A study on expression of GRP78 and CHOP in neutrophil endoplasmic reticulum and their relationship with neutrophil apoptosis in the development of sepsis.

We investigated the relationship between neutrophil apoptosis and endoplasmic reticulum stress (ERS) in sepsis and its mechanism. A prospective cohort study was conducted by recruiting a total of 58 patients with sepsis. Peripheral blood samples were collected on 1, 3, 5 and 7 days after admission to the ICU. The expressions of endoplasmic reticulum specific glucose regulatory protein 78 (GRP78), C/EBP homologous protein (CHOP), apoptosis signal-regulating kinase 1 (ASK1), Bcl-2-like 11 (BIM), death receptor 5 (DR5), c-Jun N-terminal kinases (JNK) and p38 were detected by Western blot and PCR. The subcellular location of CHOP and GRP78 was observed by immunofluorescence analysis. Spearman correlation was used to analyze the correlation between the expression of chop protein and the apoptosis rate of peripheral blood neutrophils. Healthy volunteers in the same period were selected as the healthy control group. The expression of GRP78 protein was significantly elevated on the first day of ICU admission and showed a decreasing trend on the third, fifth and seventh day, but was significantly higher than the corresponding healthy control group. The expression of CHOP protein reached the highest level on the third day. The expression of chop protein in each group was significantly higher than that in the corresponding healthy control group. Immunofluorescence staining clearly showed that the CHOP protein accumulated in the nucleus, with an elevation in the intensity of GRP78. The neutrophil apoptosis rate of sepsis patients on the 1st, 3rd, 5th and 7th day of ICU stay was significantly higher than that of the healthy control group, with the highest apoptosis rate on the 3rd day, and then decreased gradually. CHOP protein expression level was significantly positively correlated with neutrophil apoptosis rate in sepsis patients. Endoplasmic reticulum stress occurs in neutrophils during the development of sepsis. GRP78 protein and CHOP protein may be involved in the pathological process of neutrophil apoptosis in sepsis.

Updated Pseudo-seq Protocol for Transcriptome-Wide Detection of Pseudouridines.

Pseudouridine (Ψ), the most prevalent modified base in cellular RNAs, has been mapped to numerous sites not only in rRNAs, tRNAs, and snRNAs but also mRNAs. Although there have been multiple techniques to identify Ψs, due to the recent development of sequencing technologies some reagents are not compatible with the current sequencer. Here, we show the updated Pseudo-seq, a technique enabling the genome-wide identification of pseudouridylation sites with single-nucleotide precision. We provide a comprehensive description of Pseudo-seq, covering protocols for RNA isolation from human cells, library preparation, and detailed data analysis procedures. The methodology presented is easily adaptable to any cell or tissue type with high-quality mRNA isolation. It can be used for discovering novel pseudouridylation sites, thus constituting a crucial initial step toward understanding the regulation and function of this modification. Key features • Identification of Ψ sites on mRNAs. • Updated Pseudo-seq provides precise positional and quantitative information of Ψ. • Uses a more efficient library preparation with the latest, currently available materials.

Hydrodynamics-Controlled Single-Particle Electrocatalysis.

Electrocatalysis is considered promising in renewable energy conversion and storage, yet numerous efforts rely on catalyst design to advance catalytic activity. Herein, a hydrodynamic single-particle electrocatalysis methodology is developed by integrating collision electrochemistry and microfluidics to improve the activity of an electrocatalysis system. As a proof-of-concept, hydrogen evolution reaction (HER) is electrocatalyzed by individual palladium nanoparticles (Pd NPs), with the development of microchannel-based ultramicroelectrodes. The controlled laminar flow enables the precise delivery of Pd NPs to the electrode-electrolyte interface one by one. Compared to the diffusion condition, hydrodynamic collision improves the number of active sites on a given electrode by 2 orders of magnitude. Furthermore, forced convection enables the enhancement of proton mass transport, thereby increasing the electrocatalytic activity of each single Pd NP. It turns out that the improvement in mass transport increases the reaction rate of HER at individual Pd NPs, thus a phase transition without requiring a high overpotential. This study provides new avenues for enhancing electrocatalytic activity by altering operating conditions, beyond material design limitations.

