Real-time non-invasive hemoglobin prediction using deep learning-enabled smartphone imaging.

BACKGROUND: Accurate measurement of hemoglobin concentration is essential for various medical scenarios, including preoperative evaluations and determining blood loss. Traditional invasive methods are inconvenient and not suitable for rapid, point-of-care testing. Moreover, current models, due to their complex parameters, are not well-suited for mobile medical settings, which limits the ability to conduct frequent and rapid testing. This study aims to introduce a novel, compact, and efficient system that leverages deep learning and smartphone technology to accurately estimate hemoglobin levels, thereby facilitating rapid and accessible medical assessments. METHODS: The study employed a smartphone application to capture images of the eye, which were subsequently analyzed by a deep neural network trained on data from invasive blood test data. Specifically, the EGE-Unet model was utilized for eyelid segmentation, while the DHA(C3AE) model was employed for hemoglobin level prediction. The performance of the EGE-Unet was evaluated using statistical metrics including mean intersection over union (MIOU), F1 Score, accuracy, specificity, and sensitivity. The DHA(C3AE) model's performance was assessed using mean absolute error (MAE), mean-square error (MSE), root mean square error (RMSE), and R^2. RESULTS: The EGE-Unet model demonstrated robust performance in eyelid segmentation, achieving an MIOU of 0.78, an F1 Score of 0.87, an accuracy of 0.97, a specificity of 0.98, and a sensitivity of 0.86. The DHA(C3AE) model for hemoglobin level prediction yielded promising outcomes with an MAE of 1.34, an MSE of 2.85, an RMSE of 1.69, and an R^2 of 0.34. The overall size of the model is modest at 1.08 M, with a computational complexity of 0.12 FLOPs (G). CONCLUSIONS: This system presents a groundbreaking approach that eliminates the need for supplementary devices, providing a cost-effective, swift, and accurate method for healthcare professionals to enhance treatment planning and improve patient care in perioperative environments. The proposed system has the potential to enable frequent and rapid testing of hemoglobin levels, which can be particularly beneficial in mobile medical settings. TRIAL REGISTRATION: The clinical trial was registered on the Chinese Clinical Trial Registry (No. ChiCTR2100044138) on 20/02/2021.

The antidepressant effect of Shexiang Baoxin Pills on myocardial infarction rats with depression may be achieved through the inhibition of the NLRP3 inflammasome pathway.

BACKGROUND: Patients with myocardial infarction (MI) frequently experience a heightened incidence of depression, thereby increasing the risk of adverse cardiovascular events. Consequently, early detection and intervention in depressive symptoms among patients with MI are imperative. Shexiang Baoxin Pills (SBP), a Chinese patent medicine employed for the treatment of MI, exhibits diverse mechanisms targeting this condition. Nevertheless, its therapeutic efficacy on postmyocardial infarction depressive symptoms remains unclear. The aim of this study is to investigate the effectiveness and mechanism of SBP in managing depression during acute myocardial infarction (AMI). METHODS: A rat model combining MI and depression was established, and the rats were randomly divided into four groups: the model (MOD) group, SBP group, Fluoxetine (FLX) group, and Sham group. After 28 days of drug intervention, cardiac function was assessed using echocardiography while behavior was evaluated through sucrose preference test (SPT), forced swimming test (FST), and open-field test (OFT). Additionally, levels of inflammatory factors in serum and hippocampus were measured along with NLRP3 inflammasome-related protein expression via Western blotting and immunofluorescence. RESULTS: SBP can enhance cardiac function in rats with AMI and depression, while significantly ameliorating depressive-like behavior. Compared to the Sham group, levels of IL-1ß, IL-18, TNF-α, and other inflammatory factors were markedly elevated in the MOD group. However, expressions of these inflammatory factors were reduced to varying degrees following treatment with SBP or FLX. Analysis of NLRP3 inflammasome-related proteins in the hippocampus revealed a significant upregulation of IL-1ß, IL-18, NLRP3, ASC, caspase-1, and GSDMD in the MOD group; conversely, these measures were significantly attenuated after SBP intervention. CONCLUSION: We have observed a significant amelioration in depression-like behavior upon SBP administration during the treatment of AMI, suggesting that this effect may be attributed to the inhibition of NLRP3-mediated pyroptosis. (The main findings are summarized in the graphical abstract in the supplementary file.).

