Subtyping stage 3 epiretinal membrane: a comprehensive study of ectopic inner foveal layers architecture and its clinical implications.

AIMS: To evaluate the visual function and foveal architecture in patients with stage 3 idiopathic epiretinal membrane (iERM). METHODS: A cross-sectional observational study included 56 eyes of 52 patients with stage 3 iERM. The patients were classified into type A ectopic inner foveal layers (EIFL) and type B EIFL based on the presence of a continuous hyporeflective band. Visual function and foveal microarchitecture were assessed in enrolled eyes. Best-corrected visual acuity (BCVA), metamorphopsia scores, retinal sensitivity and optical coherence tomography (OCT)/OCT angiography features were compared between two subtypes. RESULT: The BCVA in type A EIFL and type B EIFL was 0.22 logarithm of minimal angle of resolution (logMAR) (0.15 logMAR, 0.40 logMAR) and 0.53±0.23 logMAR, respectively (p=0.002). Type B EIFL had higher average metamorphopsia scores, especially horizontal metamorphopsia scores, than type A (p=0.013, p=0.007, respectively). Type B EIFL had worse central 2° foveal sensitivity than type A (p=0.034). Type B EIFL had thicker central foveal thickness and EIFL thickness (514.08±73.80 µm vs 444.41±56.57 µm, p=0.001; 159.75±78.30 µm vs 48.44±18.37 µm, p<0.0001; respectively). The foveal avascular zone area of type B EIFL was smaller than that of type A (0.042±0.022 mm2 vs 0.077±0.039 mm2, p<0.0001). The vessel density and flow area of the superficial vascular complex in type B EIFL were larger than those in type A (both p=0.001). CONCLUSIONS: Type B EIFL demonstrated significantly worse visual function than type A EIFL, along with marked differences in foveal microstructure and microvasculature. Our study complements the current staging of iERM and helps determine the optimal timing of iERM surgery.

Ginger-derived nanovesicles attenuate osteoarthritis progression by inhibiting oxidative stress via the Nrf2 pathway.

Aim: Osteoarthritis (OA) is a common degenerative joint disease. Previous studies demonstrated ginger-derived exosome-like nanovesicles (GDN) showed therapeutic effects in degenerative diseases. However, it remains unknown whether GDN could alleviate OA progression.Materials & methods: In this study, GDN were obtained and characterized. Then we evaluated the effects of GDN in tert-butyl hydroperoxide (TBHP)-induced chondrocytes, posttraumatic OA rat model and ex vivo cultured human OA cartilage explants.Results: We demonstrated GDN promoted cartilage anabolism and alleviated oxidative stress in TBHP-induced chondrocytes and OA rat. Our results also showed GDN exhibited protective effects in cultured cartilage explants. Furthermore, we verified the Nrf2 pathway was associated with protective effects of GDN.Conclusion: Altogether, our findings demonstrated GDN hold great potential for OA treatment.

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Comparison of Remimazolam and Propofol in Recovery of Elderly Outpatients Undergoing Gastrointestinal Endoscopy: A Randomized, Non-Inferiority Trial.

Purpose: We designed this trial to compare the recovery time of remimazolam and propofol in elderly patients undergoing painless gastrointestinal endoscopy. Patients and Methods: In this randomized, non-Inferiority trial, 360 patients aged 65 years or older, scheduled for elective outpatient gastrointestinal endoscopy, were randomly assigned to the remimazolam combined with fentanyl (RF) group or the propofol combined with fentanyl (PF) group. The primary outcome was the post-anesthesia care unit (PACU) stay time, defined as the time from the end of the examination to scoring 9 points using the Modified Post-Anesthetic Discharge Scoring System (MPADSS) criteria. Secondary outcomes included sedation-related adverse events, recall, injection pain, as well as postoperative Quality of Recovery-15 (QoR-15) scores and Pittsburgh Sleep Quality Index (PSQI) scores at 1 day, 1 week, and 1 month postoperatively. Results: A total of 351 patients completed the study, with 174 receiving remimazolam and 177 receiving propofol. The PACU stay time in RF group was non-inferior to that in PF group [14 (11, 18) vs 13 (10, 17), mean difference 1 (95% confidence interval 0, 2), P=0.084 for noninferiority]. However, remimazolam was associated with lower rate of hypoxemia [4.7% (8/180) vs 12.4% (22/180), P=0.011], reduced use of vasoactive drugs [1 (0, 1) vs 1 (1, 2), P<0.001], less injection pain [2 (1.2%) vs 35 (21.3%), P<0.001], and lower recall [20 (11.8%) vs 36 (20.3%), P=0.034]. There were no differences in the QoR-15 scores and PSQI scores at postoperative 1 day, 1 week, and 1 month between groups. Conclusion: This non-inferiority study revealed that in elderly outpatients undergoing gastrointestinal endoscopy, remimazolam achieved recovery times comparable to propofol, with fewer associated complications.

