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Jupiter, a rapidly rotating gas giant, features over 20 atmospheric jet streams that penetrate thousands of kilometers into the planet. This work discusses recent progress, identifies key uncertainties regarding the jets’ driving and dissipating mechanisms, and suggests future research avenues.
Monteggia-like lesions represent a rare and complex injury with diverse fracture configurations. To assess short- to mid-term outcomes of patients with Monteggia-like lesions treated surgically at our institution. To analyze the results based on fracture type and surgical experience. A single-center retrospective study including 33 patients surgically treated between 2017 and 2024 was conducted. Fractures were classified using Bado, Jupiter, Mason and Regan-Morrey systems. Clinical, surgical, and functional parameters were evaluated, including complication and reoperation rates. Mean age was 58.7years; 63.3% were female. Average joint range of motion: flexion 130.76°, extension -14.55°, pronation 80.48°, supination 82.82°. Average functional scores: MEPS 81.97, Oxford 42.73, VAS 2.4. Arthrolysis combined with prosthetic explantation was performed in 23.1% of radial head arthroplasties. Complication rate was 21.2%. No significant differences were observed based on fracture type/pattern. Outcomes were significantly better in cases managed by experienced elbow surgeons. Further studies are required to define this entity independently from the classical lesion. The results of the present study suggest that a comprehensive management of all associated injuries, performed by experienced teams, could be associated with favorable clinical outcomes.
The purpose of this study was to compare the clinical and radiographic outcomes 5 years after randomization to volar plating or combined plating for surgical treatment of an AO (Arbeitsgemeinschaft für Osteosynthesefragen) type C distal radius fracture (DRF). A total of 150 patients were previously randomized to a volar locking plate or combined plating for treatment of an AO type C DRF with strict inclusion and exclusion criteria. All participating patients were invited for a 5-year postoperative follow-up. Radiographs, pain (visual analog scale), grip strength, and range of motion were documented, along with the Patient-Rated Wrist Evaluation, Quick Disabilities of the Arm, Shoulder, and Hand, and EuroQol 5-Dimension questionnaires. Arthritis in the radiocarpal and distal radioulnar joint was graded on radiographs by a senior radiologist according to the Knirk and Jupiter classification. There were 135 patients (66 in the volar plate group and 69 in the combined plating group), corresponding to a 90% follow-up rate. Median age at follow-up was 67 years (interquartile range 57-75). There was no difference in radiographic arthritis between the two groups. The volar plate group had significantly better outcomes in flexion, extension, radial deviation, and Patient-Rated Wrist Evaluation (P < .05). There were no significant between-group differences in the Quick Disabilities of the Arm, Shoulder, and Hand, EuroQol 5-Dimension index, or EuroQol Visual Analog Scale (P > 05). Hardware removal was significantly more common in the combined plating group (64%) than in the volar plate group (30%) (P < .001). Among surgically treated patients with AO type C DRF, those operated with volar plating had better clinical outcomes 5 years after surgery compared to those treated with combined plating, but the minimal clinically important difference was not reached. These findings support volar plating as the preferred method for AO type C DRFs. Therapeutic I.
Atherosclerosis is recognized as a chronic inflammatory disease, with high-sensitivity C-reactive protein (hs-CRP) serving as a biomarker of cardiovascular risk that persists despite optimal control of traditional risk factors. Landmark trials, like JUPITER (Justification for the Use of Statins in Prevention) and PROVE-IT (Pravastatin or Atorvastatin Evaluation and Infection Therapy), demonstrate the effect of lipid-lowering medications on inflammation. This can have further implications for comprehensive cardiovascular risk reduction. Statins lower hs-CRP alongside low-density lipoprotein cholesterol (LDL-C), with greater effects from high-intensity regimens. Nonstatin medications have variable effects; for example, the addition of ezetimibe to statin therapy enhances hs-CRP reduction. Bempedoic acid exerts direct anti-inflammatory effects, producing significant hs-CRP lowering. Omega-3 fatty acids also demonstrate favorable effects on inflammatory markers. However, fibrates offer only marginal benefits, and PCSK9 inhibitors (Proprotein Convertase Subtilisin/Kexin type 9) have minimal impact. Residual inflammatory risk persists despite LDL-C control, supporting dual-target strategies. The evidence supports therapeutic strategies targeting both lipid and inflammatory pathways, with hs-CRP serving as a complementary marker to refine cardiovascular risk stratification and guide treatment intensification in primary and secondary prevention. Future studies should evaluate inflammation-targeted adjunctive therapies to address discordance between lipid control and residual inflammatory risk.
