Browse Articles

Plasmid-driven strategies for clone success in Escherichia coli

Jorunnamycin A induces apoptosis in pancreatic ductal adenocarcinoma cells, spheroids, and patient-derived organoids by modulating KRAS-mediated survival pathways

Author Correction: The dynamics of plasmon-induced hot carrier creation in colloidal gold

Impact of carbon nanodot uptake on complex impedance charge transport and energy storage mechanism in aloe vera leaves

Pathogenic mutation impairs functional dynamics of Hsp60 in mono- and oligomeric states

Addressing cross-population domain shift in chest X-ray classification through supervised adversarial domain adaptation

Fine-scale patterns of SARS-CoV-2 spread from identical pathogen sequences

Abstract Pathogen genomics can provide insights into underlying infectious disease transmission patterns1,2, but new methods are needed to handle modern large-scale pathogen genome datasets and realize this full potential3–5. In particular, genetically proximal viruses should be highly informative about transmission events as genetic proximity indicates epidemiological linkage. Here we use pairs of identical sequences to characterize fine-scale transmission patterns using 114,298 SARS-CoV-2 genomes collected through Washington State (USA) genomic sentinel surveillance with associated age and residence location information between March 2021 and December 2022. This corresponds to 59,660 sequences with another identical sequence in the dataset. We find that the location of pairs of identical sequences is highly consistent with expectations from mobility and social contact data. Outliers in the relationship between genetic and mobility data can be explained by SARS-CoV-2 transmission between postcodes with male prisons, consistent with transmission between prison facilities. We find that transmission patterns between age groups vary across spatial scales. Finally, we use the timing of sequence collection to understand the age groups driving transmission. Overall, this study improves our ability to use large pathogen genome datasets to understand the determinants of infectious disease spread.

Crypt density and recruited enhancers underlie intestinal tumour initiation

GWAS meta-analysis using a graph-based pan-genome enhanced gene mining efficiency for agronomic traits in rice

Increased risk of cardiomyopathy in individuals with methamphetamine related disorders in Taiwan

Abstract To explore whether Methamphetamine-related disorders (MRDs) will cause the risk of cardiomyopathy in the future. This study used Taiwan’s Longitudinal Generation Tracking Database (LGTD) to conduct a 1:4 paired analysis of sex, age, and inclusion year. 17,071 patients with MRDs and 153 patients with cardiomyopathy were selected; 68,264 patients without MRDs and 274 patients with cardiomyopathy were also selected. This study used SPSS 22 statistical software to conduct Cox regression analysis. Patients with MRDs had a 3.421-folds higher risk of cardiomyopathy than patients without MRDs. Men have a 0.735-fold lower risk of developing cardiomyopathy than women. In terms of age group, aged 50–64 and ≧ 65 have a 1.145- and 1.332-folds higher risk of cardiomyopathy, respectively, compared to those aged 20–49. For each one-point increase in Charlson Comorbidity Index (CCI), the risk of cardiomyopathy rises by 58.3%. Specifically, for three types of Methamphetamines (Methamphetamine and other psychostimulant dependence, Methamphetamine or related acting sympathomimetic abuse, Methamphetamine psychosis), the HR for cardiomyopathy in patients with MRDs was 3.864 (p < 0.001), 2.916 (p < 0.001), and 2.295 (p = 0.016) times higher, respectively, compared to patients without MRDs. The Kaplan-Meier log-rank test was used to calculate the cumulative risk of MRDs, showing a significant difference in the cumulative cardiomyopathy incidence between the MRDs and non-MRDs groups (long-rank test, p < 0.001). MRDs will increase the risk of cardiomyopathy. Women are more susceptible to cardiomyopathy than men, and the risk escalates for individuals aged 50–64 and those 65 years or older, compared to the 20–49-year age group. Additionally, an increase in the CCI correlates with a heightened risk of cardiomyopathy. There are important differences between these groups in terms of duration, frequency, and severity of use, with longer exposure and more frequent use increasing the risk of dependence and psychosis, but individual susceptibility, dose, and use patterns also play key roles.

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.