Search Results (139)

The transition towards smart megacities has deeply integrated Artificial Intelligence (AI) with power–transport networks. While AI empowers complex operations like multi-network coordinated dispatch and emergency rescue, current algorithm-centric perspectives largely ignore its massive physical energy costs. Accordingly, this Perspective examines the dual role of AI, considering it not only as an intelligent decision-support tool but also as a potential source of additional stress on physical infrastructure. First, through a structured synthesis of the representative literature, we deconstruct the functional dependencies between algorithms and physical infrastructures, identifying how AI reshapes the operational paradigms of power, ground transport, and aerial networks under routine and emergency scenarios. We then introduce the concept of the “Computation–Energy Paradox.” Integrating conceptual analysis with a quantitative case study of a typical community, we illustrate a plausible failure mechanism: during extreme disasters, intensified AI invocation for emergency management generates surging computational loads, which paradoxically exacerbate power shortages and reduce the operating margin of already weakened systems. In addition, we analyze core engineering bottlenecks, including spatiotemporal computation–energy mismatches and physical constraints in extreme edge environments. To address these challenges, we outline a prospective roadmap encompassing lightweight emergency AI and computation–power-coordinated offloading mechanisms. Finally, the sustainable development of such systems suggests a paradigm shift: AI must evolve from a purely virtual algorithm into a physical component of an integrated compute–power–transport system. Full article

Urban informality in amphibious territories represents a critical yet understudied dimension of contemporary urbanisation in the Global South. This article analyses the interrelations between spatial transformation, social equity, and environmental change in Las Flores, an informal settlement located between the Mallorquín Lagoon and the Magdalena River in Barranquilla, Colombia. Drawing on a mixed-methods approach combining GIS interpretation, participatory mapping, and in-depth interviews, the study examines how processes of informal territorialisation have reshaped both the physical landscape and the social fabric of this amphibious environment. Results indicate that the settlement has expanded progressively over the past two decades, occupying areas of the wetland previously covered by mangroves and natural vegetation. This expansion has been accompanied by environmental degradation, soil infilling, and declining water quality. Residents face persistent infrastructural deficits, limited access to education and healthcare, and increasing social fragmentation between the formal and informal sectors. Yet, the community also exhibits strong organisational capacity, adaptive livelihoods, and a deep sense of place that sustains local identity and resilience. These dynamics exemplify the paradox of amphibious life: coexistence with water as both a resource and a source of vulnerability. Building on these findings, the study develops an urban socio-ecological conceptualisation of Amphibious Justice, a framework for interpreting equity, recognition, and governance in hybrid territories where urbanisation and land–water dynamics intersect. The article proposes a framework of equitable amphibious urbanism that integrates environmental restoration, social inclusion, and participatory governance. The findings suggest that sustainability in such territories cannot be achieved through technocratic restoration or forced resettlement, but through co-produced strategies that recognise local knowledge, tenure security, and ecological stewardship. Ultimately, the case of Las Flores offers insights into how cities in the Global South can pursue just and adaptive coexistence with water amid growing climate and urban pressures. Full article

Cancer is increasingly recognized as an emerging concern in wildlife health and biodiversity conservation in the Anthropocene. Although traditionally viewed as an individual disease associated primarily with aging, wildlife cancer is shaped by complex interactions among environmental changes, species-specific evolutionary adaptations, and ecological processes. This review synthesizes current knowledge on the ecological and evolutionary drivers of wildlife cancer by integrating evidence from comparative oncology, environmental toxicology, wildlife pathology, and conservation biology. We examine how anthropogenic stressors, including pollution, habitat degradation, climate change, and infectious agents, influence cancer susceptibility in wild populations, and summarize intrinsic mechanisms underlying interspecific variation in cancer vulnerability, including Peto’s paradox, enhanced tumor suppression, and adaptive immune surveillance. We further highlight major methodological challenges, including limited surveillance capacity, fragmented datasets, taxonomic biases, and insufficient integration between cancer biology and conservation science. Finally, we discuss emerging interdisciplinary approaches, such as standardized monitoring frameworks, multi-omics technologies, artificial intelligence-assisted diagnosis, and One Health-based strategies, to advance wildlife cancer research and management. Collectively, this review positions wildlife cancer as an important ecological and evolutionary phenomenon and provides perspectives for incorporating cancer surveillance into biodiversity conservation and ecosystem health assessment. Full article