Unlocking Single Particle Anisotropy in Real-Time for Photoelectrochemistry Processes at the Nanoscale.

The key to rationally and rapidly designing high-performance materials is the monitoring and comprehension of dynamic processes within individual particles in real-time, particularly to gain insight into the anisotropy of nanoparticles. The intrinsic property of nanoparticles typically varies from one crystal facet to the next under realistic working conditions. Here, we introduce the operando collision electrochemistry to resolve the single silver nanoprisms (Ag NPs) anisotropy in photoelectrochemistry. We directly identify the effect of anisotropy on the plasmonic-assisted electrochemistry at the single NP/electrolyte interface. The statistical collision frequency shows that heterogeneous diffusion coefficient among crystal facets facilitates Ag NPs to undergo direction-dependent mass transfer toward the gold ultramicroelectrode. Subsequently, the current amplitudes of transient events indicate that anisotropy enables variations in dynamic interfacial electron transfer behaviors during photothermal processes. The results presented here demonstrate that the measurement precision of collision electrochemistry can be extended to the sub-nanoparticle level, highlighting the potential for high-throughput material screening with comprehensive kinetics information at the nanoscale.

Trichostatin A-modified vaccine provides superior protection against ovarian cancer formation and development.

More attention has been paid to immunotherapy for ovarian cancer and the development of tumor vaccines. We developed a trichostatin A (TSA)-modified tumor vaccine with potent immunomodulating activities that can inhibit the growth of ovarian cancer in rats and stimulate immune cell response in vivo. TSA-treated Nutu-19 cells inactivated by X-ray radiation were used as a tumor vaccine in rat ovarian cancer models. Prophylactic and therapeutic experiments were performed with TSA-modified tumor vaccine in rats. Flow cytometry and ELISpot assays were conducted to assess immune response. Immune cell expression in the spleen and thymus were detected by immunohistochemical staining. GM-CSF, IL-7, IL-17, LIF, LIX, KC, MCP-1, MIP-2, M-CSF, IP-10/CXCL10, MIG/CXCL9, RANTES, IL-4, IFN-γ, and VEGF expressions were detected with Milliplex Map Magnetic Bead Panel immunoassay. TSA vaccination in therapeutic and prophylactic models could effectively stimulate innate immunity and boost the adaptive humoral and cell-mediated immune responses to inhibit the growth and tumorigenesis of ovarian cancer. This vaccine stimulated the thymus into reactivating status and enhanced infiltrating lymphocytes in tumor-bearing rats. The expression of key immunoregulatory factors were upregulated in the vaccine group. The intensities of infiltrating CD4+ and CD8+ T cells and NK cells were significantly increased in the vaccine group compared to the control group (P<0.05). This protection was mainly dependent on the IFN-γ pathway and, to a much lesser extent, by the IL-4 pathway. The tumor cells only irradiated by X-ray as the control group still showed a slight immune effect, indicating that irradiated cells may also cause certain immune antigen exposure, but the efficacy was not as significant as that of the TSA-modified tumor vaccine. Our study revealed the potential application of the TSA-modified tumor vaccine as a novel tumor vaccine against tumor refractoriness and growth. These findings offer a better understanding of the immunomodulatory effects of the vaccine against latent tumorigenesis and progression. This tumor vaccine therapy may increase antigen exposure, synergistically activate the immune system, and ultimately improve remission rates. A vaccine strategy designed to induce effective tumor immune response is being considered for cancer immunotherapy.

Prognostic relevance of ventricular arrhythmias in surgical patients with gastrointestinal tumors.

