Unsupervised, piecewise linear decoding enables an accurate prediction of muscle activity in a multi-task brain computer interface.

Objective: Creating an intracortical brain-computer interface (iBCI) capable of seamless transitions between tasks and contexts would greatly enhance user experience. However, the nonlinearity in neural activity presents challenges to computing a global iBCI decoder. We aimed to develop a method that differs from a globally optimized decoder to address this issue. Approach: We devised an unsupervised approach that relies on the structure of a low-dimensional neural manifold to implement a piecewise linear decoder. We created a distinctive dataset in which monkeys performed a diverse set of tasks, some trained, others innate, while we recorded neural signals from the motor cortex (M1) and electromyographs (EMGs) from upper limb muscles. We used both linear and nonlinear dimensionality reduction techniques to discover neural manifolds and applied unsupervised algorithms to identify clusters within those spaces. Finally, we fit a linear decoder of EMG for each cluster. A specific decoder was activated corresponding to the cluster each new neural data point belonged to. Main results: We found clusters in the neural manifolds corresponding with the different tasks or task sub-phases. The performance of piecewise decoding improved as the number of clusters increased and plateaued gradually. With only two clusters it already outperformed a global linear decoder, and unexpectedly, it outperformed even a global recurrent neural network (RNN) decoder with 10-12 clusters. Significance: This study introduced a computationally lightweight solution for creating iBCI decoders that can function effectively across a broad range of tasks. EMG decoding is particularly challenging, as muscle activity is used, under varying contexts, to control interaction forces and limb stiffness, as well as motion. The results suggest that a piecewise linear decoder can provide a good approximation to the nonlinearity between neural activity and motor outputs, a result of our increased understanding of the structure of neural manifolds in motor cortex.

METS-IR, a Novel Simple Insulin Resistance Index, is Associated with NAFLD in Patients with Type 2 Diabetes Mellitus.

Purpose: Substantial evidence has established a strong association between non-alcoholic fatty liver disease (NAFLD), type 2 diabetes mellitus (T2DM) and insulin resistance (IR). Insulin resistance metabolic score (METS-IR) is a new and more effective comprehensive indicator for measuring IR. Our aim was to investigate the relationship between METS-IR and NAFLD in T2DM population. Patients and methods: This cross-sectional study included 1097 adult patients with T2DM. Anthropometric measurements and biochemical indicators were collected, and the NAFLD was diagnosed by ultrasound. The METS-IR was calculated. Based on the presence of NAFLD, the population was divided into non-NAFLD and NAFLD groups. The relationship between METS-IR and NAFLD was evaluated. Results: Compared with the non-NAFLD group, the METS-IR was higher in the NAFLD group (P < 0.001). The incidence rate of NAFLD increased across the quartiles of the METS-IR (P < 0.001). Spearman correlation analysis showed that METS-IR was positively correlated with NAFLD (Correlation Coefficient: 0.441, P < 0.001). The binary logistic regression analysis indicated that METS-IR was independently associated with NAFLD (OR: 1.120, 95% CI 1.080-1.161). Furthermore, the area under the receiver operating characteristic curve of the METS-IR was 0.781 (95% CI 0.746-0.817) and relatively higher than other evaluation variables. Conclusion: In patients with T2DM, METS-IR is closely associated with NAFLD, and might be a valuable predictor of NAFLD. Further research is needed to verify this association.

SCR-7952, a highly selective MAT2A inhibitor, demonstrates synergistic antitumor activities in combination with the S-adenosylmethionine-competitive or the methylthioadenosine-cooperative protein arginine methyltransferase 5 inhibitors in methylthioadenosine phosphorylase-deleted tumors.

