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The development of bimolecular homolytic substitution (S H 2) catalysis has expanded cross-coupling chemistries by enabling the selective combination of any primary radical with any secondary or tertiary radical through a radical sorting mechanism 1 – 8 . Biomimetic 9 , 10 S H 2 catalysis can be used to merge common feedstock chemicals—such as alcohols, acids and halides—in various permutations for the construction of a single C( sp 3 )–C( sp 3 ) bond. The ability to sort these two distinct radicals across commercially available alkenes in a three-component manner would enable the simultaneous construction of two C( sp 3 )–C( sp 3 ) bonds, greatly accelerating access to complex molecules and drug-like chemical space 11 . However, the simultaneous in situ formation of electrophilic and primary nucleophilic radicals in the presence of unactivated alkenes is problematic, typically leading to statistical radical recombination, hydrogen atom transfer, disproportionation and other deleterious pathways 12 , 13 . Here we report the use of bimolecular homolytic substitution catalysis to sort an electrophilic radical and a nucleophilic radical across an unactivated alkene. This reaction involves the in situ formation of three distinct radical species, which are then differentiated by size and electronics, allowing for regioselective formation of the desired dialkylated products. This work accelerates access to pharmaceutically relevant C( sp 3 )-rich molecules and defines a distinct mechanistic approach for alkene dialkylation. We use bimolecular homolytic substitution catalysis to sort an electrophilic radical and a nucleophilic radical across an unactivated alkene, accelerating access to pharmaceutically relevant C( sp 3 )-rich molecules and defining a mechanistic approach for alkene dialkylation.

The development of bimolecular homolytic substitution (SH2) catalysis has expanded cross-coupling logic by enabling the selective merger of any primary radical with any secondary or tertiary radical via a radical sorting mechanism1–8. Biomimetic9,10 SH2 catalysis can be used to merge common feedstock chemicals—such as alcohols, acids, and halides—in any permutation for the construction of a single C(sp3)–C(sp3) bond. The ability to sort these two distinct radicals across commercially available alkenes in a three-component manner would enable the simultaneous construction of two C(sp3)–C(sp3) bonds, greatly accelerating access to drug-like chemical space11. However, the simultaneous in situ formation of electrophilic and primary nucleophilic radicals in the presence of unactivated alkenes is problematic, typically leading to statistical radical recombination, hydrogen atom transfer, disproportionation, and other deleterious pathways12,13. Herein, we report the use of bimolecular homolytic substitution catalysis to sort an electrophilic radical and a nucleophilic radical across an unactivated alkene. This reaction involves the in situ formation of three distinct radical species, which are then differentiated by size and electronics, allowing for regioselective formation of desired dialkylated products. This work accelerates access to pharmaceutically relevant C(sp3)-rich molecules and defines a novel mechanistic paradigm for alkene dialkylation.

Myopia is a global cause of vision impairment, yet its molecular mechanisms remain unclear. We applied a multi-omics approach to the retina, choroid, and sclera of guinea pigs (GPs), a model of spontaneous myopia. Integrated transcriptomic and proteomic analyses suggest a two-state molecular framework. In a myopia-prone state, the choroid and sclera exhibited widespread transcript-protein discordance, with RNA and protein changes in remodeling pathways not aligned in direction, alongside metabolic down-regulation and suppressed immune transcription, a primed yet quiescent state preceding elongation. In a spontaneous myopic state, molecular regulation becomes more concordant, with RNA and protein changing in the same direction, indicating active remodeling, whereas ribosome/translation emerged as a consistent cross-tissue signal. Integration with human myopia GWAS loci, followed by validation of CYP26A1 expression in GP ocular tissues at both transcript and protein levels, highlighted post-transcriptional regulation in the sclera and underscored translational relevance. These findings provide a molecular framework for myopia development and nominate targets in neurogenesis, synaptic remodeling, and translational control for therapeutic intervention.

A new strain of coronavirus (CoV) has caused an outbreak of severe acute respiratory syndrome (SARS), with 8098 individuals being infected and 774 deaths worldwide. We carried out protein chip array profiling analysis in an attempt to identify biomarkers that might be useful in monitoring the clinical course of SARS patients. We performed surface-enhanced laser desorption ionization time-of-flight mass spectrometry on 89 sera collected from 28 SARS patients, 72 sera from 51 control patients with various viral or bacterial infections, and 10 sera from apparently healthy individuals. Nine significantly increased and three significantly decreased serum biomarkers were discovered in the SARS patients compared with the controls. Among these biomarkers, one (11,695 Da) was identified to be serum amyloid A (SAA) protein by peptide mapping and tandem mass spectrometric analysis. When we monitored the SAA concentrations longitudinally in 45 sera from four SARS patients, we found a good correlation of SAA concentration with the extent of pneumonia as assessed by a serial chest x-ray opacity score. Increased SAA occurred in three of four patients at the time of extensive pneumonia as indicated by high x-ray scores. Over the course of gradual recovery in two patients, as assessed clinically and radiologically, SAA concentrations gradually decreased. In the third patient, the concentrations were initially increased, but were further increased with superimposed multiple bacterial infections. SAA was not markedly increased in the fourth patient, who had low x-ray scores and whose clinical course was relatively mild. Protein chip array profiling analysis could be potentially useful in monitoring the severity of disease in SARS patients.