BACKGROUND: Individuals diagnosed with gastrointestinal tumors are at an increased risk of developing cardiovascular diseases. Among which, ventricular arrhythmia is a prevalent clinical concern. This suggests that ventricular arrhythmias may have predictive value in the prognosis of patients with gastrointestinal tumors. AIM: To explore the prognostic value of ventricular arrhythmias in patients with gastrointestinal tumors receiving surgery. METHODS: We retrospectively analyzed data from 130 patients undergoing gastrointestinal tumor resection. These patients were evaluated by a 24-h ambulatory electrocardiogram (ECG) at the Sixth Affiliated Hospital of Sun Yat-sen University from January 2018 to June 2020. Additionally, 41 general healthy age-matched and sex-matched controls were included. Patients were categorized into survival and non-survival groups. The primary endpoint was all-cause mortality, and secondary endpoints included major adverse cardiovascular events (MACEs). RESULTS: Colorectal tumors comprised 90% of cases. Preoperative ambulatory ECG monitoring revealed that among the 130 patients with gastrointestinal tumors, 100 (76.92%) exhibited varying degrees of premature ventricular contractions (PVCs). Ten patients (7.69%) manifested non-sustained ventricular tachycardia (NSVT). The patients with gastrointestinal tumors exhibited higher PVCs compared to the healthy controls on both conventional ECG [27 (21.3) vs 1 (2.5), P = 0.012] and 24-h ambulatory ECG [14 (1.0, 405) vs 1 (0, 6.5), P < 0.001]. Non-survivors had a higher PVC count than survivors [150.50 (7.25, 1690.50) vs 9 (0, 229.25), P = 0.020]. During the follow-up period, 24 patients died and 11 patients experienced MACEs. Univariate analysis linked PVC > 35/24 h to all-cause mortality, and NSVT was associated with MACE. However, neither PVC burden nor NSVT independently predicted outcomes according to multivariate analysis. CONCLUSION: Patients with gastrointestinal tumors exhibited elevated PVCs. PVCs > 35/24 h and NSVT detected by 24-h ambulatory ECG were prognostically significant but were not found to be independent predictors.

Chinese medicinal formula Fu Xin decoction against chronic heart failure by inhibiting the NLRP3/caspase-1/GSDMD pyroptotic pathway.

BACKGROUND: Various heart diseases ultimately lead to chronic heart failure (CHF). In CHF, the inflammatory response is associated with pyroptosis, which is mediated by the NOD-like receptor protein 3 (NLRP3) inflammasome. Fu Xin decoction (FXD) is commonly used in clinical practice to treat CHF and improve inflammatory conditions. However, the specific pharmacological mechanisms of action for FXD in these processes have yet to be fully understood. PURPOSE: The objective of this study was to examine the protective mechanism of FXT against CHF, both in H9c2 cells and mice. METHOD: A CHF mouse model was established, and the effect of FXD was observed via gavage. Cardiac function was evaluated using echocardiography, while serum BNP and LDH levels were analyzed to assess the severity of CHF. Hematoxylin and eosin staining (H&E) and Masson staining were performed to evaluate myocardial pathological changes, and TdT-mediated dUTP Nick-End Labeling staining was used to detect DNA damage. Additionally, doxorubicin was utilized to induce myocardial cell injury in H9c2 cells, establishing a relevant model. CCK8 was used to observe cell viability and detect LDH levels in the cell supernatant. Subsequently, the expression of pyroptosis-related proteins was detected using immunohistochemistry, immunofluorescence, and western blotting. Finally, the pharmacological mechanism of FXD against CHF was further validated by treating H9c2 cells with an NLRP3 activator and inducing NLRP3 overexpression. RESULT: According to current research findings, echocardiography demonstrated a significant improvement of cardiac function by FXD, accompanied by reduced levels of BNP and LDH, indicating the amelioration of cardiac injury in CHF mice. FXD exhibited the ability to diminish serum CRP and MCP inflammatory markers in CHF mice. The results of HE and Masson staining analyses revealed a significant reduction in pathological damage of the heart tissue following FXD treatment. The CCK8 assay demonstrated the ability of FXD to enhance H9c2 cell viability, improve cell morphology, decrease LDH levels in the cell supernatant, and alleviate cell damage. Immunohistochemistry, Western blotting, and immunofluorescence staining substantiated the inhibitory effect of FXD on the NLRP3/caspase-1/GSDMD pyroptosis signaling pathway in both CHF and H9c2 cell injury models. Ultimately, the administration of the NLRP3 activator (Nigericin) and the overexpression of NLRP3 counteract the effects of FXD on cardiac protection and pyroptosis inhibition in vitro. CONCLUSION: FXD exhibits a cardioprotective effect, improving CHF and alleviating pyroptosis by inhibiting the NLRP3/caspase-1/GSDMD pathway.

