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Proper organ functioning relies on adequate blood circulation; thus, monitoring blood flow is crucial for early disease diagnosis. Laser speckle contrast imaging (LSCI) is a noninvasive technique that is widely used for measuring superficial blood flow. In this study, we developed a portable LSCI system using an 805-nm near-infrared laser and a monochrome CMOS camera with a 10 × macro zoom lens. The system achieved a high-resolution imaging (1280 × 1024 pixels) with a working distance of 10 to 35 cm. The relative flow velocities were visualized via a spatial speckle contrast analysis algorithm with a 5 × 5 sliding window. In vitro experiments demonstrated the system's ability to image flow velocities in a fluid model, and a linear relationship was observed between the actual flow rate and the relative flow rate obtained by the system. The correlation coefficient (R 2 ) exceeded 0.83 for volumetric flow rates of 0 to 0.2 ml/min when channel widths were greater than 1.2 mm, and R 2  > 0.94 was obtained for channel widths exceeding 1.6 mm. Comparisons with laser Doppler flowmetry (LDF) revealed a strong positive correlation between the LSCI and LDF results. In vivo experiments captured postocclusive reactive hyperemic responses in rat hind limbs and human palms and feet. The main research contribution is the development of this compact and portable LSCI device, as well as the validation of its reliability and convenience in various scenarios and environments. Future applications of this technology include evaluating blood flow changes during skin injuries, such as abrasions, burns, and diabetic foot ulcers, to aid medical institutions in treatment optimization and to reduce treatment duration., (© 2024. International Federation for Medical and Biological Engineering.)

Digital therapy has gained popularity in the mental health field because of its convenience and accessibility. One major benefit of digital therapy is its ability to address therapist shortages. Posttraumatic stress disorder (PTSD) is a debilitating mental health condition that can develop after an individual experiences or witnesses a traumatic event. Digital therapy is an important resource for individuals with PTSD who may not have access to traditional in-person therapy. Cognitive behavioral therapy (CBT) and eye movement desensitization and reprocessing (EMDR) are two evidence-based psychotherapies that have shown efficacy in treating PTSD. This paper examines the mechanisms and clinical symptoms of PTSD as well as the principles and applications of CBT and EMDR. Additionally, the potential of digital therapy, including internet-based CBT, video conferencing-based therapy, and exposure therapy using augmented and virtual reality, is explored. This paper also discusses the engineering techniques employed in digital psychotherapy, such as emotion detection models and text analysis, for assessing patients' emotional states. Furthermore, it addresses the challenges faced in digital therapy, including regulatory issues, hardware limitations, privacy and security concerns, and effectiveness considerations. Overall, this paper provides a comprehensive overview of the current state of digital psychotherapy for PTSD treatment and highlights the opportunities and challenges in this rapidly evolving field., (© 2024. International Federation for Medical and Biological Engineering.)

Traumatic brain injury (TBI) triggers inflammatory response and glial scarring, thus substantially hindering brain tissue repair. This process is exacerbated by the accumulation of activated immunocytes at the injury site, which contributes to scar formation and impedes tissue repair. In this study, a mussel-inspired nitric oxide-release microreservoir (MINOR) that combines the features of reactive oxygen species (ROS) scavengers and sustained NO release to promote angiogenesis and neurogenesis is developed for TBI therapy. The injectable MINOR fabricated using a microfluidic device exhibits excellent monodispersity and gel-like self-healing properties, thus allowing the maintenance of its structural integrity and functionality upon injection. Furthermore, polydopamine in the MINOR enhances cell adhesion, significantly reduces ROS levels, and suppresses inflammation. Moreover, a nitric oxide (NO) donor embedded into the MINOR enables the sustained release of NO, thus facilitating angiogenesis and mitigating inflammatory responses. By harnessing these synergistic effects, the biocompatible MINOR demonstrates remarkable efficacy in enhancing recovery in mice. These findings benefit future therapeutic interventions for patients with TBI., (© 2023 Wiley‐VCH GmbH.)

Zebrafish are ideal model organisms for various fields of biological research, including genetics, neural transmission patterns, disease and drug testing, and heart disease studies, because of their unique ability to regenerate cardiac muscle. Tracking zebrafish trajectories is essential for understanding their behavior, physiological states, and disease associations. While 2D tracking methods are limited, 3D tracking provides more accurate descriptions of their movements, leading to a comprehensive understanding of their behavior. In this study, we used deep learning models to track the 3D movements of zebrafish. Videos were captured by two custom-made cameras, and 21,360 images were labeled for the dataset. The YOLOv7 model was trained using hyperparameter tuning, with the top- and side-view camera models trained using the v7x.pt and v7.pt weights, respectively, over 300 iterations with 10,680 data points each. The models achieved impressive results, with an accuracy of 98.7% and a recall of 98.1% based on the test set. The collected data were also used to generate dynamic 3D trajectories. Based on a test set with 3,632 3D coordinates, the final model detected 173.11% more coordinates than the initial model. Compared to the ground truth, the maximum and minimum errors decreased by 97.39% and 86.36%, respectively, and the average error decreased by 90.5%.This study presents a feasible 3D tracking method for zebrafish trajectories. The results can be used for further analysis of movement-related behavioral data, contributing to experimental research utilizing zebrafish., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Fan, Hsu, Hsu and Liao.)