Acute myeloid leukemia (AML) persistence is sustained by leukemic stem cells (LSCs) that survive metabolic deprivation, oxidative stress, hypoxia, proteotoxic burden, and therapeutic pressure. The integrated stress response (ISR) has emerged as a central adaptive network in this process. Through phosphorylation of a subunit of eukaryotic initiation factor 2 (eIF2α) and selective translation of activating transcription factor 4 (ATF4), the ISR coordinates stress-responsive transcriptional programs that may either preserve cellular fitness or promote apoptotic commitment, depending on the intensity, duration, and biological context of activation. In AML, ATF4 occupies a critical position at the interface between stemness, metabolic adaptation, redox control, ferroptosis resistance, and treatment response. In primitive leukemic compartments, ISR–ATF4 signaling appears to support stress tolerance, amino acid metabolism, serine biosynthesis, autophagy, and leukemic persistence. At the same time, pharmacologic or sustained ISR activation may lower the apoptotic threshold by inducing pro-apoptotic mediators such as CHOP, PUMA, and NOXA, thereby modulating MCL-1 dependency and enhancing sensitivity to venetoclax-based strategies. Conversely, adaptive ISR signaling may promote resistance through mechanisms such as ATP-binding cassette subfamily B member 1 (ABCB1) enhancer activation and mitochondrial stress tolerance. This duality creates a therapeutic paradox: ISR–ATF4 signaling may need to be inhibited in adaptive, resistance-promoting states but amplified in apoptosis-permissive contexts. This review discusses the biological and therapeutic relevance of ISR–ATF4 dysregulation in AML and highlights the need for biomarkers capable of distinguishing adaptive ATF4 dependency from inducible apoptotic vulnerability. Full article

Background/Objectives: The advent of immune checkpoint inhibitors (ICIs) and targeted therapies has revolutionized advanced melanoma treatment but introduced unique immune-related adverse events (irAEs). Hematological irAEs (Hem-irAEs) are rare but carry disproportionately high morbidity and mortality. This review systematically synthesizes current literature to comprehensively understand the incidence, pathophysiology, clinical presentation, and management of Hem-irAEs in modern melanoma therapy. Methods: A comprehensive Web of Science literature search (January 2015 to January 2026) identified studies reporting hematological adverse events associated with melanoma immunotherapy and targeted therapies. After screening 2274 records, 130 relevant studies were included for quantitative data extraction, focusing on incidence rates and toxicity grading. Results: Hem-irAEs occur infrequently (under 4% overall incidence for ICIs) but possess staggering mortality rates between 12% and 15.5%. The most common manifestations are immune thrombocytopenia (ITP), autoimmune hemolytic anemia, and neutropenia. Combination regimens significantly amplify toxicity frequency and severity. Diagnosis requires meticulous baseline monitoring and bone marrow biopsies to differentiate peripheral destruction from central marrow failure. First-line management mandates ICI discontinuation and high-dose corticosteroids, utilizing targeted second-line immunosuppressants for refractory syndromes. Conclusions: Hem-irAEs embody a profound clinical paradox: while mild toxicities often herald a robust anti-tumor response, severe hematological events drastically increase non-cancer mortality, negating these oncological benefits. Navigating this “double-edged sword” demands a paradigm shift toward proactive risk stratification. Integrating predictive biomarkers including baseline autoantibodies, Human Leukocyte Antigens (HLA) profiling, and systemic inflammatory indices is crucial to identify vulnerable populations before treatment. Optimizing outcomes requires highly personalized vigilance to balance the life-saving efficacy of immunotherapy against the catastrophic threat of hematopoietic failure. Full article

