Search Results (507)

Hemp hurds (HHs), an underutilised lignocellulosic biomass from agricultural waste, offer potential for bioconversion into high-value bioproducts within a circular bioeconomy. Building on prior work involving magnetic nanoparticle-immobilised cellulase hydrolysis of pretreated HH, this study computationally designed candidate phaCAB expression constructs for cellulolytic hosts toward future PHB production. The objective was to evaluate, in silico, the feasibility of introducing the phaC1, phaA and phaB1 genes from Cupriavidus necator H16 (assembly GCA_000009285.2; loci H16_A1437–H16_A1439) into the cellulolytic hosts Clostridium thermocellum DSM 1313 and Trichoderma reesei RUT C-30. Coding sequences were retrieved and translated individually and host-specific expression compatibility was assessed via codon adaptation index, effective number of codons, GC content and rare-codon frequency/clustering. Host-specific architectures were designed: three independent tef1-promoter cassettes with fungal Kozak contexts and cbh1 terminators for T. reesei (TrePHB3 integration construct), and a single groEL-promoter operon with graded ribosome-binding sites for the pIKM1-based C. thermocellum construct (pCtPHB1); Escherichia coli BL21 (DE3)/pET-24a(+) served only as an intermediate assembly platform. Clustal Omega alignment, virtual plasmid assembly and simulated restriction digestion (SnapGene) confirmed preservation of the open reading frames and expected fragment sizes. ProtParam analysis indicated instability indices below 40 and negative GRAVY values for PhaC, PhaA and PhaB, indicating overall hydrophilic character. This computational framework links HH valorisation, cellulolytic CBP hosts and PHB pathway design within a conceptual biorefinery, supporting future integrated biomass-valorisation platforms; it is computational only and does not demonstrate transformation, expression, PHB accumulation or biomass conversion, which require experimental validation. Full article

Cancer stem cells (CSCs) drive therapeutic resistance, metastasis, and tumor recurrence through reversible transitions among stem-like, differentiated, epithelial, and mesenchymal states, which are sustained by interconnected epigenetic mechanisms. To our knowledge, this is the first review to integrate curcumin-mediated regulation of DNA methylation, chromatin remodeling, and non-coding RNAs within a single CSC plasticity framework and to propose the concept of an “epigenetic collapse of CSC plasticity” as a mechanistic explanation for how curcumin may weaken stemness, state switching, and adaptive treatment resistance. Evidence was critically evaluated through structured searches of PubMed/MEDLINE, Scopus, Web of Science Core Collection, Google Scholar, and citation tracking, while direct curcumin–epigenetic evidence was distinguished from independent CSC evidence and inferential mechanistic links. Curcumin has been reported to modulate DNMT1 and locus-specific DNA methylation; regulate HDACs, p300/CBP, EZH2, H3K27me3, and BMI1; and alter selected microRNA, long non-coding RNA, and circular RNA pathways, with comparatively stronger evidence involving the miR-34 family, miR-200c, miR-21, H19, and circHN1. However, current evidence is constrained by the predominance of bulk cancer-cell models, heterogeneous formulations and exposure conditions, and the scarcity of epigenetic rescue experiments combined with rigorous functional CSC assays. By unifying previously fragmented epigenetic evidence, this review advances a new evidence-weighted model in which curcumin may suppress CSC persistence not through a single molecular target, but by destabilizing the multilayer epigenetic circuitry that enables plasticity. Curcumin should therefore be regarded as a context-dependent, multilayer epigenetic modulator rather than an established CSC-eradicating therapy, and its translational relevance requires validation in prospectively defined CSC models with pharmacologically justified delivery and exposure conditions. Full article