Identification of senescence-related genes for potential therapeutic biomarkers of atrial fibrillation by bioinformatics, human histological validation, and molecular docking.

Background: Cellular senescence is pivotal in the occurrence and progression of atrial fibrillation (AF). This study aimed to identify senescence-related genes that could be potential therapeutic biomarkers for AF. Methods: AF-related differentially expressed genes (DEGs) were identified using the Gene Expression Omnibus dataset. Weighted gene co-expression network analysis (WGCNA) was used to analyze important modules and potential hub genes. Integrating senescence-related genes, potential biomarkers were identified. Their differential expression levels were then validated in human atrial tissue, HL-1 cells, and Angiotensin II-infused mice. Finally, molecular docking analysis was conducted to predict potential interactions between potential biomarkers and the senolytic drug Navitoclax. Results: We identified seven genes common to AF-related DEGs and senescence-related genes. Three significant modules were selected from WGCNA analysis. Taken together, three senescence-related genes (ETS1, SP1, and WT1) were found to be significantly associated with AF. Protein-protein interaction network analysis revealed biological connections among the predicted target genes of ETS1, SP1, and WT1. Notably, ETS1, SP1, and WT1 exhibited significant differential expression in clinical samples as well as in vitro and in vivo models. Molecular docking revealed favorable binding affinity between senolytic Navitoclax and these potential biomarkers. Conclusions: This study highlights ETS1, SP1, and WT1 as crucial senescence-related genes associated with AF, offering potential therapeutic targets, with supportive evidence of binding affinity with senolytic Navitoclax. These findings provide novel insights into AF pathogenesis from a senescence perspective.

Exploring spontaneous brain activity changes in high-altitude smokers: Insights from ALFF/fALFF analysis.

INTRODUCTION: This study aims to explore the impact of smoking on intrinsic brain activity among high-altitude (HA) populations. Smoking is associated with various neural alterations, but it remains unclear whether smokers in HA environments exhibit specific neural characteristics. METHODS: We employed ALFF and fALFF methods across different frequency bands to investigate differences in brain functional activity between high-altitude smokers and non-smokers. 31 smokers and 31 non-smokers from HA regions participated, undergoing resting-state functional magnetic resonance imaging (rs-fMRI) scans. ALFF/fALFF values were compared between the two groups. Correlation analyses explored relationships between brain activity and clinical data. RESULTS: Smokers showed increased ALFF values in the right superior frontal gyrus (R-SFG), right middle frontal gyrus (R-MFG), right anterior cingulate cortex (R-ACC), right inferior frontal gyrus (R-IFG), right superior/medial frontal gyrus (R-MSFG), and left SFG compared to non-smokers in HA. In sub-frequency bands (0.01-0.027 Hz and 0.027-0.073 Hz), smokers showed increased ALFF values in R-SFG, R-MFG, right middle cingulate cortex (R-MCC), R-MSFG, Right precentral gyrus and L-SFG while decreased fALFF values were noted in the right postcentral and precentral gyrus in the 0.01-0.027 Hz band. Negative correlations were found between ALFF values in the R-SFG and smoking years. CONCLUSION: Our study reveals the neural characteristics of smokers in high-altitude environments, highlighting the potential impact of smoking on brain function. These results provide new insights into the neural mechanisms of high-altitude smoking addiction and may inform the development of relevant intervention measures.

Enhancing Orthopedic Knowledge Assessments: The Performance of Specialized Generative Language Model Optimization.