Type 1 diabetes mellitus (T1DM) can result in complications such as retinopathy, nephropathy, and peripheral neuropathy, which can lead to brain dysfunction. In this study, we investigated the effects of T1DM on cerebral neurovascular function in mice. Streptozotocin (STZ) is known to induce T1DM in animals; thus, we used an STZ-induced diabetes model to evaluate the effects of hyperglycemia on brain morphology and neurovascular tissue. Neurovascular coupling is the connection between neuronal activity and cerebral blood flow that maintains brain function. The ECoG-LSCI technique combines electrocorticography (ECoG) and laser speckle contrast imaging (LSCI) to detect cortical spreading depression (CSD) as a marker of neurovascular coupling and measure corresponding neurovascular function. Our results suggested that in the STZ group, hyperglycemia affected excitatory neurotransmission and metabolism, leading to reductions in intercellular signaling, somatosensory evoked potential (SSEP) amplitudes, and CSD transmission rates. Western blot data further revealed that brain-derived neurotrophic factor (BDNF) and neuronal nuclear antigen levels were reduced in the STZ group. Abnormalities in glucose metabolism in the brain and increased phosphorylation of AKT and GSK3 are hypothesized to be responsible for these decreases. Overall, this study highlights the importance of glucose metabolism in normal brain physiology and demonstrates that hyperglycemia disrupts neurovascular coupling and affects cerebral neurovascular function and that the degree of CSD is positively correlated with the extent of brain tissue damage. Further research is essential to gain a complete understanding of the related mechanisms and the implications of these findings., Competing Interests: The authors have no conflicts to disclose., (© 2024 Author(s).)

Here we demonstrate that cancer metastasis could be modulated by the judicious tuning of physical parameters such as photothermal temperature in nanoparticle-mediated photothermal therapy (PTT). This is supported by theranostic nanosystem design and characterization, in vitro and in vivo analyses, and transcriptome-based gene profiling. In this work, the highly efficient near-infrared II (NIR-II) photoacoustic image (PA)-guided PTT are selectively activated using our developed matrix metalloproteinase (MMP)-triggered in situ assembly of gold nanodandelions (GNDs@gelatin). Unlike other "always-on" NIR PTT agents lacking specific bioactivation and suffering from the intrinsic nonspecific pseudosignals and treatment-related side effects such as metastasis, our GNDs@gelatin possesses important advantages while deployed in cancer PTT that include the following: (1) The theranostic effects could be "turned on" only after specific MMP-2/-9 activity and with acidity in the tumor microenvironment. (2) The quantitative PA diagnosis allows for precise PTT planning for better cancer treatment. (3) GNDs@gelatin could noninvasively quantify MMP activity and efficiently harness NIR-I (808 nm) and NIR-II (1064 nm) energies for tumor ablation. (4) The multibranched nanostructures reabsorb scattered laser photons, thus enhancing the surface plasmons for the pronounced photothermal conversion of aggregated GNDs@gelatin in situ . (5) It is noteworthy that in situ tumor eradication at higher PTT temperature (>55 °C) mediated by GNDs@gelatin could induce subsequent metastasis, which could be otherwise abolished at lower PTT temperatures (50 °C > T > 43 °C). (6) Furthermore, the gene profiling using transcriptome-based microarray including GO and KEGG analyses revealed that 315 differentially expressed genes were identified in higher PTT temperature treated tumors compared with lower PTT temperature ones. These were enriched into some well-known cancer-related pathways, such as cell migration pathway, signal transductions, cell proliferation, wound healing, PPAR signaling, and metabolic pathways. These observations suggest a new perspective of "moderate-is-better" in nanoparticle-mediated PTT for maximizing its therapeutic/prognosis benefits and translational potential with metastasis inhibition.

