Search Results (1,122)

Background: Cancer progression is driven by coordinated dysregulation of intracellular transport, proteostasis, and extracellular matrix remodeling. Therapeutic strategies targeting a single pathway often fail due to tumor adaptability and resistance. Drug repurposing offers a promising approach to identify multi-target anticancer agents with established safety profiles. Pimozide, an FDA-approved antipsychotic drug, has recently emerged as a candidate with potential anticancer activity, although its molecular mechanisms remain incompletely understood. Objectives: This study aimed to investigate the anticancer effects of pimozide across breast, colorectal, and pancreatic cancer models, with a specific focus on its modulation of Ran GTPase signaling, Skp1–Cullin–F-box (SCF) ubiquitin ligase components, and matrix metalloproteinase-2–mediated extracellular matrix remodeling. Methods: Cell viability was assessed using MTT assays in MDA-MB-231, MCF-7, HT-29, and PanC-1 cell lines. Quantitative real-time polymerase chain reaction was employed to evaluate the expression of Ran, MMP2, Cullin1, Rbx1, SKP2, and FBXW10 following pimozide treatment. Molecular docking and MMGBSA analyses were performed to characterize binding interactions between pimozide and selected target proteins. Results: Pimozide induced concentration-dependent cytotoxicity in all tested cell lines with variable IC₅₀ values. Treatment resulted in consistent downregulation of Ran and MMP-2 across cancer types, alongside context-dependent modulation of SCF complex components. Notably, FBXW10 exhibited the strongest binding affinity to pimozide in silico, suggesting functional disruption of ubiquitin-mediated proteostasis. Conclusions: Pimozide exerts anticancer effects through coordinated disruption of nucleocytoplasmic transport, proteostasis regulation, and matrix remodeling. These findings support the repositioning of pimozide as a multi-target anticancer agent and provide a mechanistic foundation for further translational investigation. Full article

Under complex or harsh environmental conditions, single-data modeling approaches for photovoltaic (PV) cells often fall short in terms of accuracy. To overcome this limitation, this study proposes a hybrid Transformer–BiLSTM framework to model photovoltaic (PV) modules, addressing the limitations of traditional single-model approaches. By leveraging the Transformer’s global attention mechanism and BiLSTM (Bidirectional Long Short-Term Memory)’s ability to capture local dependencies, this hybrid model provides enhanced accuracy and generalization for PV module output prediction under various environmental conditions. We construct a multi-type PV module dataset based on real I–V characteristic data from the U.S. National Renewable Energy Laboratory (NREL), applying K-means++ clustering for data preprocessing. Comparative experiments against standalone models (Transformer, BiLSTM, SVM (Support Vector Machine)) and a Transformer–SVM hybrid demonstrate that the proposed model consistently achieves a coefficient of determination (R²) exceeding 0.989 on both training and testing datasets, significantly outperforming standalone Transformer, BiLSTM, SVM, and Transformer–SVM models. Full article

Background: Cutaneous squamous cell carcinoma (cSCC) represents one of the most common keratinocyte-derived malignancies encountered in clinical practice; however, its genomic landscape remains far less comprehensively characterized than that of other cutaneous cancers. This study aims to identify key molecular drivers and potential therapeutic targets by comprehensively characterizing the genomic landscape of cSCC using data from the American Association for Cancer Research (AACR) Project Genomics, Evidence, Neoplasia, Information, Exchange (GENIE) consortium. Methods: A retrospective cohort analysis of cSCC samples was performed utilizing AACR Project GENIE data accessed via the cBioPortal platform (v18.0-public) on 22 November 2025. Analyses included identification of recurrent somatic and copy-number alterations, pairwise gene–gene co-occurrence testing using Fisher’s exact tests with Benjamini–Hochberg False Discovery Rate (FDR) correction, and exploratory subgroup comparisons by sex and race, with statistical significance defined as p < 0.05. Results: Recurrent mutations were identified in TP53 (83.5%), NOTCH1 (56.3%), KMT2D (47.0%), CDKN2A (44.4%), TERT (41.4%), ROS1 (34.3%), FAT1 (33.3%), NOTCH2 (31.2%), ERBB4 (28.4%), and KMT2A (24.3%), reflecting disruption of the p53 pathway, cell-cycle control, Notch signaling, epigenetic regulation, telomere maintenance, RTK/MAPK pathways, and Wnt signaling. Statistically significant co-occurrence patterns were observed, and exploratory subgroup analyses evaluated mutation frequency differences by sex and race. Conclusions: This large, multi-institutional genomic analysis defines recurrent mutational and structural alterations in cSCC and highlights an integrated pattern of pathway disruption involving genomic integrity, differentiation, epigenetic control, and proliferative signaling. These findings enhance current understandings of the molecular architecture underlying this common yet genomically understudied malignancy and provide a foundation for future mechanistic studies and development of targeted diagnostic and therapeutic strategies. Full article