OBJECTIVE: This study aimed to evaluate and compare the effectiveness of knowledge base-optimized and unoptimized large language models (LLMs) in the field of orthopedics to explore optimization strategies for the application of LLMs in specific fields. METHODS: This research constructed a specialized knowledge base using clinical guidelines from the American Academy of Orthopaedic Surgeons (AAOS) and authoritative orthopedic publications. A total of 30 orthopedic-related questions covering aspects such as anatomical knowledge, disease diagnosis, fracture classification, treatment options, and surgical techniques were input into both the knowledge base-optimized and unoptimized versions of the GPT-4, ChatGLM, and Spark LLM, with their generated responses recorded. The overall quality, accuracy, and comprehensiveness of these responses were evaluated by 3 experienced orthopedic surgeons. RESULTS: Compared with their unoptimized LLMs, the optimized version of GPT-4 showed improvements of 15.3% in overall quality, 12.5% in accuracy, and 12.8% in comprehensiveness; ChatGLM showed improvements of 24.8%, 16.1%, and 19.6%, respectively; and Spark LLM showed improvements of 6.5%, 14.5%, and 24.7%, respectively. CONCLUSION: The optimization of knowledge bases significantly enhances the quality, accuracy, and comprehensiveness of the responses provided by the 3 models in the orthopedic field. Therefore, knowledge base optimization is an effective method for improving the performance of LLMs in specific fields.

Anti-HER2 biparatopic antibody KJ015 has near-native structure, functional balanced high affinity, and synergistic efficacy with anti-PD-1 treatment in vivo.

Currently approved human epidermal growth factor receptor 2 (HER2)-targeted antibody therapies are largely derived from trastuzumab, including trastuzumab-chemotherapy combinations, fixed-dose trastuzumab-pertuzumab combinations, and trastuzumab antibody-drug conjugates. To expand the options, bispecific antibodies, which may better utilize the benefits of combination therapy, are being developed. Among them, biparatopic antibodies (bpAbs) have shown improved efficacy compared to monoclonal antibody (mAb) combinations in HER2-positive patients. BpAbs bind two independent epitopes on the same antigen, which allows fine-tuning of mechanisms of action, including enhancement of on-target specificity and induction of strong antigen clustering due to the unique binding mode. To fully utilize the potential of bpAbs for anti-HER2 drug development, it is crucial to consider formats that offer stability and high-yield production, along with a functional balance between the two epitopes. In this study, we rationally designed a bpAb, KJ015, that shares a common light chain with two Fab arms and exhibits functionally balanced high affinity for two HER2 non-overlapping epitopes. KJ015 demonstrated high-expression titers over 7 g/L and stable physicochemical properties at elevated concentrations, facilitating subcutaneous administration with hyaluronidase. Moreover, KJ015 maintained comparable antibody-dependent cytotoxicity, phagocytosis, and complement-dependent cytotoxicity with trastuzumab plus pertuzumab. It exhibited enhanced synergy when administered subcutaneously with hyaluronidase and anti-PD-1 mAb in a mouse tumor model, suggesting promising clinical prospects for this combination.

Senescent CD8+ T cells: a novel risk factor in atrial fibrillation.

AIMS: Immune cell alterations may play a role in the development of atrial fibrillation (AF). Our objective was to comprehensively characterize immune cells in AF, and investigate the potential mechanisms. METHODS AND RESULTS: Single-cell RNA sequencing and multicolor flow cytometry revealed that T cells constituted the most significant subset alterations in AF, and senescent CD8+ T cells were AF-associated subset. Senescent CD8+ T cells increased in both peripheral veins (p < 0.0001) and the left atria (p < 0.05) in patients with AF compared to non-AF control. Senescent CD8+ T cells were independently associated with AF prevalence (odds ratio = 2.876, p < 0.05) and postprocedural recurrence (hazard ratio = 22.955, p < 0.0001) using a cross-sectional study and a subsequent prospective cohort study. Senescent CD8+ T cells secreted an increased amount of interferon (IFN)-γ, which induces Ca2+ handling abnormalities in human induced pluripotent stem cell-derived atrial cardiomyocytes, and translated into an increased susceptibility to AF assessed by heart optical mapping. CONCLUSIONS: An increased amount of senescent CD8+ T cells may be a hallmark of the immune senescence phenotype in AF and potentially serve as a valid biomarker for assessing prevalence and postprocedural recurrence of AF. By connecting immune senescence with electrophysiological disturbances in AF, this research provides a potential mechanism for the involvement of senescent CD8+ T cells in proarrhythmic calcium disorders and suggests novel avenues for developing new immune-modulatory and senolytic therapies for AF.