Objectives: This study aimed to explore the synergistic impact of online yoga, mindfulness practices, and probiotics on irritable bowel syndrome (IBS) by evaluating changes in physical fitness, mental health, and gut microbiota composition., Design, Setting and Interventions: The six-week randomized, double-blinded, placebo-controlled trial included 31 IBS patients categorized into three groups: online yoga with probiotics (EP), online yoga with a placebo (EC), and probiotics only (P). Assessments involved physical fitness tests, subjective questionnaires (IBS-QOL, BSRS-5), and gut microbiome analysis., Main Outcome Measures: Participants self-collected stool samples and were given a set of questionnaires at baseline and after six weeks of intervention. Their symptoms were measured by changes in the gut microbiota, physical fitness and quality of life, and psychological well-being., Results: The EP group demonstrated improved cardiovascular endurance (P < 0.001) and a significant reduction in Klebsiella bacterial strains (P < 0.05). Both the EP and EC groups exhibited significantly decreased IBS-QOL scores (P < 0.001 and P < 0.05, respectively), indicating enhanced quality of life. While BSRS-5 scores decreased in both groups, the reduction was statistically insignificant., Conclusion: Integrating online yoga, mindfulness practices, and probiotics demonstrated comprehensive benefits for IBS patients. This intervention improved physical fitness and mental well-being and positively influenced gut microbiota composition. The study highlights the potential of this multifaceted approach in managing IBS symptoms and enhancing overall health, emphasizing the relevance of the gut-muscle-brain axis in understanding and addressing IBS complexities., Trial Registration: Taiwanese Registry of Institutional Review Board IRBHP210009/CH11000259., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Drowning, as a leading cause of unintentional injury-related deaths worldwide, is a major public health concern. Swimming pool drowning is the main cause of most drowning incidents, and even with preventive measures such as surveillance cameras and lifeguards, tens of thousands of lives are lost to drowning every year. To address this issue, technology is being utilized to prevent drowning accidents and provide timely alerts for rescue. This paper explores the use of drowning prevention technology in embedded systems within enclosed environments, artificial intelligence (AI), and the Internet of Things (IoT) to decrease the likelihood of drowning incidents. Embedded systems play a critical role in such technology, enabling real-time monitoring, identification of dangerous situations, and prompt alerting. Due to their ease of installation and technical implementation, embedded devices are especially effective as drowning prevention devices. The image recognition capabilities of drowning prevention systems are enhanced through computer vision. Swimming pool drowning situations can be identified with the help of cameras and deep learning technologies, thereby increasing rescue efficiency. Finally, the IoT endows drowning prevention systems with comprehensive intelligence by connecting various devices and communication tools. Real-time alert transmission and analysis have become possible, enabling the early prediction of dangerous situations and the implementation of preventive measures, significantly reducing drowning incidents. In summary, the integration of these three types of drowning prevention technologies represents significant progress. The flexibility, accuracy, and intelligence of drowning prevention systems are enhanced through the incorporation of these technologies, providing robust support for safeguarding human lives and thus potentially saving tens of thousands of lives each year., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Lun-De Liao reports financial support and administrative support were provided by 10.13039/501100004737National Health Research Institutes, Taiwan. Lun-De Liao reports a relationship with National Health Research Institutes that includes: employment. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

To study neurovascular function in type 2 diabetes mellitus (T2DM), we established a high-fat diet/streptozotocin (HFD/STZ) rat model. Electrocorticography-laser speckle contrast imaging (ECoG-LSCI) revealed that the somatosensory-evoked potential (SSEP) amplitude and blood perfusion volume were significantly lower in the HFD/STZ group. Cortical spreading depression (CSD) velocity was used as a measure of neurovascular function, and the results showed that the blood flow velocity and the number of CSD events were significantly lower in the HFD/STZ group. In addition, to compare changes during acute hyperglycemia and hyperglycemia, we used intraperitoneal injection (IPI) of glucose to induce transient hyperglycemia. The results showed that CSD velocity and blood flow were significantly reduced in the IPI group. The significant neurovascular changes observed in the brains of rats in the HFD/STZ group suggest that changes in neuronal apoptosis may play a role in altered glucose homeostasis in T2DM., Competing Interests: The authors declare no competing interests., (© 2024 The Authors.)

Ischemic stroke can cause depolarized brain waves, termed peri-infarct depolarization (PID). Here, we evaluated whether topiramate, a neuroprotective drug used to treat epilepsy and alleviate migraine, has the potential to reduce PID. We employed a rat model of photothrombotic ischemia that can reliably and reproducibly induce PID and developed a combined electrocorticography-laser speckle contrast imaging (ECoG-LSCI) platform to monitor neuronal activity and cerebral blood flow (CBF) simultaneously. Topiramate administration after photothrombotic ischemia did not rescue CBF but significantly restored somatosensory evoked potentials in the forelimb area of the primary somatosensory cortex. Moreover, infarct volume was investigated by 2,3,5-triphenyltetrazolium chloride (TTC) staining, and neuronal survival was evaluated by Nissl staining. Mechanistically, the levels of inflammatory markers, such as ED1 (CD68), Iba-1, and GFAP, decreased significantly after topiramate administration, as did BDNF expression, while the expression of NeuN and Bcl-2/Bax increased, which is indicative of reduced inflammation and improved neuroprotection., Competing Interests: The authors declare no conflicts of interest., (© 2024 The Author(s).)