The impact of centralized band purchasing of pharmaceuticals on innovation of Chinese pharmaceutical firms: an empirical study based on double difference models.

In 2018, China began to gradually promote the pilot policy of centralized band purchasing of medicines. Implementing this policy has resulted in a significant decrease in drug prices. However, there needs to be a clear consensus on the impact and mechanism of action on the innovation of pharmaceutical companies. Therefore. Taking the data of Chinese Shanghai and Shenzhen A-share pharmaceutical listed companies from 2016 to 2022 as a sample, this paper empirically investigates the impact of the centralized banded purchasing policy of drugs on the innovation of pharmaceutical enterprises by using a double difference model and further analyzes the mechanism of its action. The results show that implementing the centralized banded purchasing policy can promote pharmaceutical enterprises' innovation input and output, which is robust under the parallel trend and placebo tests. Further exploring the impact mechanism of the centralized band purchasing policy on pharmaceutical enterprises' innovation, it can be found that it promotes innovation inputs through three channels: government subsidies, enterprise profits, and operating income. In addition, the impact of centralized band purchasing on enterprise innovation is heterogeneous in terms of region, enterprise nature, and scale. Therefore, the positive effects of the centralized band purchasing policy on promoting innovation in pharmaceutical enterprises should be fully recognized, and enterprise heterogeneity should be taken into account when implementing the policy. This study provides empirical evidence on the implementation effect of the centralized banded purchasing policy and provides lessons for continuously optimizing the policy to promote the high-quality development of pharmaceutical enterprises.

ASXLs binding to the PHD2/3 fingers of MLL4 provides a mechanism for the recruitment of BAP1 to active enhancers.

The human methyltransferase and transcriptional coactivator MLL4 and its paralog MLL3 are frequently mutated in cancer. MLL4 and MLL3 monomethylate histone H3K4 and contain a set of uncharacterized PHD fingers. Here, we report a novel function of the PHD2 and PHD3 (PHD2/3) fingers of MLL4 and MLL3 that bind to ASXL2, a component of the Polycomb repressive H2AK119 deubiquitinase (PR-DUB) complex. The structure of MLL4 PHD2/3 in complex with the MLL-binding helix (MBH) of ASXL2 and mutational analyses reveal the molecular mechanism which is conserved in homologous ASXL1 and ASXL3. The native interaction of the Trithorax MLL3/4 complexes with the PR-DUB complex in vivo depends solely on MBH of ASXL1/2, coupling the two histone modifying activities. ChIP-seq analysis in embryonic stem cells demonstrates that MBH of ASXL1/2 is required for the deubiquitinase BAP1 recruitment to MLL4-bound active enhancers. Our findings suggest an ASXL1/2-dependent functional link between the MLL3/4 and PR-DUB complexes.

Advanced Cardiac Patches for the Treatment of Myocardial Infarction.

Myocardial infarction is a cardiovascular disease characterized by a high incidence rate and mortality. It leads to various cardiac pathophysiological changes, including ischemia/reperfusion injury, inflammation, fibrosis, and ventricular remodeling, which ultimately result in heart failure and pose a significant threat to global health. Although clinical reperfusion therapies and conventional pharmacological interventions improve emergency survival rates and short-term prognoses, they are still limited in providing long-lasting improvements in cardiac function or reversing pathological progression. Recently, cardiac patches have gained considerable attention as a promising therapy for myocardial infarction. These patches consist of scaffolds or loaded therapeutic agents that provide mechanical reinforcement, synchronous electrical conduction, and localized delivery within the infarct zone to promote cardiac restoration. This review elucidates the pathophysiological progression from myocardial infarction to heart failure, highlighting therapeutic targets and various cardiac patches. The review considers the primary scaffold materials, including synthetic, natural, and conductive materials, and the prevalent fabrication techniques and optimal properties of the patch, as well as advanced delivery strategies. Last, the current limitations and prospects of cardiac patch research are considered, with the goal of shedding light on innovative products poised for clinical application.

Pin1 Exacerbates Non-Alcoholic Fatty Liver Disease by Enhancing Its Activity through Binding to ACC1.

