production which was increased linearly with increasing H2O2 as evident with comet test and 8-OHdG ELISA. Significantly reduced MAPK p38 activity revealed by indirect ELISA analysis suggests lessened suppression of cell growth. Conclusions: The study establishes that higher intracellular ROS will facilitate the TGF-β paradox leading to epithelial mesenchymal transition which can adversely affect therapeutic strategies targeting EMT

Poslovno pravo i pravo održivog razvoja – između profitabilnosti i etičnosti

As for applying the knowledge from EU law, the author points out two tendencies affecting company law in the context of sustainability. The first one is the legal duty of the companies to incorporate the statement of purpose, which is no longer limited to profit. The second one is the corporate duty of care in line with ESG standards as well as the corporate purpose. It is an integral part of a company’s business and culture. Having in mind French, German or Dutch law, directors are expected to promote long-term business success, to take care of the open list of stakeholders’ interests and to apply corporate due diligence standards. Thought leaders, however, generally describe ESG as a business strategy that creates long-term stakeholder value by addressing social, economic, and environmental opportunities and risks that are material to a company. Preservation as well as environmental protection is one of the biggest challenges that modern generations will have to face. The term green transition has been coined as an expression of the efforts to ensure the transition to a sustainable business model in order to preserve the ecosystem and the planet as such. Non-financial reporting plays a very important role in the green transition process. Integral part of the EU agenda remains the discussion about corporate directors’ duties in the context of human rights as well as environmental risks. There is no doubt that the key word of the new corporate governance paradigm is risk.

Structural phase transition in NH₄F under extreme pressure conditions.

Ammonium fluoride (NH₄F) exhibits a variety of crystalline phases depending on temperature and pressure. By employing Raman spectroscopy and synchrotron X-ray diffraction beyond megabar pressures (up to 140 GPa), we have here observed a novel dense solid phase of NH₄F, characterised by the tetragonal P4/nmm structure also observed in other ammonium halides under less extreme pressure conditions, typically a few GPa. Using detailed ab-initio calculations and reevaluating earlier theoretical models pertaining to other ammonium halides, we examine the microscopic mechanisms underlying the transition from the low-pressure cubic phase (P-43m) to the newly identified high-pressure tetragonal phase (P4/nmm). Notably, NH₄F exhibits distinctive properties compared to its counterparts, resulting in a significantly broader pressure range over which this transition unfolds, facilitating the identification of its various stages. Our analysis points to a synergistic interplay driving the transition to the P4/nmm phase, which we name phase VIII. At intermediate pressures (around 40 GPa), a displacive transition of fluorine ions initiates a tetragonal distortion of the cubic phase. Subsequently, at higher pressures (around 115 GPa), every second ammonium ion undergoes a rotational shift, adopting an anti-tetrahedral arrangement. This coupled effect orchestrates the transition process, leading to the formation of the tetragonal phase.

THE NATIONAL BUILDING POLICY IN KAZAKHSTAN: CIVIC OR ETHNOSOCIAL IDENTITY?

This study demonstrates how Kazakhstan, once entangled in the complex interaction between tradition and the challenges of modernity, is now actively shaping its national identity. Against the backdrop of the issues surrounding identity politics, nationalism, and post-Soviet transitional processes, this article sheds light on Kazakhstan's decisive steps in creating and exporting a unique national narrative in the realm of state-building. This narrative goes beyond simple adaptation of external models and reflects the country's growing academic and intellectual contribution to the global discourse on national identity formation. The article examines the synthesis of governmental efforts, public knowledge, and practical ideology that underpins the formation of national policy. Special attention is given to the fact that in the post-socialist space, Kazakhstan does not merely adhere to a policy of “de-Sovietization” but also redefines its policy as an expression of sovereign identity and national leadership. The study focuses primarily on the process of «Kazakhization» - a significant paradigm in the post-Soviet context. Unlike other post-Soviet narratives, which tend to criticize or deny history or use it merely as a political tool, the Kazakh approach is aimed at strengthening the multifaceted Kazakhstani identity. In this process, Kazakhstan balances between collective civic identity (Kazakhstani) and ethnonational Kazakh identity (Kazakh), reflecting a conscious departure from the rejection or opposition to the past. Instead, the country seeks to integrate and enhance its unique national essence.

