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A superbug rose to the top after gaining a chemical weapon
Enantio-, atrop-, and diastereoselective macrolactonization to access type III cyclophanes
Study on the effect of high energy ultrasonic wave on MIG welding deformation and welding joint performance of LC52 aluminum alloy plate
Nickel catalyzed C-N coupling of haloarenes with B2N4 reagents
Abstract Carbon-heteroatom bond (especially for C-N bond) formation through nickel catalysis has seen significant development. Well-established Ni(0)/Ni(II) redox cycle and photoinduced Ni(I)/Ni(III) redox cycle have been the dominant mechanisms. We report a thermally driven Ni-catalyzed method for C-N bond formation between haloarenes and B2N4 reagents, yielding N,N-dialkylaniline derivatives in good to excellent yields with broad functional group tolerance under base-free conditions. The catalytic protocol is useful for base-sensitive structures and late-stage modifications of complex molecules. Detailed mechanistic studies and density functional theory (DFT) calculations indicate that a Ni(I)/Ni(III) redox cycle is preferred in the C-N coupling process, and B2N4 reagent serves both as a single electron transfer donor and a N,N-dialkylation source.
Exploring the diagnostic potential of plasma circ-CCDC66 in colorectal cancer
Abstract Owing to the subtle symptoms and low sensitivity of colorectal cancer (CRC), such as rectal bleeding, anemia, and abdominal pain, CRC generally occurs in late stages. This leads to delayed diagnosis and reduced treatment efficiency. Therefore, novel and effective CRC markers are needed. In this study, we conducted circRNA expression profiling on GSE datasets and identified circ-CCDC66 as a potential marker. Through qPCR analysis of plasma samples from 50 CRC patients, 50 with colorectal polyps, and 50 healthy individuals, circ-CCDC66 emerged as a promising biomarker for CRC detection capable of identifying polyps among healthy individuals. Furthermore, plasma circ-CCDC66 levels exhibited superior diagnostic accuracy, with an AUC of 0.920, compared to traditional markers, such as serum CEA and CA19-9. Remarkably, the combined detection of circ-CCDC66, CEA, and CA19-9 further increased the AUC for distinguishing the colorectal polyps’ group from the healthy control group to 0.991, with sensitivity and specificity increasing to 98% and 96%, respectively. Additionally, a circ-CCDC66-miRNA-mRNA regulatory network was established to provide insight into how circ-CCDC66 influences CRC pathways. This pioneering study highlights circ-CCDC66’s clinical relevance as a blood-based diagnostic marker for CRC and offers valuable insights into future developments in the diagnosis and treatment of the disease.
Inhibiting acute, axonal DLK palmitoylation is neuroprotective and avoids deleterious effects of cell-wide DLK inhibition
Abstract Inhibiting dual leucine-zipper kinase (DLK) could potentially ameliorate diverse neuropathological conditions, but a direct inhibitor of DLK’s kinase domain caused unintended side effects in human patients, indicative of neuronal cytoskeletal disruption. We sought a more precise intervention and show here that axon-to-soma pro-degenerative signaling requires acute, axonal palmitoylation of DLK. To identify potential modulators of this modification, we screened >28,000 compounds using a high-content imaging readout of DLK’s palmitoylation-dependent subcellular localization. Several hits alter DLK localization in non-neuronal cells, reduce DLK retrograde signaling and protect cultured dorsal root ganglion neurons from neurodegeneration. Mechanistically, the two most neuroprotective compounds selectively prevent DLK’s stimulus-dependent palmitoylation and subsequent recruitment to axonal vesicles, but do not affect palmitoylation of other axonal proteins assessed and avoid the cytoskeletal disruption associated with direct DLK inhibition. Our hit compounds also reduce pro-degenerative retrograde signaling in vivo, revealing a previously unrecognized neuroprotective strategy.