Cellular senescence plays a complex and crucial dual role in ovarian cancer treatment: it serves as both an important tumor suppression mechanism and a potential driver of drug resistance and recurrence. This review systematically examines the intricate regulatory network of cellular senescence, encompassing multiple pathways including telomere dysfunction, DNA damage response, epigenetic remodeling, hormone signaling, and metabolic reprogramming. Studies have demonstrated that core therapeutic modalities, such as platinum-based chemotherapy, PARP inhibitors, and CDK4/6 inhibitors, can exert anti-tumor effects by inducing cellular senescence; however, their efficacy is significantly influenced by the senescence-associated secretory phenotype (SASP). Specific SASP components can activate immune surveillance, whereas others promote tumor progression, acquisition of stem cell-like characteristics, and therapeutic resistance. It is this “anti-tumor versus pro-tumor” paradox that renders senescent cells a critical variable determining treatment outcomes. In light of this, emerging strategies aim to precisely modulate the senescence process, including the use of epigenetic drugs to induce senescence, targeting metabolic vulnerabilities to eliminate senescent cells, and intervening in deleterious SASP to improve the tumor microenvironment. Integrating such strategies with conventional therapies holds promise for overcoming the resistance bottleneck in ovarian cancer and opening new avenues for improving patient prognosis. Full article

Objective: This study aims to investigate the expression of CAVIN3 in cervical cancer, its effect on radiotherapy outcomes, and its potential molecular mechanisms. Materials and Methods: The GEPIA2 database was used to screen genes that may affect cervical cancer prognosis. Then, we analyzed 133 cervical cancer patients from the TCGA database who received radiotherapy to evaluate CAVIN3 gene expression and function. Receiver operating characteristic (ROC) curves and Cox regression models were employed to assess the diagnostic value of CAVIN3 and its association with radiotherapy outcomes. GSEA, GO, and KEGG databases were used to perform pathway enrichment analysis of CAVIN3-related signaling pathways. We also collected pretreatment biopsy specimens from 66 patients who were subsequently treated with radiotherapy from our center to validate the findings from the database analysis. Results: In the TCGA database, CAVIN3 expression was significantly lower in cervical cancer tissues than in normal cervical tissues (p = 0.019), a finding that was independently corroborated in our own cohort (p = 0.002). Receiver operating characteristic analysis yielded area-under-the-curve values of 0.894 for the TCGA RNA-seq data and 0.947 for our center, underscoring the gene’s potential diagnostic utility. Next, we stratified cervical cancer patients who received radiotherapy by intratumoral CAVIN3 levels. Notably, the low-expression group consistently showed better treatment outcomes. In the TCGA cohort, high CAVIN3 expression was associated with significantly shorter median overall survival (mOS, 31.8 months versus not reached within follow-up; p = 0.043). This pattern was confirmed in our validation cohort, where high CAVIN3 expression predicted markedly inferior median progression-free survival (mPFS, 9.8 vs. 59.9 months; p < 0.05) and mOS (17.45 months vs. not reached; p < 0.05). Consistent with these survival differences, the objective response rate to radiotherapy was lower in the high-expression group than in the low-expression group (56.5% vs. 88.2%, p = 0.006), revealing better radiotherapy response among tumors with low CAVIN3 expression. Enrichment analysis revealed that the high CAVIN3 expression group was primarily enriched in pathways related to extracellular matrix formation and remodeling, extracellular matrix–cell membrane interactions, cell adhesion and migration, integrin β1 signaling, and the regulation of cell growth, differentiation, and apoptosis. Together, these functions indicate a more differentiated, matrix-attached phenotype that can promote radioresistance. Conversely, low CAVIN3 expression likely reflects a poorly differentiated state with diminished matrix interaction, which renders the tumor more vulnerable to radiation. Conclusions: CAVIN3 downregulation is a frequent event in cervical cancer and may contribute to tumor susceptibility. Paradoxically, within tumors, low expression of CAVIN3 is associated with an enhanced response to radiotherapy, likely stemming from the underlying phenotype characterized by poor differentiation and heightened radiosensitivity. Therefore, CAVIN3 expression levels are correlated with cervical cancer development and the radiotherapy response of cervical cancer patients. Full article

