High-Fidelity Assay Based on Turn-Off Fluorescence to Detect the Perturbations of Cellular Proteostasis.

The persistence of neurodegenerative diseases has necessitated the development of new strategies to monitor protein homeostasis (proteostasis). Previous efforts in our laboratory have focused on the development of fluorogenic strategies to observe the onset and progression of proteostatic stress. These works utilized solvatochromic and viscosity sensitive fluorophores to sense protein folded states, enabling stressor screening with an increase in the emission intensity upon aggregation. In this work, we present a novel, high-fidelity assay to detect perturbations of cellular proteostasis, where the fluorescence intensity decreases with the onset of proteostatic stress. Utilizing a fluorogenic, hydroxymethyl silicon-rhodamine probe to differentiate between protein folded states, we establish the validity of this technology in living cells by demonstrating a two-fold difference in fluorescence intensity between unstressed and stressed conditions.

The emerging roles of microbiota-derived extracellular vesicles in psychiatric disorders.

Major depressive disorder, schizophrenia, and bipolar disorder are three major psychiatric disorders that significantly impact the well-being and overall health of patients. Some researches indicate that abnormalities in the gut microbiota can trigger certain psychiatric diseases. Microbiota-derived extracellular vesicles have the ability to transfer bioactive compounds into host cells, altering signaling and biological processes, ultimately influencing the mental health and illness of the host. This review aims to investigate the emerging roles of microbiota-derived extracellular vesicles in these three major psychiatric disorders and discusses their roles as diagnostic biomarkers and therapies for these psychiatric disorders.

Constructing polynomial libraries for reservoir computing in nonlinear dynamical system forecasting.

Reservoir computing is an effective model for learning and predicting nonlinear and chaotic dynamical systems; however, there remains a challenge in achieving a more dependable evolution for such systems. Based on the foundation of Koopman operator theory, considering the effectiveness of the sparse identification of nonlinear dynamics algorithm to construct candidate nonlinear libraries in the application of nonlinear data, an alternative reservoir computing method is proposed, which creates the linear Hilbert space of the nonlinear system by including nonlinear terms in the optimization process of reservoir computing, allowing for the application of linear optimization. We introduce an implementation that incorporates a polynomial transformation of arbitrary order when fitting the readout matrix. Constructing polynomial libraries with reservoir-state vectors as elements enhances the nonlinear representation of reservoir states and more easily captures the complexity of nonlinear systems. The Lorenz-63 system, the Lorenz-96 system, and the Kuramoto-Sivashinsky equation are used to validate the effectiveness of constructing polynomial libraries for reservoir states in the field of state-evolution prediction of nonlinear and chaotic dynamical systems. This study not only promotes the theoretical study of reservoir computing, but also provides a theoretical and practical method for the prediction of nonlinear and chaotic dynamical system evolution.

Contralaterally Controlled Functional Electrical Stimulation for Improving Motor Function After Acquired Brain Injury: A Systematic Review and Meta-analysis.

OBJECTIVE: To systematically evaluate the effect of contralaterally controlled functional electrical stimulation (CCFES) on motor function after acquired brain injury (ABI). DATA SOURCES: We searched the PubMed, Embase, Cochrane Central Register of Controlled Trials, Physiotherapy Evidence Database (PEDro), Web of Science, SinoMed, CNKI, VIP Database for Chinese Technical Periodicals and Wanfang Database, from inception to December 2023. STUDY SELECTION: Studies were included if they were randomized controlled trials assessing the effect of CCFES on motor function compared with routine rehabilitation or routine electrical stimulation after ABI. Two independent reviewers screened 894 articles for inclusion. DATA EXTRACTION: The extracted data included study information, sample size, study population, interventions, measurement evaluated, and the test interval. DATA SYNTHESIS: This study included 24 trials with 28 intervention-control pairs and 1148 participants with stroke. Meta-analysis showed that the CCFES group demonstrated more significant improvement than the control group in the Fugl-Meyer Assessment Scale (FMA) (standardized mean difference [SMD]=0.66, 95% confidence interval [CI]=0.44-0.88, P<.001), active range of motion (AROM) (SMD=0.77, 95% CI=0.54-1.01, P<.001), modified Barthel Index (MBI) (SMD=0.55, 95% CI=0.29-0.81, P<.001), Motricity Index (MI) (SMD=0.60, 95% CI=0.26-0.94, P<.001) surface electromyography (sEMG) (SMD=0.81, 95% CI=0.56-1.06, P<.001), and Functional Ambulation Category (FAC) (SMD=0.53, 95% CI=0.24-0.83, P<.001). The CCFES group showed no significant improvement over the control group in the Action Research Arm Test (ARAT) (SMD=0.24, 95% CI=-0.10-0.58, P=.17). CONCLUSIONS: Our synthesized evidence suggests that CCFES could improve motor function in patients with stroke. More RCTs with other patients with brain injury are required to provide future evidence on the therapy effect of CCFES and make a contribution to the uniform standard of CCFES.

