Dynamic Changes Research Articles

An iridium(III) complex-based luminogenic probe for high-throughput screening of hydrogen sulfide donors in living cells.

The scarcity of suitable high-throughput screening technology for hydrogen sulfide (H2S) donors has hampered the discovery of H2S donors. In this study, a long-lived cyclometalated iridium complex was rationally designed as a mitochondria-targeted H2S probe to monitor the real-time dynamic change of H2S. By using the time-resolved emission spectroscopy (TRES) technique, an anti-interference high-throughput screening system was developed to monitor H2S in living cells with decreased false negative results. As a proof-of-concept, three natural products were identified as potential H2S donors from a natural product library using the developed TRES probe. Notably, the discovery of allicin and diallyl trisulfide demonstrated the feasibility of this screening platform, while garlic-derived allyl methyl sulfide was explored as a H2S donor candidate. The results were further validated by a commercial assay. We anticipate this high-throughput platform could facilitate the discovery of H2S donors by discriminating the endogenous interfering fluorescence from biological systems.

A prognostic nomogram for patients with III-IV nasopharyngeal carcinoma based on dynamic changes in the inflammatory and nutrition index.

The purpose of the study was to explore the value of dynamic changes in inflammatory and nutritional index after comprehensive treatment in patients with stage III-IVA nasopharyngeal carcinoma (NPC). A prognostic model was also established and validated for progression-free survival (PFS) of patients. We retrospectively selected 279 NPC patients with stage III-IVA. Their general clinical data and hematological index were collected and then calculated the changes during treatment. X-tile software was used to determine the optimal cut-off value. COX regression, Lasso method, and Boruta method were used to variable selection and model establishment. Using the bootstrap internal validation method, concordance index (C-index), calibration plot, and Kaplan-Meier curves were used to evaluate the model. To test the prognostic value of the model, we have also evaluated the performance of the nomogram against a conventional tumor metastasis staging system (TNM). Multivariable COX regression analysis demonstrated that clinical staging, delta lymphocyte, delta monocyte, delta albumin, delta platelet-to-lymphocyte ratio and delta systemic immune inflammation index were related to the PFS of NPC patients. The C-index of the model was 0.712, and the calibration curve indicated that the model had good consistency. The C-index of the TNM staging system was 0.597, which was considerably lower compared to our model (P = 0.015). We demonstrated the predictive value of dynamic changes in inflammatory and nutritional indices for the prognosis of NPC by successfully establishing and validating a prognostic model for predicting 1- and 3-year PFS after comprehensive treatment in patients with stage III-IVA NPC.

Abstract 4136598: Osteochondrogenic transdifferentiation of vascular smooth muscle cells and microenvironmental dynamics in medial arterial calcification at single-cell resolution

Background: Medial arterial calcification (MAC) significantly contributes to cardiovascular mortality, yet effective treatments remain limited due to unclear molecular mechanisms. This study aimed to develop a mouse model of MAC using O-ring-induced transverse aortic constriction (OTAC) and to elucidate key genes, pathways, and cellular interactions involved in MAC formation through lineage tracing and single-cell RNA sequencing (scRNA-seq). Methods: An OTAC mouse model was established to replicate MAC. Adult C57BL/6J male mice underwent OTAC, and subsequent analyses were conducted at various time points. Histological and immunohistochemical assessments were performed to monitor changes in vascular smooth muscle cells (VSMCs). Lineage tracing was utilized to verify the origin of osteochondrogenic VSMCs. Furthermore, scRNA-seq was employed to capture dynamic changes in VSMCs and other cell types contributing to MAC development. Results: The OTAC model successfully induced osteochondrogenic transdifferentiation of VSMCs, leading to MAC. Immunohistochemical analysis demonstrated time-dependent decreases in α-SMA expression and increases in SOX9 and RUNX2 expression. Lineage tracing using Myh11CreERT2;ROSA26-EGFP mice confirmed that osteochondrogenic VSMCs originated from contractile VSMCs. scRNA-seq identified osteochondrogenic VSMCs and revealed dynamic changes in surrounding cells, including macrophages and fibroblasts, which were implicated in calcification-related and inflammatory processes. Conclusion: The OTAC method effectively mimicked human MAC pathology, offering comprehensive insights into the microenvironmental dynamics of MAC progression at the single-cell level. This model serves as a robust platform for future research on therapeutic interventions.

