Search Results (181,333)

Laterite is an acidic tropical soil enriched in iron and manganese. It is common at tropical death scenes, yet its effect on necrophagous insect development is unstudied. We raised the forensically important blow fly Chrysomya megacephala (Fabricius, 1794) on three Hainan laterites, a yellow earth control, and a no-soil substrate. We combined larval phenotyping, inductively coupled plasma mass spectrometry (ICP-MS), and untargeted ultra-high-performance liquid chromatography–tandem mass spectrometry (UHPLC-MS/MS) metabolomics of whole larvae sampled on Days 1–3 post-burrowing. Laterites were strongly acidic (pH 4.17–4.32 vs. 7.45) and Fe/Mn-enriched. Whole-larval Fe (~10.2-fold) and Mn (~4.1-fold; whole larvae including gut contents, as no gut evacuation was performed) were consistently elevated across the three laterites, without biomagnification (bioaccumulation factors < 1). Laterite-group larvae were significantly heavier from 106 h and shorter from 130 h of age. They entered the cryptocephalic stage at 130 vs. 154 h and pupariated 24 h earlier in shallower soil (3–5 vs. 8–10 cm). In the primary merged metabolome analysis (n = 5–6 per group; 2975 metabolites), no metabolite survived the Benjamini–Hochberg correction in any laterite comparison, whereas three did in the no-soil comparison. The level-1 candidate metabolites are therefore hypothesis-generating. Laterite thus alters larval development and whole-body metal content. This implies a potential ~1-day bias in postmortem interval estimation under controlled conditions. Full article

Astragalus species have long been recognized for their pharmacological relevance, yet the antidiabetic properties of Astragalus cruciatus Link (Ac) remain poorly explored. This study aimed to investigate the antidiabetic potential of A. cruciatus Link and to elucidate possible underlying mechanisms. The ethanolic extract of Ac (AcEE) was prepared and analyzed for phenolic and flavonoid content. Antioxidant activity was assessed through a series of in vitro assays. The in vitro inhibition of α-amylase and α-glucosidase was assessed, followed by molecular docking to probe ligand-enzyme interactions. LC-ESI-MS analysis revealed a polyphenol-rich profile, with rutin (953.54 µg/g extract) and quinic acid (797.18 µg/g of extract) identified as main compounds. The AcEE showed significant inhibitory activity against both α-amylase and α-glucosidase (IC₅₀ = 239.30 ± 7.40 and 192.60 ± 15.51 μg/mL, respectively). Moreover, low cytotoxic effects were observed in hepatic cell lines. Computational analysis revealed stable interactions between rutin and both enzymes (−12.935 and −8.073 Kcal/mol, respectively). Network pharmacology revealed that AcEE may modulate key targets, including IL-6, TNF-α, IL-1β, Akt-1, STAT3, EGFR, and INSR as well as pathways related to insulin resistance, AGE-RAGE, and inflammation. These findings suggest that AcEE exerts significant antidiabetic effects through multitarget modulation, highlighting its potential as a natural therapeutic agent for T2DM. Full article

Energy planning is a growing challenge driven by the global push for decarbonization and the need to modernize aging power grids. This issue is particularly critical for islands, which often endure energy vulnerability and a high dependency on imported fossil fuels. While the electrification of transport is a popular option to reduce emissions, the integration of Electric Vehicles into weak island grids presents significant stability challenges due to the intermittent nature of renewable sources. This article provides a systematic bibliometric analysis to identify the advances made in bridging the gap between long-term energy balance and short-term dynamic stability in isolated systems. This paper analyzes islands’ stability needs and showcases smart charging systems, exploring their roles as distributed energy storage and as providers of ancillary services. First, the most relevant international scientific journals are identified to allow the subsequent selection and quantitative and qualitative analysis of articles dealing with EV-island stability pathways. A total of 7469 publications were screened, of which 284 articles were finally selected. Full article

