A novel method combining gated SPECT and vectorcardiography to guide left ventricular lead placement to improve response to cardiac resynchronization therapy: A Proof of Concept study.

BACKGROUND: The segment of the latest mechanical contraction (LMC) does not always overlap with the site of the latest electrical activation (LEA). By integrating both mechanical and electrical dyssynchrony, this proof-of-concept study aimed to propose a new method for recommending left ventricular (LV) lead placements, with the goal of enhancing response to cardiac resynchronization therapy (CRT). METHODS: The LMC segment was determined by single-photon emission computed tomography myocardial perfusion imaging (SPECT MPI) phase analysis. The LEA site was detected by vectorcardiogram. The recommended segments for LV lead placement were as follows: (1) the LMC viable segments that overlapped with the LEA site;(2) the LMC viable segments adjacent to the LEA site;(3) If no segment met either of the above, the LV lateral wall was recommended. The response was defined as ≥15% reduction in left ventricular end-systolic volume (LVESV) 6-months after CRT. Patients with LV lead located in the recommended site were assigned to the recommended group, and those located in the non-recommended site were assigned to the non-recommended group. RESULTS: The cohort comprised of 76 patients, including 54 (71.1%) in the recommended group and 22 (28.9%) in the non-recommended group. Among the recommended group, 74.1% of the patients responded to CRT, while 36.4% in the non-recommended group were responders (p=.002). Compared to pacing at the non-recommended segments, pacing at the recommended segments showed an independent association with an increased response by univariate and multivariable analysis (odds ratio 5.00, 95% confidence interval 1.73-14.44, p=.003; odds ratio 7.33, 95% confidence interval 1.53-35.14, p=.013). Kaplan-Meier curves showed that pacing at the recommended LV lead position demonstrated a better long-term prognosis. CONCLUSIONS: Our findings indicate that pacing at the recommended segments, by integrating of mechanical and electrical dyssynchrony, is significantly associated with an improved CRT response and better long-term prognosis.

Nanoelectrochemistry monitoring of intracellular reactive oxygen and nitrogen species induced by nanoplastic exposure.

Airborne nanoplastics can enter alveolar cells and trigger intracellular oxidative stress primarily. Herein, taking advantage of the high electrochemical resolution of SiC@Pt nanoelectrodes, we achieved the quantitative discrimination of the major ROS/RNS within A549 cells, disclosed the sources of their precursors, and observed that the NO (RNS precursor) level significantly increased, whereas O2˙- (ROS precursor) remained relatively stable during the nanoplastics exposure. This establishes that iNOS or mitochondrion-targeted treatment may be a preventive or therapeutic strategy for nanoplastic-induced lung injury.

Electroactive polymer tag modified nanosensors for enhanced intracellular ATP detection.

ATP plays a crucial role in cell energy supply, so the quantification of intracellular ATP levels is particularly important for understanding many physio-pathological processes. The intracellular quantification of this non-electroactive molecule can be realized using aptamer-modified nanoelectrodes, but is hindered by the limited quantity of modification and electroactive tags on the nanosized electrodes. Herein, we developed a simple but effective electrochemical signal amplification strategy for intracellular ATP detection, which replaces the regular ATP aptamer-linked ferrocene monomer with a polymer, thus greatly magnifying the amounts of electrochemical reporters linked to one chain of the aptamer and enhancing the signals. This ferrocene polymer-ATP aptamer was further immobilized onto Au nanowire electrodes (SiC@C@Au NWEs) to achieve accurate quantification of intracellular ATP in single cells, presenting high electrochemical signal output and high specificity. This work not only provides a powerful tool for quantifying intracellular ATP but also offers a simple and versatile strategy for electrochemical signal amplification in the detection of broader non-electroactive molecules involved in different kinds of intracellular physiological processes.

Refractive index measurement deflectometry for measuring gradient refractive index lens.