Structural connectivity of dopaminergic pathways in major depressive disorder: An ultra-high resolution 7-Tesla diffusion MRI study.

Accumulating evidence points to imbalanced dopamine (DA) signaling and circulating levels in the pathophysiology of major depressive disorder (MDD). However, the use of conventional MRI scanners and acquisition techniques has prevented a thorough examination of DA neural pathways in MDD. We uniquely employed ultra-high field diffusion MRI at 7.0 Tesla to map the white matter architecture and integrity of several DA pathways in MDD patients. Fifty-three MDD patients and 12 healthy controls (HCs) were enrolled in the final analysis. Images were acquired using a 7.0 Tesla MRI scanner. FreeSurfer was used to segment components of DA pathways, and MRtrix was used to perform preprocessing and tractography of mesolimbic, mesocortical, nigrostriatal, and unconventional DA pathways. Bayesian analyses assessed the impact of MDD and clinical features on DA tracts. MDD was associated with perturbed white matter microstructural properties of the nigrostriatal pathway, while several MDD features (severity of depression/age of onset/insomnia) related to connectivity changes within mesocortical, nigrostriatal, and unconventional pathways. MDD is associated with microstructural differences in the nigrostriatal pathway. The findings provide insight into the structural architecture and integrity of several DA pathways in MDD, and implicate their involvement in the clinical manifestation of MDD.

Development of Ampelopsis Radix Ethanolic Extract Loaded Phytosomes for Improved Efficacy in Colorectal Cancer: in vitro and in vivo Assessment Study.

The aim of present work was to develop and evaluate Ampelopsis Radix ethanolic extract loaded phytosomes for improved efficacy in colorectal cancer. Ampelopsis Radix ethanolic extract was prepared by Soxhlet extraction process followed by development of phytosomes using lipids and other excipients. The phytosomes were evaluated for surface morphology, particle size analysis, zeta potential, encapsulation efficiency, drug loading, in vitro drug release, Cytotoxicity assay, cellular uptake studies were performed on HCT-116 and SW480 cell lines. In vivo antitumor activity was performed. The phytosomes were found spherical shape with smooth surface characteristics. The drug loading was observed between 29.27 to 42.10 % while particle size of 85 to 130 nm was found. Phytosomes showed desired release pattern which is required for cancer treatment. Phytosomes showed maximum antiproliferative activity on cell lines over the period of 24 hours and showed highest internalization within both types of cell lines. The survival rate of animals in phytosomes treated group was found to be 100% proving the safety and efficacy. Phytosomes showed highest antitumor activity as compared to other formulations. Study confirms the potential use Ampelopsis Radix ethanolic extract loaded phytosomes for improved efficacy in colorectal cancer.

Incorporation of amylose improves rheological and textural properties of Moringa oleifera seed salt-soluble protein.

The interactions between corn amylose (CA) and Moringa oleifera seed salt-soluble protein (MOSP) were explored to improve the gel properties of MOSP. With increasing CA content, the MOSP-CA gel network structure was improved but the size of the gel porosity decreased firstly and then increased; the water holding retention (WHR) of MOSP-CA was decreased from approximately 94 % to 85.43 ± 2.54 %. The MOSP-CA-2.5 gel exhibited the best water holding stability (WHS), with a value of 37.1 ± 0.33 %. The MOSP-CA gel hardness increased with CA concentration, and MOSP-CA-2.5 showed relatively optimal cohesiveness, elasticity, adhesiveness, and chewiness. Meanwhile, MOSP-CA-2.5 exhibited gel strength. Incorporation of CA significantly increased the exposure of hydrophobic residues and the concentration-dependent increase in disulfide bonds in MOSP-CA gel. Thus, hydrophobic interactions, hydrogen bonds, and disulfide bonds collectively stabilized the structure of MOSP-CA gel. The findings would broaden the application of MOSP and improve the utilization value of MOSP in various industries.

Coronary angiography in dextrocardia with situs inversus and acute myocardial infarction: A case report and literature review.

We present the case of a 74-year-old man with dextrocardia and situs inversus who presented with non-ST-elevation acute myocardial infarction. The patient underwent successful coronary angiography without requiring percutaneous coronary intervention or coronary artery bypass grafting. We discuss the patient's clinical characteristics, electrocardiography findings, diagnosis, and treatment, and review the relevant literature.