Modeling and Control of Dual Active Bridge‐Modular Multilevel Converter‐Based Solid State Transformer for Grid Integration of SPV and Battery Energy Storage

ABSTRACTThis article deals with the modeling and control of a solid‐state transformer (SST) based on a dual active bridge (DAB) and modular multilevel converter (MMC) for integrating solar photovoltaic (SPV) and battery energy storage (BES) systems into the grid. SST uses DABs for bidirectional DC‐DC conversion and an MMC for DC‐AC conversion. A hybrid control method is developed in this study, which combines proportional‐integral (PI) controllers and model predictive control (MPC) to achieve the multiple objectives of the SST. The DABs' control system uses PI controllers for power extraction from the SPV system and to regulate the charging and discharging of the BES according to power generation and demand fluctuations. MPC is applied to control the active power injection, regulate the DC‐link and sub‐module capacitor voltages of the MMC. Moreover, the developed hybrid control method ensures reliable SST performance even under adverse conditions like grid voltage distortion, unbalance, and frequency variations. An energy management strategy is developed based on total power generation, reference active power injection, and the state of charge of the BES. This strategy ensures accurate reference power injection to the grid despite dynamic changes in operating conditions. The article also presents a detailed mathematical model of the DAB and MMC components, and the stability of the control algorithm is analyzed theoretically. The effectiveness of the SST and the proposed hybrid control scheme is demonstrated through MATLAB/Simulink simulations and hardware‐in‐the‐loop experimental results under various operating conditions.

Abstract 4121812: Longitudinal Trajectory-Based Classification of Heart Failure with preserved Ejection Fraction: A Machine Learning Approach

Background: Heart failure (HF) with preserved ejection fraction (HFpEF) is a complex syndrome characterized by heterogeneous pathophysiology and dynamic changes in cardiac structure and function. Current research predominantly focuses on left ventricular ejection fraction (LVEF) or left ventricular structures with predefined categories. This study hypothesized that applying unsupervised methodologies to longitudinal echocardiography will reveal distinct trajectory patterns in cardiac structure and function related to clinical outcomes in HFpEF patients. Methods: This retrospective cohort study, conducted at UC Davis Medical Center (2014 to 2022), consisted of adult patients with HFpEF. The inclusion criteria included ICD HF codes, a left ventricular ejection fraction (LVEF) ≥50%, and a Brain natriuretic peptide (BNP) ≥100 pg/ml or N-terminal-pro BNP (NT-proBNP) ≥225 pg/ml. Longitudinal data were analyzed using unsupervised machine learning, including UMAP for dimensionality reduction and Gaussian Mixture Models for clustering. Primary and secondary outcomes included all-cause mortality and changes in BNP levels, respectively. Results: The study included 1,626 patients. The cohort had a median age of 69 years, was 57.5% female, and 51.8% white. Three distinct echocardiographic trajectory patterns emerged (p<.05) among the HFpEF cohort. Trajectory #1 (n=568) exhibited a high-stable pattern with the highest mortality rates, Trajectory #2 (n=512) showed a high-decreasing pattern with high mortality rates, and Trajectory #3 (n=546) had a low-increasing pattern with the lowest mortality rates. Trajectories varied significantly in baseline characteristics and longitudinal echocardiographic changes, with Trajectory #3 having a lower baseline left ventricular mass index (p<.001) and a higher mean arterial pressure ( p =.001) compared to the other trajectories. Kaplan-Meier survival analysis indicated significant differences in survival among the trajectories ( p =.004). Conclusion: The study utilized unsupervised analysis of longitudinal echocardiographic data to identify three distinct HFpEF trajectories, each associated with unique clinical features and outcomes. These findings underscore the heterogeneity of HFpEF and highlight the potential trajectory-based patient stratification to improve targeted intervention strategies. Future validation in larger, multicenter cohorts is warranted to enhance HFpEF management and patient prognosis.

Dynamic risk factors for complex regional pain syndrome after distal radius fracture surgery: multivariate analysis and prediction.

