A SAW-Based Programmable Controlled RNA Detecting Device: Rapid In Situ Cytolysis-RNA Capture-RNA Release-PCR in One Mini Chamber.

Viral RNA detection is crucial in preventing and treating early infectious diseases. Traditional methods of RNA detection require a large amount of equipment and technical personnel. In this study, proposed a programmable controlled surface acoustic wave (SAW)-based RNA detecting device has been proposed. The proposed device can perform the entire viral RNA detection process, including cell lysis by cell-microparticle collision through SAW-induced liquid whirling, RNA capture by SAW-suspended magnetic beads, RNA elution through SAW-induced high streaming force, and PCR thermal cycling through SAW-generated heat. The device has completed all RNA detection steps in one mini chamber, requiring only 489 µl reagents for RNA extraction, much smaller than the amount used in manual RNA extraction (2065 µl). The experimental results have shown that PCR results from the device are comparable to those achieved via commercial qPCR instrumental detection. This work has demonstrated the potential of SAW-based lab-on-a-chip devices for point-of-care testing and provided a novel approach for rapidly detecting infectious diseases.

Photo-self-Fenton Reaction Mediated by Atomically Dispersed Ag-Co Photocatalysts toward Efficient Degradation of Organic Pollutants.

Achieving the complete mineralization of persistent pollutants in wastewater is still a big challenge. Here, we propose an efficient photo-self-Fenton reaction for the degradation of different pollutants using the high-density (Ag: 22 wt %) of atomically dispersed AgCo dual sites embedded in graphic carbon nitride (AgCo-CN). Comprehensive experimental measurements and density functional theory (DFT) calculations demonstrate that the Ag and Co dual sites in AgCo-CN play a critical role in accelerating the photoinduced charge separation and forming the self-Fenton redox centers, respectively. The bimetallic AgCo-CN exhibited excellent photocatalytic performance toward the phenol even under extreme conditions due to an efficient degradation pathway and in situ generation of the hydrogen peroxide producing the main active oxygen species (⋅OH and 1 O2 ) and showed long-term activity in a self-design photo-Filter reactor for the purification of the phenol. Our discoveries pave the way for the design of efficient single-atoms photocatalysts-based photo-self-Fenton reaction for recalcitrant pollutant treatment.

Manipulating Coherent Exciton Dynamics in CsPbI3 Perovskite Quantum Dots Using Magnetic Field.

Lead halide perovskite quantum dots (QDs) have recently emerged as a promising material platform for quantum information processing owing to their strong light-matter interaction and relatively long-lived optical and spin coherences. In particular, the coherence of the fine-structure bright excitons is sustainable up to room temperature and can be observed even at an ensemble level. Here modulation of the polarization of these excitons in CsPbI3 QDs and manipulation of their time-domain coherent dynamics using a longitudinal magnetic field are demonstrated. The manipulation is realized using femtosecond quantum beat spectroscopy performed with both circularly- and linearly-polarized pulses. The results are well captured by the density of matrix simulation and are picturized using a Bloch sphere. This study forms the basis for preparing arbitrary coherent superpositions of excitons in perovskite QDs for an array of quantum technologies under near-ambient conditions.

Chemresistor Smart Sensors from Silk Fibroin-Graphene Composites for Touch-free Wearables.

With the rapid development of wearable electronics, low-cost, multifunctional, ultrasensitive touch-free wearables for human-machine interaction and human/plant healthcare management have attracted great attention. The experience of fighting the COVID-19 epidemic has also confirmed the great significance of contactless sensation. Herein, a wearable smart-sensing platform using silk fibroin-reduced graphene oxide (SF-rGO) as bifunctional sensing active layers has been fabricated and integrated with a noncontact moisture/thermo sensor and Joule heater. As a result, the as-prepared smart sensor operated at 0.1 V exhibits good stability and sensitivity (sensor response of 60 for 97% RH) under a wide linear range of 6-97% RH, fast response/recover speed (real test: 21.51 s/85.62 s) toward touch-free humidity/temperature sensing for wearables, and thermal readings that can be accurately corrected by Joule heater. Impressively, it can achieve breath monitoring, mental state prediction, or elevator switching by identifying fingertip humidity variation. Prospectively, this all-in-one wearable smart sensor would set an example for improving sensing performance from structure-function relationship points of view and building a noncontact sensing system for daily life.