The Pangjiahe Au deposit is the largest gold deposit in the Fengxian district of the West Qinling Orogen (WQO), Central China. However, the timing of gold mineralisation and its relationship to the regional metallogenic evolution of the WQO remain poorly constrained. In this study, detailed geological investigations, TIMA mineralogical analysis, in situ Rb–Sr dating of hydrothermal sericite, and in situ Fe–S isotope analyses of auriferous pyrite were conducted to constrain the timing of mineralisation, the evolution of ore-forming components, and the regional metallogenic significance of the Pangjiahe Au deposit. Hydrothermal sericite intimately associated with gold mineralisation yields an in situ Rb–Sr isochron age of 207.6 ± 3.1 Ma, providing the first direct age constraint on gold mineralisation at Pangjiahe. This age is consistent with those reported for the nearby Huayagou Au deposit and several other major gold deposits in the West Qinling Orogen, supporting a regionally extensive Late Triassic gold mineralisation event. The Pangjiahe Au deposit shares closer geological, geochronological, and isotopic affinities with the Huayagou Au deposit and the major Au deposits of the Middle Qinling in Gansu than with the traditionally correlated Au deposits of the North Qinling. These results provide new constraints on the regional metallogenic relationship between the Fengtai Basin and the Middle Qinling metallogenic system, contributing to a better understanding of Late Triassic gold mineralisation in the West Qinling Orogen. Full article

Background/Objective: Cinnamaldehyde (CA) is a naturally occurring bioactive compound derived from the leaves, bark, roots, and flowers of the Chinese medicinal plant Cinnamomum cassia. It exhibits a broad spectrum of pharmacological properties, encompassing antioxidant, antibacterial, anti-diabetic, antifungal, and anticancer activities. Notably, it has shown potential therapeutic benefits in the management of type 2 diabetes mellitus (T2DM) and non-alcoholic fatty liver disease (NAFLD). Ochratoxin A (OTA), a common contaminant found in foods such as cereals, coffee, and raisins, is also present in traditional Chinese medicinal materials, including Astragalus and liquorice. T2DM and NAFLD share intertwined pathophysiological pathways, including insulin resistance, dyslipidaemia, chronic low-grade inflammation and oxidative stress, with insulin resistance serving as the common pathological hub for both conditions. Consequently, they frequently co-occur and exacerbate each other. OTA exerts dual-targeted toxicity to the pancreas and liver, which may synergistically drive the development of the comorbidity of T2DM and NAFLD. These two processes are mutually causal and together constitute the pathological basis of metabolic comorbidity. Methods: Network toxicology employs toxicological data, gene expression, and protein–protein interaction (PPI) networks to predict the targets of toxins, while network pharmacology, based on systems biology principles, reveals how drugs exert regulatory effects through multiple targets and pathways. In this study, we employed an integrated network toxicology and network pharmacology approach to jointly decipher the potential mechanisms by which CA intervenes in OTA-induced comorbid T2DM-NAFLD. First, a network toxicology approach was employed to preliminarily screen for core toxicological targets responsible for OTA’s pathogenicity. Subsequently, network pharmacology was used to identify potential targets of CA-mediated intervention in the disease. Finally, the common overlap among the CA intervention targets, OTA toxicity targets, and disease targets was defined as the final set of potential targets for CA-mediated intervention in OTA-induced T2DM-NAFLD comorbidity. A PPI network was constructed using the STRING database, and topological analysis was performed with Cytoscape. Core targets were selected using the median values of six parameters—betweenness centrality, closeness centrality, degree centrality, eigenvector centrality, LAC (local average connectivity) score, and network centrality—as cut-off thresholds, and the top 10 key genes were further identified using the cytoHubba plugin. Gene Ontology (GO) functional enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were conducted via the DAVID database, and the results were visualized on the CNSknowall platform. Lastly, molecular docking of the core targets was performed using the CB-DOCK2 platform to validate binding affinity. Results: Based on an integrated analysis of network toxicology, network pharmacology, and molecular docking, 10 key targets were systematically identified. These may serve as potential mediators of cinnamaldehyde in the treatment of OTA-induced T2DM-NAFLD comorbidity. Among these, six targets—albumin (ALB), glyceraldehyde-3-phosphate dehydrogenase (GAPDH), interleukin-6 (IL-6), tumor necrosis factor (TNF), actin beta (ACTB), and estrogen receptor 1 (ESR1)—possess crystal structures amenable to molecular docking. KEGG enrichment analysis revealed that CA and OTA jointly participate in key pathological processes such as the cancer pathway, the lipid and atherosclerosis pathway, the advanced glycation end-products–receptor for advanced glycation end-products (AGE-RAGE) signaling pathway, the phosphatidylinositol 3-kinase–protein kinase B (PI3K-Akt) signaling pathway, the TNF signaling pathway, and the interleukin-17 (IL-17) signaling pathway. OTA exacerbates inflammatory responses, impairs insulin signaling, promotes hepatic steatosis, and disrupts systemic metabolic homeostasis, ultimately contributing to T2DM-NAFLD comorbidity. Conversely, cinnamaldehyde counteracts these pathological processes through multiple mechanisms, including antioxidant and anti-inflammatory effects as well as regulation of glucose and lipid metabolism, thereby restoring metabolic homeostasis. Conclusions: This study has preliminarily identified the toxicological targets of OTA and the potential intervention targets of CA, offering new avenues for preventing and intervening in OTA-induced metabolic toxicity. Furthermore, it provides a theoretical basis for CA as a potential multi-target therapeutic agent and presents novel insights worthy of further investigation into the prevention of T2DM-NAFLD comorbidity. Full article