Latent tuberculosis infection (LTBI) represents a major global health concern as it constitutes the principal reservoir for future tuberculosis (TB) disease. Its identification is particularly important in Bacille Calmette–Guérin (BCG)-vaccinated populations, where cross-reactivity of purified protein derivative limits the specificity of the tuberculin skin test and hampers targeted preventive therapy. Early Mycobacterium tuberculosis antigens encoded within the RD1 region, especially ESAT-6, CFP-10 and TB7.7, have enabled the development of antigen-specific interferon-gamma release assays (IGRAs) and recombinant skin tests with improved BCG-independent specificity. This narrative review integrates and critically appraises current evidence on the immunobiological properties of early and latency-associated antigens, the cellular mechanisms underlying T-cell-dependent immune reactivity, and the diagnostic performance of IGRAs and ESAT-6/CFP-10-based skin tests, rather than merely summarizing individual studies. Although these platforms rely on different assay principles (in vitro cytokine release versus in vivo delayed-type hypersensitivity), both measure antigen-specific T-cell memory and do not define the biological stage of infection or reliably distinguish latent from incipient or active TB. Across most adult populations, IGRAs demonstrate high specificity and acceptable sensitivity, whereas reduced sensitivity and higher rates of indeterminate results are observed in young children and immunocompromised individuals. ESAT-6/CFP-10-based skin tests show diagnostic accuracy comparable to IGRAs and may offer operational advantages in resource-limited settings. Latency-associated antigens and host biomarkers such as IP-10, together with multi-analyte immune signatures, represent promising avenues for improving diagnostic sensitivity and prognostic stratification but currently lack sufficient validation for routine clinical use. Overall, RD1-encoded antigens remain central to LTBI immunodiagnosis, while future research should focus on developing stage-resolving and prognostic biomarkers, optimized antigen panels, and standardized interpretive frameworks. Full article

Objective: This study aimed to identify clinically relevant regulators of pancreatic ductal adenocarcinoma (PDAC), a disease characterized by stromal remodeling and immune suppression, and to define their links to malignant progression and microenvironmental reprogramming. Methods: We integrated multi-cohort bulk, single-cell, and spatial transcriptomic datasets and subsequently validated bulk differential expression and network analyses with machine learning-based prioritization in an independent combined cohort (TCGA-PAAD plus GSE62452). Single-cell mapping was used to assess cell-type specificity, positioning candidates along inferCNV- and pseudotime-defined malignant continua. In Visium sections, a DKK1-associated program score quantified intratumoral spatial heterogeneity and informed our analyses of ligand–receptor communication. Bulk immune deconvolution linked gene levels to immune infiltration patterns, and functional assays were used to test the impact of DKK1 knockdown on migration, proliferation, clonogenic growth, and apoptosis in PDAC cells. Results: Four reproducible tumor-associated genes—DKK1, COL10A1, SULF1, and SLC24A3—were prioritized and validated externally. DKK1 was predominantly expressed by epithelial tumor cells and tracked along a malignant progression continuum. Spatially, the DKK1 program localized to epithelial-dominant regions, revealed pronounced intratumoral heterogeneity, and highlighted epithelial–endothelial and endothelial–immune signaling in high-score areas. Immune deconvolution associated higher DKK1 expression with increased myeloid infiltration and reduced cytotoxic lymphocyte signatures. Functionally, DKK1 knockdown impaired migration, proliferation, and clonogenicity while increasing apoptosis. Conclusions: We demonstrate that DKK1 is an epithelial-derived regulator linked to malignant progression and tumor–stroma–immune remodeling, supporting its potential as a biomarker and therapeutic target in PDAC treatment, including rational combinations with stroma-modulating strategies and immunotherapy. Full article