Detecting protein-protein interaction during liquid-liquid phase separation using fluorogenic protein sensors.

The formation of cellular condensates, akin to membraneless organelles, is typically mediated by liquid-liquid phase separation (LLPS), during which proteins and RNA molecules interact with each other via multivalent interactions. Gaining a comprehensive understanding of these interactions holds significance in unraveling the mechanisms underlying condensate formation and the pathology of related diseases. In an attempt toward this end, fluorescence microscopy is often used to examine the colocalization of target proteins/RNAs. However, fluorescence colocalization is inadequate to reliably identify protein interaction due to the diffraction limit of traditional fluorescence microscopy. In this study, we achieve this goal through adopting a novel chemical biology approach via the dimerization-dependent fluorescent proteins (ddFPs). We succeeded in utilizing ddFPs to detect protein interaction during LLPS both in vitro and in living cells. The ddFPs allow us to investigate the interaction between two important LLPS-associated proteins, FUS and TDP-43, as cellular condensates formed. Importantly, we revealed that their interaction was associated with RNA binding upon LLPS, indicating that RNA plays a critical role in mediating interactions between RBPs. More broadly, we envision that utilization of ddFPs would reveal previously unknown protein-protein interaction and uncover their functional roles in the formation and disassembly of biomolecular condensates.

A Silver-Induced Absorption Red-Shifted Dual-Targeted Nanodiagnosis-Treatment Agent for NIR-II Photoacoustic Imaging-Guided Photothermal and ROS Simultaneously Enhanced Immune Checkpoint Blockade Antitumor Therapy.

Tumor metastasis remains a leading factor in the failure of cancer treatments and patient mortality. To address this, a silver-induced absorption red-shifted core-shell nano-particle is developed, and surface-modified with triphenylphosphonium bromide (TPP) and hyaluronic acid (HA) to obtain a novel nanodiagnosis-treatment agent (Ag@CuS-TPP@HA). This diagnosis-treatment agent can dual-targets cancer cells and mitochondria, and exhibits maximal light absorption at 1064 nm, thereby enhancing nesr-infrared II (NIR-II) photoacoustic (PA) signal and photothermal effects under 1064 nm laser irradiation. Additionally, the silver in Ag@CuS-TPP@HA can catalyze the Fenton-like reactions with H2 O2 in the tumor tissue, yielding reactive oxygen species (ROS). The ROS production, coupled with enhanced photothermal effects, instigates immunogenic cell death (ICD), leading to a substantial release of tumor-associated antigens (TAAs) and damage-associated molecular patterns, which have improved the tumor immune suppression microenvironment and boosting immune checkpoint blockade therapy, thus stimulating a systemic antitumor immune response. Hence, Ag@CuS-TPP@HA, as a cancer diagnostic-treatment agent, not only accomplishes targeted the NIR-II PA imaging of tumor tissue and addresses the challenge of accurate diagnosis of deep cancer tissue in vivo, but it also leverages ROS/photothermal therapy to enhance immune checkpoint blockade, thereby eliminating primary tumors and effectively inhibiting distant tumor growth.

Advanced Techniques for Detecting Protein Misfolding and Aggregation in Cellular Environments.

