Browse Articles

A quantum multi-sensor data fusion self-supervised learning framework for IIoT anomaly detection

Controlled assembly of two-dimensional porphyrin heterostructures toward directed energy transfer and charge separation

Daily stressor control buffers stressor-related negative and positive affect associations

Single-cell RNA sequencing profiles drug activity within spatially engineered 3D cultures

Abstract Spatial transcriptomic techniques provide a wealth of information useful in guiding drug development, while three-dimensional (3D) cell cultures have demonstrated power in accelerating drug approvals. However, techniques for robust spatial analysis of 3D cultures are limited. Here, we present a transfection-based method for constructing cellular spheroids through a layer-by-layer approach, in which DNA barcodes encode the spatial positioning of cells. Our technique facilitates multiplex single-cell RNA sequencing, providing spatial maps of gene expression and drug response, while correlative imaging reveals the locations of barcoded cell populations and quantifies local tissue elasticity. We show that model HeLa 3D spheroids display heterogeneous responses to drugs, which may arise through diffusion gradients of the drug, or from differences in metabolism, nutrient supply, and cellular stressors. The ability to create spatially encoded cellular assemblies may help to reveal spatial variation in gene expression within 3D culture models.

Cervicovaginal microbiome diversity was not associated with mucosal pharmacokinetics of systemically delivered HIV broadly neutralizing antibodies

Table-top three-dimensional photoemission orbital tomography with a femtosecond extreme ultraviolet light source

Abstract Following electronic processes in molecules and materials at the level of the quantum mechanical electron wavefunction with ångström-level spatial resolution and with full access to its femtosecond temporal dynamics is at the heart of ultrafast condensed matter physics. A breakthrough invention allowing experimental access to electron wavefunctions was the reconstruction of molecular orbitals from angle-resolved photoelectron spectroscopy data in 2009, termed photoemission orbital tomography (POT). This invention opens a route towards ultrafast three-dimensional (3D) POT, with many new prospects for the study of ultrafast light-matter interaction, femtochemistry, and photo-induced phase transitions. Here, we develop a synergistic experimental-algorithmic approach to realize the first 3D-POT experiment using a short-pulse extreme ultraviolet light source. We combine a new variant of photoelectron spectroscopy, namely ultrafast momentum microscopy, with a table-top spectrally-tunable high-harmonic generation light source and a tailored algorithm for efficient 3D reconstruction from sparse, undersampled data. This combination dramatically speeds up the experimental data acquisition, while at the same time reducing the sampling requirements to achieve complete 3D information. We demonstrate the power of this approach by full 3D imaging of the frontier orbitals of a prototypical organic semiconductor adsorbed on pristine Ag(110).

Phytochemical-mediated green synthesis, mechanistic insights integrated with biological evaluation, density functional theory calculations and molecular docking studies of copper oxide nanoparticles

Lateral septum GABAergic neurons mediate the effects of dexmedetomidine on allodynia and sleep in a male mouse model of neuropathic pain

Abstract Chronic pain and sleep disorders frequently co-occur and exacerbate each other, yet the neural mechanisms underlying this comorbidity remain poorly understood. Here, we found that hyperactivity of GABAergic neurons in the dorsal division of the lateral septum (LS GABA ) drives both pain-like behavior and sleep disruption induced by spared nerve injury (SNI) in male mice. We showed that systemic or local application of dexmedetomidine (DEX), with known sedative and analgesic properties, reduces LS GABA hyperactivity via α 2 A adrenergic receptor activation, alleviating pain-like behavior and sleep disruption. LS GABA can project onto the glutamatergic and GABAergic neurons in the lateral preoptic area (LPO), respectively. The LS GABA →LPO Glu circuit and the LS GABA  → LPO GABA circuit contribute to mechanical allodynia and sleep disruption, respectively. Furthermore, LS α 2 A adrenergic receptor plays an important role in DEX-regulated activity of LPO GABA and LPO Glu . Taken together, these findings reveal a shared neural substrate for chronic pain and sleep disorders and establish DEX as a potential treatment for this comorbidity through selective modulation of LS GABA -driven circuits.

