Search Results (6,563)

The Earth’s climate system exhibits nonlinear behavior driven by interactions among the atmosphere, oceans, cryosphere, land, and biosphere. These dynamics have given rise to relatively stable environments that shape the structure and function of the modern biosphere. This review is a primer for conservation practitioners and natural resource managers to develop a deep understanding of how the Earth System works. The key is to recognize that shifts in Earth System dynamics due to global climate change can destabilize the biosphere in unforeseen ways. The potential emergence of novel ecoregions must be a critical factor in adaptation planning for conservation and resource management. We review how thermodynamic constraints and global circulation dynamics determine the distribution of terrestrial and marine biomes. These dynamics stem from the Earth System functioning as a heat engine, transporting excess heat from low to high latitudes. We illustrate how biome climates are organized into climate regimes, with spatial and temporal characteristics linked to complex features of atmospheric and oceanic circulation. At centennial to millennial scales, these dynamics have created a stable envelope of natural variability in climate that has established a long-standing operating space for biota. However, this stability is becoming increasingly uncertain due to the growing positive energy imbalance in the Earth System primarily driven by anthropogenic greenhouse gas emissions. This forcing is leading to disruptive climatic change, putting the biosphere on a trajectory toward new transient states. Such global to regional climatic instability and biospheric restructuring introduce a high level of uncertainty in ecological futures, with major implications for natural resource management, biodiversity conservation strategies, and societal adaptation. We conclude by discussing frameworks for impact assessments and decision making under climate uncertainty. Full article

Prostate cancer is the third-leading cause of cancer death in men. Prostate-specific membrane antigen (PSMA) is a robust biomarker that is expressed in approximately 80% of patients diagnosed with prostate cancer; several theranostic strategies have emerged based upon targeting this biomarker. This report describes a dimeric aptamer complex (DAC) which is selective for PSMA⁺ cancer cells and is amenable to derivatization with additional diagnostic and therapeutic molecules. Confocal microscopy confirmed the selective nature of the DAC for PSMA⁺ LNCAP tumor cells. In addition, the affinity of the DAC for the PSMA protein was determined to be 2.16 ± 0.15 nM using biolayer interferometry (BLI). In proof-of-principle studies, this DAC was biotinylated (BioDAC; A10), complexed with streptavidin (SA), and radiolabeled with the positron-emitting radioisotope zirconium-89 (⁸⁹Zr: t_½ = 78.4 h, β⁺: 22.8%) to form the radiopharmaceutical [⁸⁹Zr]Zr-Df-SA-BioDAC ([⁸⁹Zr]Zr-A12). Acute biodistribution studies revealed elevated levels of radioactivity in PSMA⁺ tumors when compared to PSMA^- tumors. Radioactivity retention in the kidney was high due to the presence of streptavidin, while radioactivity retention in the liver was comparable with that of other radiolabeled aptamer complexes. Accordingly, the data suggests that the radiopharmaceutical will need to be redesigned using a strategy that is not reliant on a biotin–streptavidin paradigm before additional preclinical assessments are made and clinical translation can be attempted. Full article

The pressing need for sustainable, plant-based alternatives is highlighted by the growing resistance of agricultural pests to synthetic pesticides. This study examined the pesticidal potential of phytocompounds from C. tora discovered by GC–MS analysis against important tomato insect (T. absoluta) and fungal pathogen (A. solani). The binding stability and interaction dynamics of specific metabolites with fungal virulence (polygalacturonase, MAP kinase HOG1, and effector AsCEP50) and insect neuromuscular (ryanodine receptor and sodium channel protein) targets were assessed using molecular docking and 100 ns molecular dynamics simulations. Among the screened compounds, squalene and 4,7,10,13,16,19-docosahexaenoic acid, methyl ester (DHAME) exhibited the strongest binding affinities and conformational stability, with MM-GBSA binding free energies of −38.09 kcal·mol⁻¹ and −52.81 kcal·mol⁻¹ for squalene complexes in T. absoluta and A. solani, respectively. Persistent hydrophobic and mixed hydrophobic–polar contacts that stabilised active-site residues and limited protein flexibility were found by ProLIF analysis. These lively and dynamic profiles imply that DHAME and squalene may interfere with calcium signalling and stress-response pathways, which are essential for the survival and pathogenicity of pests. Hydrophobic interactions were further confirmed as the primary stabilising force by the preponderance of van der Waals and nonpolar solvation energies. The findings show that C. tora metabolites, especially squalene and DHAME, are promising environmentally friendly biopesticide candidates that have both insecticidal and antifungal properties. Their development as sustainable substitutes in integrated pest management systems are supported by their stability, binding efficacy and predicted biosafety. Full article