Non-alcoholic fatty liver disease (NAFLD) is a clinicopathological syndrome characterized by diffuse hepatocellular steatosis due to fatty deposits in hepatocytes, excluding alcohol and other known liver injury factors. However, there are no specific drugs for the clinical treatment of NAFLD. Therefore, research on the pathogenesis of NAFLD at the cellular and molecular levels is a promising approach to finding therapeutic targets and developing targeted drugs for NAFLD. Pin1 is highly expressed during adipogenesis and contributes to adipose differentiation, but its specific mechanism of action in NAFLD is unclear. In this study, we investigated the role of Pin1 in promoting the development of NAFLD and its potential mechanisms in vitro and in vivo. First, Pin1 was verified in the NAFLD model in vitro using MCD diet-fed mice by Western Blot, RT-qPCR and immunohistochemistry (IHC) assays. In the in vitro study, we used the oleic acid (OA) stimulation-induced lipid accumulation model and examined the lipid accumulation in each group of cells by oil red O staining as well as BODIPY staining. The results showed that knockdown of Pin1 inhibited lipid accumulation in hepatocytes in an in vitro lipid accumulation model and improved lipid indices and liver injury levels. Moreover, in vivo, WT and Pin1-KO mice were fed a methionine-choline deficient (MCD) diet for 4 weeks to induce the NAFLD model. The effects of Pin1 on lipid accumulation, hepatic fibrosis, and oxidative stress were evaluated by biochemical analysis, glucose and insulin tolerance tests, histological analysis, IHC, RT-qPCR and Western blot assays. The results indicate that Pin1 knockdown significantly alleviated hepatic steatosis, fibrosis and inflammation in MCD-induced NAFLD mice, improved glucose tolerance and alleviated insulin resistance in mice. Further studies showed that the AMPK/ACC1 signalling pathway might take part in the process by which Pin1 regulates NAFLD, as evidenced by the inhibition of the AMPK/ACC1 pathway. In addition, immunofluorescence (IF), coimmunoprecipitation (Co-IP) and GST pull-down experiments also showed that Pin1 interacts directly with ACC1 and inhibits ACC1 phosphorylation levels. Our study suggests that Pin1 promotes NAFLD progression by inhibiting the activation of the AMPK/ACC1 signalling pathway, and it is possible that this effect is achieved by Pin1 interacting with ACC1 and inhibiting the phosphorylation of ACC1.

Safety evaluation of bempedoic acid: A pharmacovigilance analysis using FDA adverse event reporting system data.

BACKGROUND: Bempedoic acid exhibits promising potential in hyperlipidemia therapy and preventing cardiovascular events. However, investigations into its adverse drug reactions remain scant. This study seeks to utilize data mining techniques with the FDA Adverse Event Reporting System (FAERS) database to assess adverse drug events (ADEs) linked to bempedoic acid. METHODS: Based on the drug's market release timeline, we extracted data from the FAERS database covering the fourth quarter of 2020 through the fourth quarter of 2023 for disproportionality analysis. RESULTS: This study gathered a total of 5,797,543 adverse event case reports, of which 735 were linked to bempedoic acid. These reports covered 19 System Organ Classes (SOCs) and 22 Preferred Terms (PTs). Predominantly, the musculoskeletal and nervous systems were implicated in these adverse events. By conducting PT-level screening, various signals for ADEs were detected, including myalgia (ROR 30.33, PRR 28.51, IC 4.83, EBGM 28.47), arthralgia (n = 34, ROR 6.34, PRR 6.09, IC 2.61, EBGM 6.09), tendon disorders (ROR 99.57, PRR 98.75, IC 6.62, EBGM 98.28), and dizziness (ROR 3.18, PRR 3.13, IC 1.65, EBGM 3.13). Particularly noteworthy was the hypertensive crisis (ROR 28.63, PRR 28.51, IC 4.83, EBGM 28.47), which exhibited a robust signal strength, an observation previously unreported in clinical studies and drug labeling. CONCLUSION: While our results are largely consistent with the drug's specifications, several new adverse reaction signals, such as hypertensive crisis, have not been previously documented. Therefore, further investigations are necessary to assess these unlabeled adverse reactions, offering crucial support for the clinical utilization of bempedoic acid.