Prostate cancer is common in older men, yet mechanisms linking aging to tumor progression remain incompletely defined. Beyond genetic alterations, aging reshapes the prostate microenvironment through cellular senescence, chronic low-grade inflammation, immune dysfunction, stromal remodeling, metabolic stress, and impaired tissue repair, collectively promoting inflammaging. This persistent inflammatory state may create a permissive niche for tumor initiation, progression, immune evasion, and treatment resistance. Senescent epithelial and stromal cells release cytokines, chemokines, growth factors, matrix-remodeling enzymes, and extracellular vesicles through the senescence-associated secretory phenotype (SASP). In parallel, immune aging alters T-cell subsets, myeloid cells, macrophages, and anti-tumor surveillance. This review summarizes how SASP programs, Th17/Treg imbalance, IL-17/IL-23 signaling, myeloid remodeling, stromal aging, metabolic stress, and immune–stromal–epithelial crosstalk shape prostate cancer biology. We further discuss therapeutic implications, including cytokine modulation, senescence-directed therapy, metabolic intervention, and biomarker-guided strategies. This review highlights key knowledge gaps and proposes a framework for age-aware prostate cancer research, biomarker development, and therapeutic strategies. Full article

Regulatory Factor X3 (RFX3—OMIM#601337) encodes a transcription factor that is highly expressed in the human brain, particularly during neurodevelopment. It has been previously associated with neurodevelopmental disorders, including autism spectrum disorder (ASD), intellectual developmental disorder, and attention-deficit/hyperactivity disorder. However, the neurological and epileptic features remain poorly characterized, and no phenotype has yet been formally annotated in OMIM. Here, we report the second known case of Infantile Epileptic Spasms Syndrome (IESS) associated with RFX3 variants. The patient developed clusters of extensor spasms associated with eye deviation and achieved complete remission within two weeks following vigabatrin and ACTH therapy, remaining seizure-free thereafter. During follow-up, he presented with global developmental delay, ASD, and facial dysmorphisms. Genetic analysis by array comparative genomic hybridization identified a de novo heterozygous microdeletion of approximately 147 kb at 9p24.2, involving the initial exons of RFX3 (NM_134428). This case expands the clinical spectrum associated with RFX3 variants, supporting a potential role in IESS and early neurodevelopmental disruption. It highlights the relevance of including RFX3 in the genetic evaluation of patients with IESS and co-occurring neurodevelopmental disorders. Full article

Background/Objectives: Nurses are frequently exposed to emotionally demanding situations, placing them at risk of adverse psychological outcomes such as secondary traumatic stress (STS) and burnout. Personality traits, particularly perfectionism, may influence these outcomes. Submissive compassion, characterized by caring behavior motivated by a desire for approval or avoidance of rejection, may play an explanatory role in these relationships. Methods: This study examined whether submissive compassion was statistically associated with the relationship between perfectionism and professional quality of life (ProQOL) among hospital nurses, while accounting for potential confounding and moderating factors. A cross-sectional online survey was conducted among ward nurses working in hospitals in Japan. Participants completed measures of perfectionism, submissive compassion, and ProQOL. Data from 218 nurses were analyzed using structural equation modeling. Results: Socially prescribed perfectionism was positively associated with submissive compassion and STS. Submissive compassion was significantly associated with the indirect relationship between socially prescribed perfectionism and STS. Age moderated the association between submissive compassion and STS, with stronger indirect effects observed among older nurses. Additionally, self-oriented perfectionism showed a relationship with stress-related outcomes, whereas socially prescribed perfectionism was associated with burnout. Conclusions: The findings suggest that submissive compassion may contribute to the association between perfectionism and adverse psychological outcomes among nurses. These results underscore the potential importance of maladaptive compassion motives in understanding how perfectionism relates to STS in this population and may help inform interventions aimed at supporting nurses’ psychological well-being. Full article