Efficiency and safety of continuous theta burst stimulation for primary insomnia: A randomized clinical trial.

OBJECTIVES: Primary insomnia is a substantial public health burden, but current treatments for this disorder have limited effectiveness and adherence. Herein, we aimed to investigate the efficacy and safety of continuous theta burst stimulation (cTBS) for the treatment of primary insomnia. METHODS: This two-armed, randomized, sham-controlled trial was conducted at Peking University Sixth Hospital and local community clinics. A total of 46 patients with primary insomnia were recruited and randomly allocated to either the cTBS group or sham group. Forty-one patients completed 10 sessions of cTBS or sham intervention and follow-up assessments. RESULTS: After the intervention, the severity of insomnia was significantly lower in the cTBS group than in the sham group, with a large effect size (Cohen's d = -1.938). Additionally, 52.4 % of patients in the cTBS group achieved a response (Insomnia Severity Index score reduction ≥8), whereas only 4 % of patients in the sham group achieved a response. The duration of objective total sleep time and slow-wave sleep were higher in the cTBS group than in the sham group. The degree of anxiety was lower in the cTBS group than in the sham group. There were no significant differences in depression, sleepiness, or cognitive function between the cTBS and sham groups. During follow-up, the sleep quality of the cTBS group significantly improved and remained stable at the 6-month follow-up. CONCLUSION: In this randomized clinical trial, cTBS improved insomnia symptoms and was generally well tolerated, thus supporting the further development of cTBS for the treatment of primary insomnia.

The reproducibility and predictivity of radiomic features extracted from dynamic contrast-enhanced computed tomography of hepatocellular carcinoma.

PURPOSE: To assess the reproducibility of radiomic features (RFs) extracted from dynamic contrast-enhanced computed tomography (DCE-CT) scans of patients diagnosed with hepatocellular carcinoma (HCC) with regards to inter-observer variability and acquisition timing after contrast injection. The predictive ability of reproducible RFs for differentiating between the degrees of HCC differentiation is also investigated. METHODS: We analyzed a set of DCE-CT scans of 39 patients diagnosed with HCC. Two radiologists independently segmented the scans, and RFs were extracted from each sequence of the DCE-CT scans. The same lesion was segmented across the DCE-CT sequences of each patient's scan. From each lesion, 127 commonly used RFs were extracted. The reproducibility of RFs was assessed with regard to (i) inter-observer variability, by evaluating the reproducibility of RFs between the two radiologists; and (ii) timing of acquisition following contrast injection (inter- and intra-imaging phase). The reproducibility of RFs was assessed using the concordance correlation coefficient (CCC), with a cut-off value of 0.90. Reproducible RFs were used for building XGBoost classification models for the differentiation of HCC differentiation. RESULTS: Inter-observer analyses across the different contrast-enhancement phases showed that the number of reproducible RFs was 29 (22.8%), 52 (40.9%), and 36 (28.3%) for the non-contrast enhanced, late arterial, and portal venous phases, respectively. Intra- and inter-sequence analyses revealed that the number of reproducible RFs ranged between 1 (0.8%) and 47 (37%), inversely related with time interval between the sequences. XGBoost algorithms built using reproducible RFs in each phase were found to be high predictive ability of the degree of HCC tumor differentiation. CONCLUSIONS: The reproducibility of many RFs was significantly impacted by inter-observer variability, and a larger number of RFs were impacted by the difference in the time of acquisition after contrast injection. Our findings highlight the need for quality assessment to ensure that scans are analyzed in the same physiologic imaging phase in quantitative imaging studies, or that phase-wide reproducible RFs are selected. Overall, the study emphasizes the importance of reproducibility and quality control when using RFs as biomarkers for clinical applications.

Clinical spectrum and possible pathogenesis of progressive outer retinal necrosis.

