Improved green and red GRAB sensors for monitoring dopaminergic activity in vivo.

Dopamine (DA) plays multiple roles in a wide range of physiological and pathological processes via a large network of dopaminergic projections. To dissect the spatiotemporal dynamics of DA release in both dense and sparsely innervated brain regions, we developed a series of green and red fluorescent G-protein-coupled receptor activation-based DA (GRABDA) sensors using a variety of DA receptor subtypes. These sensors have high sensitivity, selectivity and signal-to-noise ratio with subsecond response kinetics and the ability to detect a wide range of DA concentrations. We then used these sensors in mice to measure both optogenetically evoked and behaviorally relevant DA release while measuring neurochemical signaling in the nucleus accumbens, amygdala and cortex. Using these sensors, we also detected spatially resolved heterogeneous cortical DA release in mice performing various behaviors. These next-generation GRABDA sensors provide a robust set of tools for imaging dopaminergic activity under a variety of physiological and pathological conditions.

Long-Term Kidney Outcomes after Pediatric Acute Kidney Injury.

BACKGROUND: Acute kidney injury (AKI) is common in hospitalized children. Pediatric AKI receiving acute kidney replacement therapy (KRT) is associated with long-term chronic kidney disease (CKD), hypertension, and death. We aim to determine the outcomes after AKI in children who did not receive acute KRT, since these remain uncertain. METHODS: Retrospective cohort study of all hospitalized children (0-18 years) surviving AKI without acute KRT between 1996-2020 in Ontario, Canada, identified by validated diagnostic codes in provincial administrative health databases. Children with prior KRT, CKD, or AKI were excluded. Cases were matched with up to four hospitalized comparators without AKI by age, neonatal status, sex, intensive care unit admission, cardiac surgery, malignancy, hypertension, hospitalization era, and a propensity score for AKI. Patients were followed until death, provincial emigration, or censoring in March 2021. The primary outcome was long-term major adverse kidney events (MAKE-LT; a composite of all-cause mortality, long-term KRT, or incident CKD). RESULTS: We matched 4,173 pediatric AKI survivors with 16,337 hospitalized comparators. Baseline covariates were well-balanced following propensity score matching. During median 9.7-year follow-up, 18% of AKI survivors developed MAKE-LT vs. 5% of hospitalized comparators (hazard ratio [HR] 4.0, 95% confidence interval [CI] 3.6-4.4). AKI survivors had higher rates of long-term KRT (2% vs. <1%; HR 11.7, 95%CI 7.5-18.4), incident CKD (16% vs. 2%; HR 7.9, 95%CI 6.9-9.1), incident hypertension (17% vs. 8%; HR 2.3, 95%CI 2.1-2.6), and AKI during subsequent hospitalization (6% vs. 2%; HR 3.7, 95%CI 3.1-4.5), but no difference in all-cause mortality (3% vs. 3%; HR 0.9, 95%CI 0.7-1.1). CONCLUSIONS: Children surviving AKI without acute KRT were at higher long-term risk of CKD, long-term KRT, hypertension, and subsequent AKI vs. hospitalized comparators.

Integrated gene co-expression network analysis and experimental validation revealed potential targets of human urine extract CDA-II in treating chronic myeloid leukemia.

BACKGROUND: Cell differentiation agent II (CDA-II) exhibits potent anti-proliferative and apoptosis-inducing properties against a variety of cancer cells. However, its mechanism of action in chronic myeloid leukemia (CML) remains unclear. METHODS: Cell counting Kit 8 (CCK-8) and flow cytometry were used to investigate the effects of CDA-II on the biological characteristics of K562 cells. Gene (mRNA and lncRNA) expression profiles were analyzed by bioinformatics to screen differentially expressed genes and to perform enrichment analysis. The Pearson correlation coefficients of lncRNAs and mRNAs were calculated using gene expression values, and a lncRNA/mRNA co-expression network was constructed. The MCODE and cytoHubba plugins were used to analyze the co-expression network. RESULTS: The Results, derived from CCK-8 and flow cytometry, indicated that CDA-II exerts dual effects on K562 cells: it inhibits their proliferation and induces apoptosis. From bioinformatics analysis, we identified 316 mRNAs and 32 lncRNAs. These mRNAs were predominantly related to the meiotic cell cycle, DNA methylation, transporter complex and peptidase regulator activity, complement and coagulation cascades, protein digestion and absorption, and cell adhesion molecule signaling pathways. The co-expression network comprised of 163 lncRNA/mRNA interaction pairs. Notably, our analysis results implicated clustered histone gene families and five lncRNAs in the biological effects of CDA-II on K562 cells. CONCLUSION: This study highlights the hub gene and lncRNA/mRNA co-expression network as crucial elements in the context of CDA-II treatment of CML. This insight not only enriches our understanding of CDA-II's mechanism of action but also might provide valuable clues for subsequent experimental studies of CDA-II, and potentially contribute to the discovery of new therapeutic targets for CML.