Pin1 Downregulation Is Involved in Excess Retinoic Acid-Induced Failure of Neural Tube Closure.

Neural tube defects (NTDs), which are caused by impaired embryonic neural tube closure, are one of the most serious and common birth defects. Peptidyl-prolyl cis/trans isomerase 1 (Pin1) is a prolyl isomerase that uniquely regulates cell signaling by manipulating protein conformation following phosphorylation, although its involvement in neuronal development remains unknown. In this study, we explored the involvement of Pin1 in NTDs and its potential mechanisms both in vitro and in vivo. The levels of Pin1 expression were reduced in NTD models induced by all-trans retinoic acid (Atra). Pin1 plays a significant role in regulating the apoptosis, proliferation, differentiation, and migration of neurons. Moreover, Pin1 knockdown significantly was found to exacerbate oxidative stress (OS) and endoplasmic reticulum stress (ERs) in neuronal cells. Further studies showed that the Notch1-Nrf2 signaling pathway may participate in Pin1 regulation of NTDs, as evidenced by the inhibition and overexpression of the Notch1-Nrf2 pathway. In addition, immunofluorescence (IF), co-immunoprecipitation (Co-IP), and GST pull-down experiments also showed that Pin1 interacts directly with Notch1 and Nrf2. Thus, our study suggested that the knocking down of Pin1 promotes NTD progression by inhibiting the activation of the Notch1-Nrf2 signaling pathway, and it is possible that this effect is achieved by disrupting the interaction of Pin1 with Notch1 and Nrf2, affecting their proteostasis. Our research identified that the regulation of Pin1 by retinoic acid (RA) and its involvement in the development of NTDs through the Notch1-Nrf2 axis could enhance our comprehension of the mechanism behind RA-induced brain abnormalities.

Integrated analysis of multiple transcriptomic approaches and machine learning integration algorithms reveals high endothelial venules as a prognostic immune-related biomarker in bladder cancer.

BACKGROUND: Despite the availability of established surgical and chemotherapy options, the treatment of bladder cancer (BCa) patients remains challenging. While immunotherapy has emerged as a promising approach, its benefits are limited to a subset of patients. The exploration of additional targets to enhance the efficacy of immunotherapy is a valuable research direction. METHOD: High endothelial venules (HEV) ssGSEA analysis was conducted using BEST. Through the utilization of R packages Limma, Seurat, SingleR, and Harmony, analyses were performed on spatial transcriptomics, bulk RNA-sequencing (bulk RNA-seq), and single-cell RNA sequencing (scRNA-seq) data, yielding HEV-related genes (HEV.RGs). Molecular subtyping analysis based on HEV.RGs was conducted using R package MOVICS, and various machine learning-integrated algorithm was employed to construct prognostic model. LDLRAD3 was validated through subcutaneous tumor formation in mice, HEV induction, Western blot, and qPCR. RESULTS: A correlation between higher HEV levels and improved immune response and prognosis was revealed by HEV ssGSEA analysis in BCa patients receiving immunotherapy. HEV.RGs were identified in subsequent transcriptomic analyses. Based on these genes, BCa patients were stratified into two molecular clusters with distinct survival and immune infiltration patterns using various clustering-integrated algorithm. Prognostic model was developed using multiple machine learning-integrated algorithm. Low LDLRAD3 expression may promote HEV generation, leading to enhanced immunotherapy efficacy, as suggested by bulk RNA-seq, scRNA-seq analyses, and experimental validation of LDLRAD3. CONCLUSIONS: HEV served as a predictive factor for immune response and prognosis in BCa patients receiving immunotherapy. LDLRAD3 represented a potential target for HEV induction and enhancing the efficacy of immunotherapy.

Gustatory Receptor 206 Participates in the Foraging Behavior of Larvae of Polyphagous Pest Spodoptera litura.