The formation and disappearance of paleolakes are sensitive indicators of environmental evolution in arid and semi-arid regions. Their disappearance records comprehensive information on regional hydrological conditions, climatic changes, and tectonic activities, thereby offering unique research value for elucidating the environmental driving mechanisms behind water resource changes in historical human settlements and the concomitant rise and fall of civilizations. This study analyzed the contact interface between extensively distributed lacustrine deposits and the overlying aeolian dune sands around Tongwan City using optically stimulated luminescence (OSL), and combined with relevant documentary evidence to elucidate the relationship between paleolake disappearance and the abandonment of the ancient city. The OSL dating results demonstrated that the disappearance of paleolakes and the initiation of desertification around Tongwan City were mainly concentrated between about 1200 and 900 years before present, closely corresponding to the abandonment of Tongwan City in AD 994. Field investigations additionally revealed that well-developed fluvial erosion surfaces are pervasively present at the top of lacustrine deposits around Tongwan City, while multiple fluvial terraces are exposed along the Wuding River. These features collectively indicate that regional crustal uplift event led to fluvial incision. The results indicated that the abandonment of Tongwan City was not attributable solely to climatic aridification, but instead resulted from the combined influences of favorable hydrothermal conditions during the High-Temperature Period of the Northern Song (HTNS, AD 994–1094) and regional tectonic uplift. Tectonic uplift facilitated deep incision of the Wuding River valley, while increased precipitation during the warm period enhanced surface water infiltration and drainage, resulting in a significant decline in groundwater levels, the disappearance of paleolakes, and ultimately the depletion of water resources upon which the ancient city relied. These findings provide new evidence from an environmental geological perspective and present a key scientific explanation for the paradox that Tongwan City was abandoned during a relatively warm climatic interval. Furthermore, the coupled mechanism of tectonic uplift, fluvial incision, sharp groundwater decline, and societal collapse revealed in this study not only provides a valuable reference for investigating the abandonment of ancient cities in arid and semi-arid regions during historical periods, but also offers important implications for assessing water resource vulnerability of ancient settlements on analogous geomorphic units under global climate change, and may serve as a geological–historical warning and reference for water security management in human habitations under current and future warm-climate conditions. Full article

This study investigates the dual pathways of foreign language enjoyment (FLE) among left-behind children (LBC), a population constituting more than 20% of China’s child population and largely under investigated in the second-language learning context; the focus of this study is on the unique and joint contributions of FLE to learning engagement (LE) and learning burnout (LB) in determining academic achievement (AA). Our results confirm that FLE and LE are positively correlated with EFL achievement, while LB shows a significant negative correlation with EFL achievement. However, they also reveal counterintuitive positive correlations between FLE and LB and between LE and LB among LBC—contradicting prior findings from the general population. More importantly, our path analysis reveals a blocked positive association and an opened negative association: while FLE is significantly associated with LE, LE is not significantly linked to achievement; conversely, FLE is positively connected to LB, which is negatively associated with achievement. This “paradox of enjoyment” reveals that FLE acts as a double-edged sword for Chinese LBC, challenging the unidirectional positive view of FLE in second-language learning and demonstrating that positive emotions alone cannot drive sustainable EFL learning success within this vulnerable group. Our findings highlight the unique socioemotional complexities of LBC, underscoring that fostering enjoyment alone might be insufficient without targeted interventions to alleviate burnout and translate engagement into actual success, and offer valuable insights for educators and policy-makers aiming to improve foreign language education among LBC. Full article

Reactive oxygen species (ROS) are central regulators of cancer biology and represent a double-edged target in oncology. At physiological levels, ROS support signal transduction, proliferation, differentiation, and immune responses, whereas sustained ROS imbalance promotes DNA damage, genomic instability, metabolic reprogramming, and remodeling of the tumor microenvironment, thereby contributing to tumor initiation, progression, metastasis, and therapy resistance. Conversely, because many cancer cells operate close to the limit of tolerable oxidative stress, further ROS elevation can trigger apoptosis, ferroptosis, immunogenic cell death, and other cytotoxic programs. This review summarizes the major intracellular and microenvironmental sources of ROS, the mechanisms by which redox signaling shapes malignant transformation and tumor adaptation, and the antioxidant systems that buffer oxidative stress in cancer cells. We further discuss current therapeutic approaches based on both ROS suppression and ROS amplification, including redox-modulating small molecules, radiotherapy, photodynamic and sonodynamic therapy, catalytic nanomaterials, and ROS-responsive prodrugs and drug delivery systems. Particular attention is given to the context-dependent effects of ROS, the antioxidant paradox, tumor heterogeneity, hypoxia, off-target toxicity, and the need for robust redox biomarkers. A deeper understanding of tumor-specific redox vulnerabilities will be essential for developing precise and clinically effective ROS-oriented cancer therapies. Full article