GSG2 facilitates the progression of human breast cancer through MDM2-mediated ubiquitination of E2F1.

BACKGROUND: Breast cancer (BC) has posed a great threat to world health as the leading cause of cancer death among women. Previous evidence demonstrated that germ cell-specific gene 2 (GSG2) was involved in the regulation of multiple cancers. Thus, the clinical value, biological function and underlying mechanism of GSG2 in BC were investigated in this study. METHODS: The expression of GSG2 in BC was revealed by immunohistochemistry (IHC), qPCR and western blotting. Secondly, the biological function of GSG2 in BC was evaluated by MTT assay, flow cytometry, Transwell assay and wound healing assay. Furthermore, the potential molecular mechanism of GSG2 regulating the progression of BC by co-immunoprecipitation (Co-IP) and protein stability detection. RESULTS: Our data indicated that GSG2 was frequently overexpressed in BC. Moreover, there was a significant correlation between the GSG2 expression and the poor prognosis of BC patients. Functionally, GSG2 knockdown inhibited the malignant progression of BC characterized by reduced proliferation, enhanced apoptosis and attenuated tumor growth. Migration inhibition of GSG2 knockdown BC cells via epithelial-mesenchymal transition (EMT), such as downregulation of Vimentin and Snail. In addition, E2F transcription factor 1 (E2F1) was regarded as a target protein of GSG2. Downregulation of E2F1 attenuated the promoting role of GSG2 on BC cells. Mechanistically, knockdown of GSG2 accelerated the ubiquitination of E2F1 protein, which was mediated by E3 ubiquitin ligase MDM2. CONCLUSIONS: GSG2 facilitated the development and progression of BC through MDM2-mediated ubiquitination of E2F1, which may be a promising candidate target with potential therapeutic value.

Classification of genotypes based on the VP1 gene of feline calicivirus and study of cross-protection between different genotypes.

Feline calicivirus (FCV) causes upper respiratory tract diseases and even death in cats, thereby acting as a great threat to feline animals. Currently, FCV prevention is mainly achieved through vaccination, but the effectiveness of vaccination is limited. In this study, 105 FCV strain VP1 sequences with clear backgrounds were downloaded from the NCBI and subjected to a maximum likelihood method for systematic evolutionary analysis. Based on the genetic analysis results, FCV-positive sera were prepared using SPF mice and Chinese field cats as target animals, followed by a cross-neutralization assay conducted on the different genotype strains and in vivo challenge tests were carried out to further verify with the strain with best cross-protection effect. The results revealed that FCV was mainly divided into two genotypes: GI and GII. The GI genotype strains are prevalent worldwide, but all GII genotype strains were isolated from Asia, indicating a clear geographical feature. This may form resistance to FCV prevention in Asia. The in vitro neutralization assay conducted using murine serum demonstrated that the cross-protection effect varied among strains. A strain with broad-spectrum neutralization properties, DL39, was screened. This strain could produce neutralizing titers (10 × 23.08-10 × 20.25) against all strains used in this study. The antibody titers against the GI strains were 10 × 23.08-10 × 20.5 and those against the GII strains were 10 × 20.75-10 × 20.25. Preliminary evidence suggested that the antibody titer of the DL39 strain against GI was higher than that against GII. Subsequent cross-neutralization assays with cat serum prepared with the DL39 strain and each strain simultaneously yielded results similar to those described above. In vivo challenge tests revealed that the DL39 strain-immunized cats outperformed the positive controls in all measures. The results of several trials demonstrated that strain DL39 can potentially be used as a vaccine strain. The study attempted to combine the genetic diversity and phylogenetic analysis of FCV with the discovery of potential vaccines, which is crucial for developing highly effective FCV vaccines.

Performance evaluation of a liquid-sodium thermoacoustic engine with magnetohydrodynamic electricity generation based upon the Swift model.