Fascin actin-bundling protein 1 (Fascin) is highly expressed in a variety of cancers, including esophageal squamous cell carcinoma (ESCC), working as an important oncogenic protein and promoting the migration and invasion of cancer cells by bundling F-actin to facilitate the formation of filopodia and invadopodia. However, it is not clear how exactly the function of Fascin is regulated by acetylation in cancer cells. Here, in ESCC cells, the histone acetyltransferase KAT8 catalyzed Fascin lysine 41 (K41) acetylation, to inhibit Fascin-mediated F-actin bundling and the formation of filopodia and invadopodia. Furthermore, NAD-dependent protein deacetylase sirtuin (SIRT) 7-mediated deacetylation of Fascin-K41 enhances the formation of filopodia and invadopodia, which promotes the migration and invasion of ESCC cells. Clinically, the analysis of cancer and adjacent tissue samples from patients with ESCC showed that Fascin-K41 acetylation was lower in the cancer tissue of patients with lymph node metastasis than in that of patients without lymph node metastasis, and low levels of Fascin-K41 acetylation were associated with a poorer prognosis in patients with ESCC. Importantly, K41 acetylation significantly blocked NP-G2-044, one of the Fascin inhibitors currently being clinically evaluated, suggesting that NP-G2-044 may be more suitable for patients with low levels of Fascin-K41 acetylation, but not suitable for patients with high levels of Fascin-K41 acetylation. © 2024 The Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd., (© 2024 The Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.)

Desmoglein-2 (DSG2) is a transmembrane glycoprotein belonging to the desmosomal cadherin family, which mediates cell-cell junctions; regulates cell proliferation, migration, and invasion; and promotes tumor development and metastasis. We previously showed serum DSG2 to be a potential biomarker for the diagnosis of esophageal squamous cell carcinoma (ESCC), although the significance and underlying molecular mechanisms were not identified. Here, we found that DSG2 was increased in ESCC tissues compared with adjacent tissues. In addition, we demonstrated that DSG2 promoted ESCC cell migration and invasion. Furthermore, using interactome analysis, we identified serine/threonine-protein kinase D2 (PRKD2) as a novel DSG2 kinase that mediates the phosphorylation of DSG2 at threonine 730 (T730). Functionally, DSG2 promoted ESCC cell migration and invasion dependent on DSG2-T730 phosphorylation. Mechanistically, DSG2 T730 phosphorylation activated EGFR, Src, AKT, and ERK signaling pathways. In addition, DSG2 and PRKD2 were positively correlated with each other, and the overall survival time of ESCC patients with high DSG2 and PRKD2 was shorter than that of patients with low DSG2 and PRKD2 levels. In summary, PRKD2 is a novel DSG2 kinase, and PRKD2-mediated DSG2 T730 phosphorylation promotes ESCC progression. These findings may facilitate the development of future therapeutic agents that target DSG2 and DSG2 phosphorylation. © 2024 The Pathological Society of Great Britain and Ireland., (© 2024 The Pathological Society of Great Britain and Ireland.)

Wound monitoring is crucial for effective healing, as nonhealing wounds can lead to tissue ulceration and necrosis. Evaluating wound recovery involves observing changes in angiogenesis. Laser speckle contrast imaging (LSCI) is vital for wound assessment due to its rapid imaging, high resolution, wide coverage, and noncontact properties. When using LSCI equipment, regions of interest (ROIs) must be delineated in lesion areas in images for quantitative analysis. However, patients with serious wounds cannot maintain constant postures because the affected areas are often associated with discomfort and pain. This leads to deviations between the drawn ROI and actual wound position when using LSCI for wound assessment, affecting the reliability of relevant assessments. To address these issues, we used the channel and spatial reliability tracker object tracking algorithm to develop an automatic ROI tracking function for LSCI systems. This algorithm is used to track and correct artificial movements in blood flow images, address the ROI position offset caused by the movement of the affected body part, increase the blood flow analysis accuracy, and improve the clinical applicability of LSCI systems. ROI tracking experiments were performed by simulating wounds, and the results showed that the intraclass correlation coefficient (ICC) ranged from 0.134 to 0.976. Furthermore, the object within the ROI affected tracking performance. Clinical assessments across wound types showed ICCs ranging from 0.798 to 0.917 for acute wounds and 0.628-0.849 for chronic wounds. We also discuss factors affecting tracking performance and propose strategies to enhance implementation effectiveness., Competing Interests: The authors have no conflicts to disclose., (© 2024 Author(s).)