OBJECTIVE: Progressive outer retinal necrosis (PORN) is an alphaherpesvirus-caused panuveitis with devastating consequences for the eye. Our study aims to describe new findings in the clinical spectrum and propose a mechanism for the pathogenesis of PORN. METHODS: Observational, consecutive case series. Seven eyes from five patients diagnosed with PORN were enrolled. Detailed case histories, ocular examination findings and multimodal images of retina were collected. Optic nerve and brain imaging were obtained by MRI. RESULTS: All eyes were confirmed human alphaherpesviruses positive in ocular fluid by qPCR. Optic nerve oedema was observed on MRI in all eyes. A relative afferent pupillary defect was recorded in the affected eye for the unilateral cases. Two patients with unilateral involvement had a history of viral encephalitis and focal encephalomalacia found in the temporal lobe on brain MRI. The affected eyes were characterised by sensory retinal necrosis sparing retinal pigment epithelium, starting at the end of the retinal nerve fibre (horizontal raphe or peripheral area of the retina) and progressing rapidly along the nerve fibre. The wall of the retinal artery and vein was destroyed, resulting in blood flow interruption on fluorescein angiography and retinal haemorrhages along the large vessels. CONCLUSIONS: Combination the neurotropic characteristics of alphaherpesviruses and the signs of PORN, we hypothesised that the reactivated PORN virus originated from the lateral geniculate nucleus, then propagated along the optic nerve and was released at the terminals, causing necrosis of the entire sensory retina rather than just affecting the outer segment.

Cytological analysis of flower development, insights into suitable growth area and genomic background: implications for Glehnia littoralis conservation and sustainable utilization.

BACKGROUND: Glehnia littoralis F. Schmidt ex Miq., an endangered plant species with significant medicinal, edible, and ecological value, is now a central concern for conservation and sustainable utilization. Investigating the physiological and ecological mechanisms leading to its endangerment and elucidating its genetic background constitutes the foundation for conducting in-depth research on G. littoralis. RESULTS: Our observations have revealed a significant degree of floral sterility in wild populations of G. littoralis. The inflorescences of G. littoralis are classified into three types: completely fertile, completely sterile, and partially fertile compound umbels. Moreover, the flowers of G. littoralis can be categorized into fertile and sterile types. Sterile flowers exhibited abnormalities in the stigma, ovary, and ovules. This study is the first to discover that the presence or absence of a giant cell at the funiculus during the initiation of ovule primordium determines whether the flower can develop normally, providing cytological evidence for female sterility in G. littoralis. Conversely, both fertile and sterile flowers produced normally developed pollen. Field observations have suggested that robust plants bear more fertile umbels, while weaker ones have fewer or even no fertile umbels, indicating a close relationship between flower fertility and plant nutritional status. Our model correctly predicted that the eastern coastal regions of China, as well as prospective areas in Neimenggu and Sichuan, are suitable environments for its cultivation. Additionally, Using flow cytometry and genome survey, we estimated the genome size of G. littoralis to be 3.06 Gb and the heterozygosity to be 4.58%. CONCLUSION: The observations and findings presented in this study were expected to provide valuable insights for further conserving its genetic resources and sustainable utilization of G. littoralis.

The improvement strategy of fresh produce supply chain resilience based on extenics.

Nowadays, the world is in turmoil, climate and environmental problems are prominent, the import and export of fresh agricultural products are restricted, etc. The impact of the growing demand for fresh agricultural products and healthy lifestyle choices, and fresh agricultural products are essential for people's daily life, which are perishable, fragile, seasonal, and other unstable factors. Therefore, when the fresh produce supply chain faces various pressures and difficulties, how to enhance the resilience of the supply chain against various problems and risks with flexible and multi-dimensional strategies and methods has become the focus of extensive attention. This kind of problem is a typical contradictory problem, and previous studies have failed to achieve good results. In this paper, based on extenics, we are able to one-dimensionalise the multi-dimensional contradictory problems and multi-dimensionalise the one-dimensional contradictory problems to solve such problems in a scientific and effective way. Firstly, taking fresh agricultural products supply chain enterprise M as the research object, we constructed the fresh agricultural products supply chain enterprise toughness system and identified the toughness state of each index. Secondly, we found the low-evaluation toughness indexes that need to be solved and constructed a extension model of incompatible problems of enterprise toughness. Thirdly, we analysed the objectives and conditions of toughness incompatible problems of fresh agricultural products supply chain enterprises numerically and quantitatively, and then, with the objective of toughness improvement, we analyzed the correlation of the condition basic-elements of incompatible problems and carried out extension transformations. Again, the objectives and conditions of the incompatible problems of fresh produce supply chain enterprises are analysed numerically and quantitatively, and with toughness enhancement as the objective, the correlation analysis and extension transformation of the condition basic-elements of the incompatible problems are implemented to generate the set of toughness enhancement strategies that can solve the incompatible problems in a multidimensional and scientific way. Finally, the optimal toughness enhancement strategies are selected through the superiority evaluation and composed into a new strategy to enhance the toughness of the fresh produce supply chain. Combined with extenics calculations and screening, a new strategy for supply chain resilience enhancement of fresh agricultural products was finally formed. The existing problems are solved from six aspects: product supply type, product demand, product supply efficiency, human resource quantity, production and processing equipment, and logistics guarantee ability. It provides a certain reference significance for the fresh agricultural products supply chain toughness enhancement, and helps enterprises to strengthen their competitiveness and sustainability through the enhancement of toughness.