Liquid sodium is an attractive working fluid for thermoacoustic conversion. Herein, a numerical study on a standing-wave thermoacoustic electricity generation system with liquid sodium as the working fluid is presented, based upon the Swift model. The characteristics of the thermoacoustic conversion and the output performance of the system have been investigated. The results show that the sodium engine can reach a power density much higher than the classical gas engine. Due to the strong acoustic coupling between components, the electricity output is significantly affected by the input heating power, the magnetic flux density, and the load ratio. In a typical case, the thermal-to-electric efficiency and the relative Carnot efficiency can reach 4.6% and 7.8%, respectively, with a temperature difference of 563 K and an input heat of 5 kW. More importantly, the output electricity density reaches 150 kW/m3, higher than some commercially available technologies. These results demonstrate the potential of such technology for small-scale electricity generation. Its extremely simple structure without any mechanical moving part endows the system with high reliability and long lifetime, if risks of corrosion and exposure to air and water can be avoided.

SIRT1 in the BNST modulates chronic stress-induced anxiety of male mice via FKBP5 and corticotropin-releasing factor signaling.

Although clinical reports have highlighted association of the deacetylase sirtuin 1 (SIRT1) gene with anxiety, its exact role in the pathogenesis of anxiety disorders remains unclear. The present study was designed to explore whether and how SIRT1 in the mouse bed nucleus of the stria terminalis (BNST), a key limbic hub region, regulates anxiety. In a chronic stress model to induce anxiety in male mice, we used site- and cell-type-specific in vivo and in vitro manipulations, protein analysis, electrophysiological and behavioral analysis, in vivo MiniScope calcium imaging and mass spectroscopy, to characterize possible mechanism underlying a novel anxiolytic role for SIRT1 in the BNST. Specifically, decreased SIRT1 in parallel with increased corticotropin-releasing factor (CRF) expression was found in the BNST of anxiety model mice, whereas pharmacological activation or local overexpression of SIRT1 in the BNST reversed chronic stress-induced anxiety-like behaviors, downregulated CRF upregulation, and normalized CRF neuronal hyperactivity. Mechanistically, SIRT1 enhanced glucocorticoid receptor (GR)-mediated CRF transcriptional repression through directly interacting with and deacetylating the GR co-chaperone FKBP5 to induce its dissociation from the GR, ultimately downregulating CRF. Together, this study unravels an important cellular and molecular mechanism highlighting an anxiolytic role for SIRT1 in the mouse BNST, which may open up new therapeutic avenues for treating stress-related anxiety disorders.

Prelimbic neuron assemblies with delayed activation encode the economic decision-making process in a bandit game.

The medial prefrontal cortex (mPFC) is critical to an animal's value-based decision-making process. However, due to heterogeneity of local mPFC neurons, which neuron group and how it contributes to the alteration of the animal's decision is yet to be explored. And the effect of empty reward in this process is often neglected. Here, we adopted a two-port bandit game paradigm for mice and applied synchronized calcium imaging to the prelimbic area of the mPFC. The results showed that neurons recruited in the bandit game exhibit three distinct firing patterns. Specially, neurons with delayed activation (deA neurons1) carried exclusive information on reward type and changes of choice value. We demonstrated that these deA neurons were essential for the construction of choice-outcome correlation and the trial-to-trial modification of decision. Additionally, we found that in a long-term gambling game, members of the deA neuron assembly were dynamically shifting while maintaining the function, and the importance of empty reward feedbacks were gradually elevated to the same level as reward. Together, these results revealed a vital role for prelimbic deA neurons in the gambling tasks and a new perspective on the encoding of economic decision-making.

The early stage of adult ocular dominance plasticity revealed by near-infrared optical imaging of intrinsic signals.

Long term monocular deprivation is considered to be necessary for the induction of significant ocular dominance plasticity in the adult visual cortex. In this study, we subjected adult mice to monocular deprivation for various durations and screened for changes in ocular dominance using dual-wavelength intrinsic signal optical imaging. We found that short-term deprivation was sufficient to cause a shift in ocular dominance and that these early-stage changes were detected only by near-infrared illumination. In addition, single-unit recordings showed that these early-stage changes primarily occurred in deep cortical layers. This early-stage ocular dominance shift was abolished by the blockade of NMDA receptors. In summary, our findings reveal an early phase of adult ocular dominance plasticity and provide the dynamics of adult plasticity.