A method based on deflectometry to measure the refractive index distribution of radial gradient refractive index (GRIN) lens is proposed in this paper. The method establishes the relationship between the refractive index distribution and the direction of light ray by deriving the propagation equation of light in a non-uniform medium. By measuring the deflection angle using the principle of deflectometry and the assumption of central refraction, the refractive index distribution of the radial GRIN lens is determined. The specific principle of refractive index measurement deflectometry (RIMD) is described in detail, and the correctness and accuracy of the method are verified through numerical simulations. Furthermore, the effects of calibration error, lens surface shape on the accuracy of the measurement results are analyzed. In the experimental section, the proposed method is applied to measure a radial GRIN lens, and the results are compared with the nominal parameters in terms of shape distribution and numerical values, demonstrating good consistency. The measurement error is controlled within the order of 10-3. This method enables rapid and convenient acquisition of full-field information of GRIN lens and holds promising potential for playing an important role in lens manufacturing and production.

Underwater Gesture Recognition Meta-Gloves for Marine Immersive Communication.

Rapid advancements in immersive communications and artificial intelligence have created a pressing demand for high-performance tactile sensing gloves capable of delivering high sensitivity and a wide sensing range. Unfortunately, existing tactile sensing gloves fall short in terms of user comfort and are ill-suited for underwater applications. To address these limitations, we propose a flexible hand gesture recognition glove (GRG) that contains high-performance micropillar tactile sensors (MPTSs) inspired by the flexible tube foot of a starfish. The as-prepared flexible sensors offer a wide working range (5 Pa to 450 kPa), superfast response time (23 ms), reliable repeatability (∼10000 cycles), and a low limit of detection. Furthermore, these MPTSs are waterproof, which makes them well-suited for underwater applications. By integrating the high-performance MPTSs with a machine learning algorithm, the proposed GRG system achieves intelligent recognition of 16 hand gestures under water, which significantly extends real-time and effective communication capabilities for divers. The GRG system holds tremendous potential for a wide range of applications in the field of underwater communications.

Phase measuring deflectometry for convex aspheric surface measurement.

This paper introduces what we believe to be a novel approach to accurately measure the shape of convex aspherical surfaces with large slope gradients. This approach employs a pre-distortion system to enhance the visibility of the structured light pattern that is captured by camera. The data processing involves iterative methods to obtain surface shape data. The initial step in the experimental calibration involves establishing a reference plane, which serves as the starting point for the iterative process. The calculation for slope is subsequently utilized to determine the initial slope of the surface under test, and the height of the tested element is derived by integrating these slopes. Through multiple iterations and continuous updating of the surface height, the precise and authentic true surface height is ultimately achieved. The method's accuracy is assessed through the measurement of a highly steep convex aspherical area with a diameter of 5.2 mm and a radius of curvature of approximately 7.7 mm. The proposed method demonstrates root mean square accuracy that can reach half a wavelength when compared to the measurement results obtained from high-precision profilers.

UV-Transparent SHG Material Explored in an Alkali Metal Sulfate Selenite System.

The first examples of alkali metal selenite sulfates, namely, Na8(SeO3)(SO4)3 (1), Na2(H2SeO3)(SO4) (2), and K4(H2SeO3)(HSO4)2(SO4) (3), were successfully synthesized by hydrothermal reactions. Their structures display three different zero-dimensional configurations composed of isolated sulfate tetrahedra and selenite groups separated by alkali metals. Na8(SeO3)(SO4)3 (1) features a noncentrosymmetric structure, while Na2(H2SeO3)(SO4) (2) and K4(H2SeO3)(HSO4)2(SO4) (3) are centrosymmetric. Powder second-harmonic-generation measurements revealed that Na8(SeO3)(SO4)3 (1) shows a phase-matchable SHG intensity about 1.2 times that of KDP. UV-vis-NIR diffuse reflectance spectroscopic analysis indicated that Na8(SeO3)(SO4)3 (1) has a short UV cutoff edge and a large optical band gap, which makes it a possible UV nonlinear optical material. Theoretical calculations revealed that the birefringence of Na8(SeO3)(SO4)3 (1) is 0.041 at 532 nm, which is suitable for phase-matching condition. This work provides a good experimental foundation for the exploration of new UV nonlinear crystals in an alkali metal selenite sulfate system.

Serum klotho as a novel biomarker for metabolic syndrome: findings from a large national cohort.