The metabolic enzyme methionine adenosyltransferase 2A (MAT2A) was found to elicit synthetic lethality in methylthioadenosine phosphorylase (MTAP)-deleted cancers, which occur in about 15% of all cancers. Here, we described a novel MAT2A inhibitor, SCR-7952 with potent and selective antitumor effects on MTAP-deleted cancers in both in vitro and in vivo. The cryo-EM data indicated the high binding affinity and the allosteric binding site of SCR-7952 on MAT2A. Different from AG-270, SCR-7952 exhibited little influence on metabolic enzymes and did not increase the plasma levels of bilirubin. A systematic evaluation of combination between SCR-7952 and different types of protein arginine methyltransferase 5 (PRMT5) inhibitors indicated remarkable synergistic interactions between SCR-7952 and the S-adenosylmethionine-competitive or the methylthioadenosine-cooperative PRMT5 inhibitors, but not substrate-competitive ones. The mechanism was via the aggravated inhibition of PRMT5 and FANCA splicing perturbations. These results indicated that SCR-7952 could be a potential therapeutic candidate for the treatment of MTAP-deleted cancers, both monotherapy and in combination with PRMT5 inhibitors.

Health economic evaluation of an artificial intelligence (AI)-based rapid nutritional diagnostic system for hospitalised patients: A multicentre, randomised controlled trial.

BACKGROUND & AIMS: Malnutrition is prevalent among hospitalised patients, and increases the morbidity, mortality, and medical costs; yet nutritional assessments on admission are not routine. This study assessed the clinical and economic benefits of using an artificial intelligence (AI)-based rapid nutritional diagnostic system for routine nutritional screening of hospitalised patients. METHODS: A nationwide multicentre randomised controlled trial was conducted at 11 centres in 10 provinces. Hospitalised patients were randomised to either receive an assessment using an AI-based rapid nutritional diagnostic system as part of routine care (experimental group), or not (control group). The overall medical resource costs were calculated for each participant and a decision-tree was generated based on an intention-to-treat analysis to analyse the cost-effectiveness of various treatment modalities. Subgroup analyses were performed according to clinical characteristics and a probabilistic sensitivity analysis was performed to evaluate the influence of parameter variations on the incremental cost-effectiveness ratio (ICER). RESULTS: In total, 5763 patients participated in the study, 2830 in the experimental arm and 2933 in the control arm. The experimental arm had a significantly higher cure rate than the control arm (23.24% versus 20.18%; p = 0.005). The experimental arm incurred an incremental cost of 276.52 CNY, leading to an additional 3.06 cures, yielding an ICER of 90.37 CNY. Sensitivity analysis revealed that the decision-tree model was relatively stable. CONCLUSION: The integration of the AI-based rapid nutritional diagnostic system into routine inpatient care substantially enhanced the cure rate among hospitalised patients and was cost-effective. REGISTRATION: NCT04776070 (https://clinicaltrials.gov/study/NCT04776070).

Incremental prognostic value of left atrial strain in apical hypertrophic cardiomyopathy: a cardiovascular magnetic resonance study.

OBJECTIVES: This study aimed to evaluate the prognostic value of left atrial (LA) strain in patients with apical hypertrophic cardiomyopathy (ApHCM), as assessed by cardiac magnetic resonance (CMR) imaging. METHODS: Four hundred and five consecutive patients with ApHCM who underwent CMR examination were retrospectively included. The study endpoint included all-cause death, heart transplant, aborted sudden cardiac death, hospitalization for heart failure, stroke, and new-onset atrial fibrillation (AF). RESULTS: After a median follow-up of 97 months, 75 patients (18.5%) reached the endpoint. Patients were divided into two groups based on the median LA reservoir strain of 29.4%. The group with lower LA reservoir strain had thicker maximum wall thickness, greater late gadolinium enhancement extent, and smaller end-diastolic volume index, stroke volume index, and cardiac index (all p < 0.02). For LA parameters, this subgroup showed greater diameter and volume index and worse ejection fraction, reservoir, conduit, and booster strain (all p < 0.001). In the multivariable model, age (HR 1.88, 95% CI: 1.06-3.31, p = 0.030), baseline AF (HR 2.95, 95% CI: 1.64-5.28, p < 0.001), LA volume index (LAVi) (HR 2.07, 95% CI: 1.21-3.55, p = 0.008) and LA reservoir strain (HR 2.82, 95% CI: 1.51-5.26, p = 0.001) were all associated with the outcome. Adding LAVi and LA reservoir strain in turn to the multivariable model (age and baseline AF) resulted in significant improvements in model performance (p < 0.001). CONCLUSION: In ApHCM patients, LA reservoir strain is independently associated with cardiovascular risk events and has an incremental prognostic value. CLINICAL RELEVANCE STATEMENT: Left atrial reservoir strain measured by cardiac magnetic resonance is highly correlated with the prognosis of apical hypertrophic cardiomyopathy and has potential incremental value in the prognosis of major adverse cardiac events. KEY POINTS: Left atrial (LA) strain parameters may be useful for risk stratification and treatment of apical hypertrophic cardiomyopathy (ApHCM). Apical hypertrophic cardiomyopathy (ApHCM) is independently associated with LA morphology and function. Cardiac MR examination, especially its feature-tracking technology, provides the possibility to prognosticate ApHCM at an early stage.