Modulation of Visual Responses and Ocular Dominance by Contralateral Inhibitory Activation in the Mouse Visual Cortex.

Both hemispheres connect with each other by excitatory callosal projections, and whether inhibitory interneurons, usually believed to have local innervation, engage in transcallosal activity modulation is unknown. Here, we used optogenetics in combination with cell-type-specific channelrhodopsin-2 expression to activate different inhibitory neuron subpopulations in the visual cortex and recorded the response of the entire visual cortex using intrinsic signal optical imaging. We found that optogenetic stimulation of inhibitory neurons reduced spontaneous activity (increase in the reflection of illumination) in the binocular area of the contralateral hemisphere, although these stimulations had different local effects ipsilaterally. The activation of contralateral interneurons differentially affected both eye responses to visual stimuli and, thus, changed ocular dominance. Optogenetic silencing of excitatory neurons affects the ipsilateral eye response and ocular dominance in the contralateral cortex to a lesser extent. Our results revealed a transcallosal effect of interneuron activation in the mouse visual cortex.

Plasmon-Enhanced Fluorescence of Single Quantum Dots Immobilized in Optically Coupled Aluminum Nanoholes.

Fluorescence-based optical sensing techniques have continually been explored for single-molecule detection targeting myriad biomedical applications. Improving signal-to-noise ratio remains a prioritized effort to enable unambiguous detection at single-molecule level. Here, we report a systematic simulation-assisted optimization of plasmon-enhanced fluorescence of single quantum dots based on nanohole arrays in ultrathin aluminum films. The simulation is first calibrated by referring to the measured transmittance in nanohole arrays and subsequently used for guiding their design. With an optimized combination of nanohole diameter and depth, the variation of the square of simulated average volumetric electric field enhancement agrees excellently with that of experimental photoluminescence enhancement over a large range of nanohole periods. A maximum 5-fold photoluminescence enhancement is statistically achieved experimentally for the single quantum dots immobilized at the bottom of simulation-optimized nanoholes in comparison to those cast-deposited on bare glass substrate. Hence, boosting photoluminescence with optimized nanohole arrays holds promises for single-fluorophore-based biosensing.

Coordinated activity of a central pathway drives associative opioid analgesic tolerance.

Opioid analgesic tolerance, a root cause of opioid overdose and misuse, can develop through an associative learning. Despite intensive research, the locus and central pathway subserving the associative opioid analgesic tolerance (AOAT) remains unclear. Using a combination of chemo/optogenetic manipulation with calcium imaging and slice physiology, here we identify neuronal ensembles in a hierarchically organized pathway essential for AOAT. The association of morphine-induced analgesia with an environmental condition drives glutamatergic signaling from ventral hippocampus (vHPC) to dorsomedial prefrontal cortex (dmPFC) cholecystokininergic (CCKergic) neurons. Excitation of CCKergic neurons, which project and release CCK to basolateral amygdala (BLA) glutamatergic neurons, relays AOAT signal through inhibition of BLA µ-opioid receptor function, thereby leading to further loss of morphine analgesic efficacy. This work provides evidence for a circuit across different brain regions distinct for opioid analgesic tolerance. The components of this pathway are potential targets to treat opioid overdose and abuse.

Neural ensembles in the murine medial prefrontal cortex process distinct information during visual perceptual learning.

BACKGROUND: Perceptual learning refers to an augmentation of an organism's ability to respond to external stimuli, which has been described in most sensory modalities. Visual perceptual learning (VPL) is a manifestation of plasticity in visual information processing that occurs in the adult brain, and can be used to ameliorate the ability of patients with visual defects mainly based on an improvement of detection or discrimination of features in visual tasks. While some brain regions such as the primary visual cortex have been described to participate in VPL, the way more general high-level cognitive brain areas are involved in this process remains unclear. Here, we showed that the medial prefrontal cortex (mPFC) was essential for both the training and maintenance processes of VPL in mouse models. RESULTS: We built a new VPL model in a custom-designed training chamber to enable the utilization of miniScopes when mice freely executed the VPL task. We found that pyramidal neurons in the mPFC participate in both the training process and maintenance of VPL. By recording the calcium activity of mPFC pyramidal neurons while mice freely executed the task, distinct ON and OFF neural ensembles tuned to different behaviors were identified, which might encode different cognitive information. Decoding analysis showed that mouse behaviors could be well predicted using the activity of each ON ensemble. Furthermore, VPL recruited more reward-related components in the mPFC. CONCLUSION: We revealed the neural mechanism underlying vision improvement following VPL and identify distinct ON and OFF neural ensembles in the mPFC that tuned to different information during visual perceptual training. These results uncover an important role of the mPFC in VPL, with more reward-related components being also involved, and pave the way for future clarification of the reward signal coding rules in VPL.