The Atlantic City–South Pass (ACSP) orogenic gold district, Wind River Mountains, Wyoming, occurs in the Archean South Pass Greenstone Belt primarily within greywackes and igneous rocks metamorphosed to the upper greenschist–lower amphibolite facies. Approximately 10 Mt of gold has been produced from pyrite and arsenopyrite-bearing quartz veins in deformation zones at the brittle–ductile transition. Multiple generations of primary and/or pseudosecondary fluid inclusions in gold-bearing quartz veins include one- and two-phase gaseous CO₂-CH₄ ± N₂ inclusions and two- and three-phase gaseous CO₂-CH₄-H₂O inclusions with rare NaCl daughter minerals. These primary/pseudosecondary inclusions show a broad range of homogenization temperatures (T_h) of 177.2 to 420.0 °C, with salinities of halite-bearing inclusions of >26 wt. % NaCl, with a high concentration of CaCl₂. Secondary aqueous inclusions formed at lower values of T_h (80.9 to 243.4 °C, with one outlier of 301.1 °C). Carbon from graphitic schists associated with gold-quartz veins yields values of δ¹³C = −28.5 to −19.1 per mil, suggesting that the light C isotope compositions of some carbonates (δ¹³C = −11.0 to −1.5 per mil) involved exchange reactions with graphite in the schists. Isotopic compositions of sulfur in sulfides (δ³⁴S = −1.0 to 3.6 per mil), oxygen in vein quartz (δ¹⁸O = 7.36 to 10.38 per mil), and hydrogen in fluid inclusions in vein quartz (δD = −125 to −55 per mil) are permissive of both magmatic-hydrothermal and metamorphic dehydration models for the origin of gold mineralization. However, a potential source of magmatic–hydrothermal fluids, the post-metamorphic Louis Lake granodiorite was unlikely to transport gold in a vapor state to become focused into shear zones as previously proposed. We favor a metamorphic dehydration model in which gold was derived from the South Pass supracrustal sequence and deposited in second-order shear zones that are spatially related to the first-order Roundtop Mountain Deformation Zone. Full article

The pivotal clinical trials, CARTITUDE-1 and KarMMa-3, showed promising response rates in relapsed and refractory multiple myeloma (RRMM) with use of BCMA-directed CAR T-cell therapy; however, a major challenge is determining suitability in patients who do not meet trial inclusion criteria due to suboptimal organ function. In this multicenter retrospective study, we evaluated the safety and efficacy of BCMA CAR-T therapy in patients with RRMM and renal impairment (RI), defined as creatinine clearance (CrCL) of less than 45 mL/min. We evaluated 223 patients treated with idecabtagene vicleucel (ide-cel) or ciltacabtagene autoleucel (cilta-cel) between May 2021 and April 2024. Outcomes were compared between baseline RI (11.2%) and normal renal function (nRF) cohorts. Response rates were similar at 1 month (p = 0.09), 3 months (p > 0.9), and 6 months (p = 0.8). Progression-free survival (PFS) was 21.9 months in the RI group compared to 15 months in the nRF group (p = 0.32), while overall survival (OS) was 27.9 months for patients with RI versus not reached for patients with nRF (p = 0.87). Patients with RI had higher rates of immune effector cell-associated neurotoxicity syndrome (ICANS) (60% vs. 19%, p = 0.04) and infections (44% vs. 20%, p = 0.008). We found that BCMA CAR-T demonstrated comparable efficacy in RRMM patients with baseline RI, although these patients exhibited increased rates of neurotoxicity and infections. Full article