Cardiac rhythm and pumping function are essential outputs of cardiac homeostasis and depend on precise molecular regulation. The histone acetyltransferases CBP/p300 have been implicated in cardiac remodeling and functional regulation. nej, the Drosophila homolog of CBP/p300, may therefore represent an important regulator of cardiac function. However, the relationship between miR-276a and nej in the heart, as well as the potential involvement of the fat body in this regulatory relationship, remains unclear. Using Drosophila as a model, we first examined the effects of cardiac-specific nej overexpression and knockdown on cardiac function and tested the interaction between miR-276a and the nej 3′ untranslated region using a dual-luciferase reporter assay. We subsequently manipulated miR-276a using Hand-Gal4 and Cg-Gal4 and assessed miR-276a and nej expression in cardiac samples, cardiac function, and climbing ability. Finally, we investigated the effects of an exercise intervention on cardiac miR-276a/nej expression and functional outcomes. Both cardiac-specific overexpression and knockdown of nej impaired cardiac rhythm, reduced pumping function, and decreased climbing ability. The reporter assay supported a functional interaction between miR-276a and the nej 3′ untranslated region, while cardiac-specific miR-276a manipulation was accompanied by inverse changes in nej mRNA expression and by cardiac and climbing abnormalities. Cg-Gal4-mediated miR-276a upregulation or downregulation was associated with altered miR-276a and nej expression in cardiac samples and with cardiac and climbing impairments. Exercise improved cardiac and climbing ability in both cardiac miR-276a knockdown and overexpression groups. It increased cardiac miR-276a expression and decreased nej expression in the cardiac knockdown group but did not significantly alter either transcript in the cardiac overexpression group. Exercise also improved cardiac function in both Cg-Gal4-mediated miR-276a knockdown and overexpression groups. In the Cg-Gal4-mediated knockdown group, this improvement was accompanied by increased miR-276a and decreased nej expression in cardiac samples. These findings indicate that exercise modulates cardiac function and miR-276a/nej expression in a context-dependent manner and suggests a possible contribution of the fat body. Full article

Urban and regional planning has shifted from state-centric models toward relational, vision-based paradigms that emphasize functional spaces over fixed boundaries. In the Gulf Cooperation Council (GCC) region, cross-border planning (CBP) is gaining strategic relevance driven by national economic diversification strategies, transboundary environmental challenges, and mega-infrastructure projects. Applying a comprehensive framework across five analytical dimensions, socio-economic, social, geopolitical, spatial, and environmental, this paper examines the conceptual foundations, governance typologies, and empirical realities of regional integration. While global benchmarks like the European Union offer mature examples of institutionalized multilevel governance, GCC initiatives face unique challenges. Although spatial and socio-economic integration is advancing through projects like the GCC Railway Network, the King Fahd Causeway, and the GCC Interconnection Authority regional grid, development is frequently constrained by national sovereignty priorities, procedural friction, and implementation asymmetries. To optimize transnational corridors under Saudi Vision 2030, this study recommends delineating functional cross-border regions, establishing permanent corridor governance cells, resolving border friction through digital integration, and institutionalizing a GCC-wide planning observatory. The study’s principal original contribution is a unified five-dimensional analytical framework (socio-economic, social, geopolitical, spatial, and environmental) that is operationalized as an evaluative lens and applied consistently across global, regional, and national cases, together with an accompanying governance typology and a sequenced implementation model tailored to the sovereignty-sensitive GCC context. Full article

2,4-Dichlorophenoxyacetic acid (2,4-D), originally developed as a synthetic auxinic herbicide, is the most widely used chemical inducer of somatic embryogenesis (SE) in plants. Despite extensive use of 2,4-D in plant regeneration, the systems-level regulatory mechanisms connecting hormonal signaling, metabolic reprogramming, translational control, and embryogenic competence remain poorly resolved. Here, we hypothesize that TOR signaling functions as an integrative molecular hub coordinating transcriptional, metabolic, and developmental reprogramming during somatic embryogenesis induction. To investigate the molecular regulatory landscape associated with 2,4-D-induced SE, we performed a systems-level analysis integrating publicly available transcriptomic data from Arabidopsis thaliana with high-confidence protein–protein interaction (PPI) network analyses using STRING v12.0 (confidence score ≥ 0.900). Using a previously published transcriptomic dataset, we identified 1927 upregulated genes associated with SE induction, which were organized into 34 functional modules related to transcriptional regulation, translation metabolism, hormone signaling and cellular homeostasis. Within this interactome, TARGET OF RAPAMYCIN (TOR) kinase emerged as an integrative regulatory hub associated with multiple pathways involved in embryogenic reprogramming. Network analyses revealed three major TOR-associated regulatory axes: (1) the TOR–FKBP12–RPS6A axis, associated with ribosome biogenesis and translational regulation; (2) the TOR–CBP20 axis, connected with transcriptional reprogramming; SE master regulators (LEC1, LEC2, and FUS3); and lipid, sterol, brassinosteroid (BR), and auxin-associated pathways; and (3) the TOR–TAP46 axis, linked with one-carbon metabolism, nucleotide biosynthesis, DNA replication and repair, and genome-stability pathways. Additionally, the network contained 411 embryo-lethal (EMBL) genes distributed across multiple regulatory modules, reinforcing the biological relevance of the identified interactome and highlighting the importance of coordinated developmental, metabolic, and transcriptional regulation during embryogenesis induction. These findings support a systems-level TOR-associated regulatory framework involved in the integration of transcriptional, translational, metabolic, hormonal, and genome-maintenance pathways during embryogenesis. This interactome model provides a foundation for functional studies aimed at dissecting the molecular mechanisms underlying SE and identifying candidate targets to improve regeneration and biotechnological application and crop genetic engineering. Collectively, this study proposes a mechanistic framework in which TOR signaling integrates developmental, metabolic, translational, and genome-stability pathways to orchestrate embryogenic competence, providing candidate molecular targets for improving plant regeneration and genome engineering platforms. Full article