Insect gustatory receptors (GRs) aid in the precise identification of deterrent or stimulant compounds associated with food, mating, and egg-laying. Thus, they are promising targets for developing efficient insecticides. Here, 61 GRs in the chemosensory organs of Spodoptera litura larvae and adults were identified. Among them, SlitGR206 exhibited larval labium (LL)-specific expression characteristics. To explore the role of SlitGR206, a bacterial expression system was established to produce high-quality double-stranded RNA (dsRNA) and suppress SlitGR206 expression in LL. Subsequent behavioral assessments revealed that SlitGR206 silencing influenced larval feeding preferences and absorption. Moreover, it was found to reduce the ability of larvae to forage the five crucial host odorants. These findings demonstrate that SlitGR206 likely plays an indirect regulatory role in host recognition, consequently affecting foraging behavior. This provides a crucial foundation for the analysis of functional diversity among insect GRs and the precise development of nucleic acid pesticides in the future.

Photoacoustic Tomography with Temporal Encoding Reconstruction (PATTERN) for cross-modal individual analysis of the whole brain.

Cross-modal analysis of the same whole brain is an ideal strategy to uncover brain function and dysfunction. However, it remains challenging due to the slow speed and destructiveness of traditional whole-brain optical imaging techniques. Here we develop a new platform, termed Photoacoustic Tomography with Temporal Encoding Reconstruction (PATTERN), for non-destructive, high-speed, 3D imaging of ex vivo rodent, ferret, and non-human primate brains. Using an optimally designed image acquisition scheme and an accompanying machine-learning algorithm, PATTERN extracts signals of genetically-encoded probes from photobleaching-based temporal modulation and enables reliable visualization of neural projection in the whole central nervous system with 3D isotropic resolution. Without structural and biological perturbation to the sample, PATTERN can be combined with other whole-brain imaging modalities to acquire the whole-brain image with both high resolution and morphological fidelity. Furthermore, cross-modal transcriptome analysis of an individual brain is achieved by PATTERN imaging. Together, PATTERN provides a compatible and versatile strategy for brain-wide cross-modal analysis at the individual level.

Synergistic interaction of guanfacine or dexmedetomidine coadministered with lidocaine for cutaneous analgesia in rats.

BACKGROUND: This study examined the cutaneous analgesic effects of lidocaine co-injected with guanfacine and its comparison with dexmedetomidine. METHODS: Cutaneous analgesic effects are quantified through the blocking effects of the cutaneous trunci muscle reflex against skin pinpricks in rats. The dose-response curves of guanfacine, dexmedetomidine, and lidocaine were constructed and drug-drug interactions were analyzed by the ED50 isobologram. RESULTS: Subcutaneous injections of guanfacine, dexmedetomidine, and lidocaine produced dose-dependently nociceptive/sensory blockade. On the ED50 (50% effective dose) basis, the potency rankings of the drug are dexmedetomidine (0.09 [0.08-0.11] µmol/kg) > guanfacine (3.98 [2.96-5.34] µmol/kg) > lidocaine (25.40 [23.51-27.44] µmol/kg) (p < 0.01). On their equipotent doses (ED25, ED50, and ED75), the duration of sensory blockade induced by guanfacine or dexmedetomidine was longer than lidocaine's (p < 0.01). Both guanfacine and dexmedetomidine showed synergistic effects with lidocaine. CONCLUSIONS: We showed that guanfacine elicits dose-dependent cutaneous analgesia when administered subcutaneously. Lidocaine is less potent than guanfacine or dexmedetomidine. Both guanfacine and dexmedetomidine enhance the potency and duration of lidocaine. Better synergistic responses we are getting with guanfacine plus lidocaine.

The potential role of CMC1 as an immunometabolic checkpoint in T cell immunity.

T cell immunity is critical for human defensive immune response. Exploring the key molecules during the process provides new targets for T cell-based immunotherapies. CMC1 is a mitochondrial electron transport chain (ETC) complex IV chaperon protein. By establishing in-vitro cell culture system and Cmc1 gene knock out mice, we evaluated the role of CMC1 in T cell activation and differentiation. The B16-OVA tumor model was used to test the possibility of targeting CMC1 for improving T cell anti-tumor immunity. We identified CMC1 as a positive regulator in CD8+T cells activation and terminal differentiation. Meanwhile, we found that CMC1 increasingly expressed in exhausted T (Tex) cells. Genetic lost of Cmc1 inhibits the development of CD8+T cell exhaustion in mice. Instead, deletion of Cmc1 in T cells prompts cells to differentiate into metabolically and functionally quiescent cells with increased memory-like features and tolerance to cell death upon repetitive or prolonged T cell receptor (TCR) stimulation. Further, the in-vitro mechanistic study revealed that environmental lactate enhances CMC1 expression by inducing USP7, mediated stabilization and de-ubiquitination of CMC1 protein, in which a mechanism we propose here that the lactate-enriched tumor microenvironment (TME) drives CD8+TILs dysfunction through CMC1 regulatory effects on T cells. Taken together, our study unraveled the novel role of CMC1 as a T cell regulator and its possibility to be utilized for anti-tumor immunotherapy.