Sinogram domain metal artifact correction of CT via deep learning.

PURPOSE: Metal artifacts can significantly decrease the quality of computed tomography (CT) images. This occurs as X-rays penetrate implanted metals, causing severe attenuation and resulting in metal artifacts in the CT images. This degradation in image quality can hinder subsequent clinical diagnosis and treatment planning. Beam hardening artifacts are often manifested as severe strip artifacts in the image domain, affecting the overall quality of the reconstructed CT image. In the sinogram domain, metal is typically located in specific areas, and image processing in these regions can preserve image information in other areas, making the model more robust. To address this issue, we propose a region-based correction of beam hardening artifacts in the sinogram domain using deep learning. METHODS: We present a model composed of three modules: (a) a Sinogram Metal Segmentation Network (Seg-Net), (b) a Sinogram Enhancement Network (Sino-Net), and (c) a Fusion Module. The model starts by using the Attention U-Net network to segment the metal regions in the sinogram. The segmented metal regions are then interpolated to obtain a sinogram image free of metal. The Sino-Net is then applied to compensate for the loss of organizational and artifact information in the metal regions. The corrected metal sinogram and the interpolated metal-free sinogram are then used to reconstruct the metal CT and metal-free CT images, respectively. Finally, the Fusion Module combines the two CT images to produce the result. RESULTS: Our proposed method shows strong performance in both qualitative and quantitative evaluations. The peak signal-to-noise ratio (PSNR) of the CT image before and after correction was 18.22 and 30.32, respectively. The structural similarity index measure (SSIM) improved from 0.75 to 0.99, and the weighted peak signal-to-noise ratio (WPSNR) increased from 21.69 to 35.68. CONCLUSIONS: Our proposed method demonstrates the reliability of high-accuracy correction of beam hardening artifacts.

Vernalization-triggered expression of the antisense transcript COOLAIR is mediated by CBF genes.

To synchronize flowering time with spring, many plants undergo vernalization, a floral-promotion process triggered by exposure to long-term winter cold. In Arabidopsis thaliana, this is achieved through cold-mediated epigenetic silencing of the floral repressor, FLOWERING LOCUS C (FLC). COOLAIR, a cold-induced antisense RNA transcribed from the FLC locus, has been proposed to facilitate FLC silencing. Here, we show that C-repeat (CRT)/dehydration-responsive elements (DREs) at the 3'-end of FLC and CRT/DRE-binding factors (CBFs) are required for cold-mediated expression of COOLAIR. CBFs bind to CRT/DREs at the 3'-end of FLC, both in vitro and in vivo, and CBF levels increase gradually during vernalization. Cold-induced COOLAIR expression is severely impaired in cbfs mutants in which all CBF genes are knocked-out. Conversely, CBF-overexpressing plants show increased COOLAIR levels even at warm temperatures. We show that COOLAIR is induced by CBFs during early stages of vernalization but COOLAIR levels decrease in later phases as FLC chromatin transitions to an inactive state to which CBFs can no longer bind. We also demonstrate that cbfs and FLCΔCOOLAIR mutants exhibit a normal vernalization response despite their inability to activate COOLAIR expression during cold, revealing that COOLAIR is not required for the vernalization process.