Lightweight and Strong Cellulosic Triboelectric Materials Enabled by Cell Wall Nanoengineering.

As intelligent technology surges forward, wearable electronics have emerged as versatile tools for monitoring health and sensing our surroundings. Among these advancements, porous triboelectric materials have garnered significant attention for their lightness. However, these materials face the challenge of improving structural stability to further enhance the sensing accuracy of triboelectric sensors. In this study, a lightweight and strong porous cellulosic triboelectric material is designed by cell wall nanoengineering. By tailoring of the cell wall structure, the material shows a high mechanical strength of 51.8 MPa. The self-powered sensor constructed by this material has a high sensitivity of 33.61 kPa-1, a fast response time of 36 ms, and excellent pressure detection durability. Notably, the sensor still enables a high sensing performance after the porous cellulosic triboelectric material exposure to 200 °C and achieves real-time feedback of human motion, thereby demonstrating great potential in the field of wearable electronic devices.

High Strength and Toughness Polymeric Triboelectric Materials Enabled by Dense Crystal-Domain Cross-Linking.

Lightweight, easily processed, and durable polymeric materials play a crucial role in wearable sensor devices. However, achieving simultaneously high strength and toughness remains a challenge. This study addresses this by utilizing an ion-specific effect to control crystalline domains, enabling the fabrication of a polymeric triboelectric material with tunable mechanical properties. The dense crystal-domain cross-linking enhances energy dissipation, resulting in a material boasting both high tensile strength (58.0 MPa) and toughness (198.8 MJ m-3), alongside a remarkable 416.7% fracture elongation and 545.0 MPa modulus. Leveraging these properties, the material is successfully integrated into wearable self-powered devices, enabling real-time feedback on human joint movement. This work presents a valuable strategy for overcoming the strength-toughness trade-off in polymeric materials, paving the way for their enhanced applicability and broader use in diverse sensing applications.

Phase-Directed Assembly of Triboelectric Nanopaper for Self-Powered Noncontact Sensing.

Noncontact sensing technology serves as a pivotal medium for seamless data acquisition and intelligent perception in the era of the Internet of Things (IoT), bringing innovative interactive experiences to wearable human-machine interaction perception networks. However, the pervasive limitations of current noncontact sensing devices posed by harsh environmental conditions hinder the precision and stability of signals. In this study, the triboelectric nanopaper prepared by a phase-directed assembly strategy is presented, which possesses low charge transfer mobility (1618 cm2 V-1 s-1) and exceptional high-temperature stability. Wearable self-powered noncontact sensors constructed from triboelectric nanopaper operate stably under high temperatures (200 °C). Furthermore, a temperature warning system for workers in hazardous environments is demonstrated, capable of nonintrusively identifying harmful thermal stimuli and detecting motion status. This research not only establishes a technological foundation for accurate and stable noncontact sensing under high temperatures but also promotes the sustainable intelligent development of wearable IoT devices under extreme environments.

Directional Moisture-Wicking Triboelectric Materials Enabled by Laplace Pressure Differences.

Wearable sensors are experiencing vibrant growth in the fields of health monitoring systems and human motion detection, with comfort becoming a significant research direction for wearable sensing devices. However, the weak moisture-wicking capability of sensor materials leads to liquid retention, severely restricting the comfort of the wearable sensors. This study employs a pattern-guided alignment strategy to construct microhill arrays, endowing triboelectric materials with directional moisture-wicking capability. Within 2.25 s, triboelectric materials can quickly and directionally remove the droplets, driven by the Laplace pressure differences and the wettability gradient. The directional moisture-wicking triboelectric materials exhibit excellent pressure sensing performance, enabling rapid response/recovery (29.1/37.0 ms), thereby achieving real-time online monitoring of human respiration and movement states. This work addresses the long-standing challenge of insufficient moisture-wicking driving force in flexible electronic sensing materials, holding significant implications for enhancing the comfort and application potential of electronic skin and wearable electronic devices.

