Explore the vast range of titles available.

Action potentials have a central role in the nervous system and in many cellular processes, notably those involving ion channels. The accurate measurement of action potentials requires efficient coupling between the cell membrane and the measuring electrodes. Intracellular recording methods such as patch clamping involve measuring the voltage or current across the cell membrane by accessing the cell interior with an electrode, allowing both the amplitude and shape of the action potentials to be recorded faithfully with high signal-to-noise ratios 1 . However, the invasive nature of intracellular methods usually limits the recording time to a few hours 1 , and their complexity makes it difficult to simultaneously record more than a few cells. Extracellular recording methods, such as multielectrode arrays 2 and multitransistor arrays 3 , are non-invasive and allow long-term and multiplexed measurements. However, extracellular recording sacrifices the one-to-one correspondence between the cells and electrodes, and also suffers from significantly reduced signal strength and quality. Extracellular techniques are not, therefore, able to record action potentials with the accuracy needed to explore the properties of ion channels. As a result, the pharmacological screening of ion-channel drugs is usually performed by low-throughput intracellular recording methods 4 . The use of nanowire transistors 5 , 6 , 7 , nanotube-coupled transistors 8 and micro gold-spine and related electrodes 9 , 10 , 11 , 12 can significantly improve the signal strength of recorded action potentials. Here, we show that vertical nanopillar electrodes can record both the extracellular and intracellular action potentials of cultured cardiomyocytes over a long period of time with excellent signal strength and quality. Moreover, it is possible to repeatedly switch between extracellular and intracellular recording by nanoscale electroporation and resealing processes. Furthermore, vertical nanopillar electrodes can detect subtle changes in action potentials induced by drugs that target ion channels. Arrays of vertical nanopillar electrodes can be used for both intracellular and extracellular recording with excellent signal strength and quality, and minimal damage to the cells.

A simple, robust, chemically defined method for generating cardiomyocytes from human pluripotent stem cells is described. It should enable the identification of conditions for maturation of these cells. Existing methods for human induced pluripotent stem cell (hiPSC) cardiac differentiation are efficient but require complex, undefined medium constituents that hinder further elucidation of the molecular mechanisms of cardiomyogenesis. Using hiPSCs derived under chemically defined conditions on synthetic matrices, we systematically developed an optimized cardiac differentiation strategy, using a chemically defined medium consisting of just three components: the basal medium RPMI 1640, L -ascorbic acid 2-phosphate and rice-derived recombinant human albumin. Along with small molecule–based induction of differentiation, this protocol produced contractile sheets of up to 95% TNNT2 + cardiomyocytes at a yield of up to 100 cardiomyocytes for every input pluripotent cell and was effective in 11 hiPSC lines tested. This chemically defined platform for cardiac specification of hiPSCs will allow the elucidation of cardiomyocyte macromolecular and metabolic requirements and will provide a minimal system for the study of maturation and subtype specification.

Background Metagenomic next-generation sequencing (mNGS) is a new pathogen detection technique, but the current experience of clinical application in Coxiella burnetii infection is relatively limited. This study aimed to investigate the clinical application value of mNGS in diagnosis of Coxiella burnetii infection. Methods We conducted a retrospective study that included patients with Coxiella burnetii infection detected by mNGS from December 2018 to August 2024. Their clinical information and mNGS test results were retrieved for analysis. Results A total of 70 patients with Coxiella burnetii infection were included in this study. The mean age of these patients was 43.5 years and the common clinical manifestations were fever (67/70, 95.7%), followed by headache (43/70, 61.4%), weakness (36/70, 51.4%), and muscle and joint pain (27/70, 38.6%). The mean length of hospitalization was five days. 92.9% (65/70) patients were discharged with improvement, and one patient died. The median duration of fever for these patients was seven days. Most patients temperatures returned to normal within 2–3 days after receiving targeted antibiotic therapy. No correlation was observed between the duration of fever and the reads of mNGS in febrile patients. The specimens tested by mNGS were mainly blood specimens. The reads of mNGS detected fluctuated from one to 826, with the range of one to 50 being the most frequent. 43 (61.4%) samples of mNGS detected only Coxiella burnetii . Pathogens detected along with Coxiella burnetii include viruses, bacteria, and fungi. None of the 63 patients followed up for six months had clinical manifestations of chronic Q fever. Conclusions Q fever is a disseminated infectious disease that deserves attention for its nonspecific clinical symptoms. mNGS emerges as a powerful novel tool for pathogen detection, demonstrating significant value in diagnosing Q fever, particularly in where conventional serological and PCR testing is unavailable or inconclusive.