Background: Limited data inform the outcomes of patients with high-risk neuroblastoma (HR-NBL) who relapse after high-dose chemotherapy, autologous stem cell transplantation (ASCT), and external beam radiotherapy (EBRT). Methods: This is a multi-institutional retrospective study of 84 patients with HR-NBL diagnosed between 1997–2021 with a first recurrence after definitive upfront treatment, including ≥1 ASCT and EBRT. Site(s) of first relapse were defined with relation to a patient’s primary tumor location. Progression-free survival (PFS) and overall survival (OS) outcomes were analyzed using Kaplan–Meier curves and log-rank tests. Cox proportional hazard models were used for univariate and multivariable analyses. Results: Twenty-four patients had local recurrences with or without distant relapses (LR) and 60 had distant relapses only. The LR cohort had higher rates of MYCN amplification (70% vs. 36%, p = 0.016). At relapse, the LR cohort had lower rates of additional radiotherapy (32% vs. 61%, p = 0.029) and higher rates of additional surgery (29% vs. 5%, p = 0.005), with similar rates of chemotherapy for both cohorts. With a median follow-up after first relapse of 1.53 years (range: 0.03–15.82), there were no significant differences in interval PFS and OS between the cohorts. After controlling for age at diagnosis and pattern of recurrence, time to interval relapse ≥ 2 years was a significant predictor of improved OS (HR: 0.50, 95% CI: 0.29–0.85, p = 0.011). Conclusions: Patients with relapsed HR-NBL have poor outcomes with median OS < 2 years. Time to relapse was a significant predictor of OS. Full article

Background: Dry eye disease (DED) is characterized by tear film instability and a hyperosmolar ocular surface, which significantly impacts ocular health. Artificial tear solutions (ATSs) have been effective frontline treatments for DED, yet current commercially available products often provide only temporary relief, necessitating frequent daily administration. Significant efforts have been made to develop next-generation ATSs that can provide prolonged protective effects for DED. High-molecular-weight sodium hyaluronate (HA) is more commonly used in multi-dose preservative ATSs due to its longer chain lengths and rheological properties that can provide an enhanced retention time and clinical comfort and effects. The current methods to evaluate ATSs have largely focused on human biocompatibility and rheological testing and often overlook the dynamic nature of cellular phenotypes or the protective mechanisms at a cellular level. Therefore, this study developed novel in vitro mammalian cell assays involving human corneal epithelial cells (HCECs) to comprehensively assess ATSs with HA for biocompatibility and efficacy. Methods: We evaluated cellular viability across varying severities in two distinct DED models: desiccation and hyperosmotic stress. Simultaneously, time-lapse imaging coupled with computational image analyses quantified subtle, yet significant, cellular morphological changes under these stress condition. Results: Our assays revealed that ATSs provide significant, yet varying, protection against mild, medium, and harsh desiccation stress, as well as hyperosmotic conditions. This study also made a key insight that was the observation that DED conditions induce drastic HCEC morphological changes, including significant cellular monolayer breakage, which were effectively mitigated by the ATS products used in this work. Conclusions: The assays presented here provide a robust standard for ATS testing, ultimately guiding the selection of more effective next-generation therapies and aiding in a greater understanding of DED pathogenesis. Full article

Sulfide-bearing iron oxide deposits consisting of magnetite and silicates are common within the greenstones of north-west Finland and northern Sweden. These iron oxide deposits have variable copper, gold, and uranium content and occur in association with tuffite, black schist, and dolomitic marble. The deposits have a resource size of up to 145 Mt and an iron content of 35%–50% (e.g., Stora Sahavaara). The total sulfur content of these deposits is typically in the range of 1%–5% but can have exceptional values up to 20.8%, and disseminated pyrite, pyrrhotite, and chalcopyrite are commonly present. The prediction of acid rock drainage and metal leaching potential requires a detailed understanding of the site-specific rates and mechanisms of weathering. This has been obtained through geochemical (multi-element analysis and acid–base accounting) and mineralogical characterization testing undertaken on representative materials, including multi-element analysis, acid–base accounting, net acid generation testing, and humidity cell testing. Despite the high sulfide content and low neutralizing potential of most rock types found in these deposits, the humidity cell tests showed a delayed onset to acid generation, which is primarily attributed to sulfide crystallinity and mafic silicate dissolution leading to slow oxidation and reaction rates. The need for long-term kinetic testing is evident from the Hannukainen amphibole and schist rock types. This study provides an overview of the environmental geochemistry of the skarn-hosted sulfide-bearing iron oxide deposits in Scandinavia. These deposits show potential for acid generation but due to the buffering reactivity of mafic silicates and the high crystallinity of the sulfides, the rate of acid generation is slow and the onset of these conditions delayed by mineral buffering. Full article