Observational studies of treatment effects require adjustment for confounding variables. However, causal inference methods typically cannot deliver perfect adjustment on all measured baseline variables, and there is often ambiguity about which variables should be prioritized. Standard prioritization methods based on treatment imbalance alone neglect variables' relationships with the outcome. We propose the joint variable importance plot to guide variable prioritization for observational studies. Since not all variables are equally relevant to the outcome, the plot adds outcome associations to quantify the potential confounding jointly with the standardized mean difference. To enhance comparisons on the plot between variables with different confounding relationships, we also derive and plot bias curves. Variable prioritization using the plot can produce recommended values for tuning parameters in many existing matching and weighting methods. We showcase the use of the joint variable importance plots in the design of a balance-constrained matched study to evaluate whether taking an antidiabetic medication, glyburide, increases the incidence of C-section delivery among pregnant individuals with gestational diabetes., Competing Interests: Conflict of interest The authors report there are no competing interests to declare.

Sonodynamic therapy (SDT) is a promising approach for cancer treatment that uses sonosensitizers (SNSs) to generate reactive oxygen species (ROS) in the presence of ultrasound (US). However, SDT is oxygen-dependent and requires an imaging tool to monitor the tumor microenvironment and guide treatment. Photoacoustic imaging (PAI) is a noninvasive and powerful imaging tool that offers high spatial resolution and deep tissue penetration. PAI can quantitatively assess tumor oxygen saturation (sO2) and guide SDT by monitoring time-dependent sO2 changes in the tumor microenvironment. Here, we discuss recent advances in PAI-guided SDT for cancer therapy. We discuss various exogenous contrast agents and nanomaterial-based SNSs developed for PAI-guided SDT. Additionally, combining SDT with other therapies, including photothermal (PTT) therapy, can enhance its therapeutic effect. However, the application of nanomaterial-based contrast agents in PAI-guided SDT for cancer therapy remains challenging due to the lack of simple designs, the need for extensive pharmacokinetic studies, and high production costs. Integrated efforts from researchers, clinicians, and industry consortia are necessary for the successful clinical translation of these agents and SDT for personalized cancer therapy. PAI-guided SDT shows the potential to revolutionize cancer therapy and improve patient outcomes, but further research is necessary to realize its full potential.

Endogenous signals, namely nitric oxide (NO) and electrons, play a crucial role in regulating cell fate as well as the vascular and neuronal systems. Unfortunately, utilizing NO and electrical stimulation in clinical settings can be challenging due to NO's short half-life and the invasive electrodes required for electrical stimulation. Additionally, there is a lack of tools to spatiotemporally control gas release and electrical stimulation. To address these issues, an "electromagnetic messenger" approach that employs on-demand high-frequency magnetic field (HFMF) to trigger NO release and electrical stimulation for restoring brain function in cases of traumatic brain injury is introduced. The system comprises a NO donor (poly(S-nitrosoglutathione), pGSNO)-conjugated on a gold yarn-dynamos (GY) and embedded in an implantable silk in a microneedle. When subjected to HFMF, conductive GY induces eddy currents that stimulate the release of NO from pGSNO. This process significantly enhances neural stem cell (NSC) synapses' differentiation and growth. The combined strategy of using NO and electrical stimulation to inhibit inflammation, angiogenesis, and neuronal interrogation in traumatic brain injury is demonstrated in vivo., (© 2023 The Authors. Advanced Science published by Wiley-VCH GmbH.)

Zebrafish have become a widely accepted model organism for biomedical research due to their strong cortisol stress response, behavioral strain differences, and sensitivity to both drug treatments and predators. However, experimental zebrafish studies generate substantial data that must be analyzed through objective, accurate, and repeatable analysis methods. Recently, advancements in artificial intelligence (AI) have enabled automated tracking, image recognition, and data analysis, leading to more efficient and insightful investigations. In this review, we examine key AI applications in zebrafish research, including behavior analysis, genomics, and neuroscience. With the development of deep learning technology, AI algorithms have been used to precisely analyze and identify images of zebrafish, enabling automated testing and analysis. By applying AI algorithms in genomics research, researchers have elucidated the relationship between genes and biology, providing a better basis for the development of disease treatments and gene therapies. Additionally, the development of more effective neuroscience tools could help researchers better understand the complex neural networks in the zebrafish brain. In the future, further advancements in AI technology are expected to enable more extensive and in-depth medical research applications in zebrafish, improving our understanding of this important animal model. This review highlights the potential of AI technology in achieving the full potential of zebrafish research by enabling researchers to efficiently track, process, and visualize the outcomes of their experiments., (© 2023. International Federation for Medical and Biological Engineering.)