Mitochondrial respiratory supercomplexes are emerging as key regulators of bioenergetics, redox homeostasis, and metabolic plasticity in cancer. Their assembly enhances electron transport efficiency, limits reactive oxygen species production, and supports the high oxidative and biosynthetic demands of tumor growth. Cancer cells remodel supercomplex organization in response to hypoxia, nutrient limitation, and therapeutic stress, enabling rapid metabolic adaptation. Multiple assembly factors—including COX subunits, HIGD1A/2A, COX7A2L (SCAF1), cardiolipin remodeling enzymes, and Complex I assembly factors such as NDUFAF1 and NDUFAF2—contribute to supercomplex stabilization and can be dysregulated in malignancy. Alterations in these factors enhance respiratory flexibility and therapy resistance, particularly in aggressive tumors such as glioblastoma. However, critical gaps remain, including incomplete understanding of the molecular mechanisms controlling supercomplex assembly and remodeling, limited validation of functional findings in primary patient-derived cells or clinical samples, and uncertainty regarding the contribution of supercomplex to therapy resistance and metabolic adaptation across tumor types. Advances in structural biology and functional imaging have uncovered tumor-specific vulnerabilities within supercomplex architecture that may be exploited therapeutically. Targeting supercomplex assembly, cardiolipin–protein interactions, or electron flux through individual supercomplex modules represents a promising approach to disrupt cancer metabolism and sensitize tumors to treatment. This review synthesizes current knowledge on supercomplex regulation, function, and therapeutic potential in cancer, and outlines key unanswered questions that remain to be addressed. Full article

This study positions the podcast Question Everything as an innovative case of metanarrative podcast journalism amid the growing crisis of distrust in news media. Through in-depth interviews with host Brian Reed and producer Zach St. Louis, along with textual analysis of all 27 episodes of the first season, this study examines how self-reflexive narrative storytelling both critiques and reimagines journalism. The dual-method approach explores not only what the podcast says about journalism, but also how the performance of podcasting becomes a mode of journalistic epistemology. Grounded in Metajournalistic Discourse Theory, findings demonstrate how Question Everything challenges traditional definitions of journalism, enacting metajournalistic discourse through four mechanisms: (1) inviting and exploring criticism, (2) performing transparency in the editing process, (3) experimenting with epistemology, and (4) embracing uncertainty and ambiguity. This paper argues that podcasts like Question Everything enact a performative mode of journalism that reconfigures how audiences make sense of truth, credibility, and authority. Full article

(1) Background/Objectives: Human papillomavirus (HPV) testing is hypothesised to detect cervical intraepithelial neoplasia grade 3 (CIN3) earlier than cervical cytology, which could translate into several clinical benefits. This study aimed to confirm that HPV testing detects CIN3 lesions of smaller size (or linear extension) and to assess whether this is associated with a decreased risk of stromal microinvasion (≤3 mm) (microinvasive or stage IA1 cervical carcinoma). (2) Methods: The study was conducted in a referral centre for cervical pathology in Italy. Eligible were 3744 patients aged 30–64 years who underwent local excision of the cervix between 1992 and 2021 and were diagnosed with CIN3, with or without microinvasion. Data were analysed using logistic and multinomial regression models. (3) Results: Overall, 1156 (30.9%) CIN3 cases were detected by the HPV test, and 2588 (69.1%) by cervical cytology. The lesion size was smaller in HPV test-detected CIN3 (median, 6 mm; interquartile range (IQR), 4–8 mm) than in cytology-detected CIN3 (median, 7 mm; IQR, 5–9 mm; p < 0.001). HPV test-detected CIN3 was over 50% less likely to have a size >6 mm combined with massive glandular crypt involvement. Stromal microinvasion occurred in 20/1156 (1.7%) HPV test-detected lesions versus 87/2588 (3.4%) cytology-detected lesions (p = 0.006), corresponding to an approximately 50% lower age-adjusted risk. The smaller size of HPV test-detected CIN3 and its lower degree of glandular crypt involvement interacted additively, rather than multiplicatively, in reducing the risk of stromal microinvasion. Over 46% of the association between detection mode and stromal microinvasion was explained by the size/involvement composite variable. (4) Conclusions: HPV testing detects CIN3 lesions of smaller size than cervical cytology. HPV test-detected CIN3 has a lower risk of stromal microinvasion. This association is mediated to a substantial extent by the smaller lesion size and the less extensive glandular crypt involvement, which interact in an additive manner. These findings may have other important clinical implications. First, the prevalence of disease persistence after treatment may decrease. Second, smaller lesions are likely to be treated with more limited excisions. Third, this may contribute to a lower rate of preterm birth in subsequent pregnancies. Full article