Background: Vaspin (SERPINA12) is an adipokine implicated in the regulation of insulin sensitivity and metabolic homeostasis. Evidence regarding its association with obesity-related metabolic disturbances remains inconsistent, and potential sex-specific differences are not fully understood. Methods: This cross-sectional study included 81 adults aged 30–60 years (38 women and 43 men), divided into a metabolic syndrome group (MS+) and a control group (MS−). Anthropometric, biochemical, total antioxidant status and blood pressure parameters were assessed, and insulin resistance was estimated using the HOMA-IR index. Results: In MS+ men, serum vaspin concentrations were higher than in MS− men (p = 0.004) and were associated with BMI, waist circumference, body fat percentage, fasting insulin, HOMA-IR, and diastolic blood pressure (p < 0.05 for all). In multivariable regression analysis (adjusted for age), insulin levels, lean body mass, and diastolic blood pressure explained up to 15.2% of the variability in serum vaspin concentrations in men (p = 0.035), whereas no significant model was observed in women. ROC (receiver operating characteristic) curve analysis demonstrated better discriminative performance of serum vaspin for identifying metabolic syndrome in men than in women (AUC: 0.784 ± 0.094 vs. 0.416 ± 0.115, respectively; p = 0.013). Conclusions: Circulating vaspin concentrations are more strongly associated with metabolic disturbances in men than in women These findings suggest that sex-specific regulation of vaspin may contribute to differences in metabolic dysfunction associated with visceral obesity. Overall, these results indicate that vaspin may reflect visceral obesity-related metabolic dysfunction rather than general adiposity. Further studies are needed to clarify the mechanistic role of vaspin and to determine whether it has potential as a biomarker of metabolic dysfunction. Full article

Background: Treatment strategies for myelodysplastic syndromes (MDS) range from supportive care to disease-modifying therapies, depending on risk stratification and patient characteristics. Hypomethylating agents (HMAs) remain the standard treatment for higher-risk disease, whereas allogeneic hematopoietic stem cell transplantation (allo-HSCT) is the only potentially curative option. This study evaluated real-world survival outcomes and prognostic factors in patients with MDS treated with HMAs or allo-HSCT. Methods: A total of 79 patients with MDS who received azacitidine, decitabine, or allo-HSCT were retrospectively analyzed. Overall survival (OS) was evaluated using Kaplan–Meier and Cox proportional hazards analyses. To address potential immortal time bias, a prespecified 6-month landmark analysis was additionally performed. Results: Median OS was 14.9 months (95% CI, 9.9–20.0) with azacitidine, 10.0 months (95% CI, 6.8–13.2) with decitabine, and 48.0 months (95% CI, 19.9–76.1) after allo-HSCT. Patients undergoing allo-HSCT were significantly younger and had better ECOG performance status than those receiving HMAs. After adjustment for age, ECOG performance status, and IPSS-R risk category, treatment modality remained significantly associated with OS in the multivariable Cox regression model. In the prespecified 6-month landmark analysis, the survival advantage associated with allo-HSCT remained significant, although the adjusted association was attenuated. Conclusions: In this real-world cohort of actively treated patients with MDS, allo-HSCT was associated with longer overall survival than HMAs. Although this association persisted after adjustment for major clinical confounders and in a landmark analysis addressing immortal time bias, residual confounding related to treatment selection cannot be excluded. These findings should therefore be interpreted as an association rather than evidence of a causal treatment effect. Full article