Breast cancer is a highly heterogeneous malignancy with multiple molecular subtypes and variable treatment responses. Despite advances in endocrine therapy, HER2-targeted therapy, chemotherapy, and immunotherapy, treatment resistance and disease recurrence remain major clinical challenges. There is growing evidence that transcriptional plasticity and enhancer relinking contribute to tumor progression and treatment adaptation, highlighting the powerful role of epigenetic regulators. CREB-binding protein (CBP) and E1A-associated protein p300 (EP300) are transcriptional coactivators that regulate breast cancer enhancer activity and lineage-specific gene expression. Emerging research suggests that CBP/p300 is more of a context-dependent vulnerability point than a universal carcinogenic driver. ER-positive tumors exhibit a strong dependence on CBP/p300-mediated transcriptional programs, while the triple-negative breast cancer subgroup, including androgen receptor-positive and immunosuppressive tumors, may rely on CBP/p300-dependent signaling to maintain survival and treatment resistance. This is in contrast to their role in HER2-positive breast cancer. This review summarizes the biological functions of CBP/p300 in breast cancer and discusses subtype-specific vulnerability, biomarker-directed patient stratification, drug resistance mechanisms, rational combination strategies, and current translational challenges, emphasizing the need for precise treatment of breast cancer. Full article

Testicular receptor 4 (TR4, NR2C2) is an orphan nuclear receptor involved in the regulation of metabolism, inflammation, cardiovascular disease, and cancer. Accumulating evidence indicates that TR4 exhibits functional plasticity, exerting protective or pathogenic effects depending on tissue and disease context, and sometimes displaying opposing roles within the same disease. However, the mechanisms underlying this functional duality remain poorly understood. Recent studies indicate that TR4 activity is determined not only by the receptor itself but also by dynamic coregulatory networks. Through interactions with coactivators, corepressors, epigenetic regulators, and environmental signaling pathways, TR4 integrates metabolic cues to generate context-dependent transcriptional programs. Coactivator networks centered on PGC-1α, steroid receptor coactivator (SRC) family members, and CBP/p300 support oxidative metabolism and anti-inflammatory responses, whereas RIP140-, NCoR/SMRT-, and HDAC-associated networks promote lipid accumulation, chronic inflammation, fibrosis, and tumor progression. Regulators such as JAZF1 further influence TR4 activity by reshaping coregulator recruitment and target-gene selection. In this review, we summarize the structural basis of TR4 regulation and discuss how coregulatory network remodeling governs its functions in metabolic, cardiovascular, inflammatory, and malignant diseases. We propose that TR4 functions as a context-dependent transcriptional platform whose activities are defined by its coregulatory landscape, providing a framework for precision therapies. Full article

