Institut Químic de Sarrià

BN-isosterism, the replacement of carbon-carbon units with boron-nitrogen pairs in organic frameworks, offers a powerful means to create novel compounds, yet methods to access larger BN-containing polyaromatic cores remain scarce. Leveraging our recently developed multigram-scale synthesis of BN-naphthalene, we now combine it with a Catellani-type arene extension (Pd(OAc)2/P(2-furyl)3, norbornene) to rapidly access diverse extended BN-embedded polyaromatic cores. This strategy delivers BN-embedded benzo[c]phenanthridines and curved 8- and 7-membered ring-fused derivatives, as well as BN-embedded benzofluorenones in both normal and inverse BN-vector orientations. Importantly, the ability to access both directional BN isomers, in addition to the parent C═C core, provides a rare opportunity to directly interrogate the effect of the presence and sense of the BN moiety. Most notably, light-induced singlet oxygen (1O2) generation promoted by the benzofluorenone core shows a more than 10-fold enhancement in the "boron-up" BN isostere, while dropping to negligible levels upon inversion of the BN unit. This work thus offers a blueprint for experimental electronic tuning of optically responsive organic materials through BN-mapping.

Musculoskeletal disorders (MSDs), particularly articular cartilage injuries and the progression of osteoarthritis (OA), represent a substantial global health burden. Conventional techniques fail to consistently achieve durable regeneration, yielding biomechanically inferior fibrocartilage due to the native tissue's avascularity and complex zonal architecture. This review translates the critical biological, mechanical, and architectural requirements of the osteochondral unit into quantitative design targets and critically evaluates two major regenerative strategies: structurally precise architected biomimetic scaffolds and minimally invasive injectable hydrogels. Our analysis reveals a fundamental trade-off between technical potential and translational feasibility. Architected scaffolds, fabricated using advanced methods like 3D printing and melt electrowriting, demonstrate superior capacity to meet structural demands. They achieve precise zonal stiffness gradients, secure bone anchorage, and immediate high-load-bearing capability necessary for long-term chondrocyte phenotype stabilization and faithful tissue reconstruction. In contrast, injectable hydrogels excel in defect conformability, logistical simplicity, and microenvironmental programming (e.g., controlled growth factor release, viscoelastic tuning), offering a patient-friendly, single-stage delivery. However, clinical success is governed by a persistent paradox: the technical potential of a therapy is inversely related to its regulatory and commercial viability. Scaffold-based constructs, due to their complexity, surgical invasiveness, and customization needs, face severe regulatory hurdles (e.g., ATMP/Class III classification) and high associated costs. Conversely, the batch manufacturability and minimal invasiveness of injectable systems grant them a smoother regulatory path and broader market adoption, despite often resulting in monophasic repair with limited long-term mechanical fidelity. We conclude that the field of osteochondral regeneration is shaped by this structural asymmetry. While scaffolds represent the platforms most capable of delivering faithful structural repair, injectable systems are the primary route by which innovation reaches the patient. Future success depends on either the development of hybrid strategies that reconcile architectural control with surgical simplicity, or the evolution of regulatory frameworks to accommodate the necessary complexity for true tissue regeneration.

<strong class="journal-contentHeaderColor">Abstract.</strong> Feldspars are among the most efficient mineral ice-nucleating particles (INPs) in the atmosphere. However, their nucleation behavior varies significantly across natural samples. This study investigates six feldspar powders selected for their perthitic or anti-perthitic textures and spanning a range of K/Na compositions. All samples were comprehensively characterized in terms of mineralogy, bulk and surface chemistry, and microstructure. Droplet freezing assays revealed consistent onset temperatures between &minus;2 and &minus;4 &deg;C, suggesting the presence of shared active nucleation sites across all feldspar types. Cumulative and differential freezing spectra revealed marked differences in the density and distribution of ice-nucleating sites, which were found to correlate with both feldspar composition and microtexture. Using HUB analysis, different subpopulations of ice-nucleating sites were identified. Perthites showing microcline structures exhibited a continuous increase in nucleation site density with decreasing temperature as subpopulations became active. In contrast, samples lacking dominant microcline structures showed plateaus in the cumulative spectra within specific temperature ranges, indicating a significant reduction in certain subpopulations. These findings highlight the crucial role of exsolution textures and crystallographic structure in regulating feldspar ice-nucleation efficiency. The results have implications for understanding feldspar behavior in the atmosphere and for improving predictive models in cloud microphysics.