Distal radius fractures are a common orthopedic injury, particularly prevalent among elderly and osteoporotic patients. Although surgical treatment effectively restores fracture alignment and stabilizes the bone, Complex Regional Pain Syndrome (CRPS) can occur as a postoperative complication, severely impacting patients' rehabilitation and quality of life. Therefore, assessing the risk factors for postoperative CRPS is crucial for early clinical intervention, aiming to improve recovery outcomes and overall patient well-being. This study aims to dynamically evaluate the risk factors for CRPS following distal radius fracture surgery through a retrospective analysis. The goal is to provide scientific evidence for early clinical identification and intervention. A retrospective analysis was conducted on 191 adult patients who underwent distal radius fracture surgery between January 2021 and December 2022, comprising 89 males and 102 females, with an average age of 59.7 ± 11.6(18-75) years. Baseline and follow-up data, including demographic information, clinical characteristics, and psychological assessments, were collected. Descriptive statistics, univariate, and multivariate logistic regression analyses were used to identify independent risk factors and assess their dynamic changes over time. Age, gender, occupation, fracture type, surgical method, osteoporosis, pain score (VAS), functional disability score (DASH), anxiety score (GAD-7), depression score (PHQ-9), physical therapy, and occupational therapy significantly affected the incidence of CRPS. Age and VAS scores were consistent risk factors. Female gender, internal fixation surgery, and high DASH scores posed higher risks in the early postoperative period but decreased over time. Occupation and fracture type were more significant in the mid to late postoperative period. Psychological factors were most significant in the midterm, while physical and occupational therapy were protective factors early on. The occurrence of CRPS is the result of many factors. Elderly patients, females, and manual laborers had higher risks, with complex fractures and internal fixation surgery patients showing increased risk later on. Osteoporotic patients had higher risks in the mid to late postoperative period. VAS, DASH, GAD-7, and PHQ-9 scores were significantly associated with CRPS. Early physical and occupational therapy can effectively prevent CRPS, but further research is needed to evaluate their long-term effects.

Mechanisms Maintaining Biomass Stability in Woody Species Communities in Evergreen Broadleaved Forests of Dong Nai Culture and Nature Reserve, Dong Nai province, Southern Vietnam

Tropical forest ecosystems experience dynamic changes in response to environmental fluctuations and disturbances. Understanding the mechanisms governing their stability is crucial for maintaining ecosystem services. Among these ecosystems, evergreen broadleaved forests play a pivotal global role. This study investigates the impacts of overyielding, stand structure, species asynchrony, and the stability of dominant species on community biomass stability (CBS) within the Dong Nai Culture and Nature Reserve's evergreen broadleaved forests. The study utilized species richness, diameter-at-breast-height (DBH) variation coefficient, species asynchrony, and stability of dominant species as explanatory variables. The response variables included CBS, mean biomass (µ), and biomass standard deviation (σ). Three structural equation models (SEMs) were constructed to assess the relative strengths of direct and indirect effects among these variables. The results indicated that: (1) The SEMs achieved a good fit, explaining 41.8% of the variance in CBS. (2) Species richness negatively correlated significantly with µ (path coefficient = -0.112) and σ (-0.056). (3) DBH variation coefficient showed significant negative correlations with CBS (-0.161) and µ (-0.087). (4) Species asynchrony exhibited significant positive correlations with CBS (0.061), µ (0.076), and σ (0.061). (5) Dominant species stability showed significant positive correlations with CBS (0.588) and µ (0.153) and a negative correlation with σ (-0.588). These findings underscore that while stand structure and species asynchrony significantly influence CBS in evergreen broadleaved forests, the stability of dominant species emerges as the primary predictor of CBS. Therefore, effective forest management strategies should prioritize conserving and enhancing conditions that support dominant species, ensuring the sustainability of forest ecosystems in the study area.

A New Method of Intelligent Fault Diagnosis of Ship Dual-Fuel Engine Based on Instantaneous Rotational Speed