Aberrant glycosylation is linked to several diseases, making glycoproteins and their glycoforms promising biomarkers. Traditional methods like mass spectrometry offer high sensitivity but are costly, time-consuming, and unsuitable for point-of-care testing. Electrochemical biosensors emerge as an attractive alternative due to their simplicity, affordability, portability, and rapid response. This review focuses on electrochemical strategies developed to assess the glycosylation level of a specific glycoprotein or biological structure rather than merely glycoprotein or cell concentration, as in previous reviews. Approaches include the use of aptamers, boronic acid derivatives, antibodies, and lectins, often combined with nanomaterials for enhanced sensitivity. Applications span the diagnosis/prognosis of several illnesses such as diabetes, congenital disorders of glycosylation, cancer, and neurodegenerative diseases. Innovative designs incorporate microfluidic and paper-based platforms for faster, low-cost analysis, while strategies using dual-signal acquisition or competitive assays improve accuracy. Despite promising sensitivity and selectivity, most sensors require multi-step protocols and lack of validation in clinical samples. Future research should focus on simplifying procedures, integrating microfluidics, and exploring novel capture or detection probes such as metal complexes or metal–organic frameworks. Overall, electrochemical sensors hold significant potential for point-of-care testing, enabling rapid and precise evaluation of glycosylation status, which could drive cell-based biomarker discovery and disease diagnostics. Full article

Thyroid cancer is the most common type of endocrine cancer. Most cases are called differentiated thyroid cancer (DTC), which includes papillary, follicular, and hurthle cell types. DTC usually grows slowly and has a good prognosis, especially when found early and treated with surgery, radioactive iodine, and thyroid hormone therapy. However, cancer can come back sometimes even years after treatment. This recurrence can appear as abnormal blood tests or as lumps in the neck or other parts of the body. Being able to predict and detect these recurrences early is important for improving patient care and planning follow-up treatment. In this view, this research explores different machine learning algorithms and neural networks to effectively predict DTC recurrence. A total of 17 classifiers were utilized for the experiment, namely, logistic regression, random forest, k-nearest neighbours, Gaussian naïve Bayes, multi-layered perceptron, extreme gradient boosting, adaptive boosting, gradient boosting classifier, extra tree classifier (ETC), light gradient boosting machine, categorical boosting, Bernoulli naïve Bayes, complement naïve Bayes, multinomial naïve Bayes, histogram-based gradient boosting, and nearest centroid, followed by building an artificial neural network. Among the classifiers, ETC performed best with 95.3% accuracy, 95.1% precision, 87.92% recall, 98.18% specificity, 91.21% F1-score, 98.84% AUROC and 97.66% AUPRC on the first dataset, and 99.47% accuracy, 94.83% precision, 98.62% sensitivity, 99.54% specificity, 96.65% F1-score, 99.95% AUROC, and 99.37% AUPRC on the second dataset. To improve model interpretability, Shapley Additive Explanations (SHAP) was also used to explain the contribution of each clinical feature to the model’s predictions, allowing for transparent, patient-specific insights into which factors were most important for predicting recurrence, thereby supporting the proposed model’s clinical relevance. Full article