Long spells of cold winter weather may feel miserable, but they are often necessary for spring to blossom. Indeed, many plants need to face a prolonged period of low temperatures to be able to flower; this process is known as vernalization. While the molecular mechanisms which underpin vernalization are well-known, it is still unclear exactly how plants can 'sense' the difference between short and long periods of cold. Jeon, Jeong et al. set out to explore this question by focusing on COOLAIR, one of the rare genetic sequences identified as potentially being able to trigger vernalization. COOLAIR is a long noncoding RNA, a partial transcript of a gene that will not be 'read' by the cell to produce a protein but which instead regulates how and when certain genes are being switched on. COOLAIR emerges from the locus of the FLC gene, which is one of the main repressors of flowering, and it gradually accumulates in the plant when temperatures remain low for a long period. While some evidence suggests that COOLAIR may help to switch off FLC, other studies have raised some doubts about its involvement in vernalization. In response, Jeon, Jeong et al. examined the FLC gene in a range of plants closely related to A. thaliana, and in which COOLAIR also accumulates upon cold exposure. This helped them identify a class of proteins, known as CBFs, which could bind to sequences near the FLC gene to activate the production of COOLAIR when the plants were kept in cold conditions for a while. CBFs were already known to help plants adapt to short cold snaps, but these experiments confirmed that they could act as both short- and long-term cold sensors. This work allowed Jeon, Jeong et al. to propose a model in which CBF and therefore COOLAIR levels increase as the cold persists, until changes in the structure of the FLC gene prevent CBF from binding to it and COOLAIR production drops. Unexpectedly, examining the fate of mutants which could not produce COOLAIR revealed that these plants could still undergo vernalization, suggesting that the long noncoding RNA is in fact not necessary for this process. These results should prompt other scientists to further investigate the role of COOLAIR in vernalization; they also give insight into how coding and noncoding sequences may have evolved together in various members of the A. thaliana family to adapt to the environment.

Tactile cues are important to environmental novelty during repeated open field tests.

The open field test (OFT) is a commonly used protocol to measure anxiety-like behaviors in rodents. Exploration in the central area of the open field and rearing frequency are often readouts of anxiety measurement. However, concerns about carry-over effects associated with repeated assessments limit its application, with the underlying mechanisms of this phenomenon still to be fully described. Here, we showed that repeated OFTs in the same mice led to reductions in the percentage of time spent in the central area and frequency of rearing. This effect reduced with an increase in the intervals between test. The decay caused by repeated OFTs was due to habituation, rather than frequent handling of the experimenter, since novel environments could prevent decay from repeated OFTs. Our results also indicated that tactile cues of the environment played important roles in the habituation of repeated OFTs. Furthermore, the decay of central area activity and rearing behavior during repeated OFTs would be blocked if the hippocampal CA1 was lesioned, suggesting that CA1 is a crucial region for habituation of the OFT in mice. Taken together, our study uncovers the important roles of tactile cues and hippocampal CA1 during repeated OFTs in mice.

Corticotropin releasing factor neurons in the visual cortex mediate long-term changes in visual function induced by early adversity.

Early adversity can cause malfunction of the visual system in adulthood. Adult female but not male mice undergoing early chronic mild stress (ECMS) maintain ocular dominance (OD) plasticity after the critical period. How early stressful experiences have a long-term impact on it is largely unknown. Here, we observed a wide distribution of corticotropin-releasing factor (CRF)-positive neurons, which mainly colocalized with a subpopulation of GABAergic interneurons in the mouse primary visual cortex (V1). Optogenetic activation of CRF-positive neurons transfected with AAV-ChR2 evoked inhibitory currents in nearby pyramidal cells. ECMS induced a reduction in the expression of CRF mRNA in adult mouse V1. Chemogenetic activation of V1 CRF neurons impaired OD plasticity in adult ECMS females. We further showed that local administration of the corticotropin releasing factor receptor 1 (CRFR1) antagonist via an osmotic minipump into the visual cortex mimicked OD plasticity in adult ECMS females. Whole-cell recording in layer 2/3 pyramidal neurons revealed that the CRFR1 antagonist reduced the short-term depression (STD) of evoked inhibitory postsynaptic current (IPSC) in females but not in males. Likewise, CRF agonists have the opposite effect. In summary, our findings indicate that the local CRF-CRFR1 system within V1 may mediate the long-term and sex-dependent effect of early stress experiences on visual plasticity and provide a target for the prevention of visual deficits in adults with a history of early-life adversity.