Exploring the impact of culture techniques and patient demographics on the success rate of primary culture of human periodontal ligament stem cells.

Background/purpose: Periodontal ligament stem cells (PDLSCs) have the potential for regenerating periodontal tissue. The study aims to investigate the impact of demographics (ages, gender, disease) and culture techniques (shipping storage time and culture method) on the success of primary culture. Materials and methods: PDLSCs were collected from 51 teeth of 26 patients and cultured via outgrowth (OG) and enzymatic digestion (ED) methods. Cells characteristics were confirmed by flow cytometry, MTT, and ARS. The primary culture success rate was evaluated with a serial chi-square test to determine the relationship with culture technique (ED/OG and ≤4 h/prolonged culture) and patient demographics (Young/Old, Female/Male, and Health/Periodontitis). Results: The overall success rate of Health group (69.7%) was higher than Periodontitis (38.9%). Culturing within 4 h possessed a higher success rate (71.8%) than prolonged group (16.7%) regardless of patient demographics, and using OG method (81.5%) revealed more promising. Subgroup analysis of 39 cases (culture within 4 h) found that the success rate of OG was higher than ED in the Old group (87.5%-25.0%) and in the Periodontitis group (83.3%-25.0%). Conclusion: Primary culturing of PDLSCs within 4 h and using the outgrowth method led to higher success rates regardless of patient demographics. It can achieve successful PDLSCs culture of older patients or patients with periodontal disease by appropriate culture technique.

Association of Serum Uric Acid with Non-Valvular Atrial Fibrillation: A Retrospective Study in China.

Purpose: The association between serum uric acid (SUA) and atrial fibrillation (AF) has been widely focused on and studied in recent years. However, the exact association between SUA and AF is unclear, and the effect of gender on the association between SUA levels and AF has been controversial. This study aimed to investigate the association between SUA levels and non-valvular AF (NVAF) and the potential effect of gender on it. Patients and Methods: A total of 866 NVAF patients (463 males, age 69.44 ± 8.07 years) and 646 sex-matched control patients in sinus rhythm, with no history of arrhythmia were included in this study. t-test, ANOVA, and chi-square test were used for baseline data analysis. The receiver operating characteristic curve, logistic regression and Pearson correlation analysis were used for correlation analysis. Results: Compared to controls, NVAF patients exhibited higher SUA (P<0.001). After adjusting for confounders of NVAF, SUA remained significantly associated with NVAF, regardless of gender (OR= 1.31, 95% CI 1.18-1.43, P<0.001). SUA demonstrated higher predictability and sensitivity in predicting the occurrence of female NVAF compared to male (area under the curve was 0.68 (95% CI 0.64-0.72, P<0.001), sensitivity 87.3%), with the optimal cut-off point identified as 5.72 mg/dL. Furthermore, SUA levels correlated with APOA1, Scr and NT-proBNP in NVAF patients. SUA levels varied significantly among NVAF subtypes. Conclusion: High SUA levels were independently associated with NVAF, regardless of gender. SUA exhibited higher predictability and sensitivity in predicting the occurrence of NVAF in females compared to males. High SUA levels may affect other NVAF-related factors and participate in the pathophysiological process of NVAF.