(1) Background: Reactive oxygen species (ROS) act as physiological signaling mediators but contribute to oxidative damage, cellular dysfunction, and age-related disease when redox homeostasis fails. Forkhead box O4 (FOXO4) has emerged as a redox-sensitive regulator linking stress adaptation, antioxidant defense, and cellular senescence. This structured narrative review critically evaluates which redox- and aging-related conclusions are supported directly for FOXO4 and which remain inferred from other FOXO isoforms. (2) Methods: PubMed/MEDLINE, Scopus, and Web of Science were searched from inception to May 2026; Google Scholar was used only for supplementary citation tracking and did not contribute a separate platform-level count. Of 420 records, 300 remained after deduplication, 110 full texts were assessed, and 89 publications were retained. FOXO4-related evidence was classified as directly FOXO4-specific (n = 18), FOXO-family/conserved (n = 24), or extrapolated predominantly from FOXO1/FOXO3/DAF-16 (n = 20); 27 contextual publications on redox biology, senescence, disease, and NRF2 were tracked separately. (3) Results: The strongest FOXO4-specific evidence supports three mechanistic axes: cysteine-dependent redox sensing, stress-regulated nuclear trafficking and coactivator engagement through transportin-1 and p300/CBP, and FOXO4–p53-mediated survival of senescent cells. By contrast, direct FOXO4 regulation of commonly cited antioxidant targets, including SOD2, catalase, sestrins, and GADD45, remains insufficiently demonstrated and is inferred mainly from FOXO3 or broader FOXO-family studies. FOXO4-DRI has shown senolytic activity in preclinical models, including vascular endothelium, but has not been clinically validated. (4) Conclusions: FOXO4 is a redox-responsive transcriptional regulator with well-supported roles in cysteine-based signaling and senescent-cell survival, whereas its target-gene-level antioxidant program remains incompletely resolved. Clinical translation of FOXO4–p53 disruption requires isoform- and tissue-specific validation, pharmacokinetic and delivery studies, long-term toxicology, and explicit assessment of p53-dependent tumor surveillance. Full article

This paper proposes a regional distributed energy operation framework that integrates Power-to-X (P2X)-based sector coupling with Distributionally Robust Optimization (DRO) for distribution network operation environments in special zones established under South Korea’s Special Act on the Promotion of Distributed Energy. The conventional South Korean electricity market has primarily operated under a centralized Cost-Based Pool (CBP) structure, where the participation of small-scale renewable energy providers has been limited due to requirements for centralized dispatch generators. To address these structural limitations, the South Korean government introduced the distributed energy special zone policy and has promoted a Peer-to-Peer (P2P)-based electricity trading mechanism that enables direct electricity transactions between renewable energy providers and consumers within regional distribution networks. As a result of these policy initiatives, investment in small-scale renewable energy projects within designated special zones is expected to increase significantly; however, the limited local demand capacity of regional distribution networks simultaneously imposes clear constraints on the accommodation of renewable energy. Therefore, this study applies P2X-based sector coupling technologies to improve the capability to accommodate renewable energy within special zones while simultaneously establishing new energy business models. In addition, DRO is incorporated into the proposed framework to demonstrate the system’s economic feasibility and operational robustness under high uncertainty in electricity prices. Full article

Chronic hepatitis B virus (HBV) infection remains one of the main causes of hepatocellular carcinoma (HCC), even though vaccination and long-term viral suppression have reduced new infections and circulating viral replication. This residual cancer risk suggests that serum HBV DNA alone does not capture the full biology of HBV-related carcinogenesis. Hepatitis B virus X protein (HBx) is a relevant entry point because it maintains the transcriptional competence of covalently closed circular DNA (cccDNA), engages host chromatin regulators, and may persist in tumors as cccDNA-derived, integration-derived, full-length, truncated, or fusion forms. This review focuses on a specific question: does the available literature support HBx-associated reactivation of the IGF2 locus in chronic HBV infection and HBV-related hepatocarcinogenesis, and, if so, at which regulatory layer is the claim defensible? The most direct evidence remains promoter-proximal. Classic mechanistic work shows acute HBx-dependent activation of IGF2 promoter P4 through Sp1- and PKC/ERK-dependent signaling. Human tissue and cell-based studies also support a broader fetal-promoter compartment, including P3/P4 transcript enrichment, local promoter hypomethylation, MBD2-HBx-CBP/p300 recruitment, and increased histone H3/H4 acetylation. These observations do not, however, establish HBV exclusivity, uniform loss of imprinting, or direct HBx-mediated rewiring of the human IGF2/H19 topological domain. Recent integration-aware and long-read studies further argue against treating tumor-stage HBx as a single biological variable. In the present evidence framework, HBx-associated IGF2 locus reactivation is therefore more appropriately viewed as a stage-aware, promoter-resolved, biomarker-oriented hypothesis than as a universal mechanism or a treatment algorithm for HBV-related HCC. Full article