The Baraul Banda Formation preserves an important Paleocene–Eocene sedimentary record within the western Kohistan–Ladakh Arc (KLA) and provides new constraints on sediment provenance and tectonic evolution during the final stages of Neo-Tethyan closure. This study integrates stratigraphic observations, detrital zircon U-Pb geochronology, and quantitative provenance analyses to investigate sediment sources and basin development within the western India–Eurasia collision zone. The formation comprises a thick marine siliciclastic succession of conglomerate, sandstone, siltstone, mudstone, and slate deposited in a tectonically active forearc basin. Detrital zircon age spectra are dominated by Mesozoic–Cenozoic populations (48%) with major peaks at ~57–61 Ma, ~70 Ma, ~85–90 Ma, and ~114–115 Ma, accompanied by subordinate Neoproterozoic, Mesoproterozoic, Paleoproterozoic, and minor Archean populations. These age components closely resemble those of the KLA, Karakoram Block, and Lhasa Block. Statistical provenance analyses indicate the strongest affinity with Eurasian arc-related terranes and contemporaneous forearc basin deposits of the Tar and Indus groups, whereas affinity with Indian Plate sources is minor. The provenance record indicates that sediment supply was dominated by erosion of the KLA and the adjacent Karakoram–Lhasa continental margin, with only minor recycled contributions from Indian-derived sources. The youngest zircon populations constrain deposition to the Paleocene–Early Eocene and record rapid erosion of active arc terranes immediately prior to the India–KLA collision. Placed within the regional magmatic chronology, these results support initiation of the KLA by ca. 155 Ma, Late Cretaceous amalgamation with the Karakoram–Lhasa margin at ca. 80–70 Ma, and subsequent collision with India at ca. 60–55 Ma. The KLA therefore remained an active pre-India-collision arc system for approximately 95–100 Myr, whereas collision-related magmatism continued until ca. 40 Ma, extending its complete magmatic history to approximately 115 Myr. Full article

This paper investigates nanoparticle emissions from older diesel passenger cars in four European countries outside of PTI (periodic technical inspection) testing facilities, using a methodology similar to that of the PTI. Per opportunistic sampling and voluntary testing, 618 diesel cars with an average mileage of 163,348 km were measured between 2020 and 2022 on the streets around university campuses and in public areas in Brussels (Belgium), Aveiro (Portugal), Belgrade (Serbia) and Birkenfeld (Germany). Through subsequent research, 109 vehicles were found not to be equipped with a diesel particulate filter (DPF) and were separated. Portable nanoparticle detectors were used to measure PN emissions in a PTI-like approach at low idle. From the 509 analysed diesel cars equipped with DPF, a high share of 31% revealed PN tailpipe concentrations of over 250 kP/cm³ and would therefore have failed the PTI established in Germany. That rate is 2–9 times higher than that found in Belgian and German PTI PN measurements, possibly caused by the fact that vehicles are serviced immediately before the PTI. Moreover, 45% of all tested diesel cars with DPF emitted concentrations higher than 20 kP/cm³. This level was found, both in the literature and in our measurements, to be indicative of a DPF operating outside its normal performance range, taking into account the measurement uncertainty. Even among relatively new vehicles with DPF (up to mileages of 180,000 km), 13% emitted as much PN as diesel cars without DPF (1000 kP/cm³ or more). In Portugal and Serbia, a higher share of cars showed elevated emissions compared to Germany and Belgium. DPF technology can in principle greatly reduce particle emissions of diesel cars. However, its efficiency degrades with time and vehicle mileage. Several factors leading to higher PN emissions have been reported; however, they cannot be discriminated in the results. This is primarily because active filter regeneration generates particle emission peaks every several 100 km, which were found to be up to four orders of magnitude higher than normal. Within the fleet on the streets, up to 4% of all diesel cars equipped with a modern DPF can be found in active regeneration mode. While at present politics and carmakers focus on electrifying the new vehicle generation, the emission problem of around 69 million diesel cars with elevated PN emissions on European streets remains unresolved so far. In European countries with a particularly high share of diesel cars, an old vehicle fleet, and a low income level, emission problems may be exacerbated. Full article