Protein misfolding and aggregation, a key contributor to the progression of numerous neurodegenerative diseases, results in functional deficiencies and the creation of harmful intermediates. Detailed visualization of this misfolding process is of paramount importance for improving our understanding of disease mechanisms and for the development of potential therapeutic strategies. While in vitro studies using purified proteins have been instrumental in delivering significant insights into protein misfolding, the behavior of these proteins in the complex milieu of living cells often diverges significantly from such simplified environments. Biomedical imaging performed in cell provides cellular-level information with high physiological and pathological relevance, often surpassing the depth of information attainable through in vitro methods. This review highlights a variety of methodologies used to scrutinize protein misfolding within biological systems. This includes optical-based methods, strategies leaning on mass spectrometry, in-cell nuclear magnetic resonance, and cryo-electron microscopy. Recent advancements in these techniques have notably deepened our understanding of protein misfolding processes and the features of the resulting misfolded species within living cells. The progression in these fields promises to catalyze further breakthroughs in our comprehension of neurodegenerative disease mechanisms and potential therapeutic interventions.

Mirror therapy combined with contralaterally controlled functional electrical stimulation for the upper limb motor function after stroke: a randomized controlled trial.

PURPOSE: In this study, we investigated the effects of mirror therapy (MT) combined with contralaterally controlled functional electrical stimulation (CCFES) on upper limb motor function, activities of daily life, and corticospinal excitability in post-stroke patients. METHODS: Sixty post-stroke patients were randomly divided into four groups: CCFES, MT, MT combined with CCFES, and control. All the patients underwent routine rehabilitation. Those in the MT, CCFES, MT combined with CCFES, and control groups received MT, CCFES, MT combined with CCFES, and routine rehabilitation alone, respectively. Upper limb motor function, activities of daily living, and corticospinal excitability were evaluated before and after a 3-week intervention period. RESULTS: MT combined with CCFES demonstrated a significantly greater therapeutic effect on motor function of the paretic wrist than CCFES, MT, or routine rehabilitation alone. However, there was no significant difference in the overall motor function of the affected upper limb, activities of daily life, or corticospinal excitability between the MT combined with CCFES group and the other three groups. CONCLUSION: MT combined with CCFES may be a potential adjuvant therapy to promote motor function in paretic wrist after stroke.

The combined therapy of mirror therapy (MT) and contralaterally controlled functional electrical stimulation (CCFES) may be a potential adjuvant therapy to promote motor function in paretic wrists after stroke.MT combined with CCFES could be incorporated into rehabilitation programs for post-stroke patients with impaired upper limb motor function.Exploring the potential benefits of combining different rehabilitation therapies could inform the development of more effective interventions.

Constraint-induced movement therapy alleviates motor impairment by inhibiting the accumulation of neutrophil extracellular traps in ischemic cortex.

Stroke is a major cause of mortality and morbidity and most acute strokes are ischemic. Evidence-based medicine has demonstrated the effectiveness of constraint-induced movement therapy (CIMT) in the recovery of motor function in patients after ischemic stroke, but the specific treatment mechanism remains unclear. Herein, our integrated transcriptomics and multiple enrichment analysis studies, including Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and gene set enrichment analysis (GSEA) studies show that CIMT conduction broadly curtails immune response, neutrophil chemotaxis, and chemokine-mediated signaling pathway, CCR chemokine receptor binding. Those suggest the potential effect of CIMT on neutrophils in ischemic mice brain parenchyma. Recent studies have found that accumulating granulocytes release extracellular web-like structures composed of DNA and proteins called neutrophil extracellular traps (NETs), which destruct neurological function primarily by disrupting the blood-brain barrier and promoting thrombosis. However, the temporal and spatial distribution of neutrophils and their released NETs in parenchyma and their damaging effects on nerve cells remain unclear. Thus, utilizing immunofluorescence and flow cytometry, our analyses uncovered that NETs erode multiple regions such as primary motor cortex (M1), striatum (Str), nucleus of the vertical limb of the diagonal band (VDB), nucleus of the horizontal limb of the diagonal band (HDB) and medial septal nucleus (MS), and persist in the brain parenchyma for at least 14 days, while CIMT can reduce the content of NETs and chemokines CCL2 and CCL5 in M1. Intriguingly, CIMT failed to further reduce neurological deficits after inhibiting the NET formation by pharmacologic inhibition of peptidylarginine deiminase 4 (PAD4). Collectively, these results demonstrate that CIMT could alleviate cerebral ischemic injury induced locomotor deficits by modulating the activation of neutrophils. These data are expected to provide direct evidence for the expression of NETs in ischemic brain parenchyma and novel insights into the mechanisms of CIMT protecting against ischemic brain injury.