Brain-computer interfaces (BCIs) allow communication between the brain and the external world. This type of technology has been extensively studied. However, BCI instruments with high signal quality are typically heavy and large. Thus, recording electroencephalography (EEG) signals is an inconvenient task. In recent years, system-on-chip (SoC) approaches have been integrated into BCI research, and sensors for wireless portable devices have been developed; however, there is still considerable work to be done. As neuroscience research has advanced, EEG signal analyses have come to require more accurate data. Due to the limited bandwidth of Bluetooth wireless transmission technology, EEG measurement systems with more than 16 channels must be used to reduce the sampling rate and prevent data loss. Therefore, the goal of this study was to develop a multichannel, high-resolution (24-bit), high-sampling-rate EEG BCI device that transmits signals via Wi-Fi. We believe that this system can be used in neuroscience research. The EEG acquisition system proposed in this work is based on a Cortex-M4 microcontroller with a Wi-Fi subsystem, providing a multichannel design and improved signal quality. This system is compatible with wet sensors, Ag/AgCl electrodes, and dry sensors. A LabVIEW-based user interface receives EEG data via Wi-Fi transmission and saves the raw data for offline analysis. In previous cognitive experiments, event tags have been communicated using Recommended Standard 232 (RS-232). The developed system was validated through event-related potential (ERP) and steady-state visually evoked potential (SSVEP) experiments. Our experimental results demonstrate that this system is suitable for recording EEG measurements and has potential in practical applications. The advantages of the developed system include its high sampling rate and high amplification. Additionally, in the future, Internet of Things (IoT) technology can be integrated into the system for remote real-time analysis or edge computing., (© 2023. International Federation for Medical and Biological Engineering.)

Clinical and preclinical studies on epileptic seizures are closely linked to the study of neurovascular coupling. Obtaining reliable information about cerebral blood flow (CBF) in the area of epileptic activity through minimally invasive techniques is crucial for research in this field. In our studies, we used laser speckle contrast imaging (LSCI) to gather information about the local blood circulation in the area of epileptic activity. We used two models of epileptic seizures: one based on 4-aminopyridine (4-AP) and another based on pentylenetetrazole (PTZ). We verified the duration of an epileptic seizure using electrocorticography (ECoG). We applied the antiepileptic drug topiramate (TPM) to both models, but its effect was different in each case. However, in both models, TPM had an effect on neurovascular coupling in the area of epileptic activity, as shown by both LSCI and ECoG data. We demonstrated that TPM significantly reduced the amplitude of 4-AP-induced epileptic seizures (4-AP+TPM: 0.61 ± 0.13 mV vs 4-AP: 1.08 ± 0.19 mV; p  < 0.05), and it also reduced gamma power in ECoG in PTZ-induced epileptic seizures (PTZ+TPM: 38.5% ± 11.9% of the peak value vs PTZ: 59.2% ± 3.0% of peak value; p  < 0.05). We also captured the pattern of CBF changes during focal epileptic seizures induced by 4-AP. Our data confirm that the system of simultaneous cortical LSCI and registration of ECoG makes it possible to evaluate the effectiveness of pharmacological agents in various types of epileptic seizures in in vivo models and provides spatial and temporal information on the process of ictogenesis., Competing Interests: The authors have no conflicts to disclose., (© 2023 Author(s).)

Objective: COVID-19 would kill fewer people if health programmes can predict who is at higher risk of mortality because resources can be targeted to protect those people from infection. We predict mortality in a very large population in Mexico with machine learning using demographic variables and pre-existing conditions., Design: Cohort study., Setting: March 2020 to November 2021 in Mexico, nationally represented., Participants: 1.4 million laboratory-confirmed patients with COVID-19 in Mexico at or over 20 years of age., Primary and Secondary Outcome Measures: Analysis is performed on data from March 2020 to November 2021 and over three phases: (1) from March to October in 2020, (2) from November 2020 to March 2021 and (3) from April to November 2021. We predict mortality using an ensemble machine learning method, super learner, and independently estimate the adjusted mortality relative risk of each pre-existing condition using targeted maximum likelihood estimation., Results: Super learner fit has a high predictive performance (C-statistic: 0.907), where age is the most predictive factor for mortality. After adjusting for demographic factors, renal disease, hypertension, diabetes and obesity are the most impactful pre-existing conditions. Phase analysis shows that the adjusted mortality risk decreased over time while relative risk increased for each pre-existing condition., Conclusions: While age is the most important predictor of mortality, younger individuals with hypertension, diabetes and obesity are at comparable mortality risk as individuals who are 20 years older without any of the three conditions. Our model can be continuously updated to identify individuals who should most be protected against infection as the pandemic evolves., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY. Published by BMJ.)