Sleep apnea is associated with reduced daytime blood pressure variability in adults with Down syndrome
A lanthanide MOF with nanostructured node disorder
Abstract Structural disorder can be used to tune the properties of functional materials and is an important tool that can be employed for the development of complex framework materials, such as metal-organic frameworks. Here we show the synthesis and structural characterization of a metal-organic framework, UoB-100(Dy). Average structure refinements indicate that the node is disordered between two orientations of the nonanuclear secondary building unit (SBU). By performing 3D diffuse scattering (DS) analysis and Monte Carlo (MC) simulations, we confirm the presence of strong correlations between the metal clusters of UoB-100(Dy). These nodes assemble into a complex nanodomain structure. Quantum mechanical calculations identify linker strain as the driving force behind the nanodomain structure. The implications of such a nanodomain structure for the magnetic, gas storage, and mechanical properties of lanthanide MOFs are discussed.
LY6E as a new prognostic biomarker of multiple myeloma-related bone disease
Abstract Osteolytic bone disease, which deteriorates the quality of life, is a prevalent complication of multiple myeloma (MM). In this study, we utilized bioinformatics analysis to identify the differentially expressed genes (DEGs) associated with MM bone disease (MBD) from the Gene Expression Omnibus (GEO) databases. Here, the Kaplan-Meier (K-M) curve and Cox regression analyses demonstrated that the key molecule lymphocyte antigen 6 complex (LY6E) was closely correlated with the MM progression, unfavorable prognosis and the formation of MBD. Furthermore, we confirmed that higher LY6E expression promoted MM cell proliferation and osteoclast differentiation in vitro. Taken together, these findings may illuminate the theoretical foundation for LY6E in MBD formation and identify it as a neoteric therapeutic target for MM.
Artificial non-monotonic neurons based on nonvolatile anti-ambipolar transistors
Abstract Non-monotonic neurons integrate monotonic input into a non-monotonic response, effectively improving the efficiency of unsupervised learning and precision of information processing in peripheral sensor systems. However, non-monotonic neuron-synapse circuits based on conventional technology require multiple transistors and complicated layouts. By leveraging the advantages of compact design for complex functions with two-dimensional materials, herein, we used anti-ambipolar transistor with airgaps configuration to fabricate the non-monotonic neuron with a bell-shaped response function. The anti-ambipolar transistor demonstrated near-ideal subthreshold swings of 60 mV/dec, a benchmark combination of a high peak-to-valley ratio of ~105. By utilizing the floating gate architecture, the non-volatile transistors achieved a high operating speed ~10−7 s and robust durability exceeding 104 cycles. The non-volatile anti-ambipolar transistor showed spike amplitude, width, and number-dependent excitation and inhibition synaptic behaviors. Furthermore, its non-volatile performance can replicate biological neurons showing a reconfigurable monotonic and non-monotonic response by modulating the amplitude and width of presynaptic input. We encoded systolic blood pressure and resting heart rate data to train non-monotonic neurons, achieving the prediction of health conditions with a detection accuracy surpassing 85% at the device level, closely corresponding to the recognized medical standards.
A stratified precision screening strategy for enhancing hepatitis B- and C-associated liver cancer detection: a prospective study
Ancient shackles testify to brutality of Egypt’s gold mines
Global floating kelp forests have limited protection despite intensifying marine heatwave threats
Abstract Kelp forests are one of the earth’s most productive ecosystems and are at great risk from climate change, yet little is known regarding their current conservation status and global future threats. Here, by combining a global remote sensing dataset of floating kelp forests with climate data and projections, we find that exposure to projected marine heatwaves will increase ~6 to ~16 times in the long term (2081–2100) compared to contemporary (2001–2020) exposure. While exposure will intensify across all regions, some southern hemisphere areas which have lower exposure to contemporary and projected marine heatwaves may provide climate refugia for floating kelp forests. Under these escalating threats, less than 3% of global floating kelp forests are currently within highly restrictive marine protected areas (MPAs), the most effective MPAs for protecting biodiversity. Our findings emphasize the urgent need to increase the global protection of floating kelp forests and set bolder climate adaptation goals.