Background: Metabolic syndrome is a cluster of metabolic abnormalities that significantly increase the risk of cardiovascular disease and mortality. The identification of novel biomarkers associated with mortality in patients with metabolic syndrome could facilitate early risk stratification and targeted interventions. Methods: We conducted a large prospective cohort study using data from five cycles (2009-2016) of the National Health and Nutrition Examination Survey (NHANES) database, including a total of 40,439 participants. Logistic regression analysis was used to assess the association between serum klotho protein levels and metabolic syndrome, while Cox regression analysis was employed to examine the correlation between serum klotho levels and all-cause mortality. Mortality data were updated until December 31, 2019. Results: After adjusting for demographic and socioeconomic confounders, the logistic regression model demonstrated that higher serum klotho levels were significantly associated with a decreased prevalence of metabolic syndrome (OR [95% CI] Highest vs. lowest quartile: 0.84 [0.70-0.99], P=0.038). In the Cox regression model, elevated klotho levels were found to significantly reduce the risk of all-cause mortality among individuals with metabolic syndrome (HR [95% CI] Highest vs. lowest quartile: 0.68 [0.51-0.90], P=0.006). Conclusion: Serum klotho levels were found to be inversely associated with the prevalence of metabolic syndrome, independent of potential confounding factors such as demographics, socioeconomic status, and lifestyle factors. Furthermore, higher klotho levels strongly indicated a lower risk of all-cause mortality in individuals with metabolic syndrome.

A new method of modeling the multi-stage decision-making process of CRT using machine learning with uncertainty quantification.

Aims: Current machine learning-based (ML) models usually attempt to utilize all available patient data to predict patient outcomes while ignoring the associated cost and time for data acquisition. The purpose of this study is to create a multi-stage machine learning model to predict cardiac resynchronization therapy (CRT) response for heart failure (HF) patients. This model exploits uncertainty quantification to recommend additional collection of single-photon emission computed tomography myocardial perfusion imaging (SPECT MPI) variables if baseline clinical variables and features from electrocardiogram (ECG) are not sufficient. Methods: 218 patients who underwent rest-gated SPECT MPI were enrolled in this study. CRT response was defined as an increase in left ventricular ejection fraction (LVEF) > 5% at a 6±1 month follow-up. A multi-stage ML model was created by combining two ensemble models: Ensemble 1 was trained with clinical variables and ECG; Ensemble 2 included Ensemble 1 plus SPECT MPI features. Uncertainty quantification from Ensemble 1 allowed for multi-stage decision-making to determine if the acquisition of SPECT data for a patient is necessary. The performance of the multi-stage model was compared with that of Ensemble models 1 and 2. Results: The response rate for CRT was 55.5% (n = 121) with overall male gender 61.0% (n = 133), an average age of 62.0±11.8, and LVEF of 27.7±11.0. The multi-stage model performed similarly to Ensemble 2 (which utilized the additional SPECT data) with AUC of 0.75 vs. 0.77, accuracy of 0.71 vs. 0.69, sensitivity of 0.70 vs. 0.72, and specificity 0.72 vs. 0.65, respectively. However, the multi-stage model only required SPECT MPI data for 52.7% of the patients across all folds. Conclusions: By using rule-based logic stemming from uncertainty quantification, the multi-stage model was able to reduce the need for additional SPECT MPI data acquisition without sacrificing performance.

Discovery of Novel 4-Hydroxyquinazoline Derivatives: In Silico, In Vivo and In Vitro Studies Using Primary PARPi-Resistant Cell Lines.

A series of novel 4-Hydroxyquinazoline derivatives were designed and synthesized to enhance sensitivity in primary PARPi-resistant cells. Among them, the compound B1 has been found to have superior cytotoxicity in primary PARPi-resistant HCT-15 and HCC1937 cell lines, and dose-dependently suppressed the intracellular PAR formation and enhanced the γH2AX aggregation. Mechanistic study showed that B1 stimulated the formation of intracellular ROS and the depolarization of the mitochondrial membrane, which could increase apoptosis and cytotoxicity. An in vivo study showed that B1 significantly suppressed tumor growth at a dose of 25 mg/kg, and an acute toxicity study confirmed its safety. Molecular docking and dynamics simulations revealed that hydrogen bonding between B1 and ASP766 may be helpful to enhance anti-drug resistance ability. This study suggests that B1 is a potent PARP inhibitor that can overcome PARPi resistance and deserves further investigation.