Effectiveness analysis of multiple epidemic prevention measures in the context of COVID-19 using the SVIRD model and ensemble Kalman filter.

The ability to accurately forecast the spread of coronavirus disease 2019 (COVID-19) is of great importance to the resumption of societal normality. Existing methods of epidemic forecasting often ignore the comprehensive analysis of multiple epidemic prevention measures. This paper aims to analyze various epidemic prevention measures through a compound framework. Here, a susceptible-vaccinated-infected-recovered-deceased (SVIRD) model is constructed to consider the effects of population mobility among origin and destination, vaccination, and positive retest populations. And we further use real-time observations to correct the model trajectory with the help of data assimilation. Seven prevention measures are used to analyze the short-term trend of active cases. The results of the synthetic scene recommended that four measures-improving the vaccination protection rate (IVPR), reducing the number of contacts per person per day (RNCP), selecting the region with less infected people as origin A (SES-O) and limiting population flow entering from A to B per day (LAIP-OD)-are the most effective in the short-term, with maximum reductions of 75%, 53%, 35% and 31%, respectively, in active cases after 150 days. The results of the real-world experiment with Hong Kong as the origin and Shenzhen as the destination indicate that when the daily vaccination rate increased from 5% to 9.5%, the number of active cases decreased by only 7.35%. The results demonstrate that reducing the number of contacts per person per day after productive life resumes is more effective than increasing vaccination rates.

Effects of sequential inhibitory and facilitatory repetitive transcranial magnetic stimulation on neurological and functional recovery of a patient with chronic stroke: A case report and literature review.

Background and purpose: The effects of conventional protocols of repetitive transcranial magnetic stimulation (rTMS) in the chronic phase of stroke are limited. This study aimed to apply the sequential inhibitory and facilitatory rTMS for upper limb motor dysfunction post-stroke to observe the efficacy and explore the possible neurophysiological mechanism. We hypothesize that this protocol would both enhance the excitability of affected M1 and promote connections among motor areas. Case description: We reported a 55-year-old female patient with a 1-year chronic stroke and right-sided hemiplegia, who underwent the 14-session rTMS with seven sessions of low frequency (LF) and with seven sessions of high frequency (HF). Clinical scales mainly including Fugl-Meyer Assessment of Upper Extremity (FMA-UE), Action Research Arm Test (ARAT), neurophysiological measures, and functional near-infrared spectroscopy (fNIRS) were assessed before (T0), at the midpoint (T1), and after the intervention (T2). Outcomes: The patient exhibited post-intervention improvement in upper extremity function. There was increased excitability in the ipsilesional hemisphere and the opposite in the contralesional hemisphere. The interhemispheric inhibition (IHI) ratio increased from 2.70 to 10.81 and finally decreased to 1.34. Oxy-Hb signal was significantly decreased in affected M1 and mildly decreased in unaffected M1, while that of PMC and SMA on the affected side increased significantly. Conclusion: The sequential inhibitory and facilitatory rTMS significantly promoted motor recovery in the patient. Related mechanisms include upregulation of excitability in the ipsilesional hemisphere, return of interhemispheric balance, and neuroplasticity-induced cortical reorganization.

Corticostriatal Projections Relying on GABA Levels Mediate Exercise-Induced Functional Recovery in Cerebral Ischemic Mice.