[Rapamycin and HPPH Co-Loaded Nanodrug Delivered via Dissolvable Microneedles to Treat Port-Wine Stains]. / å ±è½½é›·å¸•éœ‰ç´ å’Œå ‰å ‹æ´›çš„çº³ç±³è¯ç‰©å¤åˆå¯æº¶è§£å¾®é’ˆæ²»ç–—é²œçº¢æ–‘ç—£çš„å®žéªŒç ”ç©¶.

Objective: Port-wine stains are a kind of dermatological disease of congenital capillary malformation. Based on the biological characteristics of port-wine stains and the advantages of microneedle transdermal administration, we intend to construct a nanodrug co-loaded with rapamycin (RPM), an anti-angiogenesis drug, and photochlor (HPPH), a photosensitizer, and integrate the nanodrug with dissolvable microneedles (MN) to achieve anti-angiogenesis and photodynamic combination therapy for port-wine stains. Methods: First, RPM and HPPH co-loaded nanoparticles (RPM-HPPH NP) were prepared by the emulsification solvent-volatilization method, and its ability to generate reactive oxygen species (ROS) was investigated under 660 nm laser irradiation. Mouse hemangioendothelioma endothelial cells (EOMA) were used as the subjects of the study. The cellular uptake behaviors were examined by fluorescence microscopy and flow cytometry. The cytotoxicity effects of RPM-HPPH NP with or without 660 nm laser irradiation on EOMA cells were examined by MTT assays (with free RPM serving as the control). Then, hyaluronic acid (HA) dissolvable microneedles loaded with RPM-HPPH NP (RPM-HPPH NP@HA MN) were obtained by compounding the nanodrug with HA dissolvable microneedle system through the molding method. The morphological characteristics and mechanical properties of RPM-HPPH NP@HA MN were investigated by scanning electron microscope and electronic universal testing machine. The penetration ability of RPM-HPPH NP@HA MN on the skin of nude mice was evaluated by trypan blue staining and H&E staining experiment. Results: The RPM-HPPH NP prepared in the study had a particle size of 150 nm and generated large amounts of ROS under laser irradiation. At the cellular level, RPM-HPPH NP was taken up by EOMA cells in a time-dependent manner. The cytotoxicity of RPM-HPPH NP was higher than that of free RPM with or without laser irradiation. Under laser irradiation, RPM-HPPH NP exhibited stronger cytotoxic effects and the difference was statistically significant (P<0.05). The height of the needle tip of RPM-HPPH NP@HA MN was 600 µm and the mechanical property of a single needle was 0.75048 N. Trypan blue staining and HE staining showed that pressing on the microneedles could produce pores on the skin surface and penetration of the stratum corneum. Conclusion: RPM-HPPH NP@HA MN can deliver RPM-HPPH NP percutaneously to the lesion tissue and realize the synergistic treatment of port-wine stains with anti-angiogenic therapy and photodynamic therapy, providing a new strategy for the construction of nanodrug-loaded microneedle delivery system and the clinical treatment of port-wine stains.

Stachydrine hydrochloride protects the ischemic heart by ameliorating endoplasmic reticulum stress through a SERCA2a dependent way and maintaining intracellular Ca2+ homeostasis.