Asbestos remains a leading occupational carcinogen, particularly in countries where its use persists despite known health risks. This study provides a systematic analysis of the burden of cancer attributable to occupational asbestos exposure in the Americas from 1990 to 2023, using estimates from the Global Burden of Disease (GBD) Study 2023. Age-standardised mortality and disability-adjusted life-years (DALYs) attributable to asbestos were analysed for mesothelioma, lung, laryngeal, and ovarian cancers, stratified by sex and region. We conducted a descriptive analysis to assess spatiotemporal trends in the burden of cancer attributable to occupational asbestos in the Americas from 1990 to 2023. We analysed trends in age-standardized mortality and DALY rates using segmented joinpoint regression. Age-period-cohort analyses were performed for age-specific mortality and DALY rates. All analyses were stratified by cancer type, sex and GBD regions, with estimated 95% uncertainty intervals (95% UI). In 2023, High-income North America had the highest burden of cancer attributable to occupational asbestos, with 5·1 deaths (95% UI 3·9; 6·4) and 84·9 DALYs (65·6; 108·5) per 100,000 population for both sexes. However, the region also experienced the most pronounced decline, with average annual reductions of 2·0% (-2·0; -1·9) in mortality and 2·5% (-2·5; -2·4) in DALYs. Southern Latin America had the second highest rates for cancer attributable to occupational asbestos, with 2·7 deaths (2·1; 3·5) and 53·1 DALYs (40·4; 69·3) for both sexes in 2023, and showed the strongest increase in women with 2·3% (2·2; 2·4) both in mortality and DALYs annually. Age-period-cohort modelling revealed marked increases in burden of cancer attributable to occupational asbestos among women, with mortality and DALY rate ratios (RR) for lung cancer rising to 1·31 (1·20; 1·44) in Tropical and Southern Latin America, and RR for mesothelioma rising to 1·22 (1·06; 1·40) in Southern Latin America. Our study revealed inequalities in the burden of cancer attributable to occupational asbestos exposure among regions in the Americas, as well as remarkable sex disparities. Although rates were declining in North America, there is growing concern over rising rates of lung cancer and mesothelioma among women in Tropical and Southern Latin America regions, especially in Argentina and Brazil. These disparities likely reflect differences in environmental and industrial regulatory practices, as well as gendered occupational exposure patterns. Also, upward trends in female lung cancer rates may reflect increased smoking among women, while mesothelioma is much more specific to asbestos exposure. Despite regulatory advances, legacy exposures and ongoing asbestos use persist in parts of Latin America, reinforcing the need for stricter occupational health policies and asbestos bans. The findings underscore the shifting epidemiology of asbestos-related cancers and call for targeted prevention efforts, improved surveillance, and gender-responsive occupational protections. This study was partially funded by the Bill & Melinda Gates Foundation and "Coordenação de Aperfeiçoamento de Pessoal de Nível Superior-Brasil (CAPES)".
CD8+ T cells responding to chronic infections are functionally and spatially heterogeneous. In this issue of Immunity, Shen et al. and Geng et al. demonstrate that the transcription factors KLF2 and KLF3 have integrated but opposing roles in regulating tissue residency and terminal exhaustion.
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Despite extensive research, molecular differences in human populations and the influence of ancestry, age, geography, and diet are poorly understood. We performed comprehensive multiomics profiling (including genomics, transcriptomics, proteomics, metabolomics, lipidomics, metallomics, glycomics, and microbiomics) on samples from 322 healthy individuals of European, East Asian, and South Asian ancestry across multiple continents. We identified ethnicity-associated molecular features linked to host metabolism, autoimmune disease risk, drug metabolism, and neurodegenerative pathways. We uncovered ancestry- and geography-related molecular changes affecting metabolism, immune function, microbiome composition, and biological aging. Specific genetic variants and gene expression differences were associated with lipid metabolism and immune regulation. Geography influenced biological age: East Asians showed lower biological age in their ancestral regions, whereas individuals of European ancestry exhibited lower biological age in the US/Canada than in Europe. Diet-microbiome metabolism interactions displayed ethnicity-specific patterns, many related to health. This open access resource advances understanding of ethnicity-environment interactions and supports precision medicine.
Viruses are abundant and widespread in extreme marine environments, such as sea ice, hydrothermal vents, and ocean trenches. They occur at temperatures up to 122 °C and down to -30 °C and pressures exceeding 100 MPa. Their distribution in these environments is closely correlated with that of their extremophile hosts, which are mostly bacteria, archaea, and microeukaryotes. Viruses have been shown to be capable of long-term survival in conditions simulating interstellar conditions. However, for them to reproduce, they would still need a host. Many recent astro-biological investigations have focused on habitability, specifically the ability of a planet to support the activity of at least one lifeform. The most likely candidates for extraterrestrial habitability in our solar system are the sea ice moons of Jupiter and Saturn, namely Europa and Enceladus. These are both thought to contain subsurface oceans of liquid water and potentially access to the necessary elements for microbial growth. If microorganisms were to be detected in these extraterrestrial environments, viruses might also be found coexisting with their host cells.