Suffering and theodicy are two interconnected concepts: while the former indicates the embodied personal experience of pain, the latter represents the theological effort to explain the existence of suffering and evil by reconciling them with the idea of a world created by an omnipotent, omniscient, and infinitely good God. From a sociological perspective, the first scholar to address the problematic relationship between these two concepts was Max Weber. The problem of suffering in Weber was linked, first of all, to the process of social rationalization, that is, to the growing predominance of formal rationality in Western social life, the ultimate outcome of which he famously described through the metaphor of the “iron cage” as the existential suffering of modern Western humanity. Subsequently, in his Sociology of Religion, he adopted the concept of “disenchantment” to refer to the cultural rationalization of worldviews as a process characterizing most Asian religions within a broader universal perspective. According to Weber’s comparative investigation, at the origin of all attempts at religious rationalization lies the same universal problem of theodicy, namely the search for an explanation capable of justifying the unequal distribution of the goods of happiness among human beings and the resulting suffering, perceived as unjust. For Weber, the paradox of theodicy consists in the fact that the rationalization of thought (worldviews) and action (conducts of life), in an attempt to confer meaning on and alleviate suffering on the basis of one of the two conceptions of salvation (rebirth or redemption), instead produces the unintended consequence of making the human condition even more vulnerable to the experience of suffering, since it comes to be regarded as morally more outrageous and intellectually more unacceptable. Later, the founders of the Frankfurt School, Horkheimer and Adorno, essentially took up and expanded the Weberian thesis of the paradox of theodicy by showing that the second disenchantment brought about by modernity affected the rationalization of metaphysical–religious worldviews through the return of the irrational mythical–magical forces that had once been subjugated and turned into myth by the Enlightenment. As a consequence, the loss of individual freedom, reduced to a mere functional response within modern political and economic bureaucratic systems, comes to coincide with the loss of meaning of any autonomous cultural framework rationally grounded in value orientations. Habermas further developed Weber’s thesis of the loss of freedom by situating the process of social rationalization within a broader paradox that illustrates the contemporary inability of colonized lifeworlds, now completely bureaucratized and technicized, to confer meaning on the subjective experience of suffering. More recently, in the so-called Anthropocene, a non-linear and non-unidirectional dialectic of disenchantment and re-enchantment has emerged, in which the two coexist as constitutive processes of modernity, allowing the paradox of theodicy and suffering to be reconsidered in terms of a new anthropodicy. Full article

Polyploid giant cancer cells (PGCCs) are increasingly recognized as major drivers of therapy resistance and tumor relapse, yet the conserved molecular programs underlying their persistence remain incompletely defined. To identify genes consistently deregulated across eight independent datasets, we performed an integrative transcriptomic analysis of PGCCs derived from prostate, ovarian, and breast cancers. By focusing on consistently up- or down-regulated genes that were expressed in at least five datasets and showed a concordant direction of expression across more than 70% of datasets and met a significance threshold of adjusted p < 0.05, we defined the core regulatory architecture stabilizing the PGCC state under therapeutic stress. Our analysis reveals that PGCCs exhibit a paradoxical ranscriptomic signature consistent with cytolytic activity alongside reduced immune detection. These cells activated pro-inflammatory cytokine and chemokine signaling while simultaneously engaging immune-evasion mechanisms, including PD-L1-associated and virus-like escape programs. Concurrently, PGCCs displayed transcriptional features characteristic of immune-privileged cellular states, including embryonic development, reproductive programs, senescence-associated survival, apoptosis resistance, and deep dormancy marked by coordinated suppression of major housekeeping processes. Notably, PGCCs also activated neuronal differentiation and neurodegeneration-associated pathways, including axon guidance, neurogenesis, and calcium signaling. This neuron-like, calcium-dependent stress adaptation program may further enhance immune privilege and long-term survival capacity. We propose that PGCCs represent an immune-adaptive polyploid survival state in which inflammatory and ontogenetic pathways are repurposed to support immune evasion and tumor persistence. By identifying actionable vulnerabilities within calcium signaling, neuronal mimicry, and checkpoint-associated pathways, this study provides a framework for therapeutic strategies aimed at dismantling the PGCC reservoir and preventing tumor relapse. Full article