Mediating Role of Rumination in Second Victim Experience to Turnover Intention in Psychiatric Nurses.

BACKGROUND: Psychiatric nurses often face patient safety incidents that can cause physical and emotional harm, even leading to s econd victim syndrome and staff shortages. Rumination-a common response after nurses suffer a patient safety event-may play a specific role between the second victim experience and turnover intention. Understanding these mechanisms is crucial for supporting psychiatric nurses and retaining psychiatric nursing resources. OBJECTIVES: The study aimed to explore the associations among second victim experience, rumination, and turnover intention in psychiatric nurses and confirm how second victim experience influences turnover intention through rumination and its subtypes. METHODS: A descriptive, cross-sectional study was adapted to survey 252 psychiatric nurses who experienced a patient safety incident at three hospitals in China between March and April 2023. We used the Sociodemographic and Patient Safety Incident Characteristics Questionnaire (the Chinese version of the Second Victim Experience and Support Tool), the Event-Related Rumination Inventory, and the Turnover Intention Scale. Path analysis with bootstrapping was employed to accurately analyze and estimate relationships among the study variables. RESULTS: There was a positive association between second victim experience and turnover intention. In addition, both invasive and deliberate rumination showed significant associations with second victim experience and turnover intention. Notably, our results revealed that invasive and deliberate rumination played partial mediating roles in the relationship between second victim experience and turnover intention in psychiatric nurses. DISCUSSION: The negative experience and turnover intention of the psychiatric nurse second victims are at a high level. Our results showed that invasive rumination positively mediated the relationship between second victim experience and turnover intention, and deliberate rumination could weaken this effect. This study expands the knowledge of the mechanisms underlying the effect of the second victim experience on turnover intention. Organizations must attach importance to the professional dilemmas of the psychiatric nurses' second victims. Nurse managers can reduce nurses' turnover intention by taking measures to reduce invasive rumination and fostering deliberate meditation to help second victims recover from negative experiences.

Salicylic acid enhances cell growth, fatty acid and astaxanthin production in heterotrophic Chromochloris zofingiensis without reactive oxygen species elevation.

BACKGROUND: The induction of lipid and astaxanthin accumulation in microalgae is often achieved through abiotic stress. However, this approach usually leads to oxidative stress, which results in relatively low growth rate. Phytohormones, as important small molecule signaling substances, not only affect the growth and metabolism of microalgae but also influence the intracellular reactive oxygen species level. This study aimed to screen phytohormones that could promote the fatty acids and astaxanthin yield of heterotrophic Chromochloris zofingiensis without causing oxidative damage, and further investigate the underlying mechanisms. RESULTS: In the present study, among all the selected phytohormones, the addition of exogenous salicylic acid (SA) could effectively promote cell growth along with the yield of total fatty acids (TFA) and astaxanthin in heterotrophic C. zofingiensis. Notably, the highest yields of TFA and astaxanthin were achieved at 100 µM SA, 43% and 97.2% higher compared with the control, respectively. Interestingly, the intracellular reactive oxygen species (ROS) levels, which are usually increased with elevated TFA content under abiotic stresses, were significantly decreased by SA treatment. Comparative transcriptome analysis unveiled significant alterations in overall carbon metabolism by SA. Specifically, the upregulation of fatty acid synthesis pathway, upregulation of ß-carotene-4-ketolase (BKT) in carotenoid synthesis aligned with biochemical findings. Weighted gene co-expression network analysis highlighted ABC transporters and GTF2B-like transcription factor as potential key regulators. CONCLUSION: This study found that salicylic acid can serve as an effective regulator to promote the celling growth and accumulation of fatty acids and astaxanthin in heterotrophic C. zofingiensis without ROS elevation, which provides a promising approach for heterotrophic production of TFA and astaxanthin without growth inhibition.

Palladium-Catalyzed C2-Selective Direct Arylation of Benzo[b]thiophene 1,1-Dioxides with Arylboronic Acids.

A novel oxidative cross-coupling of benzo[b]thiophene 1,1-dioxides with arylboronic acids was reported. The efficient reaction occurred at the C2-position via C-H activation, followed by Pd(II)-catalyzed arylation. Furthermore, a series of C2-arylated products with significant photoluminescence properties have been synthesized and characterized, which illustrates the potential applications of our method in the aggregation-induced emission field.