A new diverse Famennian echinoderm fauna (∼600 specimens representing 33 genera and 47 species) dominated by blastoids and cladid, small-calyx camerate, and flexible crinoids is reported from the Hongguleleng Formation, Junggar Basin, Xinjiang-Uygar Autonomous Region, China. Two stratigraphically distinct pelmatozoan faunas were collected: one from the lower member of the Hongguleleng Formation (crepida Zone to marginifera Zone) and one from the upper member of the Hongguleleng Formation (praesulcata Zone). Both faunas are distinctively “Carboniferous” in aspect. The older fauna is dominated by cladids and small-calyx camerates, whereas the younger fauna is dominated by blastoids. Discovery of these two faunas has more than doubled the number of Famennian echinoderm specimens known in the world and more than quadrupled the number of known taxa. Latest Devonian (Famennian) and earliest Carboniferous stemmed-echinoderm (pelmatozoan) faunas traditionally have been considered to be very low diversity relative to earlier Frasnian and later Early Carboniferous faunas. Furthermore, Carboniferous pelmatozoan faunas seemingly arose suddenly, with unclear ancestral ties to Devonian taxa. The Hongguleleng faunas are critical in understanding pelmatozoan biogeography and evolution in the aftermath of Devonian extinction event(s) prior to the Carboniferous echinoderm diversification, as they indicate that diversification and re-radiation of stemmed echinoderms already were well underway before the close of the Famennian. Collections from field excursions in 1993 and 1995 include seven new taxa of blastoids and nine new taxa of crinoids among the twenty-four total taxa reported. New blastoid taxa are Emuhablastus planus, Tripoblastus plicatus, Breimeriblastus pyramidalis, B. gracilis, Conoblastus invaginatus, Sinopetaloblastus grabaui, and Hyperoblastus emuhaensis. Together with collections from 1991, we have amassed 333 blastoid specimens, representing 13 genera and 15 species. Emuhablastus planus, new genus and species, is the oldest genus of the Family Codasteridae, extending the familial record back from the Viséan to the Famennian. The hyperoblastid genera, Breimeriblastus, new genus, and Conoblastus, new genus, apparently represent transitional genera between a Pentremitidea-like ancestor and a Pentremites-like descendant. These taxa imply that the fissiculate-spiraculate transition may have occurred in a mosaic fashion during the Middle to Upper Devonian. Hyperoblastus emuhaensis, new species, is the first report of the genus from rocks of Famennian age or from Asia. New crinoid taxa include Athabascocrinus orientale, Hexacrinites pinnulata, Abactinocrinus devonicus, Euonychocrinus websteri,? Parisocrinus nodosus,? P. conicus, Bridgerocrinus discus, Julieticrinus romeo, and Sostronocrinus quadribrachiatus. In addition, we propose several other taxonomic reassignments based on new collections. Uperocrinus zhaoae is reassigned to the genus Actinocrinus based on the presence of pentagonal or hexagonal primibrachials in the cup, even though the primibrachials have a pseudo-quadrate appearance. Bridgerocrinus delicatulus is reassigned to Logocrinus based on the presence of three, rather than two, primibrachials. Sostronocrinidae, new family, is erected for genera with 20 arms that otherwise might be placed in the Family Scytalocrinidae. Genera included within the Sostronocrinidae, new family, are Sostronocrinus, Hertocrinus, Tundracrinus, and Amadeusicrinus new genus. Bridgerocrinus minutus is reassigned to the genus Sostronocrinus. Pachylocrinus subpentagonalis is reassigned to Amadeusicrinus new genus. “Decadocrinus” xinjiangensis is reassigned to Grabauicrinus new genus, which is erected for decadocrinids with 10 arms, all of which branch on the second primibrachial.

The Oil Refinery (OR) consortium is a model methanogenic enrichment culture used to study anaerobic benzene degradation. Over half of the culture’s bacterial community consists of two closely related Desulfobacterota strains, designated ORM2a and ORM2b, whose mechanisms of benzene activation are unknown. Two new metagenomes, including a complete circularized metagenome-assembled genome (MAG) for ORM2a, enabled a thorough investigation of this culture’s proteome. Among the proteins identified were Bam-like subunits of an ATP-independent benzoyl-CoA degradation pathway, as well as downstream β-oxidation proteins yielding acetate. The most abundant proteins identified mapped to two ORM2a gene clusters of unknown function. Homologous and syntenic gene clusters were identified in genomes of ORM2b and a sulfate-reducing Pelotomaculum that also degrades benzene, as well as in nine contigs assembled from hydrothermal vent metagenomes. Extensive homology and structural predictions suggest that the first cluster – termed the “Magic” gene cluster – encodes for enzymes catalyzing the chemically challenging activation of benzene and subsequent transformation steps yielding benzoyl-CoA. The second (“Nanopod”) gene cluster encodes a transmembrane complex that may facilitate benzene transport across the cell membrane. Phylogenomic analyses place ORM2a and ORM2b within a novel genus of strict anaerobes specialized for benzene degradation, which we propose naming “Candidatus Anaerobenzenivorax”. Benzene is a widespread, persistent and toxic pollutant that can accumulate in anoxic environments such as groundwater and sediments. Despite decades of study, the biochemical mechanisms by which benzene is activated under anaerobic conditions remain unproven. This study provides strong genetic and proteomic evidence for a new class of enzymes that initiate anaerobic benzene activation and proposes a preliminary model for their underlying biochemistry. These findings lay a foundation for future biochemical studies and expand our understanding of how microbes carry out extreme redox chemistry in the absence of oxygen.

Radiotherapy has been an integral treatment modality for cancer. The field arose from and progressed through innovations in physics, engineering, and biology. The evolution of radiation oncology will rely on the continued adoption of advances from other fields. A new area of science that possesses the ability to impact radiation oncology is nanomedicine. Materials on the nanoscale provide many unique properties such as enhanced permeability and retention effect and superparamagnetism that are well suited for applications in radiation oncology. In this review, we will provide a comprehensive summary on how nanotechnology can improve cancer radiotherapy in aspects of treatment delivery and monitoring as well as diagnosis.