Digital virtual reduction combined with individualized guide plate of lateral tibial condyle osteotomy for the treatment of tibial plateau fracture.

BACKGROUND: Current treatments do not support direct exposure of fracture fragments, resulting in the inability to directly observe the articular surface during surgery for accurate reduction and firm fixation. OBJECTIVE: The aim of the study was to explore the treatment effect of digital virtual reduction combined with individualized guide plate of lateral tibial condyle osteotomy on tibial plateau fracture involving the lateral posterior condyle collapse. METHODS: 41 patients with tibial plateau fracture involving the lateral posterior condyle collapse were recruited in the trial. All patients underwent Computed Tomography (CT) scanning before operation. After operation, fracture reduction was evaluated using Rasmussen score and function of knee joint was assessed using hospital for special surgery (HSS) score. RESULTS: 41 patients were followed-up 6-26 months (mean, 15.2 months). Fracture reduction was good after operation, with an average of 13.3 weeks of fracture healing without serious complications. The excellent and good rate was 97.6%. The joint movement degree was -5∘∼0∘∼135∘ with an average of 125.5∘. CONCLUSIONS: Digital virtual reduction combined with individualized guide plate of lateral tibial condyle osteotomy was effectively for treating tibial plateau fracture involving the lateral posterior condyle collapse.

Novel catalytic behavior of defective nanozymes with catalase-mimicking characteristics for the degradation of tetracycline.

Although nanozymes have shown significant potential in wastewater treatment, enhancing their degradation performance remains challenging. Herein, a novel catalytic behavior was revealed for defective nanozymes with catalase-mimicking characteristics that efficiently degraded tetracycline (TC) in wastewater. Hydroxyl groups adsorbed on defect sites facilitated the in-situ formation of vacancies during catalysis, thereby replenishing active sites. Additionally, electron transfer considerably enhanced the catalytic reaction. Consequently, numerous reactive oxygen species (ROS) were generated through these processes and subsequent radical reactions. The defective nanozymes, with their unique catalytic behavior, proved effective for the catalytic degradation of TC. Experimental results demonstrate that •OH, •O2-, 1O2 and e- were the primary contributors to the degradation process. In real wastewater samples, the normalized degradation rate constant for defective nanozymes reached 26.0 min-1 g-1 L, exceeding those of other catalysts. This study reveals the new catalytic behavior of defective nanozymes and provides an effective advanced oxidation process for the degradation of organic pollutants.

Lightweight tomato ripeness detection algorithm based on the improved RT-DETR.