Ship engine misfire faults not only pose a serious threat to the safe operation of ships but may also cause major safety accidents or even lead to ship paralysis, which brings huge economic losses. Most traditional fault diagnosis methods rely on manual experience, with limited feature extraction capability, low diagnostic accuracy, and poor adaptability, which make it difficult to meet the demand for high-precision diagnosis. To this end, a fusion intelligent diagnostic model—ResNet–BiLSTM—is proposed based on a residual neural network (ResNet) and a bidirectional long short-term memory network (BiLSTM). Firstly, a multi-scale decomposition of the instantaneous rotational speed signal of a ship’s engine is carried out by using the continuous wavelet transform (CWT), and features containing misfire fault information are extracted. Subsequently, the extracted features are fed into the ResNet–BiLSTM model for learning. Finally, the intelligent diagnosis of ship dual-fuel engine misfire faults is realized by the classifier. The model combines the advantages of ResNet18 in image feature extraction and the capability of BiLSTM in temporal information processing, which can efficiently capture the time-frequency features and dynamic changes in the fault signal. Through comparison experiments with fusion models AlexNet–BiLSTM, VGG–BiLSTM, and the existing AlexNet–LSTM and VGG–LSTM models, the results show that the ResNet–BiLSTM model outperforms the other models in terms of diagnostic accuracy, robustness, and generalization ability. This model provides an effective new method for intelligent diagnosis of ship dual-fuel engine misfire faults to solve the traditional diagnostic methods’ limitations.

Potential-Driven Coordinated Oxygen Migration in an Electrocatalyst for Sustainable H2O2 Synthesis.

Local coordination environment (LCE) manipulation has emerged as a significant approach for modulating the electrocatalytic behavior of low-dimensional nanomaterials. However, challenges persist in accurately identifying active sites and understanding dynamic changes during operation. Here, we underscore the influence of LCE on the electrochemical production of H2O2, utilizing the Pd cluster as a model catalyst. Density functional theory (DFT) calculations illustrate the role of first- and second-coordinated sulfur and oxygen in modulating the binding strength of HOO*. Guided by DFT screening, the as-prepared Pd cluster (Pdx/HMCS) catalyst presents exceptional catalytic performance with a high mass activity of 4.06 A mg-1 at 0.45 V and selectivity above 94%. The Pdx/HMCS catalyst also delivers promising potential for industrial practices with a production rate of 16.3 mol gcat-1 h-1 in flow cell evaluation. Elaborated in situ characterizations confirm that under operation, oxygen migrates from the second coordination sphere (CS) to the first CS to achieve oxygen coverage on the catalyst surface. Such an oxygen migration phenomenon and the optimized first and second coordination environment give rise to the outstanding performance.

Abstract 4117256: EFFECT OF CORONARY MICROEMBOLIZATION ON AUTOPHAGY-RELATED MICRORNA AND PROTEIN PATHWAYS STUDY

Background: Coronary microembolization (CME) commonly occurs during PCI in acute coronary syndrome, leading to myocardial damage. The purpose of this study is to explore the effects of CME on autophagy-related microRNAs and protein pathways, and to identify possible mechanisms of myocardial injury caused by CME. Methods: This study randomly divided rats into 6 groups: sham and CME1h, 3h, 6h, 9h, 12h groups. A rat model of CME was established by injecting autologous microthrombi into the left ventricle. Echocardiography and HE staining were performed to evaluate myocardial infarct size in each group. The expression of microRNA-144-3p and microRNA-214-3p, LC3-II, p62/SQSTM1, phosphatase, and PTEN was detected. Results: Compared with the sham group, LVEF and LVFS decreased,LVESD increased (P<0.05) in the CME3h, 6h, 9h, and 12h groups,the myocardial infarct area significantly increased in the CME6h group (P<0.05). The expression of microRNA-144-3p and microRNA-214-3p in myocardial tissue increased after CME, reaching a peak at 1h (P<0.05); LC3II decreased at CME1h (P<0.05) and significantly increased in the CME6h group (P<0.05). p62/SQSTM1 increased at CME1h (P<0.05) and then gradually decreased, while PTEN increased after CME3h (all P<0.05), with a peak at 6h. Conclusion: Autophagy showed dynamic changes after CME, suggesting that enhanced autophagy aggravates myocardial damage after CME. Related microRNAs and PTEN are involved in the regulation of autophagy after CME.

Abstract 4135035: Liver kinase B1 (LKB1) loss links vascular smooth muscle cell fate switch to aortic aneurysm formation