A solid solution treatment (SST) followed by single-stage aging (0–30 h, 140 °C) was performed on 7075 aluminum alloy specimens with longitudinal axes oriented at 0°, 45° and 90° to the rolling direction. The mechanical properties and microstructure were analyzed by tensile testing, optical microscope (OM), electron backscatter diffraction (EBSD), scanning electron microscope (SEM) and transmission electron microscope (TEM). The results show that the average tensile strengths of the as-received 7075 aluminum alloy in the three directions were 304 MPa (0°), 295 MPa (45°) and 297 MPa (90°), respectively, with an anisotropy index (AI) of 0.97, indicating that the as-received samples exhibited negligible anisotropic mechanical properties. After SST, elongated grains with coarse size were formed, which is primarily attributed to the inheritance of the deformed fiber texture introduced by hot rolling. EBSD analysis of the 30 h aged specimens revealed that, within the same analyzed area, the total grain-boundary length in the 45° direction (16.4 cm) was much larger than that in the 0° (10.4 cm) and 90° (13.5 cm) directions. As the grain morphology showed no significant change between the SST and aged conditions, this grain-boundary distribution was representative of the microstructural state established during SST and persisted throughout the artificial aging process, contributing to the anisotropic mechanical properties. During artificial aging, prolonged aging time significantly facilitated the precipitation, with the 30 h aged sample exhibiting a significantly higher density of precipitates compared to the 6 h aged sample, leading to enhanced mechanical properties. The tensile strengths of the 30 h aged samples increased to 165 MPa, 236 MPa and 196 MPa in the three directions, respectively. Meanwhile, due to the fixed crystallographic orientation relationship between the precipitates and the Al matrix, the precipitates tended to form on specific planes, which enhanced the anisotropic mechanical properties. Consequently, the AI value increased from 0.97 (as-received) to 1.43 (30 h aged) with prolonged aging time. Full article

Alternative fine aggregates are often assessed using compressive strength at a single reference age, which may conceal an early maximum followed by later strength loss. This preliminary screening study compared mortars containing river sand (RS), standard sand (StS), desert sand (DS), soil sand (SS), coal gangue sand (CGS), and metamorphic rock sand (MRS) under one nominal mixture design. For each aggregate, one mortar batch was prepared and nine 70.7 mm cubes were cast, with three specimens tested at 3, 7, and 28 d. RS, StS, DS, and SS continued to gain strength. Within the single CGS batch, strength decreased from 15.56 ± 0.31 MPa at 7 d to 11.68 ± 0.15 MPa at 28 d; within the single MRS batch, it decreased from 21.63 ± 0.48 MPa to 15.75 ± 0.20 MPa. The corresponding losses were 24.95% and 27.18%, and exploratory within-batch Tukey tests yielded p < 0.001. These statistics describe specimen-level variation within the tested batches and do not establish batch-to-batch reproducibility. Representative 28 d SEM fields, raw-aggregate EDS, and qualitative XRD provide contextual observations but lack the temporal and spatial resolution needed to reconstruct a defect-formation process between 7 and 28 d. Because aggregate moisture state, absorption, flow, air content, and compaction were not independently controlled, the results identify a screening signal that requires independent-batch validation rather than a general material mechanism. Full article

The telomere is one of the biological hallmarks of skin aging. Sodium acetylated hyaluronate (SAH) is an acetylated derivative of sodium hyaluronate, produced by a grafting technology that confers higher resistance to hyaluronidase. This study aimed to explore whether SAH is associated with telomere-related endpoints and with clinical signs of skin aging. Two vitro studies were performed, assessing telomerase activity in human adult keratinocytes and telomere length in human normal fibroblasts by quantitative PCR (qPCR) assay kits, with or without SAH. A randomized, split-face, double-centered, double-blind, placebo-controlled clinical trial was then conducted on 44 Caucasian and Asian female volunteers, comparing a facial cream containing 0.1% SAH with a placebo cream over 28 days; crow’s feet wrinkle depth, area, and volume, under-eye roughness (Rz), elasticity (R2), and firmness (F4) were measured by PRIMOS 3D and Cutometer^® MPA 580 at baseline, day 7, and day 28. In vitro, only the highest SAH concentration (0.15%) was associated with a significant increase in telomerase activity and in telomere length versus control, whereas lower concentrations had no significant effect. Clinically, the SAH cream significantly reduced crow’s feet wrinkle volume and area, improved skin elasticity, and reduced under-eye roughness versus placebo, with non-significant trends for wrinkle depth and firmness. These exploratory findings make SAH an interesting active ingredient for anti-aging skincare cosmetics, combining a curative dimension (clinical improvement of skin-aging parameters) with a preventive dimension (telomere preservation observed in vitro for the first time), and warrant further mechanistic investigation. Full article