Porcine reproductive and respiratory syndrome (PRRS) is one of the costliest diseases in swine production, causing >$1.2 billion USD in annual losses in the United States. Oral fluids are widely used for PRRS virus (PRRSV) surveillance, accounting for 42% of nearly 480,000 PRRSV RT-qPCR cases submitted to six Midwestern U.S. laboratories between 2020 and 2025. Despite this reliance, few studies have applied appropriate methodological approaches to compare the performance of commercial extraction and PRRSV RT-qPCR protocols for oral fluid specimens. In this study, we evaluated nine extraction-amplification protocols for PRRSV RNA detection, based on three commercial extraction kits and three commercial RT-qPCR assays. For each protocol, performance was evaluated using 314 oral fluid samples of known status (215 positive, 99 negative), collected under controlled conditions from 72 pigs assigned to five groups inoculated with contemporary PRRSV isolates and from one negative control group. The Cq values were normalized as efficiency-standardized Cqs (ECqs) and then analyzed by receiver operating characteristic (ROC) analysis. The mean amplification efficiencies ranged from 67 to 92%, repeatability from 0.98 to 0.99, and overall reproducibility was 0.91. The ROC AUCs ranged from 0.916 to 0.986, with significant pairwise differences (p < 0.05). At optimal ECq cutoffs, sensitivities ranged from 83 to 98.1% with 100% specificity. Normalization enabled objective protocol comparisons and statistically valid diagnostic cutoffs and supports future improvements in PRRSV diagnostics. Full article

Background: Current guidelines for NSCLC follow-up lack specific recommendations on surveillance duration. This study aims to analyze survival and surveillance data in resected stage I NSCLC. Methods: We retrospectively reviewed 759 pathological stage I NSCLC (9thTNM ed.) patients with no history of lung cancer (LC) undergoing surgery from January 2003 to December 2018. Overall survival (OS), incidence of relapse (IR), and incidence of new primary LC (NP) were analyzed. Long-term effect of follow-up beyond 5 years was assessed by landmark analysis of OS, IR, and NP at 10 years, restricted to individuals alive without relapse or NP at 5 years (5-year event-free survivors, 5y-EFSs). Results: The rates of 10-year OS, 10-year IR, NP incidence, and 5y-EFSs were, respectively, 75%, 18%, 1.1%/year, and 59.1% (449 patients). Carcinoid IA/IB (0–10%) and adenocarcinoma IA/IB without lung nodules (LNs) (8–12%) had a similarly lower risk of relapse (p = 0.5088) compared to adenocarcinoma with LNs (p = 0.0191). Similarly, carcinoid (0–0.2%/year) and adenocarcinoma without LNs (0-0.3%/year) had the same lower incidence of NP (p = 0.8062) compared to patients with LNs (p < 0.0001). The group of 5y-EFSs had a conditional 10-year OS, IR, and NP incidence of 92%, 5%, and 0.8%/year. In 5y-EFSs, 10-year OS was better in carcinoid (100%) and adenocarcinoma (94%, p = 0.0009) patients; 10-year IR was lower in stage IA (4%) vs. IB (10%, p = 0.0444), and NP was lower in patients with no pre-surgery (0.5 vs. 1.5%/year, p = 0.0147) and no post-surgery LNs (0.6 vs. 1.1%/year, p = 0.0202). Conclusions: Based on our results, we propose a tailored surveillance strategy by de-escalating follow-up for low-risk patients while maintaining intensive monitoring for high-risk individuals. Full article