Background: Acquisition and maintenance of vascular smooth muscle cell (VSMC) fate are important for vascular development and homeostasis; however, little is known about the key determinant for VSMC fate and vascular homeostasis. Methods: Lkb1 flox/flox ; Tagln- Cre, Lkb1 flox /flox ; Myh11-Cre/ERT2 , and lineage tracing Lkb1 flox/flox ; Myh11-Cre/ERT2 ; ROSA mT/mG mice were generated to study the impact of Lkb1 on VSMC and vascular function in vivo . Single aortic cells isolated from wild-type and Lkb1 flox/flox ; Myh11-Cre/ERT2 mice were analyzed by single-cell RNA sequencing (sc-RNA seq). The dynamic changes of vascular morphology and VSMC fate were investigated using high-frequency ultrasound and various histological techniques. In addition, VSMC phenotype and molecular mechanisms were further explored by mouse arterial ring assay ex vivo , in cultured human aortic VSMC in vitro, and in human aneurysmal aortic tissues. Results: We found that SMC-specific Lkb1 ablation in Lkb1 flox/flox ; Tagln-Cre mice caused severe vascular abnormalities and embryonic lethality. SMC-specific deletion of Lkb1 in tamoxifen-inducible Lkb1 flox/flox ; Myh11-Cre/ERT2 mice spontaneously and progressively induced aortic/arterial dilation, aneurysm, rupture, and premature death. Sc-RNA seq and imaging-based lineage tracing showed that Lkb1 -deficient VSMCs transdifferentiated gradually from early modulated VSMCs to fibroblast-like and chondrocyte-like cells, leading to ossification and blood-vessel rupture. Moreover, we found that SMC-specific Lkb1 ablation resulted in decreased vascular contractility and hypotension in vivo . Mechanistically, Lkb1 regulates polypyrimidine tract binding protein 1 (Ptbp1) expression and controls alternative splicing of pyruvate kinase muscle (PKM) isoforms 1 and 2. Lkb1 loss in VSMC results in an increased PKM2/PKM1 ratio and alters the metabolic profile by promoting aerobic glycolysis. Treatment with PKM2 activator TEPP-46 rescues VSMC transformation and aortic dilation in Lkb1 flox/flox ; Myh11-Cre/ERT2 mice. Furthermore, we found that Lkb1 expression decreased in human aortic aneurysm tissue compared to control tissue, along with changes in markers of VSMC fate. Conclusions: Lkb1, via its regulation of Ptbp1-dependent alterative splicing of PKM, maintains VSMC in contractile states and sustains vascular homeostasis. Our findings have important implications for understanding the pathogenesis of aortic aneurysm.

Phospholipid dynamics in Aspergillus species: relations between biological membrane composition and cellular morphology.

Biological membranes, primarily composed of phospholipid bilayers, are essential structures that compartmentalize the cell from the extracellular environment. The biosynthesis and regulation of membrane lipids have been extensively studied in model organisms such as Saccharomyces cerevisiae and mammalian cells. However, our understanding of biological membrane regulation in filamentous fungi, some of which are significant in medicine, pharmacy, and agriculture, remains limited. This minireview provides a comprehensive overview of the latest knowledge, focusing on filamentous fungi of Aspergillus species. Recent progress in understanding dynamic changes in membrane lipid profiles, driven by improvements in analytical techniques for lipidomics, is also presented. Furthermore, known that the cell morphology of filamentous fungi is closely linked to its harmful and beneficial characteristics, the influence of membrane composition on cell morphology is discussed. The integration of these findings will further enhance our understanding of the biological functions of membranes in filamentous fungi.

Sequential Hemodynamic Analysis of Ruptured Posterior Communicating Artery Aneurysms Treated With Coil Embolization and Delayed Flow Diversion.

Computational fluid dynamics has advanced our knowledge of the pathogenesis of intracranial aneurysms and the dynamic changes observed after treatment. Herein, we analyze hemodynamic changes throughout the intervention stages for ruptured posterior communicating artery (PComA) aneurysms, treated with acute coiling and delayed flow diversion (FD). We performed a retrospective analysis of ruptured PComA aneurysms treated with the acute coiling and delayed FD strategy between June 2013 to November 2022, using 3-dimensional reconstructions of digital subtraction angiographies. Hemodynamic simulations using ANSYS® calculated aneurysmal and adjacent arteries' wall shear stress (WSS), aneurysmal low shear areas (LSA), and mean velocities in the distal arteries. Six of the 22 patients were selected for computational fluid dynamics analysis, including 4 females and 2 males with a median age of 60 years. The average aneurysm volume was 984.12 mm3, with an average surface area of 386.11 mm2; LSA was 22.90%, and the average WSS was 3.39 Pa. The 2 largest aneurysms also had the highest LSA values. After coiling, there was a reduction in the aneurysmal volume (-78.42%) and the average surface area (-55.28%), and aneurysmal WSS increased to 6.10 Pa (+79.90%). WSS values for the middle cerebral artery (MCA) increased to 10.76 Pa, while anterior cerebral artery (ACA) increased to 7.51 Pa. Complete occlusion was achieved with delayed FD at a median follow-up of 19.7 months. After FD, average WSS increased to 14.94 Pa for the MCA (+70.64%) and to 10.82 Pa for the ACA (+30.10%). The mean MCA velocity increased to 43.04 cm/s (+36.85%), and 3 cases showed an increase in ACA velocities. LSA may have triggered rupture for the PComA aneurysms analyzed. After coiling, average WSS increased in the aneurysm wall and downstream vessels in the majority of cases analyzed. Delayed FD caused hemodynamic disturbances distal to deployment, reflected in the sequential increase in the WSS and velocities in both the ACA and MCA.