HFM-Tracker: a cell tracking algorithm based on hybrid feature matching.

Cell migration is known to be a fundamental biological process, playing an essential role in development, homeostasis, and diseases. This paper introduces a cell tracking algorithm named HFM-Tracker (Hybrid Feature Matching Tracker) that automatically identifies cell migration behaviours in consecutive images. It combines Contour Attention (CA) and Adaptive Confusion Matrix (ACM) modules to accurately capture cell contours in each image and track the dynamic behaviors of migrating cells in the field of view. Cells are firstly located and identified via the CA module-based cell detection network, and then associated and tracked via a cell tracking algorithm employing a hybrid feature-matching strategy. This proposed HFM-Tracker exhibits superiorities in cell detection and tracking, achieving 75% in MOTA (Multiple Object Tracking Accuracy) and 65% in IDF1 (ID F1 score). It provides quantitative analysis of the cell morphology and migration features, which could further help in understanding the complicated and diverse cell migration processes.

Key oncogenic signaling pathways affecting tumor-infiltrating lymphocytes infiltration in hepatocellular carcinoma: basic principles and recent advances.

The incidence of hepatocellular carcinoma (HCC) ranks first among primary liver cancers, and its mortality rate exhibits a consistent annual increase. The treatment of HCC has witnessed a significant surge in recent years, with the emergence of targeted immune therapy as an adjunct to early surgical resection. Adoptive cell therapy (ACT) using tumor-infiltrating lymphocytes (TIL) has shown promising results in other types of solid tumors. This article aims to provide a comprehensive overview of the intricate interactions between different types of TILs and their impact on HCC, elucidate strategies for targeting neoantigens through TILs, and address the challenges encountered in TIL therapies along with potential solutions. Furthermore, this article specifically examines the impact of oncogenic signaling pathways activation within the HCC tumor microenvironment on the infiltration dynamics of TILs. Additionally, a concise overview is provided regarding TIL preparation techniques and an update on clinical trials investigating TIL-based immunotherapy in solid tumors.

A von-Neumann-like photonic processor and its application in studying quantum signature of chaos.

Photonic quantum computation plays an important role and offers unique advantages. Two decades after the milestone work of Knill-Laflamme-Milburn, various architectures of photonic processors have been proposed, and quantum advantage over classical computers has also been demonstrated. It is now the opportune time to apply this technology to real-world applications. However, at current technology level, this aim is restricted by either programmability in bulk optics or loss in integrated optics for the existing architectures of processors, for which the resource cost is also a problem. Here we present a von-Neumann-like architecture based on temporal-mode encoding and looped structure on table, which is capable of multimode-universal programmability, resource-efficiency, phase-stability and software-scalability. In order to illustrate these merits, we execute two different programs with varying resource requirements on the same processor, to investigate quantum signature of chaos from two aspects: the signature behaviors exhibited in phase space (13 modes), and the Fermi golden rule which has not been experimentally studied in quantitative way before (26 modes). The maximal program contains an optical interferometer network with 1694 freely-adjustable phases. Considering current state-of-the-art, our architecture stands as the most promising candidate for real-world applications.

Building-Envelope-Inspired, Thermomechanically Robust All-Fiber Ceramic Meta-Aerogel for Temperature-Controlled Dominant Infrared Camouflage.