Background: Lung cancer is the leading cause of cancer-related death worldwide. Screening with low-dose computed tomography (LDCT) enables early detection of low-stage non-small cell lung cancer (NSCLC), increasing the chances of curative surgery. The aim of the present study was to analyze selected surgical aspects of treatment among patients diagnosed with NSCLC through LDCT-based screening in Szczecin, the first program of this kind in Poland. Methods: A group of 52 patients who were screened and operated on was compared with patients diagnosed and operated on outside the screening program during the same time period and a group of patients diagnosed and operated on prior to the screening program being implemented. Results: The screened population demonstrated a significantly higher frequency of stage IA cancer diagnosis, smaller tumor volume, more lobectomies, and fewer pneumonectomies compared with the other two groups. In addition, the waiting time for surgery was shorter, the duration of the procedure longer, and the length of hospitalization was reduced among the screened patients. No significant differences were observed in postoperative mortality or perioperative complications. Adenocarcinoma occurred significantly more often in the screened population than in the other groups, and tumors were more frequently classified as grade G2. A significant correlation was found between the need for blood transfusion and the occurrence of perioperative complications. Conclusions: The implementation of an LDCT-based screening program for lung cancer has a significant impact on the workload and case profile of thoracic surgery departments. Several aspects of surgical treatment differ significantly between patients diagnosed through screening and patients diagnosed outside of the program. Full article

Background/Objectives: Epilepsy is characterized by unpredictable seizures and drug resistance, along with rising antimicrobial resistance (AMR), highlighting the urgent need for innovative dual-action therapies. This study aimed to design, develop, and evaluate novel pyrazolone derivatives for a dual antimicrobial and antiepileptic potential. Methods: Novel pyrazolone derivatives were designed, synthesized (using 2,4-dinitrophenylhydrazine/semicarbazide condensation with ethyl acetoacetate), and evaluated through molecular docking against antimicrobial (4URM, 3FYV, 3FRA) and neuronal targets (4COF, 5TP9, 5L1F). The in vitro antimicrobial activity was assessed against Gram-positive (S. aureus) and in vitro Gram-negative (E. coli, P. aeruginosa) strains via agar cup plate assays, while in vivo antiepileptic efficacy was tested in a PTZ-induced seizure model in Swiss albino mice. Results: Compound IIa showed potent dual activity, inhibiting E. coli (9 mm zone at 80 μg/mL) and S. aureus (9.5 mm at 80 μg/mL), alongside a significantly delayed seizure onset in the PTZ-induced mouse model (100% survival rate, 45 sec delayed seizure onset, p < 0.001). Compounds Ia and Id showed selective activity against E. coli (6 mm at 80 μg/mL) and P. aeruginosa (7 mm at 80 μg/mL), respectively. Docking studies revealed that compound IIa has a superior binding affinity (−7.57 kcal/mol for 3FYV) compared to standards, driven by hydrogen bonds (SER X: 49) and hydrophobic interactions (LEU X: 20). Conclusions: This study presents a novel approach by proposing a rationally designed pyrazolone scaffold exhibiting both antimicrobial and antiepileptic activity, which integrates in silico modeling with experimental validation. Compound IIa emerged with preliminary dual biological activities, exhibiting strong antibacterial activity, a superior binding affinity toward both bacterial and neuronal targets, and notable seizure prevention in vivo. These findings show the potential of multifunctional pyrazolone derivatives as a new treatment strategy for addressing drug-resistant infections linked to epilepsy and support further optimization toward clinical development. Full article