It has been proposed that differential activation kinetics allows cells to use a common set of signaling pathways to specify distinct cellular outcomes. For example, nerve growth factor (NGF) and epidermal growth factor (EGF) induce different activation kinetics of the Raf/MEK/ERK signaling pathway and result in differentiation and proliferation, respectively. However, a direct and quantitative linkage between the temporal profile of Raf/MEK/ERK activation and the cellular outputs has not been established due to a lack of means to precisely perturb its signaling kinetics. Here, we construct a light-gated protein-protein interaction system to regulate the activation pattern of the Raf/MEK/ERK signaling pathway. Light-induced activation of the Raf/MEK/ERK cascade leads to significant neurite outgrowth in rat PC12 pheochromocytoma cell lines in the absence of growth factors. Compared with NGF stimulation, light stimulation induces longer but fewer neurites. Intermittent on/off illumination reveals that cells achieve maximum neurite outgrowth if the off-time duration per cycle is shorter than 45 min. Overall, light-mediated kinetic control enables precise dissection of the temporal dimension within the intracellular signal transduction network.

Human skin relies on cutaneous receptors that output digital signals for tactile sensing in which the intensity of stimulation is converted to a series of voltage pulses. We present a power-efficient skin-inspired mechanoreceptor with a flexible organic transistor circuit that transduces pressure into digital frequency signals directly. The output frequency ranges between 0 and 200 hertz, with a sublinear response to increasing force stimuli that mimics slow-adapting skin mechanoreceptors. The output of the sensors was further used to stimulate optogenetically engineered mouse somatosensory neurons of mouse cortex in vitro, achieving stimulated pulses in accordance with pressure levels. This work represents a step toward the design and use of large-area organic electronic skins with neural-integrated touch feedback for replacement limbs.

Q fever is a worldwide zoonosis caused by Coxiella burnetii (Cb). From January 2018 to November 2019, plasma samples from 2,382 patients with acute fever of unknown cause at a hospital in Zhuhai city of China were tested using metagenomic next-generation sequencing (mNGS). Of those tested, 138 patients (5.8%) were diagnosed with Q fever based on the presence of Cb genomic DNA detected by mNGS. Among these, 78 cases (56.5%) presented from Nov 2018 to Mar 2019, suggesting an outbreak of Q fever. 55 cases with detailed clinical information that occurred during the outbreak period were used for further analysis. The vast majority of plasma samples from those Cb-mNGS-positive patients were positive in a Cb-specific quantitative polymerase chain reaction (n = 38) and/or indirect immunofluorescence assay (n = 26). Mobile phone tracing data was used to define the area of infection during the outbreak. This suggested the probable infection source was Cb-infected goats and cattle at the only official authorized slaughterhouse in Zhuhai city. Phylogenic analysis based on genomic sequences indicated Cb strains identified in the patients, goat and cattle were formed a single branch, most closely related to the genomic group of Cb dominated by strains isolated from goats. Our study demonstrates Q fever was epidemic in 2018–2019 in Zhuhai city, and this is the first confirmed epidemic of Q fever in a contemporary city in China.

Intracellular recording of action potentials is important to understand electrically-excitable cells. Recently, vertical nanoelectrodes have been developed to achieve highly sensitive, minimally invasive and large-scale intracellular recording. It has been demonstrated that the vertical geometry is crucial for the enhanced signal detection. Here we develop nanoelectrodes of a new geometry, namely nanotubes of iridium oxide. When cardiomyocytes are cultured upon those nanotubes, the cell membrane not only wraps around the vertical tubes but also protrudes deep into the hollow centre. We show that this nanotube geometry enhances cell-electrode coupling and results in larger signals than solid nanoelectrodes. The nanotube electrodes also afford much longer intracellular access and are minimally invasive, making it possible to achieve stable recording up to an hour in a single session and more than 8 days of consecutive daily recording. This study suggests that the nanoelectrode performance can be significantly improved by optimizing the electrode geometry. Nanoelectrode intracellular recording of action potential may be used to study cell electrophysiology. Here, the authors demonstrate vertical nanotube electrodes which improve recording quality and duration, as the cell membrane wraps the nanotubes surfaces and protrudes into their hollow centres.

The mechanical stability and deformability of the cell nucleus are crucial to many biological processes, including migration, proliferation and polarization. In vivo , the cell nucleus is frequently subjected to deformation on a variety of length and time scales, but current techniques for studying nuclear mechanics do not provide access to subnuclear deformation in live functioning cells. Here we introduce arrays of vertical nanopillars as a new method for the in situ study of nuclear deformability and the mechanical coupling between the cell membrane and the nucleus in live cells. Our measurements show that nanopillar-induced nuclear deformation is determined by nuclear stiffness, as well as opposing effects from actin and intermediate filaments. Furthermore, the depth, width and curvature of nuclear deformation can be controlled by varying the geometry of the nanopillar array. Overall, vertical nanopillar arrays constitute a novel approach for non-invasive, subcellular perturbation of nuclear mechanics and mechanotransduction in live cells. Arrays of vertical nanopillars are used to study the deformability of the cell nucleus and its mechanical coupling with the cell membrane.