The unsatisfactory properties of ceramic aerogels when subjected to thermal shock, such as strength degradation and structural collapse, render them unsuitable for use at large thermal gradients or prolonged exposure to extreme temperatures. Here, a building-envelope-inspired design for fabricating a thermomechanically robust all-fiber ceramic meta-aerogel with interlocked fibrous interfaces and an interwoven cellular structure in the orthogonal directions is presented, which is achieved through a two-stage physical and chemical process. Inspired by the reinforced concrete building envelope, a solid foundation composed of fibrous frames is constructed and enhanced through supramolecular in situ self-assembly to achieve high compressibility, retaining over 90% of maximum stress under a considerable compressive strain of 50% for 10 000 cycles, and showing temperature-invariance when compressed at 60% strain within the range of -100 to 500 °C. As a result of its distinct response to oscillation tolerance coupled with elastic recovery, the all-fiber ceramic meta-aerogel exhibits exceptional suitability for thermal shock resistance and infrared camouflage performance in cold (-196 °C) and hot (1300 °C) fields. This study provides an opportunity for developing ceramic aerogels for effective thermal management under extreme conditions.

Scallop-bacteria symbiosis from the deep sea reveals strong genomic coupling in the absence of cellular integration.

Previous studies have revealed tight metabolic complementarity between bivalves and their endosymbiotic chemosynthetic bacteria, but little is known about their interactions with ectosymbionts. Our analysis of the ectosymbiosis between a deep-sea scallop (Catillopecten margaritatus) and a gammaproteobacterium showed that bivalves could be highly interdependent with their ectosymbionts as well. Our microscopic observation revealed abundant sulfur-oxidizing bacteria (SOB) on the surfaces of the gill epithelial cells. Microbial 16S rRNA gene amplicon sequencing of the gill tissues showed the dominance of the SOB. An analysis of the SOB genome showed that it is substantially smaller than its free-living relatives and has lost cellular components required for free-living. Genomic and transcriptomic analyses showed that this ectosymbiont relies on rhodanese-like proteins and SOX multienzyme complex for energy generation, mainly on the Calvin-Benson-Bassham (CBB) cycle and peripherally on a phosphoenolpyruvate carboxylase for carbon assimilation. Besides, the symbiont encodes an incomplete tricarboxylic acid (TCA) cycle. Observation of the scallop's digestive gland and its nitrogen metabolism pathways indicates it does not fully rely on the ectosymbiont for nutrition. Analysis of the host's gene expression provided evidence that it could offer intermediates for the ectosymbiont to complete its TCA cycle and some amino acid synthesis pathways using exosomes, and its phagosomes, endosomes, and lysosomes might be involved in harvesting nutrients from the symbionts. Overall, our study prompts us to rethink the intimacy between the hosts and ectosymbionts in Bivalvia and the evolution of chemosymbiosis in general.

Emerging Data Processing Methods for Single-Entity Electrochemistry.

Single-entity electrochemistry is a powerful tool that enables the study of electrochemical processes at interfaces and provides insights into the intrinsic chemical and structural heterogeneities of individual entities. Signal processing is a critical aspect of single-entity electrochemical measurements and can be used for data recognition, classification, and interpretation. In this review, we summarize the recent five-year advances in signal processing techniques for single-entity electrochemistry and highlight their importance in obtaining high-quality data and extracting effective features from electrochemical signals, which are generally applicable in single-entity electrochemistry. Moreover, we shed light on electrochemical noise analysis to obtain single-molecule frequency fingerprint spectra that can provide rich information about the ion networks at the interface. By incorporating advanced data analysis tools and artificial intelligence algorithms, single-entity electrochemical measurements would revolutionize the field of single-entity analysis, leading to new fundamental discoveries.

Progress of Drug Nanocrystal Self-Stabilized Pickering Emulsions: Construction, Characteristics In Vitro, and Fate In Vivo.

A drug nanocrystal self-stabilized Pickering emulsion (DNSPE) is a novel Pickering emulsion with drug nanocrystals as the stabilizer. As a promising drug delivery system, DNSPEs have attracted increasing attention in recent years due to their high drug loading capacity and ability to reduce potential safety hazards posed by surfactants or specific solid particles. This paper comprehensively reviews the progress of research on DNSPEs, with an emphasis on the main factors influencing their construction, characteristics and measurement methods in vitro, and fate in vivo, and puts forward issues that need to be studied further. The review contributes to the advancement of DNSPE research and the promotion of their application in the field of drug delivery.