The value of phenylalanine in predicting atrial fibrillation risk in chronic heart failure.

Backgrounds: Atrial fibrillation (AF) is a common complication of chronic heart failure (HF). Serum phenylalanine (Phe) levels are related to inflammation disorder. It is meaningful to study the circulating Phe with AF occurrence in HF. Methods: The cross-sectional study recruited 300 patients (78.0% male; mean age, 65 ± 13 years) with HF (left ventricular ejection fraction of ≤50%, containing 70 AF patients) and 100 normal controls. Serum Phe value was measured by liquid chromatography-tandem mass spectrometry. Logistic regression analysis was conducted to measure the association between Phe and AF risk in HF. The association between Phe and high-sensitivity C-reactive protein (hsCRP) was assessed by simple correlation analysis. In the prospective study, the 274 HF subjects (76.6% male; mean age, 65 ± 13 years) were followed up for a mean year (10.99 ± 3.00 months). Results: Serum Phe levels increased across the control, the HF without AF, and the HF with AF groups (77.60 ± 8.67 umol/L vs. 95.24 ± 28.58 umol/L vs. 102.90 ± 30.43 umol/L, ANOVA P < 0.001). Serum Phe value was the independent risk factor for predicting AF in HF [odds ratio (OR), 1.640; 95% CI: 1.150-2.339; P = 0.006]. Phe levels were correlated positively with hsCRP value in HF patients with AF (r = 0.577, P < 0.001). The elevated Phe levels were associated with a higher risk of HF endpoint events in HF patients with AF (log-rank P = 0.005). Conclusions: In HF with AF subjects, elevated Phe value confers an increased risk for prediction AF and was more related to poor HF endpoint events. Phe can be a valuable index of AF in HF.

The Nuclear Speckles Protein SRRM2 Is Exposed on the Surface of Cancer Cells.

The membrane composition of extracellular vesicles (EVs) largely reflects that of the plasma membrane of the cell of origin. We therefore hypothesized that EVs could be used for immunizations to generate monoclonal antibodies against well-known tumor antigens but possibly also against hitherto unknown tumor-associated target molecules. From an immunization experiment, we obtained a monoclonal antibody specific for SRRM2, an RNA-binding protein involved in splicing and a major component of nuclear speckles. Here, we used this antibody to demonstrate that SRRM2 is exposed on the surface of most cancer cell lines from various entities and, even more important, on cancer cells in vivo. Moreover, we demonstrated that SRRM2-specific CAR-T cells are functional in vitro and in vivo. Collectively, we identified SRRM2 as a promising new target molecule exposed on the cancer cell surface and showed that our SRRM2-specific antibody can be used as a basis for the development of new targeted cancer therapies.

Memory Reconsolidation Updating in Substance Addiction: Applications, Mechanisms, and Future Prospects for Clinical Therapeutics.

Persistent and maladaptive drug-related memories represent a key component in drug addiction. Converging evidence from both preclinical and clinical studies has demonstrated the potential efficacy of the memory reconsolidation updating procedure (MRUP), a non-pharmacological strategy intertwining two distinct memory processes: reconsolidation and extinction-alternatively termed "the memory retrieval-extinction procedure". This procedure presents a promising approach to attenuate, if not erase, entrenched drug memories and prevent relapse. The present review delineates the applications, molecular underpinnings, and operational boundaries of MRUP in the context of various forms of substance dependence. Furthermore, we critically examine the methodological limitations of MRUP, postulating potential refinement to optimize its therapeutic efficacy. In addition, we also look at the potential integration of MRUP and neurostimulation treatments in the domain of substance addiction. Overall, existing studies underscore the significant potential of MRUP, suggesting that interventions predicated on it could herald a promising avenue to enhance clinical outcomes in substance addiction therapy.