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Iron accumulation in tumors contributes to disease progression and chemoresistance. Although targeting this process can influence various hallmarks of cancer, the immunomodulatory effects of iron chelation in the tumor microenvironment are unknown. Here, we report that treatment with deferiprone, an FDA-approved iron chelator, unleashes innate immune responses that restrain ovarian cancer. Deferiprone reprogrammed ovarian cancer cells toward an immunostimulatory state characterized by the production of type-I IFN and overexpression of molecules that activate NK cells. Mechanistically, these effects were driven by innate sensing of mitochondrial DNA in the cytosol and concomitant activation of nuclear DNA damage responses triggered upon iron chelation. Deferiprone synergized with chemotherapy and prolonged the survival of mice with ovarian cancer by bolstering type-I IFN responses that drove NK cell-dependent control of metastatic disease. Hence, iron chelation may represent an alternative immunotherapeutic strategy for malignancies that are refractory to current T-cell-centric modalities. Significance: This study uncovers that targeting dysregulated iron accumulation in ovarian tumors represents a major therapeutic opportunity. Iron chelation therapy using an FDA-approved agent causes immunogenic stress responses in ovarian cancer cells that delay metastatic disease progression and enhance the effects of first-line chemotherapy. See related commentary by Bell and Zou, p. 1771., (©2024 American Association for Cancer Research.)

Objective: Cerebral amyloidomas (CA) are exceptionally rare tumor-like lesions composed of cerebral amyloid-beta, which is derived from the cleavage of the amyloid precursor protein., Methods: We presented a case of recurrent CA and performed a systematic review, comparing their initial presentation, imaging features, neurosurgical treatment, and natural history of the disease., Illustrative Case: A 65-year-old male with a history of right homonymous hemianopsia, who underwent subtotal resection of a CA 19 years before, presents to the emergency department with right hemiparesis, dysarthria, and a new onset of clonic seizures. Imaging revealed a left parieto-occipital lesion with calcifications and vasogenic edema. A gross-total resection was performed. Histopathology revealed a hypocellular eosinophilic lesion consistent with CA. Postoperatively, the patient recovered without new neurological deficits. One-year follow-up magnetic resonance imaging showed no residual or recurrence lesion., Search Results: Eighty-seven cases, including ours, revealed that 65.5% (n = 57) were females with a median age of 54 years (IQR: 46-62). Most lesions were solitary (82.7%; 72 of 87 lesions). Frontal and parietal lobes were most commonly affected with 32.9% (n = 28) and 30.5% (n = 26), respectively. Seizures were the most common symptom followed by visual compromise. Calcifications were present in 19.5% (n = 17) of the lesions., Conclusions: This systematic review provides insights into the epidemiological, clinical, and neurosurgical characteristics, as well as the long-term prognosis of CA. This marks the first case in the reviewed literature with a 19-year period of follow-up where the patient had reoperation due to disease progression., (Copyright © 2024 Elsevier Inc. All rights reserved.)

The recent acceleration of commercial, private and multi-national spaceflight has created an unprecedented level of activity in low Earth orbit, concomitant with the largest-ever number of crewed missions entering space and preparations for exploration-class (lasting longer than one year) missions. Such rapid advancement into space from many new companies, countries and space-related entities has enabled a 'second space age'. This era is also poised to leverage, for the first time, modern tools and methods of molecular biology and precision medicine, thus enabling precision aerospace medicine for the crews. The applications of these biomedical technologies and algorithms are diverse, and encompass multi-omic, single-cell and spatial biology tools to investigate human and microbial responses to spaceflight. Additionally, they extend to the development of new imaging techniques, real-time cognitive assessments, physiological monitoring and personalized risk profiles tailored for astronauts. Furthermore, these technologies enable advancements in pharmacogenomics, as well as the identification of novel spaceflight biomarkers and the development of corresponding countermeasures. In this Perspective, we highlight some of the recent biomedical research from the National Aeronautics and Space Administration, Japan Aerospace Exploration Agency, European Space Agency and other space agencies, and detail the entrance of the commercial spaceflight sector (including SpaceX, Blue Origin, Axiom and Sierra Space) into aerospace medicine and space biology, the first aerospace medicine biobank, and various upcoming missions that will utilize these tools to ensure a permanent human presence beyond low Earth orbit, venturing out to other planets and moons., (© 2024. Springer Nature Limited.)

Spaceflight induces molecular, cellular and physiological shifts in astronauts and poses myriad biomedical challenges to the human body, which are becoming increasingly relevant as more humans venture into space 1-6 . Yet current frameworks for aerospace medicine are nascent and lag far behind advancements in precision medicine on Earth, underscoring the need for rapid development of space medicine databases, tools and protocols. Here we present the Space Omics and Medical Atlas (SOMA), an integrated data and sample repository for clinical, cellular and multi-omic research profiles from a diverse range of missions, including the NASA Twins Study 7 , JAXA CFE study 8,9 , SpaceX Inspiration4 crew 10-12 , Axiom and Polaris. The SOMA resource represents a more than tenfold increase in publicly available human space omics data, with matched samples available from the Cornell Aerospace Medicine Biobank. The Atlas includes extensive molecular and physiological profiles encompassing genomics, epigenomics, transcriptomics, proteomics, metabolomics and microbiome datasets, which reveal some consistent features across missions, including cytokine shifts, telomere elongation and gene expression changes, as well as mission-specific molecular responses and links to orthologous, tissue-specific mouse datasets. Leveraging the datasets, tools and resources in SOMA can help to accelerate precision aerospace medicine, bringing needed health monitoring, risk mitigation and countermeasure data for upcoming lunar, Mars and exploration-class missions., (© 2024. The Author(s).)