Defining pre-emptive living kidney donor transplantation as a quality indicator.

Quality indicators in kidney transplants are needed to identify care gaps and improve access to transplants. We used linked administrative health care databases to examine multiple ways of defining pre-emptive living donor kidney transplants, including different patient cohorts and censoring definitions. We included adults from Ontario, Canada with advanced chronic kidney disease between January 1, 2013, to December 31, 2018. We created 4 unique incident patient cohorts, varying the eligibility by the risk of progression to kidney failure and whether individuals had a recorded contraindication to kidney transplant (eg, home oxygen use). We explored the effect of 4 censoring event definitions. Across the 4 cohorts, size varied substantially from 20 663 to 9598 patients, with the largest reduction (a 43% reduction) occurring when we excluded patients with ≥1 recorded contraindication to kidney transplantation. The incidence rate (per 100 person-years) of pre-emptive living donor kidney transplant varied across cohorts from 1.02 (95% CI: 0.91-1.14) for our most inclusive cohort to 2.21 (95% CI: 1.96-2.49) for the most restrictive cohort. Our methods can serve as a framework for developing other quality indicators in kidney transplantation and monitoring and improving access to pre-emptive living donor kidney transplants in health care systems.

Genome-wide analysis of MYB transcription factor family and AsMYB1R subfamily contribution to ROS homeostasis regulation in Avena sativa under PEG-induced drought stress.

BACKGROUND: The myeloblastosis (MYB) transcription factor (TF) family is one of the largest and most important TF families in plants, playing an important role in a life cycle and abiotic stress. RESULTS: In this study, 268 Avena sativa MYB (AsMYB) TFs from Avena sativa were identified and named according to their order of location on the chromosomes, respectively. Phylogenetic analysis of the AsMYB and Arabidopsis MYB proteins were performed to determine their homology, the AsMYB1R proteins were classified into 5 subgroups, and the AsMYB2R proteins were classified into 34 subgroups. The conserved domains and gene structure were highly conserved among the subgroups. Eight differentially expressed AsMYB genes were screened in the transcriptome of transcriptional data and validated through RT-qPCR. Three genes in AsMYB2R subgroup, which are related to the shortened growth period, stomatal closure, and nutrient and water transport by PEG-induced drought stress, were investigated in more details. The AsMYB1R subgroup genes LHY and REV 1, together with GST, regulate ROS homeostasis to ensure ROS signal transduction and scavenge excess ROS to avoid oxidative damage. CONCLUSION: The results of this study confirmed that the AsMYB TFs family is involved in the homeostatic regulation of ROS under drought stress. This lays the foundation for further investigating the involvement of the AsMYB TFs family in regulating A. sativa drought response mechanisms.

Liver tropism of ER mutant breast cancer is characterized by unique molecular changes and immune infiltration.

PURPOSE: Hotspot estrogen receptor alpha (ER/ESR1) mutations are recognized as the driver for both endocrine resistance and metastasis in advanced ER-positive (ER+) breast cancer, but their contributions to metastatic organ tropism remain insufficiently understood. In this study, we aim to comprehensively profile the organotropic metastatic pattern for ESR1 mutant breast cancer. METHODS: The organ-specific metastatic pattern of ESR1 mutant breast cancer was delineated using multi-omics data from multiple publicly available cohorts of ER+ metastatic breast cancer patients. Gene mutation/copy number variation (CNV) and differential gene expression analyses were performed to identify the genomic and transcriptomic alterations uniquely associated with ESR1 mutant liver metastasis. Upstream regulator, downstream pathway, and immune infiltration analysis were conducted for subsequent mechanistic investigations. RESULTS: ESR1 mutation-driven liver tropism was revealed by significant differences, encompassing a higher prevalence of liver metastasis in patients with ESR1 mutant breast cancer and an enrichment of mutations in liver metastatic samples. The significant enrichment of AGO2 copy number amplifications (CNAs) and multiple gene expression changes were revealed uniquely in ESR1 mutant liver metastasis. We also unveiled alterations in downstream signaling pathways and immune infiltration, particularly an enrichment of neutrophils, suggesting potential therapeutic vulnerabilities. CONCLUSION: Our data provide a comprehensive characterization of the behaviors and mechanisms of ESR1 mutant liver metastasis, paving the way for the development of personalized therapy to target liver metastasis for patients with ESR1 mutant breast cancer.