Proteins containing a CAAX motif at the C-terminus undergo prenylation for localization and activity and include a series of key regulatory proteins, such as RAS superfamily members, heterotrimeric G proteins, nuclear lamina protein, and several protein kinases and phosphatases. However, studies of prenylated proteins in esophageal cancer are limited. Here, through research on large-scale proteomic data of esophageal cancer in our laboratory, we found that paralemmin-2 (PALM2), a potential prenylated protein, was upregulated and associated with poor prognosis in patients. Low-throughput verification showed that the expression of PALM2 in esophageal cancer tissues was higher than that in their paired normal esophageal epithelial tissues, and it was generally expressed in the membrane and cytoplasm of esophageal cancer cells. PALM2 interacted with the two subunits of farnesyl transferase (FTase), FNTA and FNTB. Either the addition of an FTase inhibitor or mutation in the CAAX motif of PALM2 (PALM2 C408S ) impaired its membranous localization and reduced the membrane location of PALM2, indicating PALM2 was prenylated by FTase. Overexpression of PALM2 enhanced the migration of esophageal squamous cell carcinoma cells, whereas PALM2 C408S lost this ability. Mechanistically, PALM2 interacted with the N-terminal FERM domain of ezrin of the ezrin/radixin/moesin (ERM) family. Mutagenesis indicated that lysine residues K253/K254/K262/K263 in ezrin's FERM domain and C408 in PALM2's CAAX motif were important for PALM2/ezrin interaction and ezrin activation. Knockout of ezrin prevented enhanced cancer cell migration by PALM2 overexpression. PALM2, depending on its prenylation, increased both ezrin membrane localization and phosphorylation of ezrin at Y146. In summary, prenylated PALM2 enhances the migration of cancer cells by activating ezrin., Competing Interests: Conflict of interest The authors declare no competing interests., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Ischemic stroke-reperfusion (S/R) injury is a crucial issue in the protection of brain function after thrombolysis. The vasodilation induced by ultrasound (US)-stimulated microbubble cavitation has been applied to reduce S/R injury through sonoperfusion. The present study uses oxygen-loaded microbubbles (OMBs) with US stimulation to provide sonoperfusion and local oxygen therapy for the reduction of brain infarct size and neuroprotection after S/R., Methods: The murine S/R model was established by photodynamic thrombosis and thrombolysis at the remote branch of the anterior cerebral artery. In vivo blood flow, partial oxygen pressure (pO 2 ), and brain infarct staining were examined to analyze the validity of the animal model and OMB treatment results. The animal behaviors and measurement of the brain infarct area were used to evaluate long-term recovery of brain function., Results: The percentage of blood flow was 45 ± 3%, 70 ± 3%, and 86 ± 2% after 60 min stroke, 20 min reperfusion, and 10 min OMB treatment, respectively, demonstrating sonoperfusion, and the corresponding pO 2 level was 60 ± 1%, 76 ± 2%, and 79 ± 4%, showing reoxygenation. After 14 days of treatment, a 87 ± 3% reduction in brain infarction and recovery of limb coordination were observed in S/R mice. The expression of NF-κB, HIF-1α, IL-1β, and MMP-9 was inhibited and that of eNOS, BDNF, Bcl2, and IL-10 was enhanced, indicating activation of anti-inflammatory and anti-apoptosis responses and neuroprotection. Our study demonstrated that OMB treatment combines the beneficial effects of sonoperfusion and local oxygen therapy to reduce brain infarction and activate neuroprotection to prevent S/R injury., (© 2023. The Author(s).)

The COVID-19 pandemic brought the world to a standstill, posing unprecedented challenges for healthcare systems worldwide. The overwhelming number of patients infected with the virus placed an enormous burden on healthcare providers, who struggled to cope with the sheer volume of cases. Furthermore, the lack of effective treatments or vaccines means that quarantining has become a necessary measure to slow the spread of the virus. However, quarantining places a significant burden on healthcare providers, who often lack the resources to monitor patients with mild symptoms or asymptomatic patients. In this study, we propose an Internet of Things (IoT)-based wearable health monitoring system that can remotely monitor the exact locations and physiological parameters of quarantined individuals in real time. The system utilizes a combination of highly miniaturized optoelectronic and electronic technologies, an anti-epidemic watch, a mini-computer, and a monitor terminal to provide real-time updates on physiological parameters. Body temperature, peripheral oxygen saturation (SpO 2 ), and heart rate are recorded as the most important measurements for critical care. If these three physiological parameters are aberrant, then it could represent a life-endangering situation and/or a short period over which irreversible damage may occur. Therefore, these parameters are automatically uploaded to a cloud database for remote monitoring by healthcare providers. The monitor terminal can display real-time health data for multiple patients and provide early warning functions for medical staff. The system significantly reduces the burden on healthcare providers, as it eliminates the need for manual monitoring of patients in quarantine. Moreover, it can help healthcare providers manage the COVID-19 pandemic more effectively by identifying patients who require medical attention in real time. We have validated the system and demonstrated that it is well suited to practical application, making it a promising solution for managing future pandemics. In summary, our IoT-based wearable health monitoring system has the potential to revolutionize healthcare by providing a cost-effective, remote monitoring solution for patients in quarantine. By allowing healthcare providers to monitor patients remotely in real time, the burden on medical resources is reduced, and more efficient use of limited resources is achieved. Furthermore, the system can be easily scaled to manage future pandemics, making it an ideal solution for managing the health challenges of the future., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Wu, Wang, Ching, Wang and Liao.)