Unremitting increases in lung vascular permeability is the pathophysiological hallmark of acute lung injuries (ALI) and drives both severity and mortality. Therapies with the capacity to quickly restore vascular integrity in ALI remains a serious unmet need. Our laboratory was first to report both the vascular barrier-protective effects of sphingosine-1 -phosphate (S1P) and S1P analogues, such as Tysiponate (TySIP), and the efficacy of peptide inhibitors (PIK) of non-muscle myosin light chain kinase (nmMLCK) as dual complementary strategies to reduce vascular permeability. The current study evaluates a novel nanocarrier (NTyP-100) containing conjugated TySIP and encargoed PIK as a pharmacologic approach to vascular barrier restoration in rodent models of LPS-induced ALI. NTyP-100 (or controls) was delivered IV to wild-type C57BL/6J mice exposed to a "one-hit" lipopolysaccharide (LPS, 18 h) ALI model or to Sprague-Dawley (SD) rats challenged by a "two-hit" ALI model combining LPS (18 h) and exposure to high tidal volume mechanical ventilation (MV, 4 h). Compared to TySIP or PIK alone, IV NTyP-100 produced the highest reduction (∼40%) in inflammatory injury in murine and rat ALI models (H&E, IHC p-MLC staining, BAL cells) with marked reductions in vascular leak (Evan Blue Dye leakage, BAL protein) and biochemical indices of inflammation. Genomic studies underscored NTyP-100 attenuation of ALI-mediated dysregulated barrier-regulatory signaling pathways (inflammatory response, innate immunity, TNF, IL-17, apoptosis). These studies demonstrate the successful therapeutic targeting of vascular barrier properties and supports the NTyP-100 nanocarrier as a strategy to address the unmet need for novel therapeutics that mitigate inflammatory injury and vascular permeability.
Here we show that large language models (LLMs) can be transformed via supervised fine-tuning of engineered prompts into SmileyLlama for exploring the chemical space of drug molecules. We benchmark SmileyLlama against pretrained LLMs and chemical language models trained from scratch for generating valid and novel drug-like molecules, and use direct preference optimization to both improve SmileyLlama's adherence to a prompt and as part of the iMiner reinforcement learning framework to predict molecules with optimized three-dimensional conformations and high binding affinity to drug targets. By training an LLM to speak directly as a chemical language model, while retaining most of its natural language capabilities, we show that SmileyLlama can reliably generate molecules with user-specified properties rather than acting only as a chatbot with knowledge of chemistry or as a virtual assistant. While SmileyLlama is geared toward drug discovery, the supervised fine-tuning/direct preference optimization/LLM framework can be extended to other chemical, biological and materials applications.
Postherpetic neuralgia (PHN) is a possible chronic sequela of trigeminal herpes zoster characterized by persistent neuropathic pain that can complicate odontogenic pain assessment. Little is known about potential associations between zoster/PHN and periapical complications years after the acute episode, or whether such pathology might respond to conservative antiviral-antibiotic therapy. This case report describes a 40-year-old man with a childhood varicella history who developed trigeminal herpes zoster in the right mandibular division-preceded by prodromal odontalgia, followed by a vesicular rash, and mild PHN persisting thereafter. At age 46, despite no clinical symptoms in the affected region beyond stable PHN and no prior radiographic evidence of periapical abnormality, a new periapical radiolucency appeared at tooth #29 (Universal), while tooth #30 showed an area of altered opacity. Tooth #29 was nonresponsive to cold testing and was diagnosed with pulp necrosis with asymptomatic apical periodontitis, requiring endodontic treatment. In contrast, tooth #30 remained responsive to cold testing, indicating a vital pulp, but developed acute localized pain and gingival inflammation several weeks later; this resolved with valacyclovir-amoxicillin, and the tooth has remained radiographically stable for over 2 years without further intervention. This case illustrates successful conservative management of delayed apical pathology in chronic trigeminal PHN and the diagnostic challenge of distinguishing neuropathic from odontogenic pain. Future research should explore links between varicella-zoster virus reactivation/PHN and periapical disease, including PHN as a potential risk factor or marker.