The recent review by Veron et al. (2025) posits that quantitative genomic evidence used to understand coral evolution should be secondary to species hypotheses derived from expert opinion based on field experience. The authors argue that morphological “biological entities” should take precedence over molecular evidence when conflicts arise. This perspective required the rejection of extensive, independent molecular datasets that have progressively converged on a robust evolutionary framework for reef corals. Here, we reaffirm how prioritising subjective visual assessments over quantitative genetic and genomic data is methodologically unsound and scientifically regressive. We reject the framing of this perspective as “morphology versus molecules”. Rather, it is a fundamental divergence between two opposing philosophies: a static system anchored in non-reproducible expert judgement, and an integrative framework where genetic data provide the necessary independent test of morphological hypotheses. We show how a reliance on “field entities” obscures true morphological patterns by failing to distinguish between phenotypic plasticity, convergence, and evolutionary divergence. Effective taxonomy requires species hypotheses to be testable, and to stand or fall on the strength of reproducible evidence. Such a framework does not replace morphology; it validates it by providing an explicit, testable basis for evaluating morphological hypotheses. The integration of testable, reproducible molecular analysis with other lines of evidence including morphology is the benchmark of modern taxonomy across all Kingdoms of Life. We address the logical inconsistencies in the general arguments put forward by Veron et al. (2025) and refute their specific rejection of recent Acropora species-level revision with reproducible data. Full article

Cocoa production in West Africa supplies most of the global demand but is increasingly constrained by yield stagnation, soil degradation, disease pressure, and climate variability. This review examines how integrating regenerative agriculture (RA) with unmanned aerial systems (UAS) and artificial intelligence (AI) can support more precise and resilient cocoa management across heterogeneous smallholder landscapes. A PRISMA-guided systematic review of peer-reviewed literature published between 2000 and 2024 was conducted, yielding 49 core studies analyzed alongside supporting evidence. The synthesis evaluates regenerative agronomic outcomes, UAV-derived multispectral, thermal, and structural diagnostics, and AI-based analytical approaches for stress detection, yield estimation, and management zoning. Results indicate that regenerative practices consistently improve soil health and yield stability, while UAS data enhance spatial targeting of rehabilitation, shade management, and stress interventions. AI models further improve predictive capacity and decision relevance when aligned with data availability and institutional context, although performance varies across systems. Reported yield stabilization or improvement typically ranges from 12–30% under integrated approaches, with concurrent reductions in fertilizer and water inputs where spatial targeting is applied. The review concludes that effective scaling of RA–UAS–AI systems depends less on technical sophistication than on governance arrangements, extension integration, and cooperative service models, positioning these tools as enabling components rather than standalone solutions for sustainable cocoa intensification. Full article

Periodically supported beams are widely employed in engineering structures, where effective control of low-frequency vibration and noise is often required. To achieve broadband elastic wave manipulation, an inertial amplification (IA) mechanism was introduced to generate low-frequency and ultra-wide bandgaps. Based on the Timoshenko beam theory, analytical models for flexural wave propagation in periodically supported beams with IA structures were established using the generalized state transfer matrix method and the Floquet transform method, respectively. The validity of the analytical models was verified by vibration transmission analysis using a finite element model. The results demonstrate that the Floquet transform method enables rapid and accurate solution of the wave model. The introduction of the IA mechanism can generate low-frequency bandgaps, which are most sensitive to the amplification angle and amplification mass. The bandgap formation mechanism arises from the modulation of Bragg scattering in the periodically supported beam by the IA structure. This modulation causes the standing wave mode frequencies to shift to lower frequencies, thereby widening the bandgaps. Furthermore, hybrid IA structure configuration can achieve broader bandgaps, facilitating elastic wave control in the ultra-wide low-frequency range. These findings provide valuable insights for low-frequency vibration and noise attenuation in engineering structures. Full article