Smartphone-Based Free-to-Total Prostate Specific Antigen Ratio Detection System Using a Colorimetric Reaction Integrated with Proximity-Induced Bio-Barcode and CRISPR/Cas12a Assay.

The free-to-total prostate-specific antigen (f/t-PSA) ratio is of great significance in the accurate diagnosis of prostate cancer. Herein, a smartphone-based detection system is reported using a colorimetric reaction integrated with proximity-induced bio-barcode and the clustered regularly interspaced short palindromic repeats (CRISPR)/Cas12a assay for f/t-PSA ratio detection. DNA/antibody recognition probes are designed to bind f-PSA or t-PSA and induce the release of the DNA bio-barcode. The CRISPR/Cas12a system is activated by the DNA bio-barcode to release Ag+ from the C-Ag+-C structure of the hairpin DNA. The released Ag+ is used to affect the tetramethylbenzidine (TMB)-H2O2-based colorimetric reaction catalyzed by Pt nanoparticles (NPs), as the peroxidase-like activity of the Pt NPs can be efficiently inhibited by Ag+. A smartphone with a self-developed app is used as an image reader and analyzer to analyze the colorimetric reaction and provide the results. A limit of detection of 0.06 and 0.04 ng mL-1 is achieved for t-PSA and f-PSA, respectively. The smartphone-based method showed a linear response between 0.1 and 100 ng mL-1 of t-PSA or f-PSA. In tests with clinical samples, the smartphone-based method successfully diagnosed prostate cancer patients from benign prostatic hyperplasia patients and healthy cases with high sensitivity and specificity.

Interfacial Plasticization Strategy Enabling a Long-Cycle-Life Solid-State Lithium Metal Battery.

The limited ionic conductivity and unstable interface due to poor solid-solid interface pose significant challenges to the stable cycling of solid-state batteries (SSBs). Herein, an interfacial plasticization strategy is proposed by introducing a succinonitrile (SN)-based plastic curing agent into the polyacrylonitrile (PAN)-based composite polymer electrolytes (CPE) interface. The SN at the interface strongly plasticizes the PAN in the CPE, which reduces the crystallinity of the PAN drastically and enables the CPE to obtain a low modulus surface, but it still maintains a high modulus internally. The reduced crystallinity of PAN provides more amorphous regions, which are favorable for Li+ transport. The gradient modulus structure not only ensures intimate interfacial contact but also favors the suppression of Li dendrites growth. Consequently, the interfacial plasticized CPE (SF-CPE) obtains a high ionic conductivity of 4.8 × 10-4 S cm-1 as well as a high Li+ transference number of 0.61. The Li-Li symmetric cell with SF-CPE can cycle for 1000 h at 0.1 mA cm-2, the LiFeO4 (LFP)-Li full-cell demonstrates a high capacity retention of 86.1% after 1000 cycles at 1 C, and the LiCoO2 (LCO)-Li system also exhibits an excellent cycling performance. This work provides a novel strategy for long-life solid-state batteries.

Dynamic Thermostable Cellulosic Triboelectric Materials from Multilevel-Non-Covalent Interactions.

Triboelectric materials present great potential for harvesting huge amounts of dispersed energy, and converting them directly into useful electricity, a process that generates power more sustainably. Triboelectric nanogenerators (TENGs) have emerged as a technology to power electronics and sensors, and it is expected to solve the problem of energy harvesting and self-powered sensing from extreme environments. In this paper, a high-temperature-resistant triboelectric material is designed based on multilevel non-covalent bonding interactions, which achieves an ultra-high surface charge density of 192 µC m-2 at high temperatures. TENGs based on the triboelectric material exhibit more than an order of magnitude higher power output (2750 mW m-2 at 200 °C) than the existing devices at high temperatures. These remarkable properties are achieved based on enthalpy-driven molecular assembly in highly unbonded states. Thus, the material maintains bond strength and ultra-high surface charge density in entropy-dominated high-temperature environments. This molecular design concept points out a promising direction for the preparation of polymers with excellent triboelectric properties.