The search for life now extends beyond the traditional habitable zone to include the icy moons of Jupiter and Saturn. These moons feature ice-covered surfaces overlying substantial oceans formed primarily of liquid water and other potential constituents, such as ammonia. On Earth, ammonia supports biochemistry at low concentrations by providing nitrogen but becomes disruptive at higher concentrations. Ammonia could therefore influence the habitability of extraterrestrial oceans, yet this topic has received limited attention in the literature. This review synthesises current research on ammonia in Saturn's icy moons, Enceladus and Titan, and its effects on terrestrial life. We summarize the celestial incorporation, speciation, and phase behaviour of ammonia and review data on its occurrence and concentration in icy moon oceans. We examine the role of ammonia in prebiotic chemistry, biochemistry, and toxicity. Focusing on bacteria, we compare known survival limits in ammonia to estimated ammonia concentrations on Enceladus and Titan. We find that bacterial survival limits exceed concentrations estimated on Enceladus, but are below those estimated on Titan, and propose that ammonia measurements are crucial for assessing extraterrestrial habitability. Finally, we highlight outstanding knowledge gaps and challenges that influence our understanding of how ammonia shapes the potential for life beyond Earth.
Design of high-performance ammonia electrosynthesis systems based on the lithium redox-mediated nitrogen reduction reaction (Li-NRR) requires an understanding of the interplay between the reaction kinetics and mass transport. To advance this currently insufficient understanding, we developed a wall-jet electrode flow cell and used it to investigate the Li-NRR and key processes occurring in the system, namely, the reduction of Li+, formation of Li3N and LiH, and protonation of the lithium-based electrodeposits, as a function of mass-transport conditions. The effects of the latter were found to be electrolyte-dependent when tetrahydrofuran was used as a solvent and 0.1 M C2H5OH as a proton carrier. In 1 M LiBF4, the Li-NRR showed high mass-transport sensitivity, achieving the highest faradaic efficiency of 75 ± 2% when the optimal Li3N-to-LiH ratio was provided. The performance with 2 M LiNTf2 was also defined by the Li3N:LiH ratio but followed opposite dependencies on the flow rate as compared to LiBF4. The overall reduction rate with 2 M LiNTf2 exhibited minimal sensitivity to mass transport, likely due to the intensified passivation of the cathode at high flow rates. The 1 M LiNTf2 electrolyte demonstrated pronounced effects of the mass transport on the overall reduction rate, which, however, was dominated by side reactions rather than the Li-NRR under examined conditions. Our study shows that intensifying mass transport only cannot improve the ammonia production rates while maintaining high faradaic efficiency. Adjusting the electrolyte solution flow rate in the Li-NRR systems necessitates reoptimization of N2 pressure, proton carrier concentration, and/or electrolyte composition.
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Protein kinase R (PKR) is a critical component of mammalian intracellular antiviral immunity. Here, we examine the process of PKR activation in response to Middle East respiratory syndrome coronavirus (MERS-CoV) and Zika virus (ZIKV) using super-resolution confocal microscopy, proximity ligation assay, immunogold transmission electron microscopy, and live-cell imaging. Our data support that PKR activates upon condensation on double-stranded RNA (dsRNA) exposed at membrane-associated viral replication complexes. Subsequently, p-PKR condensates disassociate from dsRNA and dissolve, releasing activated PKR molecules into the cytosol, where they phosphorylate eIF2α to initiate the integrated stress response (ISR). Importantly, the disassociation of p-PKR from dsRNA allows for the exchange of inactive PKR monomers, thus promoting robust PKR activation from limited exposed viral dsRNA substrates. MERS-CoV NS4a prevents PKR activation via competitive condensation on viral dsRNA. These findings establish a comprehensive model for PKR activation in response to positive-strand RNA viruses that replicate within membrane-associated complexes.
We discovered a thiolate-reactive α,α-gem-dibromo lactam warhead that activates transcription factor Nrf2 and demonstrates anti-inflammatory activities, which have implications in cancer, neurodegeneration, and cardiovascular diseases. Our findings originated from new compounds accessed through aza-oxyallyl cation-mediated [3+2]-cycloadditions of ajmalicine and inspired indoles. RNA-seq and Ingenuity Pathway Analysis illuminated detailed transcriptional profiles of α,α-gem-dibromo lactams to show activation of the antioxidant Keap1/Nrf2 pathway and suppressed NF-κB-mediated inflammatory signaling. We demonstrated the importance of the α,α-gem-dibromo lactam, as the corresponding α,α-gem-dichloro lactam is unable to activate the Nrf2 pathway. Chemical reactions with cysteine-containing compounds suggested α,α-gem-dibromo lactams react with cysteine residues to transfer electrophilic bromine to target molecules, linking unique chemistry to our biological findings. In contrast to electrophiles that activate the canonical Nrf2 pathway by covalently targeting C151 of Keap1, the α,α-gem-dibromo lactams function in a C151-independent manner, indicating a distinct selectivity and consequently mode of action. Pharmacological profiling of several α,α-gem-dibromo lactams compared with ajmalicine against adrenergic receptors revealed substantial differences, indicating tunability and novel pharmacology. Future investigations aim to explore the fundamental activities of the dibromo lactam warhead related to human disease. Installation of this warhead into various molecular scaffolds may be a generalizable method to create cystein-reactive electrophiles.