Energy Associated With Dynamic Network Changes in Patients With Multiple Sclerosis and Cognitive Impairment.

Patients with multiple sclerosis (MS) often experience cognitive impairment, and this is related to structural disconnection and subsequent functional reorganization. It is unclear how specific patterns of functional reorganization might make it harder for cognitively impaired (CI) patients with MS to dynamically adapt how brain regions communicate, which is crucial for normal cognition. We aimed to identify dynamic functional network patterns that are relevant to cognitive impairment in MS and investigate whether these patterns can be explained by altered energy costs. Resting-state functional and diffusion MRI was acquired in a cross-sectional design, as part of the Amsterdam MS cohort. Patients with clinically definitive MS (relapse-free) were classified as CI (≥2/7 domains Z < -2), mildly CI (MCI) (≥2/7 domains Z < -1.5), or cognitively preserved (CP) based on an expanded Brief Repeatable Battery of Neuropsychological Tests. Functional connectivity states were determined using k-means clustering of moment-to-moment cofluctuations (i.e., edge time series), and the resulting state sequence was used to characterize the frequency of transitions. Control energy of the state transitions was calculated using the structural network with network control theory. Imaging and cognitive data were available for 95 controls and 330 patients (disease duration: 15 years; 179 CP, 65 MCI, and 86 CI). We identified a "visual network state," "sensorimotor network state," "ventral attention network state," and "default mode network state." CI patients transitioned less frequently between connectivity states compared with CP (β = -5.78; p = 0.038). Relative to the time spent in a state, CI patients transitioned less from a "default mode network state" to a "visual network state" (β = -0.02; p = 0.004). The CI patients required more control energy to transition between states (β = 0.32; p = 0.007), particularly for the same transition (β = 0.34; p = 0.049). This study showed that it costs more energy for MS patients with cognitive impairment to dynamically change the functional network, possibly explaining why these transitions occur less frequently. In particular, transitions from a default mode network state to a visual network state were relevant for cognition in these patients. To further study the order of events leading to these network disturbances, future work should include longitudinal data across different disease stages.

Molecular mechanisms underlying floral fragrance in Camellia japonica ‘High Fragrance’: a time-course assessment

Camellia japonica ‘High Fragrance’ is a camellia hybrid known for its unique and intense floral scent. The current understanding of the dynamic changes in its fragrance and the underlying mechanisms are still limited. This study employed a combination of metabolomic and transcriptomic approaches to reveal the characteristics of the metabolites involved in the remarkable fragrance of this camellia and their biosynthetic mechanisms along three flower developmental stages (flower bud, initial bloom, and full bloom). Among the 349 detected volatile organic compounds (VOCs), the majority were terpenes (57, 16.33%) and esters (53, 15.19%). Of these, 136 VOCs exhibited differential accumulation over time. Transcriptomic data from floral organs at different flowering stages identified 56,303 genes, with 13,793 showing significant differential expression. KEGG enrichment analysis revealed 57, 91, and 33 candidate differential genes related to the biosynthesis of terpenes, phenylpropanoids, and fatty acid derivatives, respectively. This indicates that terpenes, esters, and their related synthetic genes might play a crucial role in the formation of ‘High Fragrance’ characteristics. During the entire flowering process, the majority of genes exhibited an elevated expression pattern, which correlated with the progressive accumulation of VOCs. Interestingly, the expression patterns of the differentially expressed genes in the mevalonate (MVA) and 2-C-methyl-D-erythritol 4-phosphate (MEP) pathways, associated with terpene synthesis, showed opposite trends. A transcriptional-metabolic regulatory network linking terpenoid compounds, related synthetic enzymes, and potential transcription factors could be outlined for ‘High Fragrance’ camellia, thus providing a theoretical basis for further exploring these events and breeding more fragrant camellias.