Tomatoes, widely cherished for their high nutritional value, necessitate precise ripeness identification and selective harvesting of mature fruits to significantly enhance the efficiency and economic benefits of tomato harvesting management. Previous studies on intelligent harvesting often focused solely on identifying tomatoes as the target, lacking fine-grained detection of tomato ripeness. This deficiency leads to the inadvertent harvesting of immature and rotten fruits, resulting in economic losses. Moreover, in natural settings, uneven illumination, occlusion by leaves, and fruit overlap hinder the precise assessment of tomato ripeness by robotic systems. Simultaneously, the demand for high accuracy and rapid response in tomato ripeness detection is compounded by the need for making the model lightweight to mitigate hardware costs. This study proposes a lightweight model named PDSI-RTDETR to address these challenges. Initially, the PConv_Block module, integrating partial convolution with residual blocks, replaces the Basic_Block structure in the legacy backbone to alleviate computing load and enhance feature extraction efficiency. Subsequently, a deformable attention module is amalgamated with intra-scale feature interaction structure, bolstering the capability to extract detailed features for fine-grained classification. Additionally, the proposed slimneck-SSFF feature fusion structure, merging the Scale Sequence Feature Fusion framework with a slim-neck design utilizing GSConv and VoVGSCSP modules, aims to reduce volume of computation and inference latency. Lastly, by amalgamating Inner-IoU with EIoU to formulate Inner-EIoU, replacing the original GIoU to expedite convergence while utilizing auxiliary frames enhances small object detection capabilities. Comprehensive assessments validate that the PDSI-RTDETR model achieves an average precision mAP50 of 86.8%, marking a 3.9% enhancement over the original RT-DETR model, and a 38.7% increase in FPS. Furthermore, the GFLOPs of PDSI-RTDETR have been diminished by 17.6%. Surpassing the baseline RT-DETR and other prevalent methods regarding precision and speed, it unveils its considerable potential for detecting tomato ripeness. When applied to intelligent harvesting robots in the future, this approach can improve the quality of tomato harvesting by reducing the collection of immature and spoiled fruits.

Expression of CXCL8 and its relationship with prognosis in patients with non-small cell lung cancer.

To determine the expression of chemokine 8 (CXCL8) in non-small cell lung cancer (NSCLC) patients and analyze its correlation with tumor characteristics and patient prognosis. We conducted a retrospective analysis of 149 NSCLC patients treated between January 2016 and April 2018, measuring serum CXCL8 expression upon admission or prior to treatment. The clinical characteristics, including lymph node metastasis and staging, based on CXCL8 expression levels, were analyzed. Receiver Operating Characteristic (ROC) curves was drawn to assess its predictive value for lymph node metastasis and staging in NSCLC patients. Furthermore, the Kaplan-Meier curve was plotted to assess the impact of CXCL8 on 5-year survival in NSCLC Patients. NSCLC patients exhibited significantly higher serum CXCL8 levels than those with benign tumors (P<0.001), with the high CXCL8 expression group showing a higher incidence of lymph node metastasis or stage III NSCLC (P<0.01). CXCL8 was identified as an independent predictor of lymph node metastasis (AUC=0.730) and higher TNM stage (AUC=0.708), as well as a validated biomarker for predicting five-year survival in NSCLC patients. This study highlights the strong association between CXCL8 expression in NSCLC and patient prognosis, particularly regarding lymph node metastasis and clinical staging, suggesting the need for further research to explore CXCL8's specific role in the tumor microenvironment and its impact on different NSCLC subtypes.

Characterization of the complete chloroplast genome of Rhodiola sachalinensis and comparative analysis with its congeneric plants.

Rhodiola, belonging to the Crassulaceae family, is a perennial herbaceous plant genus. There are about 90 Rhodiola species worldwide, some of which have been reported to have medicinal properties. Rhodiola sachalinensis is a perennial medicinal herb within this genus and, in the present study, its chloroplast genome was sequenced, assembled, annotated and compared with 24 other Rhodiola species. The results obtained show that the chloroplast genome of R. sachalinensis is 151 595 bp long and has a CG content of 37.7%. The inverted repeats (IR) region of the Rhodiola chloroplast genome is the most conserved region, with the main differences being observed in the ycf1 and ndhF genes at the IRb-small single copy boundary, and rps19 and trnH genes at the IRa-large single copy boundary. Phylogenetic analysis showed that Rhodiola species form two major clades, and species with recorded medicinal properties, clustered together in one branch except for R. dumulosa. Within the genus, R. sachalinensis is most closely related to Rhodiola rosea, although comparative analyses showed that only R. sachalinensis and Rhodiola subopposita contained the psbZ gene, which encodes a highly conserved protein subunit of the Photosystem II core complex. Overall, the present study contributes to the understanding of the chloroplast genome of Rhodiola species, and provides a theoretical basis for the study of their genetic diversity and possible use as medicinal plants.