Although radiotherapy is one of the most important curative treatments for cancer, its clinical application is associated with undesired therapeutic effects on normal or healthy tissues. The use of targeted agents that can simultaneously achieve therapeutic and imaging functions could constitute a potential solution. Herein, we developed 2-deoxy-d-glucose (2DG)-labeled poly(ethylene glycol) (PEG) gold nanodots (2DG-PEG-AuD) as a tumor-targeted computed tomography (CT) contrast agent and radiosensitizer. The key advantages of the design are its biocompatibility and targeted AuD with excellent sensitivity in tumor detection via avid glucose metabolism. As a consequence, CT imaging with enhanced sensitivity and remarkable radiotherapeutic efficacy could be attained. Our synthesized AuD displayed linear enhancement of CT contrast as a function of its concentration. In addition, 2DG-PEG-AuD successfully demonstrated significant augmentation of CT contrast in both in vitro cell studies and in vivo tumor-bearing mouse models. In tumor-bearing mice, 2DG-PEG-AuD showed excellent radiosensitizing functions after intravenous injection. Results from this work indicate that 2DG-PEG-AuD could greatly potentiate theranostic capabilities by providing high-resolution anatomical and functional images in a single CT scan and therapeutic capability.

Adoptive T cells and immunotherapy suppress the most destructive metastatic tumors and prevent tumor recurrence by inducing T lymphocytes. However, the heterogeneity and immune privilege of invasive metastatic clusters often reduce immune cell infiltration and therapeutic efficacy. Here, the red blood cells (RBC)-hitchhiking mediated lung metastasis delivery of multi-grained iron oxide nanostructures (MIO) programming the antigen capture, dendritic cell harnessing, and T cell recruitment is developed. MIO is assembled to the surface of RBCs by osmotic shock-mediated fusion, and reversible interactions enable the transfer of MIO to pulmonary capillary endothelial cells by intravenous injection by squeezing RBCs at the pulmonary microvessels. RBC-hitchhiking delivery revealed that >65% of MIOs co-localized in tumors rather than normal tissues. In alternating magnetic field (AMF)-mediated magnetic lysis, MIO leads to the release of tumor-associated antigens, namely neoantigens and damage-associated molecular patterns. It also acted as an antigen capture agent-harnessed dendritic cells delivers these antigens to lymph nodes. By utilizing site-specific targeting, erythrocyte hitchhiker-mediated delivery of MIO to lung metastases improves survival and immune responses in mice with metastatic lung tumors., Competing Interests: Declaration of Competing Interest The authors declare no conflict of interest., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Esophageal cancer is the seventh most common cancer in the world. Although traditional treatment methods such as radiotherapy and chemotherapy have good effects, their side effects and drug resistance remain problematic. The repositioning of drug function provides new ideas for the research and development of anticancer drugs. We previously showed that the Food and Drug Administration-approved drug sulconazole can effectively inhibit the growth of esophageal cancer cells, but its molecular mechanism is not clear. Here, our study demonstrated that sulconazole had a broad spectrum of anticancer effects. It can not only inhibit the proliferation but also inhibit the migration of esophageal cancer cells. Both transcriptomic sequencing and proteomic sequencing showed that sulconazole could promote various types of programmed cell death and inhibit glycolysis and its related pathways. Experimentally, we found that sulconazole induced apoptosis, pyroptosis, necroptosis, and ferroptosis. Mechanistically, sulconazole triggered mitochondrial oxidative stress and inhibited glycolysis. Finally, we showed that low-dose sulconazole can increase radiosensitivity of esophageal cancer cells. Taken together, these new findings provide strong laboratory evidence for the clinical application of sulconazole in esophageal cancer., Competing Interests: Conflict of interest The authors declare no conflicts of interest with the contents of this article., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)