Stroke is a neurological disorder characterized by high disability and death worldwide. The occlusion of the middle cerebral artery (MCAO) supplying the cortical motor regions and its projection pathway regions can either kill the cortical neurons or block their projections to the spinal cord and subcortical structure. The cerebral cortex is the primary striatal afferent, and the medium spiny neurons of the striatum have been identified as the major output neurons projecting to the substantia nigra and pallidum. Thus, disconnection of the corticostriatal circuit often occurs in the model of MCAO. In this study, we hypothesize that striatal network dysfunction in cerebral ischemic mice ultimately modulates the activity of striatal projections from cortical neurons to improve dysfunction during exercise training. In this study, we observed that the corticostriatal circuit originating from glutamatergic neurons could partially medicate the improvement of motor and anxiety-like behavior in mice with exercise. Furthermore, exercising or activating a single optogenetic corticostriatal circuit can increase the striatal gamma-aminobutyric acid (GABA) level. Using the GABA-A receptor antagonist, bicuculline, we further identified that the striatal glutamatergic projection from the cortical neurons relies on the GABAergic synapse's activity to modulate exercise-induced functional recovery. Overall, those results reveal that the dorsal striatum-projecting subpopulation of cortical glutamatergic neurons can influence GABA levels in the striatum, playing a critical role in modulating exercise-induced improvement of motor and anxiety-like behavior.

An improved sparse identification of nonlinear dynamics with Akaike information criterion and group sparsity.

A crucial challenge encountered in diverse areas of engineering applications involves speculating the governing equations based upon partial observations. On this basis, a variant of the sparse identification of nonlinear dynamics (SINDy) algorithm is developed. First, the Akaike information criterion (AIC) is integrated to enforce model selection by hierarchically ranking the most informative model from several manageable candidate models. This integration avoids restricting the number of candidate models, which is a disadvantage of the traditional methods for model selection. The subsequent procedure expands the structure of dynamics from ordinary differential equations (ODEs) to partial differential equations (PDEs), while group sparsity is employed to identify the nonconstant coefficients of partial differential equations. Of practical consideration within an integrated frame is data processing, which tends to treat noise separate from signals and tends to parametrize the noise probability distribution. In particular, the coefficients of a species of canonical ODEs and PDEs, such as the Van der Pol, Rössler, Burgers' and Kuramoto-Sivashinsky equations, can be identified correctly with the introduction of noise. Furthermore, except for normal noise, the proposed approach is able to capture the distribution of uniform noise. In accordance with the results of the experiments, the computational speed is markedly advanced and possesses robustness.

Repetitive Transcranial Magnetic Stimulation of the Brain After Ischemic Stroke: Mechanisms from Animal Models.

Stroke is a common cerebrovascular disease with high morbidity, mortality, and disability worldwide. Post-stroke dysfunction is related to the death of neurons and impairment of synaptic structure, which results from cerebral ischemic damage. Currently, transcranial magnetic stimulation (TMS) techniques are available to provide clinically effective interventions and quantitative diagnostic and prognostic biomarkers. The development of TMS has been 40 years and a range of repetitive TMS (rTMS) protocols are now available to regulate neuronal plasticity in many neurological disorders, such as stroke, Parkinson disease, psychiatric disorders, Alzheimer disease, and so on. Basic studies in an animal model with ischemic stroke are significant for demonstrating potential mechanisms of neural restoration induced by rTMS. In this review, the mechanisms were summarized, involving synaptic plasticity, neural cell death, neurogenesis, immune response, and blood-brain barrier (BBB) disruption in vitro and vivo experiments with ischemic stroke models. Those findings can contribute to the understanding of how rTMS modulated function recovery and the exploration of novel therapeutic targets. The mechanisms of rTMS in treating ischemic stroke from animal models. rTMS can prompt synaptic plasticity by increasing NMDAR, AMPAR and BDNF expression; rTMS can inhibit pro-inflammatory cytokines TNF and facilitate the expression of anti-inflammatory cytokines IL-10 by shifting astrocytic phenotypes from A1 to A2, and shifting microglial phenotypes from M1 to M2; rTMS facilitated the release of angiogenesis-related factors TGFß and VEGF in A2 astrocytes, which can contribute to vasculogenesis and angiogenesis; rTMS can suppress apoptosis by increasing Bcl-2 expression and inhibiting Bax, caspase-3 expression; rTMS can also suppress pyroptosis by decreasing caspase-1, IL-1ß, ASC, GSDMD and NLRP1 expression. rTMS, repetitive transcranial magnetic stimulation; NMDAR, N-methyl-D-aspartic acid receptors; AMPAR: α-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors; BDNF, brain-derived neurotrophic factor; VEGF, vascular endothelial growth factor; GSDMD: cleaved Caspase-1 cleaves Gasdermin D; CBF: cerebral blood flow.