A promising metabolite, 9-aminominocycline, restores the sensitivity of tigecycline against tet(X4)-positive Escherichia coli.

The emergence and widespread of tigecycline resistance undoubtedly poses a serious threat to public health globally. The exploration of combination therapies has become preferred antibacterial strategies to alleviate this global burden. In this study, tigecycline-resistant tet(X4)-positive Escherichia coli were selected for adjuvant screening. Interestingly, 9-aminominocycline (9-AMC), one of the tigecycline metabolites, exhibits synergistic antibacterial activity with tigecycline using checkerboard assay. The efficacy in vitro and in vivo was evaluated, and the synergistic mechanism was further explored. The results suggested that 9-AMC combined with tigecycline could inhibit the growth of antibiotic resistant bacteria, efficiently retard the evolution of tet(X4) gene and narrow the drug mutant selection window. In addition, the combination of tigecycline and 9-AMC could destroy the normal membrane structure of bacteria, inhibit the formation of biofilm, remarkably reduce the level of intracellular ATP level, and accelerate the oxidative damage of bacteria. Furthermore, 9-AMC is more stable in the bind of Tet(X4) inactivating enzyme. The transcriptomics analysis revealed that the genes related to the 9-AMC and tigecycline were mainly enriched in ABC transporters. Collectively, the results reveal the potentiation effects on tigecycline and the probability of 9-AMC as a novel tigecycline adjuvant against tet(X4)-positive Escherichia coli, which provides new insights for adjuvant screening.

Right Ventricular Strain Derived from Cardiac MRI Feature Tracking for the Diagnosis and Prognosis of Arrhythmogenic Right Ventricular Cardiomyopathy.

Purpose To demonstrate the myocardial strain characteristics of patients with arrhythmogenic right ventricular cardiomyopathy (ARVC), based on revised Task Force Criteria (rTFC), and to explore the prognostic value of strain analysis in ARVC. Materials and Methods This retrospective study included 247 patients (median age, 38 years [IQR, 28-48 years]; 167 male, 80 female) diagnosed with ARVC, based on rTFC, between 2014 and 2018. Patients were divided into "possible" (n =25), "borderline" (n = 40), and "definite" (n = 182) ARVC groups following rTFC. Biventricular global strain parameters were calculated using cardiac MRI feature tracking (FT). The primary outcome was defined as a composite of cardiovascular events, including cardiovascular death, heart transplantation, and appropriate implantable cardioverter defibrillator discharge. Univariable and multivariable cumulative logistic regression and Cox proportional hazards regression analysis were used to evaluate the diagnostic and prognostic value of right ventricle (RV) strain parameters. Results Patients with definite ARVC had significantly reduced RV global strain in all three directions compared with possible or borderline groups (all P < .001). RV global longitudinal strain (GLS) was an independent predictor for disease (odds ratio, 1.09 [95% CI: 1.02, 1.16]; P = .009). During a median follow-up of 3.4 years (IQR, 2.0-4.9 years), 55 patients developed primary end point events. Multivariable analysis showed that RV GLS was independently associated with the occurrence of cardiovascular events (hazard ratio, 1.15 [95% CI: 1.07, 1.24]; P < .001). Kaplan-Meier analysis showed that patients with RV GLS worse than median had a higher risk of combined cardiovascular events (log-rank P < .001). Conclusion RV GLS derived from cardiac MRI FT demonstrated good diagnostic and prognostic value in ARVC. Keywords: MR Imaging, Image Postprocessing, Cardiac, Right Ventricle, Cardiomyopathies, Arrhythmogenic Right Ventricular Cardiomyopathy, Revised Task Force Criteria, Cardiovascular MR, Feature Tracking, Cardiovascular Events Supplemental material is available for this article. © RSNA, 2024.