Unveiling the Antibacterial Mechanism of Gold Nanoparticles by Analyzing Bacterial Metabolism at the Molecular Level.

The threat of drug-resistant bacteria is challenging, and it is urgent to explore new antibiotics. Gold nanoparticles (AuNPs) are known to be a group of promising antibacterial agents for replacing conventional antibiotics. Nevertheless, their antibacterial mechanism remains to be elucidated. Herein, we directly observed the interaction between antibacterial AuNPs and bacteria at the molecular level using neutral desorption extractive electrospray ionization mass spectrometry (ND-EESI-MS). We monitored and analyzed the dynamic changes of bacterial metabolites in real time after AuNP treatment. Ten substances representing 3 major metabolic pathways, including protein and nucleic acid synthesis, energy metabolism, and quorum sensing, were identified, indicating that AuNPs may exert antibacterial effects through multiple mechanisms influencing bacterial metabolism and communication. This study deepens the understanding of the antibacterial mechanism of AuNPs and is insightful for designing and screening new antibacterial agents.

Assessing the Impact and Cost-Effectiveness of Exposome Interventions on Alzheimer’s Disease: A Review of Agent-Based Modeling and Other Data Science Methods for Causal Inference

Background: The exposome (e.g., totality of environmental exposures) and its role in Alzheimer’s Disease and Alzheimer’s Disease and Related Dementias (AD/ADRD) are increasingly critical areas of study. However, little is known about how interventions on the exposome, including personal behavioral modification or policy-level interventions, may impact AD/ADRD disease burden at the population level in real-world settings and the cost-effectiveness of interventions. Methods: We performed a critical review to discuss the challenges in modeling exposome interventions on population-level AD/ADRD burden and the potential of using agent-based modeling (ABM) and other advanced data science methods for causal inference to achieve this. Results: We describe how ABM can be used for empirical causal inference modeling and provide a virtual laboratory for simulating the impacts of personal and policy-level interventions. These hypothetical experiments can provide insight into the optimal timing, targeting, and duration of interventions, identifying optimal combinations of interventions, and can be augmented with economic analyses to evaluate the cost-effectiveness of interventions. We also discuss other data science methods, including structural equation modeling and Mendelian randomization. Lastly, we discuss challenges in modeling the complex exposome, including high dimensional and sparse data, the need to account for dynamic changes over time and over the life course, and the role of exposome burden scores developed using item response theory models and artificial intelligence to address these challenges. Conclusions: This critical review highlights opportunities and challenges in modeling exposome interventions on population-level AD/ADRD disease burden while considering the cost-effectiveness of different interventions, which can be used to aid data-driven policy decisions.

Response of the nephron arterial network and its interactions to acute hypertension: a simulation.

We simulated the dynamics of a group of 10 nephrons supplied from an arterial network and subjected to acute increases in blood pressure. Arterial lengths and topology were based on measurements of a vascular cast. The model builds on a previous version exercised at a single blood pressure with 2 additional features: pressure diuresis and the effect of blood pressure on efferent arteriolar vascular resistance. The new version simulates autoregulation, and reproduces tubule pressure oscillations. Individual nephron dynamics depended on mean arterial pressure and the axial pressure gradient required to cause blood flow through the arteries. Rhythmic blood withdrawal into afferent arterioles caused blood flow fluctuations in downstream vessels. Blood pressure dependent changes in nephron dynamics affected synchronization metrics. The combination of vascular pressure gradients and oscillations created a range of arterial pressures at the origins of the 10 afferent arterioles. Because arterial blood pressure in conscious animals has 1/f dynamics, we applied an arterial pressure pattern with such dynamics to the model. Amplitude of tubule pressure oscillations were affected by the 1/f blood pressure fluctuations, but the oscillation frequencies did not change. The pressure gradients required to deliver blood to all afferent arterioles impose a complexity that affects nephrons according to their locations in the network, but other interactions compensate to ensure the stability of the system. The sensitivity of nephron response to location on the network, and the constancy of the tubular oscillation frequency provide a spatial and time context.