Background: Lung adenocarcinoma (LUAD) remains a leading cause of cancer-related mortality. The prognostic significance and functional role of sodium overload-induced necrosis (a novel form of regulated cell death driven by disrupted sodium homeostasis, hereafter abbreviated as NECSO) in LUAD are largely unexplored. Methods: A prognostic model was constructed utilizing the NECSO key gene TRPM4 and analyzed through Cox, LASSO, and multivariate Cox regression analyses. LUAD patients were stratified into high- and low-risk groups. The model’s predictive performance was evaluated using time-dependent ROC curves and nomograms. Functional enrichment analysis elucidated underlying biological disparities. The tumor immune microenvironment was characterized using ESTIMATE, ssGSEA, CIBERSORTx, and TIDE algorithms, with results corrected for multiple testing. Drug sensitivity to chemotherapeutic and targeted agents was predicted. The functional role of a key gene, DENND1C, was validated in vitro. Its association with immunotherapy survival outcomes was assessed in a real-world cohort. Results: The NECSO-based prognostic signature demonstrated robust performance in risk stratification across training and independent validation cohorts. Patients in the high-risk group exhibited significantly shorter overall survival. Functional enrichment revealed associations with processes related to plasma membrane integrity, cell death, metabolism, and immune response. Multi-algorithm immunogenomic analyses consistently identified an immunosuppressive microenvironment in high-risk patients. The risk score was predictive of differential sensitivity to therapeutics, including taxanes and EGFR inhibitors. In vitro experiments confirmed DENND1C as a tumor suppressor, inhibiting LUAD cell proliferation, invasion, and migration. Furthermore, high DENND1C expression was associated with improved survival in patients receiving immunotherapy. Conclusions: This study establishes and validates a novel NECSO-based prognostic model for LUAD. DENND1C is identified as a key tumor suppressor and a potential biomarker for immunotherapy, offering insights for personalized treatment strategies in LUAD. Full article

Poorly differentiated gastric carcinoma (PGC) is aggressive, yet subtype-specific genomics are under-characterized. We queried AACR Project GENIE^® (cBioPortal v18.0-public; 12 August 2025) for PGC and analyzed somatic alterations from targeted panels (depth ≥ 100×; variant allele frequency ≥ 5%). Mutation and copy number frequencies were summarized, co-occurrence and exclusivity were tested, and primary versus metastatic tumors were compared using chi-square with Benjamini–Hochberg correction. The cohort included 189 tumors from 188 patients (71% primary; 25% metastatic), with primary and metastatic tumor samples being collected from different patients. Recurrently mutated genes were TP53 (48.7%), CDH1 (31.2%), ARID1A (21.2%), KMT2C (8.5%), and POLD1 (7.4%); additional alterations involved ERBB3, KMT2D, KEL, CDKN2A, and FAT1 (≈1–7%). Amplifications in CCNE1 (8.2%) and FGFR2 (7.6%) were common, alongside gains in MET, MYC, KRAS, and ERBB2 and losses in CDKN2A/CDKN2B, CDH1, and PTEN. Significant co-occurrence was observed for POLD1–KMT2D (p < 0.001), POLD1–ARID1A (p < 0.001), and ARID1A–KMT2D (p < 0.001), while TP53 was mutually exclusive with ARID1A (p = 0.029) and CDH1 (p = 0.041). CDH1 (48.9% vs. 29.6%; p = 0.021) and MLH1 (8.5% vs. 1.5%; p = 0.040) were enriched in metastases, and CCNE1 alterations showed female predominance (p = 2.83 × 10⁻⁴). Several “primary-only” findings likely reflect small denominators and require replication. PGC demonstrates a mutational framework dominated by TP53, CDH1, ARID1A, and recurrent CCNE1/FGFR2 amplifications, underscoring dysregulation of cell cycle and chromatin-remodeling pathways as key drivers. Co-occurrence of POLD1, ARID1A, and KMT2D suggests coordinated disruption of DNA repair and epigenetic regulation, whereas mutual exclusivity of TP53, ARID1A, and CDH1 indicates distinct tumorigenic routes. Metastatic enrichment of CDH1 and MLH1 supports their roles in invasion and therapeutic resistance. Together, these findings highlight candidate biomarkers and actionable pathways warranting validation in larger, multi-omic cohorts to refine precision treatment strategies for this aggressive gastric cancer subtype. Full article