Aptamer and Thiol Co-Regulated Color-Shifting Fluorophores via Dynamic Through-Bond/Space Conjugation for Constructing Ratiometric RNA Sensor.

Fluorophores with color-shifting characteristics have attracted enormous research interest in the quantitative application of RNA sensors. It reports here a simple synthesis, luminescent properties, and co-transcription ability of de-conjugated triphenylmethane leucomalachite green (LMG). This novel clusteroluminescence fluorophore is rapidly synthesized from malachite green (MG) in reductive transcription system containing dithiothreitol, emitting fluorescence in the UV region through space conjugation. The co-transcribed MG RNA aptamer (MGA) bound to the ligand, resulting in red fluorescence from the through-bond conjugation. Given the equilibrated color-shifting fluorophores, they are rationally employed in a 3WJ-based rolling circle transcription switch, with the target-aptamer acting as an activator to achieve steric allosterism. This one-pot system allows the target to compete continuously for allosteric sites, and the activated transcription switches continue to amplify MGA forward, achieving accurate Aflatoxin 1 quantification at the picomolar level in 1 h. Due to the programmability of this RNA sensor, the design method of target-competitive aptamers is standardized, making it universally applicable.

Effects of multi-frequency ultrasound-assisted immersion freezing processing on myofibrillar protein structure and lipid oxidation of large yellow croaker (Larimichthys crocea) during long-time frozen storage.

In this study, large yellow croaker (Larimichthys crocea) was frozen using multi-frequency ultrasound-assisted freezing (MUIF) with different powers (160 W, 175 W, and 190 W, respectively) and stored at -18 °C for ten months. The effect of different ultrasound powers on the myofibrillar protein (MP) structures and lipid oxidation of large yellow croaker was investigated. The results showed that MUIF significantly slowed down the oxidation of MP by inhibiting carbonyl formation and maintaining high sulfhydryl contents. These treatments also held a high activity of Ca2+-ATPase in the MP. MUIF maintained a higher ratio of α-helix to ß-sheet during frozen storage, thereby protecting the secondary structure of the tissue and stabilizing the tertiary structure. In addition, MUIF inhibited the production of thiobarbituric acid reactive substances value and the loss of unsaturated fatty acid content, indicating that MUIF could better inhibit lipid oxidation of large yellow croaker during long-time frozen storage.

Less is more: selection from a small set of options improves BCI velocity control.

We designed the discrete direction selection (DDS) decoder for intracortical brain computer interface (iBCI) cursor control and showed that it outperformed currently used decoders in a human-operated real-time iBCI simulator and in monkey iBCI use. Unlike virtually all existing decoders that map between neural activity and continuous velocity commands, DDS uses neural activity to select among a small menu of preset cursor velocities. We compared closed-loop cursor control across four visits by each of 48 naïve, able-bodied human subjects using either DDS or one of three common continuous velocity decoders: direct regression with assist (an affine map from neural activity to cursor velocity), ReFIT, and the velocity Kalman Filter. DDS outperformed all three by a substantial margin. Subsequently, a monkey using an iBCI also had substantially better performance with DDS than with the Wiener filter decoder (direct regression decoder that includes time history). Discretizing the decoded velocity with DDS effectively traded high resolution velocity commands for less tortuous and lower noise trajectories, highlighting the potential benefits of simplifying online iBCI control.

Bisphenol S exposure induces intestinal inflammation via altering gut microbiome.