This study aimed to explore the effects and mechanism of action of stachydrine hydrochloride (Sta) against myocardial infarction (MI) through sarcoplasmic/endoplasmic reticulum stress-related injury. The targets of Sta against MI were screened using network pharmacology. C57BL/6 J mice after MI were treated with saline, Sta (6 or 12 mg kg-1) for 2 weeks, and adult mouse and neonatal rat cardiomyocytes (AMCMs and NRCMs) were incubated with Sta (10-4-10-6 M) under normoxia or hypoxia for 2 or 12 h, respectively. Echocardiography, Evans blue, and 2,3,5-triphenyltetrazolium chloride (TTC) staining were used for morphological and functional analyses. Endoplasmic reticulum stress (ERS), unfolded protein reaction (UPR), apoptosis signals, cardiomyocyte contraction, and Ca2+ flux were detected using transmission electron microscopy (TEM), western blotting, immunofluorescence, and sarcomere and Fluo-4 tracing. The ingredient-disease-pathway-target network revealed targets of Sta against MI were related to apoptosis, Ca2+ homeostasis and ERS. Both dosages of Sta improved heart function, decreased infarction size, and potentially increased the survival rate. Sta directly alleviated ERS and UPR and elicited less apoptosis in the border myocardium and hypoxic NRCMs. Furthermore, Sta upregulated sarcoplasmic reticulum Ca2+-ATPase 2a (SERCA2a) in both ischaemic hearts and hypoxic NRCMs, accompanied by restored sarcomere shortening, resting intracellular Ca2+, and Ca2+ reuptake time constants (Tau) in Sta-treated hypoxic ARCMs. However, 2,5-di-t-butyl-1,4-benzohydroquinone (BHQ) (25 µM), a specific SERCA inhibitor, totally abolished the beneficial effect of Sta in hypoxic cardiomyocytes. Sta protects the heart from MI by upregulating SERCA2a to maintain intracellular Ca2+ homeostasis, thus alleviating ERS-induced apoptosis.

Anthraquinone/activated carbon electrochemical sensor and its application in acetaminophen analysis.

Acetaminophen (AC) can inhibit the synthesis of prostaglandins in the body, and has antipyretic and analgesic effects. In this paper, a two-step microwave impregnation method was used to prepare anthraquinone (AQ)-doped carbon composite, which were applied to the surface modification of glassy carbon electrodes (GCE) for the determination of acetaminophen (AC) using differential pulse voltammetry (DPV). The composites were characterized by X-ray diffraction (XRD), scanning electron microscopy (SEM), Raman and Fourier infrared spectroscopy (FT-IR). The results showed that anthraquinone was successfully modified on the surface of activated carbon. The peak current of AC increased with its concentration in the range of 0.1 µM to 700 µM (R2 = 0.998) and a detection limit of 0.05 µM was obtained with 20%AQ doped carbon electrochemical sensor (20%AQ-C/GCE). Electrochemical Impedance Spectroscopy (EIS) test results indicated that the charge transfer resistance (Rct) of 20%AQ-C/GCE is only the one-fourth of that of bare GCE. The proposed 20%AQ-C/GCE sensor has good stability, reproducibility and selectivity for the detection of AC. The sensor is also suitable for the detection of real samples, indicating its good practicality.

Construct validity, responsiveness, minimal detectable change, and minimal clinically important difference of the stroke self-efficacy questionnaire in individuals receiving stroke rehabilitation.

PURPOSE: To assess the clinimetric properties of the Stroke Self-Efficacy Questionnaire (SSEQ) and estimate the minimal detectable change (MDC) and minimal clinically important difference (MCID) from the database of our randomized controlled trials (RCT) of individuals receiving stroke rehabilitation. METHODS: We retrieved the pre- and post-intervention scores of the SSEQ and Stroke Impact Scale (SIS) from 80 stroke survivors. The analysis of clinimetric properties was performed using: (1) confirmatory factor analysis and item response theory modeling (IRT) for construct validity; (2) standardized response mean and Glass's delta for responsiveness; (3) MDC based on the standard deviation (SD) or standard error of measurement (SEM) of the SSEQ change scores; (4) MCID determined by the external anchor-SIS; (5) conditional MDC (cMDC) derived from the IRT analysis. RESULTS: There was a bi-factorial construct with excellent model-data fit and marked responsiveness. The MDC determined by the SD and SEM were 1.5 and 3.0, respectively, and the MCIDs were 3.3 and 3.7. CONCLUSIONS: This study confirmed that SSEQ is a valid and reliable assessment tool for patients receiving stroke rehabilitation. We also provided practical threshold values, especially demonstrating the benefit of using individualized cMDC, to help clinicians better interpret the change in the SSEQ scores.