Focal vibration of the plantarflexor and dorsiflexor muscles improves poststroke spasticity: a randomized single-blind controlled trial.

BACKGROUND: Post-stroke spasticity is a cause of gait dysfunction and disability. Focal vibration (FV) of agonist-antagonist upper limb muscle pairs reduces flexor spasticity; however, its effects on ankle plantarflexor spasticity are uncertain. OBJECTIVE: To assess the effects of focal vibration administered by a trained operator to the ankle plantarflexor and dorsiflexor muscles on post-stroke lower limb spasticity. METHODS: A randomized, single-blind controlled trial of 64 participants with stroke and plantarflexor spasticity assigned to 3 groups by centralized, computer-generated randomization (1:1:1): 1) physiotherapy alone (CON), 2) physiotherapy+gastrocnemius vibration (FV_GM) and 3) physiotherapy+tibialis anterior vibration (FV_TA). Physiotherapists and assessors were blinded to group assignment. The experimental groups underwent 15, 20-min vibration sessions at 40 Hz. We performed evaluations at baseline and after the final treatment: Modified Ashworth Scale (MAS), Clonus scale, Functional Ambulation Categories (FAC), Fugl-Meyer Assessment - Lower Extremity (FMA_LE), Modified Barthel Index (MBI), and electromyography and ultrasound elastography. Primary outcome was remission rate (number and proportion of participants) of the MAS. RESULTS: MAS remission rate was higher in FV_GM and FV_TA than CON groups (CON vs. FV_GM: p=0.009, odds ratio 0.15 [95% confidence interval 0.03-0.67]; CON vs. FV_TA: p=0.002, 0.12 [0.03-0.51]). Remission rate was higher in the experimental than CON groups for the Clonus scale (CON vs. FV_GM: p<0.001, OR 0.07 [95% CI 0.01-0.31]; CON vs. FV_TA: p=0.006, 0.14 [95% CI 0.03-0.61]). FAC remission rate was higher in the FV_TA than the CON (p=0.009, 0.18 [0.05-0.68]) and FV_GM (p=0.014, 0.27 [0.07-0.99]) groups. Ultrasound variables of the paretic medial gastrocnemius decreased more in FV_GM than CON and FV_TA groups (shear modulus: p=0.006; shear wave velocity: p=0.008). CONCLUSIONS: Focal vibration reduced post-stroke spasticity of the plantarflexor muscles. Vibration of the tibialis anterior improved ambulation more than vibration of the gastrocnemius or physiotherapy alone. Gastrocnemius vibration may reduce spasticity by changing muscle stiffness.

The microRNA target site profile is a novel biomarker in the immunotherapy response.

MicroRNAs (miRNAs) bind on the 3' untranslated region (3'UTR) of messenger RNAs (mRNAs) and regulate mRNA expression in physiological and pathological conditions, including cancer. Thus, studies have identified miRNAs as potential biomarkers by correlating the miRNA expression with the expression of important mRNAs and/or clinical outcomes in cancers. However, tumors undergo pervasive 3'UTR shortening/lengthening events through alternative polyadenylation (APA), which varies the number of miRNA target sites in mRNA, raising the number of miRNA target sites (numTS) as another important regulatory axis of the miRNA binding effects. In this study, we developed the first statistical method, BIOMATA-APA, to identify predictive miRNAs based on numTS features. Running BIOMATA-APA on The Cancer Genome Atlas (TCGA) and independent cohort data both with immunotherapy and no immunotherapy, we demonstrated for the first time that the numTS feature 1) distinguishes different cancer types, 2) predicts tumor proliferation and immune infiltration status, 3) explains more variation in the proportion of tumor-infiltrating immune cells, 4) predicts response to immune checkpoint blockade (ICB) therapy, and 5) adds prognostic power beyond clinical and miRNA expression. To the best of our knowledge, this is the first pan-cancer study to systematically demonstrate numTS as a novel type of biomarker representing the miRNA binding effects underlying tumorigenesis and pave the way to incorporate miRNA target sites for miRNA biomarker identification. Another advantage of examining the miRNA binding effect using numTS is that it requires only RNA-Seq data, not miRNAs, thus resulting in high power in the miRNA biomarker identification.