Transition readiness assessment in Portuguese adolescents and young adults with pediatric-onset rheumatic diseases: a single-center study.

In this study, we aimed to assess the transition readiness levels amongst patients with childhood-onset rheumatic diseases. Additionally, we sought to identify and analyze predictive factors associated with better transition readiness skills in adolescent and young adult (AYAs) patients. This is a monocentric cross-sectional study that includes patients between 14 and 26 years of age who attended outpatient pediatric and young adult rheumatology appointments between October and December of 2023 and that were diagnosed with an immune-mediated rheumatic disease before reaching 18 years of age, with at least 1 year of disease duration. Patients were presented with a questionnaire that contained demographic and clinical questions, TRACS (Questionário de Preparação da Transição para a Autonomia nos Cuidados de Saúde) questionnaire - a validated Portuguese version of the Transition Readiness Assessment Questionnaire (TRAQ), and Hospital Anxiety and Depression Scale (HADS) questionnaire. Data was analyzed to assess the significant associations between the different variables and transition readiness outcome measured by the TRACS. Descriptive statistics, statistical comparisons and logistic regression analysis were performed. A total of 69 patients with a median age of 20 [17.5-22.5] were included in this study. The median TRACS score was 4.41 [4.09-4.74]. Significantly higher TRACS scores were observed in patients who were female, 18 years of age or older, had a higher level of education, were employed, had active disease or that belonged to middle-class (when compared to patients belonging to upper- middle class). The logistic regression analysis demonstrated that being a female or having an educational status equal to 12th grade or superior emerged as predictors of higher transition readiness levels. Our study identified female sex and higher level of education as predictors of increased transition readiness levels. Therefore, healthcare providers should consider these variables when assessing patients for transition readiness and focus on improving transition process, especially in male and less educated AYAs.

Influence of livelihood functional diversity on agro-food systems in rural communities from different macro regions of Brazil

Urbanization has changed the livelihood diversity of rural communities worldwide. This study aimed to fit an indicator of the functional diversity of livelihood activities to assess the heterogeneity of socioeconomic conditions and their influence on agro-food changes in rural communities in Brazil. This study was conducted in three macro regions of Brazil, through semi-structured questionnaire interviews conducted in 1012 households to verify details about food patterns, self-consumption farms, and socioeconomic conditions. Data from questionnaires were analyzed using multivariate statistical models to appraise similarities among communities and determine the relative influence of socioeconomic factors on agro-food patterns. Specific socioeconomic status and use of natural resource data were analyzed while adjusting for Petchey and Gaston's indicator of functional diversity to evaluate the heterogeneity of local livelihood activities and socioeconomic conditions. This indicator summarizes the proportional livelihood richness in all sampled places, as better conditions for survival were found in specific localities of the central-west and eastern Amazon regions of Brazil. We also verified that the remote areas of the Goiás and Pará states were regions with the most significant maintenance of traditional food habits and use of natural resources. Although these results do not allow us to establish that all of these areas are undergoing an agro-food transition process, some localities are more likely than others to adjust their livelihood strategies to face global food changes. This interdisciplinary approach facilitated the identification of the most similar groups regarding their livelihoods and socioeconomic conditions that influenced the agro-food transition process in rural regions.