Procedures for the preparation of transition metal complexes having intact bicyclic cepham or penam systems as ligands have been developed. Starting from readily available 4-azido-2-azetidinones, a synthetic approach has been tuned using a copper-catalyzed azide-alkyne cycloaddition between 3-azido-2-azetinones and alkynes, followed by methylation and transmetalation to Au(I) and Ir(III) complexes from the mesoionic carbene Ag(I) complexes. This methodology was applied to 6-azido penam and 7-azido cepham derivatives to build 6-(1,2,3-triazolyl)penam and 7-(1,2,3-triazolyl)cepham proligands, which upon methylation and metalation with Au(I) and Ir(III) complexes yielded products derived from the coordination of the metal to the penam C 6 and cepham C 7 positions, preserving intact the bicyclic structure of the penicillin and cephalosporin scaffolds. The crystal structure of complex 28b , which has an Ir atom directly bonded to the intact penicillin bicycle, was determined by X-ray diffraction. This is the first structural report of a penicillin-transition-metal complex having the bicyclic system of these antibiotics intact. The selectivity of the coordination processes was interpreted using DFT calculations.

Maintenance of astronaut health during spaceflight will require monitoring and potentially modulating their microbiomes. However, documenting microbial shifts during spaceflight has been difficult due to mission constraints that lead to limited sampling and profiling. Here we executed a six-month longitudinal study to quantify the high-resolution human microbiome response to three days in orbit for four individuals. Using paired metagenomics and metatranscriptomics alongside single-nuclei immune cell profiling, we characterized time-dependent, multikingdom microbiome changes across 750 samples and 10 body sites before, during and after spaceflight at eight timepoints. We found that most alterations were transient across body sites; for example, viruses increased in skin sites mostly during flight. However, longer-term shifts were observed in the oral microbiome, including increased plaque-associated bacteria (for example, Fusobacteriota), which correlated with immune cell gene expression. Further, microbial genes associated with phage activity, toxin-antitoxin systems and stress response were enriched across multiple body sites. In total, this study reveals in-depth characterization of microbiome and immune response shifts experienced by astronauts during short-term spaceflight and the associated changes to the living environment, which can help guide future missions, spacecraft design and space habitat planning., (© 2024. The Author(s).)

Objectives: Serratia marcescens (SM) may cause nosocomial outbreaks in Neonatal Intensive Care Units (NICU). We describe an outbreak of SM in a NICU and propose additional prevention and control recommendations., Methods: Between March 2019 and January 2020, samples were taken from patients in the NICU (rectal, pharyngeal, axillary and other locations) and from 15 taps and their sinks. Control measures were implemented including thorough cleaning of incubators, health education to staff and neonates'relatives, and use of single-dose containers. PFGE was performed in 19 isolates from patients and in 5 environmental samples., Results: From the first case in March 2019 to the detection of the outbreak, a month elapsed. Finally, 20 patients were infected and 5 colonized. 80% of infected neonates had conjunctivitis, 25% bacteremia, 15% pneumonia, 5% wound infection, and 5% urinary tract infection. Six neonates had two foci of infection. Among the 19 isolates studied, 18 presented the same pulsotype and only one of the isolates from the sinkhole showed a clonal relationship with those of the outbreak. Initial measures established were ineffective to control de outbreak and were implemented with exhaustive cleaning, use of individual eye drops, environmental sampling and changing sinks., Conclusion: This outbreak presented a high number of neonates affected due to its late detection and torpid evolution. The microorganisms isolated from the neonates were related to an environmental isolate. Additional prevention and control measures are proposed, including routine weekly microbiological sampling., (Copyright © 2023 Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica. Published by Elsevier España, S.L.U. All rights reserved.)

Antimicrobial resistance (AMR) poses a critical threat to global health and development, with environmental factors-particularly in urban areas-contributing significantly to the spread of antibiotic resistance genes (ARGs). However, most research to date has been conducted at a local level, leaving significant gaps in our understanding of the global status of antibiotic resistance in urban environments. To address this issue, we thoroughly analyzed a total of 86,213 ARGs detected within 4,728 metagenome samples, which were collected by the MetaSUB International Consortium involving diverse urban environments in 60 cities of 27 countries, utilizing a deep-learning based methodology. Our findings demonstrated the strong geographical specificity of urban environmental resistome, and their correlation with various local socioeconomic and medical conditions. We also identified distinctive evolutionary patterns of ARG-related biosynthetic gene clusters (BGCs) across different countries, and discovered that the urban environment represents a rich source of novel antibiotics. Our study provides a comprehensive overview of the global urban environmental resistome, and fills a significant gap in our knowledge of large-scale urban antibiotic resistome analysis., (© 2024. Science China Press.)