Acid mine drainage (AMD) and acid-generating mine wastes exhibit low pH, high sulfate levels, and complex multi-metal loads that strain conventional treatment. Thermoacidophilic red algae of the order Cyanidiales, particularly Galdieria sulphuraria (G. sulphuraria), have attracted interest as a biological option because they tolerate extreme acidity and elevated temperatures, grow under low light in mixotrophic or heterotrophic modes, and display rapid metal binding at the cell surface. This review synthesizes about two decades of peer-reviewed work to clarify how G. sulphuraria can be deployed as a practical module within mine water treatment trains. We examine the mechanisms of biosorption and bioaccumulation and show how they map onto two distinct configurations. Processed freeze-dried biomass functions as a regenerable sorbent for rare earth elements (REEs) and selected transition metals in packed beds with acid elution for recovery. Living cultures serve as polishing units for divalent metals and, when present, nutrients or dissolved organics under low light. We define realistic operating windows centered on pH 2–5 and temperatures of approximately 25–45 °C, and we identify matrix effects that govern success, including competition from ferric iron and aluminum, turbidity and fouling risks, ionic strength from sulfate, and suppression of REE uptake by phosphate in living systems. Building on laboratory studies, industrial leachate tests, and ecosystem observations, we propose placing G. sulphuraria upstream of bulk neutralization and outline reporting practices that enable cross-site comparison. The goal is an actionable framework that reduces reagent use and sludge generation while enabling metal capture and potential recovery of valuable metals from mine-influenced waters. Full article

2-acetylfuran is a product of the Maillard reaction and is widely found, especially in heat-processed foods such as grain products, baked goods, and dairy products. Although 2-acetylfuran contributes to flavor, high concentrations may be toxic. Its target organs and dose–response relationships remain poorly characterized. In this study, transgenic zebrafish with fluorescently labeled immune and neural systems were used to assess the effects of 2-acetylfuran on immune and neural development. Wild-type zebrafish were employed to assess the toxicity of 2-acetylfuran on locomotor ability, gastrointestinal development, and liver function. The maximum non-lethal concentration (MNLC) and the 10% lethal concentration (LC₁₀) for zebrafish embryos were 0.844 and 0.889 μL/mL, respectively. Regarding immunotoxicity, at concentrations of 0.281, 0.844, and 0.889 μL/mL, 2-acetylfuran significantly reduced the numbers of neutrophils, T cells, and macrophages. Regarding locomotor and neurotoxicity, motor speed and total locomotor distance were significantly reduced at 0.844 and 0.889 μL/mL. These findings were consistent with neurodevelopmental assessments, in which 0.844 μL/mL 2-acetylfuran resulted in a significant increase in apoptotic cells in the central nervous system and markedly shortened peripheral motor nerve lengths. Regarding gastrointestinal toxicity, 0.844 and 0.889 μL/mL 2-acetylfuran significantly reduced the gastrointestinal area, while neutrophil counts showed no significant changes, suggesting a relatively mild effect on the gastrointestinal tract. Regarding hepatic toxicity, all tested concentrations of 2-acetylfuran primarily increased the delayed yolk sac absorption area. Furthermore, at 0.844 μL/mL, histological examination revealed hepatic pathological changes characterized by hepatocyte nuclear swelling, vacuolar degeneration, and hepatocyte necrosis. In summary, this study reveals the multi-organ toxicity profile of 2-acetylfuran in the zebrafish model, with particularly high sensitivity in the immune system and liver. This research provides theoretical support for risk assessment and process control of 2-acetylfuran in foods. Full article

The development of high-performance wood-based materials has attracted increasing interest as a means of enhancing the mechanical properties of wood for structural applications. Mechanical densification combined with chemical pretreatment is an effective approach; however, many reported methods rely on complex multi-component chemical systems or severe chemical conditions designed to dissolve lignin or hemicelluloses. In this study, a simplified NaOH-only pretreatment followed by hot-press densification was investigated, targeting selective cell-wall plasticization rather than extensive polymer dissolution. Juniper (Juniperus communis), hawthorn (Crataegus monogyna), and birch (Betula pendula) were used as samples of softwood and hardwood species. Wood specimens were pretreated in 1 M NaOH at 145 °C for 10–30 min and subsequently densified by radial compression. Changes in chemical composition were evaluated by HPLC after acid hydrolysis and FTIR spectroscopy, while microstructural changes were examined using SEM. Physical and mechanical properties were assessed through density measurements and three-point bending tests. The results show that NaOH-only pretreatment induces hemicellulose deacetylation and modification of interpolymer linkages without substantial changes in the main wood polymer contents. Densification resulted in effective lumen collapse and a compact microstructure, leading to a significant increase in density and mechanical properties. Overall, the results demonstrate that efficient wood densification and mechanical enhancement can be achieved by promoting polymer mobility through selective cleavage of interpolymer bonds, using a simplified, single-alkali pretreatment that reduces chemical complexity and material loss while avoiding extensive lignin or hemicellulose dissolution. Full article