Clinical Implications of the Lung Ultrasound Score in Patients after Cardiopulmonary Resuscitation.

Background: Lung ultrasound score (LUS) is a clinical index used to measure lung injury, but its clinical value in patients after cardiopulmonary resuscitation (CPR) remains relatively unknown. The purpose of this study was to investigate the clinical value of LUS in patients after CPR. Methods: This retrospective study included a total of 34 patients older than 18 years with a nontraumatic cause of in-hospital cardiac arrest, who received standard resuscitation and achieved return of spontaneous circulation (ROSC). All patients underwent bedside lung ultrasound examination within half an hour once ROSC was achieved, and LUSs were calculated. The study included patient death as the endpoint event. Results: Compared with the group with lower LUSs, the patients with higher LUSs had a lower oxygenation index, longer duration of CPR, and lower 72 h survival rate. The initial LUS had good clinical value in predicting the secondary outcomes of CPR (adjusted odds ratio (aOR): 1.353, 95% confidence interval (CI): 1.018-1.797, and P = 0.037) and 72 h survival rate of patients who underwent CPR (aOR: 1.145, 95% CI: 1.014-1.294, and P = 0.029). Conclusions: LUS was shown to be helpful and had a prognostic value in patients after CPR.

Effectiveness of contralaterally controlled functional electrical stimulation vs. neuromuscular electrical stimulation for recovery of lower extremity function in patients with subacute stroke: A randomized controlled trial.

Objective: This study aimed to compare the efficacy of contralaterally controlled functional electrical stimulation (CCFES) vs. neuromuscular electrical stimulation (NMES) for motor recovery of the lower extremity in patients with subacute stroke. Materials and methods: Seventy patients within 6 months post-stroke were randomly assigned to the CCFES group (n = 35) and the NMES group (n = 35). Both groups underwent routine rehabilitation plus 20-min electrical stimulation (CCFES or NMES) on ankle dorsiflexion muscles per day, 5 days a week, for 3 weeks. Ankle AROM (dorsiflexion), Fugl-Meyer assessment-lower extremity (FMA-LE), Barthel Index (BI), Functional Ambulation Category scale (FAC), 10-meter walking test, and surface electromyography (sEMG) were assessed at the baseline and at the end of the intervention. Result: Ten patients did not complete the study (five in CCFES and five in NMES), so only 60 patients were analyzed in the end. After the 3-week intervention, FMA-LE, BI, Ankle AROM (dorsiflexion), and FAC increased in both groups (p < 0.05). Patients in the CCFES group showed significantly greater improvements only in the measurement of Fugl-Meyer assessment-lower extremity compared with the NMES group after treatment (p < 0.05). The improvement in sEMG response of tibialis anterior by CCFES was greater than NMES (p < 0.05). Conclusion: Contralateral controlled functional electrical stimulation can effectively improve the motor function of the lower limbs better than conventional neuromuscular electrical stimulation in subacute patients after stroke, but the effect on improving the ability to walk, such as walking speed, was not good. Clinical trial registration: http://www.chictr.org.cn/, identifier: ChiCTR2100045423.

Covalent Solvatochromic Proteome Stress Sensor Based on the Schiff Base Reaction.

Covalent-type probes or sensors have been seldom reported for aggregated proteins. Herein, we reported a series of covalent solvatochromic probes to selectively modify and detect aggregated proteomes through the Schiff base reaction. Such covalent modification was discovered by serendipity using the P1 probe with an aldehyde functional group, exhibiting enhanced fluorescence intensity and unusually large blue shift upon protein aggregation. Supported by the biochemical and mass spectrometry results, we identified that this probe can modify the lysine residue of aggregated proteins selectively over folded ones via the Schiff base reaction. The generality of designing such a covalent-type probe was demonstrated in multiple probe scaffolds using different model proteins. Finally, we exploited the distinct solvatochromism of P1 after Schiff base linkage with aggregated proteins to visualize the distinct morphology of aggregated proteomes, as well as to quantify the polarity heterogeneity inside it. This work may intrigue the exploration of other chemical reaction types to covalently functionalize aggregated proteins that were difficult to analyze.