Dopamine modification of glycolytic enzymes impairs glycolysis: possible implications for Parkinson's disease.

BACKGROUND: Parkinson's disease (PD), a chronic and severe neurodegenerative disease, is pathologically characterized by the selective loss of nigrostriatal dopaminergic neurons. Dopamine (DA), the neurotransmitter produced by dopaminergic neurons, and its metabolites can covalently modify proteins, and dysregulation of this process has been implicated in neuronal loss in PD. However, much remains unknown about the protein targets. METHODS: In the present work, we designed and synthesized a dopamine probe (DA-P) to screen and identify the potential protein targets of DA using activity-based protein profiling (ABPP) technology in combination with liquid chromatography-tandem mass spectrometry (LC-MS/MS). In situ pull-down assays, cellular thermal shift assays (CETSAs) and immunofluorescence were performed to confirm the DA modifications on these hits. To investigate the effects of DA modifications, we measured the enzymatic activities of these target proteins, evaluated glycolytic stress and mitochondrial respiration by Seahorse tests, and systematically analyzed the changes in metabolites with unbiased LC-MS/MS-based non-targeted metabolomics profiling. RESULTS: We successfully identified three glycolytic proteins, aldolase A, α-enolase and pyruvate kinase M2 (PKM2), as the binding partners of DA. DA bound to Glu166 of α-enolase, Cys49 and Cys424 of PKM2, and Lys230 of aldolase A, inhibiting the enzymatic activities of α-enolase and PKM2 and thereby impairing ATP synthesis, resulting in mitochondrial dysfunction. CONCLUSIONS: Recent research has revealed that enhancing glycolysis can offer protection against PD. The present study identified that the glycolytic pathway is vulnerable to disruption by DA, suggesting a promising avenue for potential therapeutic interventions. Safeguarding glycolysis against DA-related disruption could be a potential therapeutic intervention for PD.

Nanosensor detection of reactive oxygen and nitrogen species leakage in frustrated phagocytosis of nanofibres.

Exposure to widely used inert fibrous nanomaterials (for example, glass fibres or carbon nanotubes) may result in asbestos-like lung pathologies, becoming an important environmental and health concern. However, the origin of the pathogenesis of such fibres has not yet been clearly established. Here we report an electrochemical nanosensor that is used to monitor and quantitatively characterize the flux and dynamics of reactive species release during the frustrated phagocytosis of glass nanofibres by single macrophages. We show the existence of an intense prolonged release of reactive oxygen and nitrogen species by single macrophages near their phagocytic cups. This continued massive leakage of reactive oxygen and nitrogen species damages peripheral cells and eventually translates into chronic inflammation and lung injury, as seen during in vitro co-culture and in vivo experiments.

The metabolic mechanisms of Cd-induced hormesis in photosynthetic microalgae, Chromochloris zofingiensis.

Cadmium, an environmental pollutant, is highly toxic and resistant to degradation. It exhibits toxicity at elevated doses but triggers excitatory effects at low doses, a phenomenon referred to as hormesis. Microalgae, as primary producers in aquatic ecosystems, demonstrate hormesis induced by cadmium, though the specific mechanisms are not yet fully understood. Consequently, we examined the hormesis of cadmium in Chromochloris zofingiensis. A minimal Cd2+ concentration (0.05 mg L-1) prompted cell proliferation, whereas higher concentrations (2.50 mg L-1) inhibited growth. The group exposed to higher doses exhibited increased levels of reactive oxygen species (ROS), malondialdehyde (MDA), glutathione (GSH), superoxide dismutase (SOD), and catalase (CAT). Contrastingly, the group exposed to low doses exhibited a moderate antioxidant response without significantly increasing ROS. This implies that increased levels of antioxidative components counteract excessive ROS, maintaining cellular redox balance and promoting growth under conditions of low Cd2+. Validation experiments have established that NADPH oxidase-derived ROS primarily coordinates the hormesis effect in microalgae. Comparative transcriptome analysis has proved the involvement of antioxidant systems and photosynthesis in regulating hormesis. Notably, Aurora A kinases consistently displayed varying expression levels across all Cd2+ treatments, and their role in microalgal hormesis was confirmed through validation with SNS-314 mesylate. This study unveils the intricate regulatory mechanisms of Cd-induced hormesis in C. zofingiensis, with implications for environmental remediation and industrial microalgae applications.