FGFR1 genetic alterations are associated with brain malignancies, including FGFR1 mutations in familial and sporadic cases of low-grade glioneuronal tumors, suggesting intrinsic mechanisms of selective pressure toward FGFR1 multiple events arising in the context of a quiet genome. To decipher the molecular mechanisms triggered by multiple concurrent FGFR1 mutations, we have mapped the proximal interactome of wild-type, single- and double-mutant FGFR1 proteins through a BioID-MS approach. Our data reveal novel oncogenic functionality for the two hotspot mutations N546K and K656E, linked to evasion of lysosomal degradation. Further, we identified a modulatory tumor-suppressive role for the susceptibility variant R661P, which hampers the oncogenic potential of both hotspot N546K and K656E mutations by rescuing receptor degradation and reducing N546K affinity for the downstream effector PLCγ. Introducing the R661P missense variant was sufficient to abolish self-renewal capacity of oligodendroglioma cells and downregulate genes involved in neurodevelopment and neuro-glial cell fate decisions, both aspects overcome in the double mutants. This study sheds light on contextual oncogenic effects associated with FGFR1 alterations and their recurrence in low-mutation burden and therapy naive tumors.

ABSTRACTHigh‐fat (HF) diets contribute to obesity, insulin resistance, fatty liver, gut microbiota dysbiosis, oxidative stress, and low‐grade chronic inflammation. This study evaluated the preventive effects of dietary Type 2 resistant starch (RS2) from high‐amylose maize and low‐dose d‐fagomine (FG) from buckwheat on these metabolic disturbances. Male Wistar‐Kyoto rats (9–10 weeks old) were assigned to four diet groups for 10 weeks: standard (STD) diet, HF diet (45% kcal from fat), HF + RS diet (15% RS2), and HF + FG diet (0.1% FG). Body characteristics, metabolic parameters, oxidative stress, gut microbiota, short‐chain fatty acids (SCFAs), and eicosanoids were analyzed. Both HF + RS and HF + FG diets reduced perigonadal fat, plasma triacylglycerols, and oxidative stress. HF + RS diet improved glucose tolerance without significantly affecting insulin sensitivity, while HF + FG diet showed a tendency for improvement at later stages. Additionally, HF + RS diet showed greater beneficial effects on body weight and liver steatosis than HF + FG diet, likely due to gut microbiota and SCFA modulation. RS2 exerted stronger metabolic effects than FG under HF diet conditions, suggesting its greater potential in mitigating obesity‐related complications. FG effects may require longer exposure to manifest.

StachCel5, a novel endo-β-1,4-glucanase from Stachybotrys chartarum IBT 7711, was identified through genome mining and exhibited 65% sequence identity with known glycoside hydrolase family 5 (GH5) cellulases. The gene was codon-optimized, excluding its native signal peptide, and heterologously expressed in Komagataella phaffii under the control of constitutive glyceraldehye-3-phosphate dehydrogenase (GAP) promoter. The purified enzyme displayed a high specific activity of 287.6U/mg on carboxymethyl cellulose (Na-CMC), retained over 87% activity across pH4-7, and maintained 77% residual activity after 60min at 50°C. Structural modeling predicted a canonical (β/α)₈ TIM-barrel fold, with Glu228 and Glu335 as conserved catalytic residues. Application trials on industrial hardwood and softwood pulps demonstrated that enzymatic pre-treatment with StachCel5 enhanced fiber fibrillation, reduced refining energy, and improved mechanical properties. In softwood pulp, the enzyme enabled equivalent tensile strength (67.8Nm/g) as untreated controls with 25% fewer refining revolutions (4500 vs 6000), reflecting significant energy savings. Improved tensile and burst indices, and preserved fiber integrity (zero-span tensile index) confirm the biorefining potential of StachCel5. These results establish StachCel5 as a thermostable and pH-tolerant biocatalyst suitable for enzymatic fiber modification in pulp and paper processing under industrially relevant conditions.

Traumatic brain injury (TBI) is a major cause of disability leading to multiple sequelae in cognitive, sensory, and physical domains, including posttraumatic epilepsy. Despite extensive research, our understanding of its impact on macroscopic brain circuitry remains incomplete. We analyzed electrophysiological functional connectomes in the gamma band from an animal model of blast-induced TBI over multiple time points after injury. We revealed differences in small-world propensity and rich-club structure compared with age-matched controls, indicating functional reorganization following injury. We further investigated cost-efficiency trade-offs, propose a computationally efficient normalization procedure for quantifying the cost of spatially embedded networks that controls for connectivity strength differences, and observed dynamic changes across the injury timeline. To explore potential links between altered network topology and epileptic activity, we employed a brain-wide computational model of seizure dynamics and attribute brain reorganization to a homeostatic mechanism of activity regulation with the potential unintended consequence of driving generalized seizures. Finally, we demonstrated post-injury hyperexcitability that manifests as an increase in sound-evoked response amplitudes at the cortical level. Our work characterizes, for the first time, gamma-band functional network reorganization in a model of brain injury and proposes potential causes of these changes, thus identifying targets for future therapeutic interventions.