Consolidated bioprocessing (CBP) is difficult to monitor because enzyme production, lignocellulose degradation, sugar release, and fermentation occur simultaneously under sparse measurement, feedstock variability, and plant–model mismatch conditions. This study proposes a computational sensor-set design framework for digital-twin-assisted CBP monitoring. A five-state virtual plant, consisting of active biomass, cellulolytic enzyme activity, residual insoluble substrate, soluble sugar, and ethanol, was used to evaluate all 16 ethanol-mandatory measurement packages formed from ethanol, sugar, biomass, enzyme, and residual-substrate proxy channels. Candidate sensor sets were assessed using finite-difference output sensitivities, Fisher-information-based state-observability and parameter-identifiability analyses, eigenvalue and parameter-correlation diagnostics, and paired Monte Carlo unscented Kalman filter soft-sensing reconstruction. Within the tested five-state virtual-plant benchmark and with the specified excitation schedule, noise assumptions, burden indices, and scoring objective, ethanol-only sensing provided the weakest support for state-aware CBP digital-twin reconstruction. At a $6\mathrm{h}$ sampling interval, the state-observability log-pseudodeterminant increased from 4.18 with ethanol-only sensing to 8.56 after adding soluble sugar and to 16.42 with full-proxy monitoring. The ethanol–sugar–biomass–substrate package also gave strong reduced state-observability performance, with log-pseudodeterminants of 15.12, 13.76, and 12.51 at 6, 12, and $24\mathrm{h}$, respectively. Biomass and enzyme proxies contributed strongly to parameter learning, and the ethanol–sugar–biomass–enzyme package gave the strongest active parameter-identifiability performance, with log-pseudodeterminants of 10.82, 9.06, and 6.67 at 6, 12, and $24\mathrm{h}$, respectively. In the paired soft-sensing analysis, full-proxy monitoring reduced the mean latent-state RMSE from 1.1899 to 0.3756, followed by ethanol–biomass–enzyme–substrate with 0.3843 and ethanol–sugar–biomass–substrate with 0.4121. The primary aggregate ranking identified ethanol–sugar–biomass–substrate as the best overall package, with a sensor-value score of 0.8432 and a burden index of 7.0, followed by full-proxy monitoring with a score of 0.8173 and a burden index of 10.0. Robustness tests showed that ethanol–sugar–biomass–substrate remained top-ranked under uniform noise scaling, full UKF missingness, delay and bias stress test conditions, most scoring-weight scenarios, and all tested sensor-specific burden workflows. Full-proxy monitoring remained a close competitor under independent sensor-specific noise variation conditions and became top-ranked for some alternative operating trajectories. The proposed framework provides a simulation-based method for prioritizing informative measurement packages before implementing CBP digital twins in laboratory and pilot-plant settings. Full article

Recently, the problem of food waste management has attracted the attention of producers, processors, retailers, and consumers due to economic, environmental, food safety, and sustainability consequences, affecting the entire food supply chain. This article reviews data on food waste of animal origin at different stages along the production and transformation systems, from an environmental, economic, or social perspective. Results show differences between developed and developing countries. While in developed countries, most waste occurs at the end of the food chain, in developing countries, most waste occurs in primary production and transportation. Food waste is very expressive in production and retail, but also in final consumption in households and food services. Mitigating measures include upcycling, i.e., recovering valuable food components for industrial use with economic and environmental benefits, and alternatives for food waste reutilization. The role of the consumer is unquestionable, particularly when shopping for food for the household or when consuming food in restaurants or canteens. Hence, it is crucial to understand the behaviours leading to food waste as a way to reduce it and implement strategies to effectively reduce food waste at various levels. The role of education, regulation, and policies is pivotal in achieving minimal food waste. Full article