The reaction between bis(1,2,3-triazol-1-yl)methane derivatives and n BuLi and various aldehydes, yielded novel neutral ligand precursors incorporating alcohol functional groups. The resulting compounds exhibited distinct characteristics depending on the steric hindrance of the aldehyde employed. In instances where aromatic aldehydes were utilized, functionalization occurred at the methine group bridging both triazole rings. Conversely, the use of pivalic aldehyde prompted functionalization at the C 5 position of the triazole ring. These compounds were subsequently employed as ligand precursors in the synthesis of organometallic aluminum and zinc complexes, yielding dinuclear complexes with high efficiency. The structural elucidation of all compounds was accomplished through spectroscopic methods and validated by X-ray crystallography. Preliminary catalytic investigations into the coupling reaction of cyclohexene oxide and CO 2 revealed that aluminum and zinc complexes catalyzed the selective formation of polyether and polycarbonate materials, respectively., (© 2024 The Authors. Chemistry - A European Journal published by Wiley-VCH GmbH.)

Improving human healthspan in our rapidly aging population has never been more imperative. Telomeres, protective "caps" at the ends of linear chromosomes, are essential for maintaining genome stability of eukaryotic genomes. Due to their physical location and the "end-replication problem" first envisioned by Dr. Alexey Olovnikov, telomeres shorten with cell division, the implications of which are remarkably profound. Telomeres are hallmarks and molecular drivers of aging, as well as fundamental integrating components of the cumulative effects of genetic, lifestyle, and environmental factors that erode telomere length over time. Ongoing telomere attrition and the resulting limit to replicative potential imposed by cellular senescence serves a powerful tumor suppressor function, and also underlies aging and a spectrum of age-related degenerative pathologies, including reduced fertility, dementias, cardiovascular disease and cancer. However, very little data exists regarding the extraordinary stressors and exposures associated with long-duration space exploration and eventual habitation of other planets, nor how such missions will influence telomeres, reproduction, health, disease risk, and aging. Here, we briefly review our current understanding, which has advanced significantly in recent years as a result of the NASA Twins Study, the most comprehensive evaluation of human health effects associated with spaceflight ever conducted. Thus, the Twins Study is at the forefront of personalized space medicine approaches for astronauts and sets the stage for subsequent missions. We also extrapolate from current understanding to future missions, highlighting potential biological and biochemical strategies that may enable human survival, and consider the prospect of longevity in the extreme environment of space., (© 2024. The Author(s).)

Importance: A reliable evaluation of anterolateral rotatory instability in the anterior cruciate ligament (ACL) deficient knee is important to help surgeons determine which patients might need concurrent anterolateral augmentation procedures., Objective: The purpose of this study was to systematically review studies that assess the intra-observer and inter-observer reliability of instruments used to measure anterolateral rotatory laxity of the knee., Evidence Review: A comprehensive literature review was conducted according to the 2020 Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement, using PubMed, Embase, Scopus, and Google Scholar databases for original, English-language studies evaluating the reliability of objective or instrument-based anterolateral rotatory laxity of the knee until October 31, 2022. Reliability data were extracted from text, tables, and figures., Findings: Twelve studies, with patients between the ages of 14-63 years, were included. The instruments used to measure anterolateral rotatory knee laxity included inertial sensors (n ​= ​9), magnetic resonance imaging (n ​= ​1), and navigation systems (n ​= ​2). The global intra-observer intraclass correlation coefficient for these devices was between 0.63 and 0.97, and the global inter-observer reliability was between 0.63 and 0.99., Conclusion and Relevance: Instrument-based anterolateral rotatory knee laxity assessment has moderate to good intra- and inter-observer reliability. Evaluating anterolateral instability in ACL-deficient knees with these devices could help in decision-making when considering anterolateral augmentation., Level of Evidence: IV., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

A method has been developed for synthesizing [FeFe]-H 2 ase mimics with diverse structures and properties, employing cross-metathesis of olefins. Vinylmetallocenes (5 and 6) and vinyl half-sandwich complexes (10 and 11) have been used as cross-metathesis partners with [FeFe]-H 2 ase mimics (4, 8, and 9) bearing a double bond in the moiety attached to the ADT-bridge nitrogen. Electrochemical studies of these complexes, encompassing metallocene-type (7a-b, 12a-b, and 13a-b) as well as half-sandwich derivatives (12c and 13c-d), have demonstrated that the introduction of a redox unit has a marginal impact on the reduction potential of these [FeFe]-H 2 ase mimics. The application of this cross-metathesis approach has allowed the synthesis of [FeFe]-H 2 ase mimics featuring an Ir(III) electrochemical antenna (16-18) as well as systems having an electron-donor-photosensitizer structure (ED-PS) (23). The electrocatalytic properties of these complexes have been elucidated through electrochemical studies.