Bridging the Gap: Addressing Educator and Caregiver Challenges in Transitioning Students with ASD to Higher Education and TVET - A Scoping Review

Students with Autism Spectrum Disorder (ASD) often struggle with communication and social skills, necessitating significant support from family, caregivers, and educators. In Malaysia, while Special Education Needs (SEN) students are typically integrated into general education during their school years, their presence in tertiary education or TVET remains underrepresented. This scoping review aims to identify and understand the challenges general educators and caregivers face in facilitating the transition of ASD students from higher education to tertiary education and TVET. A comprehensive analysis of literature from Scopus, ProQuest, and Science Direct databases, focusing on studies published between 2013 and 2023, was conducted. The findings reveal mixed experiences, highlighting significant difficulties and areas for improvement. General educators and caregivers report numerous challenges, including inadequate training, insufficient resources, and a lack of tailored support systems, which collectively hinder the smooth transition of ASD students into higher educational settings. It suggests that targeted interventions and increased collaboration between educators and caregivers can lead to more positive outcomes. This study provides original insights into the specific needs and barriers faced by ASD students in Malaysia, offering valuable implications for policymakers, educators, and caregivers to create more inclusive and effective educational transitions. Future research on transitioning students with ASD to higher education and TVET should focus on longitudinal studies to track long-term outcomes, the development and evaluation of targeted intervention programs, and the role of assistive technologies in the transition process.

Designing a model predictive controller for graphite baking process

Model predictive controller provides better control quality for graphite products baking process than PID and its variations. The drawback of MPC is its high sensitivity to object modelling errors. If all of object parameters are varied just by 3 % simultaneously then MPC provides satisfactory control no more. In the current paper we design an adaptive MPC for baking process control. In order to identify furnace section “under the fire” on-line, we utilize recursive least squares algorithm with forgetting factor equal to 0,98. We compare conventional and adaptive MPCs in the following cases: accurate model; undesirable deviations of object parameters from model parameters (object is time invariant); desirable deviations; time variant object with step-changing parameters. In each case adaptive MPC provides control that ensures temperature difference inside the hottest (the most “dangerous”) graphite bar to be small enough, and even gives some margin for it (0,8 % to 8 %). However, the cost for this is increased process duration (4,8 % to 142,1 %) and more fuel-consuming (1,2 % to 106,2 %) than in case of non-adaptive MPC, even if the latter provides satisfactory control as well. In general, it is reasonable to use an adaptive MPC instead of a conventional one. Margin of economical reasonability needs further research. Also, it is necessary to compare different identification methods in order to achieve faster transition process.

From Hospital to Home: Applying a Co-design Approach to Determine Key Components of an Intervention to Support Transition-to-Home After Stroke

Abstract Background When people with stroke transition from the hospital back to their homes, they and their families frequently experience multi-faceted unmet needs and feelings of abandonment. Uncertainty surrounds the fundamental components of an intervention intended to support transition-to-home after a stroke. The aim of this study was to utilise a co-design process to identify key components for a patient-centred support intervention facilitating the transition home after stroke, and to explore what might be feasible within a real-world context. Methods The primary researcher, a larger team of researchers, and an individual with lived experience of stroke facilitated a series of three workshops for 12 people with stroke, 6 caregivers, 26 healthcare professionals, and 6 representatives from stroke organisations. World Café methodology and Liberating Structures facilitation techniques were adapted to meet the study aim. Data collection involved making observations during workshops, summarising findings, and reaching group consensus agreement on outputs. The final output was the consequence of facilitated consensus on a prioritisation task. Individuals with lived experience of stroke contributed to study design, ethics, and co-design outputs, providing input for future research and co-facilitating workshops with the research team. Results The co-design group identified 10 key intervention components to support people with stroke and their families during the transition from hospital-to-home. These components focussed on enhancing collaboration, streamlining transition processes, and facilitating post-discharge support. While a stroke coordinator was considered a top priority, increased cross-setting information sharing and community-based healthcare staff in-reach, were considered most feasible to implement. Conclusion The co-design approach, involving a multi-stakeholder group, was strengthened by patient and public involvement. This ensured that the identified transition-to-home intervention components are meaningful and relevant for people with stroke and their families. To further refine, and feasibility test the components for generalisability within the wider Irish healthcare context, additional co-design workshops are required.