Nuclear factor erythroid 2-related factor 2 (NRF2) has traditionally been framed as a Kelch-like ECH-associated protein 1 (KEAP1)-regulated stress-response transcription factor, but three observations now require a broader framework: NRF2 turnover is controlled by parallel E3 ligase systems; transcriptional output can be limited by coactivator assembly despite unchanged NRF2 abundance; and NRF2 activation can be beneficial or harmful depending on disease context, as illustrated by lung cancer models in which NRF2 paradoxically promotes metastasis through BTB and CNC homology 1 (BACH1) stabilization. We synthesize these observations into an NRF2 partner-code framework in which NRF2 acts as a context-dependent transcriptional platform assembled through four partly independent modules: a degradation module (KEAP1; β-transducin repeat-containing protein, β-TrCP; HMG-CoA reductase degradation protein 1/synoviolin 1, Hrd1/SYVN1; WD repeat-containing protein 23/DDB1- and CUL4-associated factor 11, WDR23/DCAF11); a cytoplasmic scaffold module (p62/sequestosome 1, p62/SQSTM1; IQ motif-containing GTPase-activating protein 1, IQGAP1; type I phosphatidylinositol 4-phosphate 5-kinase γ/heat shock protein 27, PIPKIγ–HSP27; peptidyl-prolyl cis-trans isomerase NIMA-interacting 1, PIN1; peptidyl-prolyl isomerase A/cyclophilin A, PPIA); a nuclear coactivator module at Neh4/5 (CREB-binding protein/p300, CBP/p300; receptor-associated coactivator 3/steroid receptor coactivator 3, RAC3/SRC-3; protein arginine methyltransferase 1/coactivator-associated arginine methyltransferase 1, PRMT1/CARM1; Mediator complex subunit 16, MED16); and a DNA/chromatin module at Neh1 (small musculoaponeurotic fibrosarcoma [Maf] proteins, BACH1, and chromodomain helicase DNA-binding protein 6, CHD6). Mapping 22 partners onto the Neh-domain architecture identifies approximately 25 pharmacologically addressable interfaces, stratified into four translational tiers. The framework reframes NRF2 pharmacology around one principle: the most actionable target is often a partner rather than NRF2 itself, with disease context dictating the direction of modulation. We close with five testable hypotheses and a partner-code decision matrix linking disease, biomarker, and candidate target. Full article

Background: Macrophage pyroptosis contributes substantially to sepsis-induced lung injury, yet effective therapeutic strategies remain limited. This study aimed to determine the protective effects of meloxicam, a non-steroidal anti-inflammatory drug, and the underlying mechanisms in this context. Methods:In vivo, CLP mice were treated with meloxicam (20 mg/kg). In vitro, LPS-primed macrophages were stimulated with ATP or nigericin in the presence or absence of meloxicam. Levels of pyroptosis-associated proteins (cleaved Caspase-1, mature IL-1β, GSDMD-NT), NLRP3 inflammasome assembly, and the CBP/TXNIP/p38 signaling axis were assessed by Western blot. Mitochondrial membrane potential (ΔΨm) and intracellular ROS were measured. Overexpression of COX-2, TXNIP, and CBP was also performed. Results: Meloxicam significantly improved survival, reduced lung injury, and suppressed pyroptosis-associated proteins in CLP mice. In vitro, meloxicam dose-dependently enhanced macrophage viability and reduced LDH, IL-1β, and IL-18 release. The protective effects of meloxicam were mediated by inhibition of NLRP3 inflammasome priming and assembly, disruption of NLRP3-ASC-pro-Caspase-1 complex formation, and suppression of ASC oligomerization. Meloxicam also inhibited the CBP/TXNIP/p38 axis, an effect reversed by TXNIP or CBP overexpression. Furthermore, meloxicam restored ΔΨm and reduced ROS accumulation; these effects were abrogated by the ROS inducer imiquimod. Importantly, the anti-pyroptotic effects of meloxicam were independent of COX-2 inhibition. Conclusions: These findings expand the pharmacological profile of meloxicam and support its repurposing as a therapeutic agent for sepsis-associated lung injury. Full article

Slug test interpretation can fail when measured recovery follows a time scale that differs from the classical Cooper–Bredehoeft–Papadopulos (CBP) finite-diameter well solution. This study derives a conformable slug test formulation by showing that a local weighted derivative converts the governing problem into the classical solution evaluated in transformed time. The formulation therefore does not introduce a nonlocal memory kernel; instead, it provides a reproducible diagnostic with one fitted exponent for testing power law time scaling while retaining the finite-diameter wellbore storage boundary condition. The solution is evaluated using double-precision Stehfest numerical inversion with 12 terms and is verified by the exact classical limit and by sensitivity tests on the number of inversion terms. Type curves, Morris sensitivity indices, objective function slices, synthetic benchmarks, and measured slug test data from the Minnelusa and Madison aquifer system near Spearfish, South Dakota, are used to evaluate the added exponent. A benchmark with an exponent above one recovered fitted exponents of 1.397 without noise and 1.417 under Gaussian noise with a standard deviation of 0.01. Field fitting over exponents from 0.5 to 2.0 reduces root mean square error and information criteria relative to the classical model for the analyzed datasets, especially the LA-88B pressure tests. However, exponents above one are interpreted only as accelerated transformed time behavior, not as conventional fractional orders or unique physical mechanisms. Comparison with a published semi-analytical slug test model that represents near-well formation damage and non-Darcy flow for the same field dataset supports using the conformable exponent as a diagnostic indicator of time-scale mismatch alongside mechanistic slug test models. Full article