The Respiratory Syncytial Virus (RSV) G Protein Enhances the Immune Responses to the RSV F Protein in an Enveloped Virus-Like Particle Vaccine Candidate.

Respiratory syncytial virus (RSV) is a serious human respiratory pathogen, but no RSV vaccine has been licensed. Many vaccine candidates are focused on the viral F protein since the F protein is more conserved than the viral G protein across RSV strains and serotypes; thus, the F protein is thought more likely to induce a broader range of protection from infection. However, it is the G protein that binds the likely receptor, CX3CR1, in lung ciliated epithelial cells, raising the question of the importance of the G protein in vaccine candidates. Using virus-like particle (VLP) vaccine candidates, we have directly compared VLPs containing only the prefusion F protein (pre-F), only the G protein, or both glycoproteins. We report that VLPs containing both glycoproteins bind to anti-F-protein-specific monoclonal antibodies differently than do VLPs containing only the prefusion F protein. In RSV-naive cotton rats, VLPs assembled with only the pre-F protein stimulated extremely weak neutralizing antibody (NAb) titers, as did VLPs assembled with G protein. However, VLPs assembled with both glycoproteins stimulated quite robust neutralizing antibody titers, induced improved protection of the animals from RSV challenge compared to pre-F VLPs, and induced significantly higher levels of antibodies specific for F protein antigenic site 0, site III, and the AM14 binding site than did VLPs containing only the pre-F protein. These results indicate that assembly of pre-F protein with G protein in VLPs further stabilized the prefusion conformation or otherwise altered the conformation of the F protein, increasing the induction of protective antibodies. IMPORTANCE Respiratory syncytial virus (RSV) results in significant disease in infants, young children, and the elderly. Thus, development of an effective vaccine for these populations is a priority. Most ongoing efforts in RSV vaccine development have focused on the viral fusion (F) protein; however, the importance of the inclusion of G in vaccine candidates is unclear. Here, using virus-like particles (VLPs) assembled with only the F protein, only the G protein, or both glycoproteins, we show that VLPs assembled with both glycoproteins are a far superior vaccine in a cotton rat model compared with VLPs containing only F protein or only G protein. The results show that the presence of G protein in the VLPs influences the conformation of the F protein and the immune responses to F protein, resulting in significantly higher neutralizing antibody titers and better protection from RSV challenge. These results suggest that inclusion of G protein in a vaccine candidate may improve its effectiveness.

Structural characterization of M8C10, a neutralizing antibody targeting a highly conserved prefusion-specific epitope on the metapneumovirus fusion trimerization interface.

IMPORTANCE: Human metapneumovirus (hMPV) is a common pathogen causing lower respiratory tract infections worldwide and can develop severe symptoms in high-risk populations such as infants, the elderly, and immunocompromised patients. There are no approved hMPV vaccines or neutralizing antibodies available for therapeutic or prophylactic use. The trimeric hMPV fusion F protein is the major target of neutralizing antibodies in human sera. Understanding the immune recognition of antibodies to hMPV-F antigen will provide critical insights into developing efficacious hMPV monoclonal antibodies and vaccines.

Tensor Decomposition of Largest Convolutional Eigenvalues Reveals Pathologic Predictive Power of RhoB in Rectal Cancer Biopsy.

RhoB protein belongs to the Rho GTPase family, which plays an important role in governing cell signaling and tissue morphology. Its expression is known to have implications in pathologic processes of diseases. In particular, the role of RhoB in rectal cancer is not well understood. Investigation in the regulation and communication of this protein, detected by immunohistochemical staining on the microscope, can help gain insightful information leading to optimal disease treatment options. Herein, deep learning-based image analysis and the decomposition of multiway arrays were used to study the predictive factor of RhoB in two cohorts of patients with rectal cancer having survival rates of <5 and >5 years. The results show distinctions between the tensor decomposition factors of the two cohorts.

Regulation of cluster synchronization in multilayer networks of delay coupled semiconductor lasers with the use of disjoint layer symmetry.