Abstract 4145822: The Enigma of Chest Pain: Rare Presentation of ALCAPA Syndrome in a Young Adult

Introduction: Anomalous Left Coronary Artery Arising from the Pulmonary Artery (ALCAPA), also known as Bland-White-Garland syndrome, is a rare congenital anomaly(incidence:1 in 300,000 live births) typically presenting during infancy. Adult presentations are even rarer due to a high mortality rate of nearly 90% in the first year of life without surgical intervention. This report examines an adult patient with exercise-induced chest pain who received a delayed diagnosis of ALCAPA via multimodal imaging. Case Summary: A 21-year-old male presented to the emergency department(ED) with severe retrosternal chest pain radiating to both shoulders and arms, which began during exercise 30 minutes prior. He had a history of similar, milder episodes during exercise, previously treated as musculoskeletal pain and gastroesophageal reflux disease in the ED. His medical, social, and family histories were unremarkable. Physical examination revealed a soft, continuous murmur along the left sternal border. During this visit, An EKG done showed sinus tachycardia at 110 bpm and deep T-wave inversions in the anterolateral leads, a dynamic ST-T changes from his baseline.Serial Cardiac biomarkers and a lipid profile were within normal ranges. Initially managed for acute coronary syndrome-unstable angina with antithrombotic therapy, beta-blockers, and nitrates, he underwent urgent coronary angiography. This revealed a dilated right coronary artery (RCA) with retrograde flow to the left coronary artery (LCA) into the main pulmonary artery (PA) via collaterals, with no evidence of atherosclerosis (Figure 1).Echocardiography (Figure 2) and coronary CT angiography (Figure 3) confirmed the diagnosis of ALCAPA. The patient underwent successful surgical repair with aortic reimplantation of the LCA and was discharged in good health. Discussion: In adult ALCAPA patients, good collateral circulation may develop; however, myocardial ischemia can occur due to the "coronary steal phenomenon" and poor collateral flow regulation, leading to angina, arrhythmias, and sudden cardiac death. ALCAPA should be considered a differential diagnosis in adults presenting with exercise intolerance, as most sudden cardiac death cases occur by the fourth decade. A high index of clinical suspicion and a multimodality imaging approach is essential for the early diagnosis of this rare coronary anomaly, underscoring the critical role of early surgical intervention in preventing catastrophic, life-threatening events.

Global, regional, and national burden of tuberculosis and attributable risk factors for 204 countries and territories, 1990-2021: a systematic analysis for the Global Burden of Diseases 2021 study.

Tuberculosis (TB) remains a major global health threat. Despite ongoing efforts to control and eradicate TB, various factors including socioeconomic issues, policy modifications, and unexpected public health crises like COVID-19 pandemic have posed new obstacles to achieving TB elimination. This study aims to analyze the changes in global tuberculosis burden over the past 32 years, and provide scientific support for global initiatives targeting the eradication of TB in the post-pandemic period. The data for this study were obtained from the Global Burden of Disease (GBD) 2021 database, with age-standardized incidence rate (ASIR), prevalence rate (ASPR), mortality rate (ASDR), and disability-adjusted life years (DALYs) as the primary assessment indicators. Dynamic changes in the TB burden were analyzed by estimating the annual percentage changes (EAPCs). The attributable ratios of six main risk factors to TB burden were calculated, and the correlation between the Socio-Demographic Index (SDI) and the TB burden was analyzed using Pearson correlation tests. The global TB incidence decreased from 8.6million cases in 1990 to 8.4million cases in 2021, with a corresponding decline in deaths. However, the TB burden remains higher among men than women. The highest incidence and mortality rates were observed in the age group of 15-69 years, with a notable gender disparity, especially in Eastern Europe. These rates were generally elevated in low-income and lower-middle-income regions, with significantly higher Age-Standardized Incidence Rates and Age-Standardized Death Rates in males compared to females. A significant negative correlation was found between SDI values and TB burden. Analyzing risk factors from the Global Burden of Disease study, it was determined that globally, dietary risks, high body-mass index, high fasting plasma glucose, low physical activity, tobacco, and alcohol use were the main contributors to TB age-standardized Disability-Adjusted Life Years, with tobacco and alcohol use having the most significant impact. Analysis of risk factors suggests that tailored public health interventions for specific genders and regions can effectively lessen the TB burden.