Precise short-term load forecasting is critical for smart grid reliability, yet the resilience of predictive models against ambient noise and sensor degradation remains insufficiently explored. This study systematically evaluates the noise sensitivity and operational stability of three forecasting paradigms (baseline LSTM, EEMD-LSTM, and CEEMD-LSTM) across varying signal-to-noise ratios (0–25 dB SNR) and sampling densities. Empirical analyses reveal a critical operational paradox: despite its theoretical sophistication, the CEEMD-LSTM architecture exhibits severe algorithmic instability and vulnerability to residual noise artifacts, yielding an RMSE standard deviation of ±1918 MW under high-fidelity conditions. Conversely, the EEMD-LSTM framework demonstrates superior robustness. Acting as an effective noise-mitigating filter, it sustains a Mean Absolute Percentage Error (MAPE) below 3.5% across all noise regimes, notably achieving sub-3.0% errors under severe interference (5 dB SNR). Furthermore, evaluating memory-optimized sparse sampling exposes a predictive trade-off, whereby reduced sampling density substantially exacerbates forecasting errors. These findings indicate that the EEMD-LSTM model, underpinned by dense sampling, provides a highly stable, noise-resilient predictive mechanism for smart grids subjected to uncertain measurements. Full article

Hypoxia and the evolving concept of pseudohypoxia are critical in driving tumor angiogenesis, contributing to malignancy progression and therapeutic resistance. Angiogenesis, a common feature of many solid tumors, is promoted by hypoxia-induced overexpression of pro-angiogenic factors (e.g., VEGF, FGF) and genetic mutations (e.g., VHL, SDH) that stabilize hypoxia-inducible factors (HIF) even in normal oxygen conditions, a phenomenon known as pseudohypoxia. Recent experimental studies challenge the view that hypoxia universally enhances vessel growth. In certain models, severe oxygen deprivation impairs angiogenesis. Furthermore, tumor-mediated metabolic reprogramming can drive immune evasion via HIF stabilization in immune cells. These paradoxes, together with persistent therapy resistance and the limited effectiveness of current anti-angiogenic treatments, reveal critical gaps in our understanding of how hypoxic signaling modulates vascular and immune dynamics within the tumor microenvironment. These complexities demand more detailed exploration of underlying processes and the development of innovative therapeutic strategies. Here, we review recent mechanistic studies on tumor angiogenesis, summarizing therapeutic and diagnostic advances from both preclinical and clinical studies. We further discuss strategies to exploit hypoxic vulnerabilities, including HIF inhibitors, hypoxia-activated prodrugs, vascular normalization, combination regimens to restore immunity, biomarker-guided patient selection, and advanced hypoxia-targeted imaging to improve outcomes in angiogenesis-driven cancers. Full article

This study examines whether the green transition alleviates or exacerbates poverty in developing countries, utilizing a dynamic panel dataset of 74 developing economies from 2000 to 2022. The paper investigates four key dimensions of the green transition: ecological footprints, green finance (proxied by public investment in renewable energy), renewable energy production, and renewable energy consumption. The findings reveal a compelling “green transition paradox”. While renewable energy production, green finance, and economic growth contribute significantly to poverty reduction, renewable energy consumption is adversely associated with higher poverty levels. This suggests that, in the absence of sufficient supply capacity and robust institutional support, the demand-side transition toward renewable energy may impose short-term economic burdens on vulnerable populations. Furthermore, ecological footprint exhibits a poverty-reducing effect, underscoring the reliance on resource-intensive economic expansion in developing economies, albeit with potential long-term environmental trade-offs. The results remain robust across alternative model specifications and exhibit heterogeneous across income and regional groups. The study contributes to the extant literature by disentangling the supply and demand mechanisms of renewable energy, thereby highlighting the complex distributional consequences of green transition policies. Ultimately, the policy implications emphasize the critical need to align renewable energy expansion with social protection, skill development, and inclusive financial frameworks to ensure that green transformation fosters both environmental sustainability and poverty alleviation. Full article