In real-world complex systems, heterogeneous components often interact in complex connection patterns and could be schematized by a formalism of multilayer network. In this work, the synchronization characteristics of multilayer network composed of semiconductor lasers (SLs) are investigated systematically. It is demonstrated that the interplay between different layers plays an important role on the synchronization patterns. We elucidate that the performance of cluster synchronization could be facilitated effectively with the introduction of disjoint layer symmetry into network topology. Intertwined stability of clusters from different layers could be decoupled into independent, and the parameter spaces for stable synchronization are extended significantly. The robustness of our proposed regulation scheme on operation parameters is numerically evaluated. Furthermore, the generality of presented theoretical results is validated in networks with more complex topology and multiple layers.

Fast fiber nonlinearity compensation method for PDM coherent optical transmission systems based on the Fourier neural operator.

Fiber nonlinearity compensation (NLC) is likely to become an indispensable component of coherent optical transmission systems for extending the transmission reach and increasing capacity per fiber. In this work, we introduce what we believe to be a novel fast black-box neural network model based on the Fourier neural operator (FNO) to compensate for the chromatic dispersion (CD) and nonlinearity simultaneously. The feasibility of the proposed approach is demonstrated in uniformly distributed as well as probabilistically-shaped 32GBaud 16/32/64-ary quadrature amplitude modulation (16/32/64QAM) polarization-division-multiplexed (PDM) coherent optical communication systems. The experimental results demonstrate that about 0.31 dB Q-factor improvement is achieved compared to traditional digital back-propagation (DBP) with 5 steps per span for PDM-16QAM signals after 1600 km standard single-mode fiber (SSMF) transmission at the optimal launched power of 4 dBm. While, the time consumption is reduced from 6.04 seconds to 1.69 seconds using a central processing unit (CPU), and from 1.54 seconds to only 0.03 seconds using a graphic processing unit (GPU), respectively. This scheme also reveals noticeable generalization ability in terms of launched power and modulation format.

Multiple-access ultrastable frequency dissemination based on optical frequency combs via a fiber link.

We demonstrate an optical fiber-based, multiple-access frequency transmission using two optical frequency combs. The experimental results using the Allan deviation analysis show that with the phase compensation technique, the frequency instabilities at the remote site are 8.7 × 10-15/1 s and 1.0 × 10-17/103 s, and at the accessing node along the fiber link, the frequency instabilities are 6.9 × 10-15/1 s and 1.1 × 10-17/103 s. Similarly, the power spectral density of phase noise was analyzed in the frequency domain. These experimental results demonstrate that the compensation scheme improved the performance by two to three orders of magnitude. Thus, the proposed frequency transmission technique has potential application for disseminating ultrastable frequency references in the optical fiber network.

Development and validation of a disulfidptosis and disulfide metabolism-related risk index for predicting prognosis in lung adenocarcinoma.

BACKGROUND: Disulfidptosis is a recently proposed novel cell death mode in which cells with high SLC7A11 expression induce disulfide stress and cell death in response to glucose deficiency. The purpose of the research was to explore the function of disufidptosis and disulfide metabolism in the progression of lung adenocarcinoma (LUAD). METHODS: The RNA-seq data from TCGA were divided into high/low expression group on the base of the median expression of SLC7A11, and the characteristic of differentially expressed disulfide metabolism-related genes. Least absolute shrinkage and selection operator (LASSO) algorithm was conducted the disulfidptosis and disulfide metabolism risk index. The tumor mutation burden (TMB), mechanism, pathways, tumor microenvironment (TME), and immunotherapy response were assessed between different risk groups. The role of TXNRD1 in LUAD was investigated by cytological experiments. RESULTS: We established the risk index containing 5 genes. There are significant differences between different risk groups in terms of prognosis, TMB and tumor microenvironment. Additionally, the low-risk group demonstrated a higher rate of response immunotherapy in the prediction of immunotherapy response. Experimental validation suggested that the knockdown of TXNRD1 suppressed cell proliferation, migration, and invasion of LUAD. CONCLUSION: Our research highlights the enormous potential of disulfidptosis and disulfide metabolism risk index in predicting the prognosis of LUAD. And TXNRD1 has great clinical translational ability.