Bisphenol S (BPS), a substitute for bisphenol A, is widely used in the manufacture of food packaging materials, raising concern over its toxicity. However, evidence is still lacking on whether gut microbiota involved in BPS induced intestinal inflammation in mammals, as well as its underlying mechanism. Using mouse BPS exposure model, we found intestinal inflammation characterized by shortened colon length, crypt distortion, macrophage accumulation and increased apoptosis. As for gut microbiota, 16s rRNA gene amplicon sequencing showed BPS exposure induced gut dysbiosis, including increased pro-inflammatory microbes such as Ileibacterium, and decreased anti-inflammatory genera such as Lactobacillus, Blautia and Romboutsia. Besides, LC-MS/MS-based untargeted metabolomic analysis indicated BPS impaired both bacteria and host metabolism. Additionally, transcriptome analysis of the intestine revealed abnormal gene expression in intestinal mucosal barrier and inflammation. More importantly, treating mice with antibiotics significantly attenuated BPS-induced gut inflammation via the regulation of both bacterial and host metabolites, indicating the role of gut microbiota. Collectively, BPS exposure induces intestinal inflammation via altering gut microbiota in mouse. This study provides the possibility of madecassic acid, an anti-inflammatory metabolite, to prevent BPS-induced intestinal inflammation and also new insights in understanding host-microbiota interaction in BPS toxicity.

Prenylated indole diketopiperazine alkaloids as phosphatase inhibitors from the marine-derived fungus Talaromyces purpureogenus.

Six previously undescribed prenylated indole diketopiperazine alkaloids, talaromyines A-F (1-6), were isolated from the marine-derived fungus Talaromyces purpureogenus SCSIO 41517. Their structures including absolute configurations were elucidated on the basis of comprehensive spectroscopic data including NMR, HR-ESI-MS, and electronic circular dichroism calculations, together with chemical analysis of hydrolysates. Compounds 1-5 represent the first example of spirocyclic indole diketopiperazines biosynthesized from the condensation of L-tryptophan and L-alanine. Compounds 2 and 4-5 showed selective inhibitory activities against phosphatases TCPTP and MEG2 with IC50 value of 17.9-29.7 µM, respectively. Compounds 4-5 exhibited mild cytotoxic activities against two human cancer cell lines H1975 and HepG-2.

Predicting mitophagy-related genes and unveiling liver endothelial cell heterogeneity in hepatic ischemia-reperfusion injury.

Background: Hepatic Ischemia-Reperfusion Injury (HIRI) is a major complication in liver transplants and surgeries, significantly affecting postoperative outcomes. The role of mitophagy, essential for removing dysfunctional mitochondria and maintaining cellular balance, remains unclear in HIRI. Methods: To unravel the role of mitophagy-related genes (MRGs) in HIRI, we assembled a comprehensive dataset comprising 44 HIRI samples alongside 44 normal control samples from the Gene Expression Omnibus (GEO) database for this analysis. Using Random Forests and Support Vector Machines - Recursive Feature Elimination (SVM-RFE), we pinpointed eight pivotal genes and developed a logistic regression model based on these findings. Further, we employed consensus cluster analysis for classifying HIRI patients according to their MRG expression profiles and conducted weighted gene co-expression network analysis (WGCNA) to identify clusters of genes that exhibit high correlation within different modules. Additionally, we conducted single-cell RNA sequencing data analysis to explore insights into the behavior of MRGs within the HIRI. Results: We identified eight key genes (FUNDC1, VDAC1, MFN2, PINK1, CSNK2A2, ULK1, UBC, MAP1LC3B) with distinct expressions between HIRI and controls, confirmed by PCR validation. Our diagnostic model, based on these genes, accurately predicted HIRI outcomes. Analysis revealed a strong positive correlation of these genes with monocytic lineage and a negative correlation with B and T cells. HIRI patients were divided into three subclusters based on MRG profiles, with WGCNA uncovering highly correlated gene modules. Single-cell analysis identified two types of endothelial cells with different MRG scores, indicating their varied roles in HIRI. Conclusions: Our study highlights the critical role of MRGs in HIRI and the heterogeneity of endothelial cells. We identified the macrophage migration inhibitory factor (MIF) and cGAS-STING (GAS) pathways as regulators of mitophagy's impact on HIRI. These findings advance our understanding of mitophagy in HIRI and set the stage for future research and therapeutic developments.