Pathogenic variants in GNAO1 cause a spectrum of epilepsy, movement disorders, and developmental impairment. Clinical heterogeneity complicates prognosis and therapeutic development. We present the first longitudinal natural history study of GNAO1-related disorders (GNAO1-RD) to delineate phenotypic trajectories. Sixty-six individuals with GNAO1-RD were included in a cross-sectional analysis. Of these, 21 were enrolled in a prospective natural history arm (March 2021-December 2024), undergoing annual standardized evaluations with validated clinical scales to monitor phenotypic progression. Our cohort exhibited broad phenotypic and severity variability. GNAO1-RD severity scores ranged from 0.5 to 13. Neurodevelopmental impairment varied: 45.5% lacked head control, whereas 22.7% achieved independent walking; and 65% had no expressive language. Movement disorders were nearly universal (95.5%), with dyskinetic crises in 54.5%. Epilepsy affected 51.5%, with different seizure types. Individuals carrying recurrent variants showed consistent phenotypes and severity, supporting a genotype-phenotype correlation reinforced by molecular functional data. Molecular functional analysis for 20 of 31 missense variants correlated with severity scores. Longitudinal data from 21 patients in the natural history cohort showed overall stability or mild improvement across most functional domains. No significant deterioration was observed in global severity, motor function, cognition, or quality of life. However, severe patients experienced progressive worsening of movement disorder. This largest GNAO1-RD cohort and first longitudinal natural history study provide insights into disease progression. GNAO1-RD generally follows a non-degenerative course, showing stability or mild improvements over time in cognition, language, adaptive skills, and motor function. Importantly, although global severity scores remained stable overall, severe cases showed cumulative functional burden driven by progressive movement disorder, rather than global neurodegeneration. Mortality occurred in a subset of patients because of complications from dyskinetic crises, infections, and epilepsy-related events. Genotype-phenotype data and the GNAO1-RD severity score support early risk stratification and personalized treatment development. ANN NEUROL 2026.
Accessible autonomous racing can engage undergraduate students emersed in artificial intelligence (AI) and robotics to receive an education through the excitement of maneuvering sharp corners and overtaking opponents. In particular, the construction and programming of miniature mobile racing robots can facilitate head-to-head racing competitions for use indoors within classrooms and hallways. Unfortunately, existing racing platforms remain inaccessible for overtaking maneuvers in such confined settings because they are physically large or expensive due to the computational cost of enabling such high performance. In an attempt to address these issues, we present Pocket Racer, an open-source, pocket-sized racing robot capable of head-to-head racing within indoor environments in education, i.e. university hallways or classrooms. We demonstrate head-to-head autonomous racing with our Pocket Racer platforms, enabling high speed overtaking upwards of 15 km/h. Designed to be easily assembled with off the shelf components and a low-cost edge device (Raspberry Pi Zero 2 W), our Pocket Racer platform is made accessible through an open source website and dataset detailing build instructions. By making a pocket-sized head-to-head autonomous racing platform accessible for undergraduate students, our work hopes to further hands on education in the age of physical AI.
We review the key observations and theories relevant to the origin and evolution of the Galilean satellites. Key observations include: the potentially undifferentiated nature of Callisto; the increasing ice fraction with semi-major axis; the present-day existence of the Laplace resonance; the potential resurfacing of Ganymede mid-way through its evolution; and the metal-enriched nature of Jupiter's envelope. The most widely accepted theory for the formation of the satellites is the so-called "starved disk" model, although newer alternatives including decretion disks and pebble accretion have also been proposed. Models that allow slow satellite formation in a cold disk are preferred, based on the density progression and Callisto's apparent differentiation state. Major model uncertainties include the angular momentum distribution of the material infalling to the circumplanetary disk, the source of the solids, and the thermal and viscosity structure of the disk. We identify six outstanding questions, some of which will be answered by JUICE, Europa Clipper and Tianwen-4. A major difficulty in answering some questions is overprinting of primordial characteristics by later events.