This study indicated that the Stroke Self-Efficacy Questionnaire (SSEQ) is reliable and may involve a bi-factor structure.The SSEQ total scale and the activity domain were highly responsive to change.The self-management domain of the SSEQ was moderately responsive.Using conditional minimal detectable change (cMDC) along with MDC may improve the interpretability of treatment change.

Advances and Trends of Photoresponsive Hydrogels for Bone Tissue Engineering.

The development of static hydrogels as an optimal choice for bone tissue engineering (BTE) remains a difficult challenge primarily due to the intricate nature of bone healing processes, continuous physiological functions, and pathological changes. Hence, there is an urgent need to exploit smart hydrogels with programmable properties that can effectively enhance bone regeneration. Increasing evidence suggests that photoresponsive hydrogels are promising bioscaffolds for BTE due to their advantages such as controlled drug release, cell fate modulation, and the photothermal effect. Here, we review the current advances in photoresponsive hydrogels. The mechanism of photoresponsiveness and its advanced applications in bone repair are also elucidated. Future research would focus on the development of more efficient, safer, and smarter photoresponsive hydrogels for BTE. This review is aimed at offering comprehensive guidance on the trends of photoresponsive hydrogels and shedding light on their potential clinical application in BTE.

Integrated Automatic Optical Inspection and Image Processing Procedure for Smart Sensing in Production Lines.

An integrated automatic optical inspection (iAOI) system with a procedure was proposed for a printed circuit board (PCB) production line, in which pattern distortions and performance deviations appear with process variations. The iAOI system was demonstrated in a module comprising a camera and lens, showing improved supportiveness for commercially available hardware. The iAOI procedure was realized in a serial workflow of image registration, threshold setting, image gradient, marker alignment, and geometric transformation; furthermore, five operations with numerous functions were prepared for image processing. In addition to the system and procedure, a graphical user interface (GUI) that displays sequential image operation results with analyzed characteristics was established for simplicity. To demonstrate its effectiveness, self-complementary Archimedean spiral antenna (SCASA) samples fabricated via standard PCB fabrication and intentional pattern distortions were demonstrated. The results indicated that, compared with other existing methods, the proposed iAOI system and procedure provide unified and standard operations with efficiency, which result in scientific and unambiguous judgments on pattern quality. Furthermore, we showed that when an appropriate artificial intelligence model is ready, the electromagnetic characteristic projection for SCASAs can be simply obtained through the GUI.

Erinacine S, a small active component derived from Hericium erinaceus, protects oligodendrocytes and alleviates mood abnormalities in cuprizone-exposed rodents.

Hericium erinaceus mycelium extract (HEM), containing erinacine A (HeA) and erinacine S (HeS), has shown promise in promoting the differentiation of oligodendrocyte precursor cells (OPCs) into mature oligodendrocytes (OLs), crucial for myelin production in the central nervous system (CNS). The main aim of this study was to characterize the protective effects of HEM and its components on OLs and myelin in demyelinating rodents by exposure to cuprizone (CPZ), a copper chelating agent commonly used to induce demyelination in the corpus callosum of the brain. Rats were fed by CPZ-containing diet and simultaneously orally administered HEM, HeA, or HeS on a daily basis for three weeks. We found that HEM and HeS preserved myelin and OLs in the corpus callosum of CPZ-fed rats, along with reduced microglia and astrocyte activation, and downregulated IL-1ß expression. Furthermore, post-treatment with HeS, in mouse models with acute (6 weeks) or chronic (12 weeks) CPZ-induced demyelination demonstrated oral administration during the final 4 weeks (HeS4/6 or HeS4/12) effectively preserved myelin in the corpus callosum. Additionally, HeS4/6 and HeS4/12 inhibited anxious and depressive-like behaviors in CPZ-fed mice. In summary, simultaneous administration of HEM and HeS in rats during short-term CPZ intoxication preserved OLs and myelin. Furthermore, post-administration of HeS not only inhibited demyelination and gliosis but also alleviated anxiety and depression in both acute and chronic CPZ-fed mice. This study presents compelling evidence supporting the potential of HeS as a promising small active compound for protecting OLs and preserving myelin in demyelinating diseases associated with emotional disorders.