Analysis of an Aqueous Extract from Turkish Galls Based on Multicomponent Qualitative and Quantitative Analysis Combined with Network Pharmacology and Chemometric Analysis.

The current quality control method for Turkish gall (TG) is limited to assessing total tannin or gallic acid (GA), which offers a basic level of quality control but does not fully capture the true quality of TG. Therefore, it is essential to establish a comprehensive method that utilizes multiple indicators to assess the intrinsic quality of TG. This research utilized UPLC-Q-TOF-MS/MS technology to qualitatively analyze the chemical composition of TG. Subsequently, the potential main active ingredients, targets, and pathways of TG in treating recurrent aphthous ulcers (RAU) were explored and analyzed using network pharmacology technology. Quantitative analysis of multicomponents by single marker (QAMS) was then employed to quantify the primary pharmacodynamic components in TG. Finally, chemometrics analysis was utilized to interpret the measured results and identify the markers of scavenging quality. The study identified 36 chemical components in TG, highlighting ellagic acid (EA), GA, and so on as key components in treating RAU. A method for simultaneously determining GA, EA, 1,2,3,6-tetra-O-galloyl-ß-D-glucose (TEGG) and 1,2,3,4,6-penta-O-galloyl-ß-D-glucose (PEGG) in TG was established. Statistical analysis revealed significant differences in the content of these 4 components across 14 batches of TG, with GA and PEGG identified as the primary contributors to the variations. This study determined a quality index for TG, providing a reference for quality evaluation and introducing a cost-effective and efficient quality control method. Furthermore, it addressed the challenge of developing new Chinese medicine by overcoming the lack of reference substances.

A Comparison of the Association of Septal Scar Burden on Responses to LBBAP-CRT and BVP-CRT.

BACKGROUND: Left bundle branch area pacing (LBBAP) is an alternative to biventricular pacing (BVP) for cardiac resynchronization therapy (CRT). However, despite the presence of left bundle branch block, whether cardiac substrate may influence the effect between the 2 strategies is unclear. OBJECTIVES: This study aims to assess the association of septal scar on reverse remodeling and clinical outcomes of LBBAP compared with BVP. METHODS: We analyzed patients with nonischemic cardiomyopathy who had CRT indications undergoing preprocedure cardiac magnetic resonance examination. Changes in left ventricular ejection fraction (LVEF) and echocardiographic response (ER) (≥5% absolute LVEF increase) were assessed at 6 months. The clinical outcome was the composite of all-cause mortality, heart failure hospitalization, or major ventricular arrhythmia. RESULTS: There were 147 patients included (51 LBBAP and 96 BVP). Among patients with low septal scar burden (below median 5.7%, range: 0% to 5.3%), LVEF improvement was higher in the LBBAP than the BVP group (17.5% ± 10.9% vs 12.3% ± 11.8%; P = 0.037), with more than 3-fold increased odds of ER (OR: 4.35; P = 0.033). In high sepal scar subgroups (≥5.7%, range: 5.7%-65.9%), BVP trended towards higher LVEF improvement (9.2% ± 9.4% vs 6.4% ± 12.4%; P = 0.085). Interaction between septal scar burden and pacing strategy was significant for ER (P = 0.002) and LVEF improvement (P = 0.011) after propensity score adjustment. During median follow-up of 33.7 (Q1-Q3: 19.8-42.1) months, the composite clinical outcome occurred in 34.7% (n = 51) of patients. The high-burden subgroups had worse clinical outcomes independent of CRT method. CONCLUSIONS: Remodeling response to LBBAP and BVP among nonischemic cardiomyopathy patients is modified by septal scar burden. High septal scar burden was associated with poor clinical prognosis independent of CRT methods.