Carrier dynamic identification enables wavelength and intensity sensitivity in perovskite photodetectors

Deciphering the composite information within a light field through a single photodetector, without optical and mechanical structures, is challenging. The difficulty lies in extracting multi-dimensional optical information from a single dimension of photocurrent. Emerging photodetectors based on information reconstruction have potential, yet they only extract information contained in the photoresponse current amplitude (responsivity matrix), neglecting the hidden information in response edges driven by carrier dynamics. Herein, by adjusting the thickness of the absorption layer and the interface electric field strength in the perovskite photodiode, we extend the transport and relaxation time of carriers excited by photons of different wavelengths, maximizing the spectrum richness of the edge waveform in the light-dark transition process. For the first time, without the need for extra optical and electrical components, the reconstruction of two-dimensional information of light intensity and wavelength has been achieved. With the integration of machine learning algorithms into waveform data analysis, a wide operation spectrum range of 350–750 nm is available with a 100% accuracy rate. The restoration error has been lowered to less than 0.1% for light intensity. This work offers valuable insights for advancing perovskite applications in areas such as wavelength identification and spectrum imaging.

TRANSITIVITY ANALYSIS OF SENATOR HAWLEY AND PROFESSOR BRIDGE’S GENDER IDENTITY DEBATE

Using Halliday’s transitivity concept, this paper analyzes the debate between Senator Hawley and Professor Bridges conducted on July 12, 2022. The debate focuses on the topic of people with a capacity for pregnancy, which led to views of gender identity. The way individuals identify their gender has become a social phenomenon, as the idea of gender has broadened to the point that it is seen as a spectrum. The creation of new words outside the two polarizations (i.e., man and woman) could create acknowledgment for the minority group of people with lesser-known gender identities. Using Halliday’s (1994) Transitivity Concept in Systemic Functional Linguistics, this study analyzes the clause structures of both Senator Hawley and Professor Bridges to examine the distribution of the six transitivity processes and their relation to the clauses chosen to represent each participant's ideology regarding their views on gender. The different approaches in their arguments regarding gender identity also show the different ideological beliefs of their parties, which are the Republicans and the Democrats. Senator Hawley dominantly uses mental processes consisting of the desideration process, cognition process, and emotion process. In comparison, Professor Bridges shows a high use of relational processes consisting of the attribution process and identification process. Professor Bridges' relational processes point out Senator Hawley's rigid idea of gender by identifying and valuing the variety of genders. The many clauses stated by Professor Bridges also affirm her liberal belief that views gender as more than just two polarizations while also supporting equality in the idea of abortion rights as something that is needed for women and other groups of genders. Senator Hawley counters Professor Bridges' allegations using mental processes by seeking clarification to align their awareness of gender, which reveals his gender polarization. The use of clauses mentioned by Senator Hawley is done to showcase his implied Republican ideology, which does not find significance in the topic of people with the capacity for pregnancy leading to transphobia.

Caregivers' burden of care during emergency department care transitions among older adults: a mixed methods cohort study.

Improving care transitions for older adults can reduce emergency department (ED) revisits, and the strain placed upon caregivers. We analyzed whether caregivers felt a change in burden following a care transition, and what may be improved to reduce it. This mixed-methods observational study nested within LEARNING WISDOM included caregivers of older patients who experienced an ED care transition. Burden was collected with the brief Zarit Burden Interview (ZBI-12), and caregivers also commented on the care transition. A qualitative coding scheme of patient care transitions was created to reflect themes important to caregivers. Comments were randomly analyzed until saturation and themes were extracted from the data. We followed both the SRQR and STROBE checklists. Comments from 581 caregivers (mean age (SD) 64.5 (12.3), 68% women) caring for patients (mean age (SD) 77.2 (7.54), 48% women) were analyzed. Caregivers overwhelmingly reported dissatisfaction and unmet service expectations, particularly with home care and domestic help. Communication and follow-up from the ED emerged as an area for improvement. Caregivers who reported an increased level of burden following a patient's care transition had significantly higher ZBI scores than caregivers who self-reported stable burden levels. Caregivers with increasing, stable, and improved levels of subjective burden all reported areas for improvement in the care transition process. Themes centering on the capacity to live at home and inadequate communication were most frequently mentioned and may represent serious challenges to caregivers. Addressing these challenges could improve both caregiver burden and ED care transitions.