Autonomous Multi-modality Burn Wound Characterization using Artificial Intelligence.

INTRODUCTION: Between 5% and 20% of all combat-related casualties are attributed to burn wounds. A decrease in the mortality rate of burns by about 36% can be achieved with early treatment, but this is contingent upon accurate characterization of the burn. Precise burn injury classification is recognized as a crucial aspect of the medical artificial intelligence (AI) field. An autonomous AI system designed to analyze multiple characteristics of burns using modalities including ultrasound and RGB images is described. MATERIALS AND METHODS: A two-part dataset is created for the training and validation of the AI: in vivo B-mode ultrasound scans collected from porcine subjects (10,085 frames), and RGB images manually collected from web sources (338 images). The framework in use leverages an explanation system to corroborate and integrate burn expert's knowledge, suggesting new features and ensuring the validity of the model. Through the utilization of this framework, it is discovered that B-mode ultrasound classifiers can be enhanced by supplying textural features. More specifically, it is confirmed that statistical texture features extracted from ultrasound frames can increase the accuracy of the burn depth classifier. RESULTS: The system, with all included features selected using explainable AI, is capable of classifying burn depth with accuracy and F1 average above 80%. Additionally, the segmentation module has been found capable of segmenting with a mean global accuracy greater than 84%, and a mean intersection-over-union score over 0.74. CONCLUSIONS: This work demonstrates the feasibility of accurate and automated burn characterization for AI and indicates that these systems can be improved with additional features when a human expert is combined with explainable AI. This is demonstrated on real data (human for segmentation and porcine for depth classification) and establishes the groundwork for further deep-learning thrusts in the area of burn analysis.

Fast Antioxidation Kinetics of Glutathione Intracellularly Monitored by a Dual-Wire Nanosensor.

The glutathione (GSH) system is one of the most powerful intracellular antioxidant systems for the elimination of reactive oxygen species (ROS) and maintaining cellular redox homeostasis. However, the rapid kinetics information (at the millisecond to the second level) during the dynamic antioxidation process of the GSH system remains unclear. As such, we specifically developed a novel dual-wire nanosensor (DWNS) that can selectively and synchronously measure the levels of GSH and ROS with high temporal resolution, and applied it to monitor the transient ROS generation as well as the rapid antioxidation process of the GSH system in individual cancer cells. These measurements revealed that the glutathione peroxidase (GPx) in the GSH system is rapidly initiated against ROS burst in a sub-second time scale, but the elimination process is short-lived, ending after a few seconds, while some ROS are still present in the cells. This study is expected to open new perspectives for understanding the GSH antioxidant system and studying some redox imbalance-related physiological.

[Drug Resistance Mechanism and Therapeutic Strategy of Targeted Therapy of 
Non-small Cell Lung Cancer with MET Alterations].

Mesenchymal to epithelial transition factor (MET) gene alterations involve in the proliferation, invasion, and metastasis of non-small cell lung cancer. MET-tyrosine kinase inhibitors (TKIs) have been approved to treat non-small cell lung cancer with MET alterations, and resistance to these TKIs is inevitable. Molecular mechanisms of resistance to MET-TKIs are completely unclear. The review focused on potential mechanisms of MET-TKIs resistance and therapeutics strategies to delay and prevent resistance.
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Remarkable response to PD-1 inhibitor in a patient with extensive-stage small cell lung cancer: a case report and literature review.

We report a case of a 59-year-old male diagnosed with extensive-stage small cell lung cancer (SCLC). He received first-line platinum doublet chemotherapy and second-line topotecan-based regimen, but experienced disease progression after each line of therapy. He was then treated with Sintilimab, a PD-1 inhibitor, in combination with nab-paclitaxel in the third-line setting, which resulted in significant tumor shrinkage. Restaging scans showed a partial response per RECIST criteria with 62% reduction in tumor burden. This case highlights the application and efficacy of immune checkpoint inhibitors in extensive-stage SCLC.