Screening of CPT1A-Targeting Lipid Metabolism Modulators Using Mitochondrial Membrane Chromatography.

Carnitine palmitoyltransferase 1A (CPT1A), which resides on the mitochondrial outer membrane, serves as the rate-limiting enzyme of fatty acid ß-oxidation. Identifying the compounds targeting CPT1A warrants a promising candidate for modulating lipid metabolism. In this study, we developed a CPT1A-overexpressed mitochondrial membrane chromatography (MMC) to screen the compounds with affinity for CPT1A. Cells overexpressing CPT1A were cultured, and subsequently, their mitochondrial membrane was isolated and immobilized on amino-silica gel cross-linked by glutaraldehyde. After packing the mitochondrial membrane column, retention components of MMC were performed with LC/MS, whose analytic peaks provided structural information on compounds that might interact with mitochondrial membrane proteins. With the newly developed MMC-LC/MS approach, several Chinese traditional medicine extracts, such as Scutellariae Radix and Polygoni Cuspidati Rhizoma et Radix (PCRR), were analyzed. Five noteworthy compounds, baicalin, baicalein, wogonoside, wogonin, and resveratrol, were identified as enhancers of CPT1A enzyme activity, with resveratrol being a new agonist for CPT1A. The study suggests that MMC serves as a reliable screening system for efficiently identifying modulators targeting CPT1A from complex extracts.

Electrochemical Visualization of Single-Molecule Thiol Substitution with Nanopore Measurement.

Reactions involving sulfhydryl groups play a critical role in maintaining the structure and function of proteins. However, traditional mechanistic studies have mainly focused on reaction rates and the efficiency in bulk solutions. Herein, we have designed a cysteine-mutated nanopore as a biological protein nanoreactor for electrochemical visualization of the thiol substitute reaction. Statistical analysis of characteristic current signals shows that the apparent reaction rate at the single-molecule level in this confined nanoreactor reached 1400 times higher than that observed in bulk solution. This substantial acceleration of thiol substitution reactions within the nanopore offers promising opportunities for advancing the design and optimization of micro/nanoreactors. Moreover, our results could shed light on the understanding of sulfhydryl reactions and the thiol-involved signal transduction mechanisms in biological systems.

Laser-light cueing shoes with integrated foot pressure and inertial sensing for investigating the impact of visual cueing on gait characteristics in Parkinson's disease individuals.

Gait disorders are a fundamental challenge in Parkinson's disease (PD). The use of laser-light visual cues emitted from shoes has demonstrated effective in improving freezing of gait within less restrictive environments. However, the effectiveness of shoes-based laser-light cueing may vary among individuals with PD who have different types of impairments. We introduced an innovative laser-light visual shoes system capable of producing alternating visual cues for the left and right feet through one-side cueing at a time, while simultaneously recording foot inertial data and foot pressures. The effects of this visual cueing system on gait patterns were assessed in individuals with PD, both those with well-gait and those with worse-gait. Our device successfully quantified gait characteristics, including the asymmetry in the center of pressure trajectory, in individuals with PD. Furthermore, visual cueing prolonged stride times and increased the percentage of stance phase, while concurrently reducing stride length in PD individuals with well-gait. Conversely, in PD individuals with worse-gait, visual cueing resulted in a decreased freeze index and a reduction in the proportion of intervals prone to freezing episodes. The effects of visual cueing varied between PD individuals with well-gait and those with worse-gait. Visual cueing slowed down gait in the well-gait group while it appeared to mitigate freezing episodes in worse-gait group. Future researches, including enhancements to extend the projection distance of visual cues and clinical assessments conducted in real-world settings, will help establish the clinical utility of our proposed visual cueing system.