The Importance of Graduates' Perceived Network Quality in Their Transition to Work: A Longitudinal Approach

ABSTRACTTo navigate the labour market graduates turn to their social network for valuable resources. However, existing disparities in accessing and exerting network resources may result in more precarious transition outcomes for first‐generation graduates. To gain deeper insight into how social networks facilitate the transition process, this study focuses on the network actors and resources that are perceived as valuable by graduates. Over a 4‐month period commencing at graduation, 22 graduates, encompassing both first‐generation and continuing‐generation students, were bi‐weekly tasked with mapping their social networks. Results show that graduates rely strongly on close contacts, making graduates dependent on the experience of their parents with a certain field of work, which often results in an implicit advantage for continuing‐generation graduates. Moreover, higher education institutions fail to use their power to embed valuable institutional resources or network actors into graduates' networks after graduation, which creates limited opportunity structures, in particular, for first‐generation graduates.

Engineered Biomimetic Nanovesicles Synergistically Remodel Folate-Nucleotide and γ-Aminobutyric Acid Metabolism to Overcome Sunitinib-Resistant Renal Cell Carcinoma.

Reprogramming of cellular metabolism in tumors promoted the epithelial-mesenchymal transition (EMT) process and established immune-suppressive tumor microenvironments (iTME), leading to drug resistance and tumor progression. Therefore, remodeling the cellular metabolism of tumor cells was a promising strategy to overcome drug-resistant tumors. Herein, CD276 and MTHFD2 were identified as a specific marker and a therapeutic target, respectively, for targeting sunitinib-resistant clear cell renal cell carcinoma (ccRCC) and its cancer stem cell (CSC) population. The blockade of MTHFD2 was confirmed to overcome drug resistance via remodeling of folate-nucleotide metabolism. Moreover, the manganese dioxide nanoparticle was proven here by a high-throughput metabolome to be capable of remodeling γ-aminobutyric acid (GABA) metabolism in tumor cells to reconstruct the iTME. Based on these findings, engineered CD276-CD133 dual-targeting biomimetic nanovesicle EMφ-siMTHFD2-MnO2@Suni was designed to overcome drug resistance and terminate tumor progression of ccRCC. Using ccRCC-bearing immune-humanized NPG model mice, EMφ-siMTHFD2-MnO2@Suni was observed to remodel folate-nucleotide and GABA metabolism to deactivate the EMT process and reconstruct the iTME thereby overcoming the drug resistance. In the incomplete-tumor-resection recurrence model and metastasis model, EMφ-siMTHFD2-MnO2@Suni reduced recurrence and metastasis in vivo. This work thus provided an innovative approach that held great potential in the treatment of drug-resistant ccRCC by remodeling cellular metabolism.

BATF is involved in the malignant phenotype and epithelial-mesenchymal transition of colon cancer cells via ERK/PD-L1 signaling.

Transcription factors have emerged as primary regulators in colon cancer. Basic Leucine Zipper Transcription Factor (BATF) was found to be differentially expressed in colon cancer. This study aimed to explore the impact of BATF on the malignant phenotype and epithelial-mesenchymal transition (EMT) process. Based on The Cancer Genome Atlas (TCGA) data, the correlation between BATF and patients' overall prognosis was analyzed. BATF expression in epithelial and colon cancer cells was evaluated. By knocking down its levels in colon cancer cells, its effects on the malignant phenotype, apoptosis, EMT progression, and ERK/PD-L1 were evaluated. Cells were treated with ERK/PD-L1 agonists, and the BATF cell regulation was re-examined. BATF levels were negatively correlated with patients' overall survival. BATF is upregulated in colon cancer cell lines, and BATF knockdown in HCT116 cells suppressed the malignant cellular phenotypes (proliferation, migration, and invasion) and increased apoptosis. BATF knockdown inhibited EMT and ERK/PD-L1 signaling activation, whereas upon agonist treatment, BATF potency was disrupted. This study revealed that BATF is involved in the malignant phenotype and EMT of colon cancer cells, and this process may be mediated by ERK/PD-L1 signaling.