Contamination levels and health risk assessment of heavy metals in edible leafy vegetables distributed in Rafsanjan, southeast Iran

Mechanistic and antigenic boundaries of Henipavirus and Parahenipavirus glycoproteins

Interfacial Charge Transfer Directing Intermolecular Hydrogen Transfer for On-Surface C–H Activation

Personalized optimal pillow shape and pneumatic smart pillow maintaining natural cervical curvature: a pilot study

Recurrent intra-tumour heterogeneity is a hallmark of metastatic prostate cancer

Abstract The evolution to metastatic disease is a major determinant of cancer mortality. Cancer evolution involves a complex interplay between intrinsic genetics and transcriptional alterations and the microenvironment. To define mechanisms underpinning metastatic heterogeneity in late-stage disease, we focus on metastatic castration-resistant prostate cancer and employed single-cell multi-omics and whole-genome sequencing to deeply profile 34 metastatic lesions obtained from 9 patients through rapid autopsy. We find evolutionary convergence of intra-tumour heterogeneity, characterised by recurrent tumour populations acting as critical functional components of the tumour ecosystem, irrespective of clonal and microenvironmental backgrounds. We find little evidence of the microenvironment driving transcriptional heterogeneity, but there are signatures of co-adaptation between the microenvironment and tumour cells. In contrast, clonal evolution primarily foster widespread transcriptional changes that did not result in de novo functional states. Intra-patient functional convergence of tumour ecosystems across metastases indicates system-level selection pressures that drive the heterogeneity landscape of metastatic castration-resistant prostate cancer. Our findings reveal functional evolutionary convergence of metastatic disease into distinct intra-tumour subpopulations, identifying critical determinants for therapeutic targeting.

Latent twins: a framework for scene recognition and fast radiative transfer inversion in FORUM all-sky observations

Asymmetric architecture and adaptation of Treponema flagella

Gut microbiome signatures discriminate deep vein thrombosis through machine learning and metabolic analysis

Extension of overlap measures for Multi-Class Biomarker Evaluation in Alzheimer's Disease

A qualitative study of stakeholders and beneficiaries perspective on community-based mobile nutrition services in Gombe state of Nigeria

Protective effects of propofol, ketamine, and their combination against H2O2-induced oxidative stress in A549 cells: an evaluation of metabolic activity and antioxidant defense

A single lysergyl peptide synthetase assembles lysergic acid amides in Aspergillus species

The agriculturally and pharmaceutically important lysergic acid amides ergonovine and lysergic acid α-hydroxyethylamide (LAH) are synthesized from a lysergyl-alanine precursor. In ergot-alkaloid producing fungi of the family Clavicipitaceae, lysergyl-alanine is assembled and then reduced to ergonovine by a complex of two monomodular nonribosomal peptide synthetases: lysergyl peptide synthetase 2 (Lps2) and Lps3. LAH is the major ergot alkaloid product of these fungi when the Lps2/Lps3 complex interacts with the Bayer-Villiger monooxygenase encoded by easO . An α/β hydrolase fold protein encoded by easP increases LAH accumulation but is not essential for LAH biosynthesis. Lps2 and Lps3 do not occur in the several species of Aspergillus (including A. leporis ) that produce LAH and ergonovine. Instead, ergot alkaloid synthesis clusters of these Aspergillus species encode a novel two-module Lps gene, lpsD . We hypothesized the product of lpsD was functionally equivalent to the two separately encoded, monomodular enzymes of the Clavicipitaceae and tested this hypothesis by introducing lpsD of A. leporis into a strain of Aspergillus fumigatus that had been modified previously to accumulate lysergic acid as substrate. Introduction of lpsD resulted in accumulation of ergonovine as evidenced by high-performance liquid chromatography and liquid chromatography-mass spectrometry. The addition of the A. leporis allele of easO into the lpsD -transformed A. fumigatus strain led to accumulation of LAH. Introduction of a construct containing easP as well as easO into the lpsD -transformed A. fumigatus strain resulted in higher concentrations of LAH than in strains containing only lpsD and easO , consistent with previous studies in the Clavicipitaceae. The data support the hypothesis that ergot alkaloid-producing Aspergillus species independently evolved a single enzyme that serves the purpose of the two monomodular peptide synthetases of the Clavicipitaceae.