Emotional state dynamics impacts temporal memory.

Emotional fluctuations are ubiquitous in everyday life, but precisely how they sculpt the temporal organisation of memories remains unclear. Here, we designed a novel task - the Emotion Boundary Task - wherein participants viewed sequences of negative and neutral images surrounded by a colour border. We manipulated perceptual context (border colour), emotional-picture valence, as well as the direction of emotional-valence shifts (i.e., shifts from neutral-to-negative and negative-to-neutral events) to create events with a shared perceptual and/or emotional context. We measured memory for temporal order and temporal distances for images processed within and across events. Negative images processed within events were remembered as closer in time compared to neutral ones. In contrast, temporal distances were remembered as longer for images spanning neutral-to-negative shifts - suggesting temporal dilation in memory with the onset of a negative event following a previously-neutral state. The extent of negative-picture induced temporal dilation in memory correlated with dispositional negativity across individuals. Lastly, temporal order memory was enhanced for recently-presented negative (versus neutral) images. These findings suggest that emotional-state dynamics matters when considering emotion-temporal memory interactions: While persistent negative events may compress subjectively remembered time, dynamic shifts from neutral-to-negative events produce temporal dilation in memory, with implications for adaptive emotional functioning.

Transient paper-based electrochemical biosensor Fabricated by superadditive Cu-TCPP(Fe)/Mxene for Multipathway non-invasive, highly sensitive detection of Bodily metabolites.

Current advances in non-invasive fluid diagnostics highlight unique benefits for monitoring metabolic diseases. However, the low concentrations and complex compositions of biomarkers in fluids such as sweat, urine, and saliva impose stringent demands on the sensitivity and stability of detection technologies. Here, we developed a high-sensitivity, low-cost instantaneous electrochemical sensor based on the superadditive effect mechanism of Cu-TCPP(Fe)/Mxene (MMs Paper-ECL Sensor), which has been successfully applied for the simultaneous real-time detection of glucose and uric acid. Strong interfacial interactions between Mxene and Cu-TCPP(Fe) were revealed through precise simulation calculations and multi-dimensional characterization analysis, significantly enhancing the sensor's electrocatalytic performance and reaction kinetics. Experimentally, this exceptional electrocatalytic activity was demonstrated in its unprecedented high sensitivity and wide linear detection range for glucose and uric acid, with a non-invasive linear range from 0.001 nM to 5 mM, 0.025 nM-5 mM, detection limits as low as 1.88 aM and 5.80 pM, and stability extending up to 100 days. This represents not only a breakthrough in sensitivity and stability but also provides an effective, low-cost solution that overcomes the limitations of existing electronic devices, enabling multi-channel simultaneous detection. The universality of this sensor holds vast potential for application in the field of non-invasive fluid diagnostics.

Esketamine Exposure Impairs Cardiac Development and Function in Zebrafish Larvae.

Esketamine is a widely used intravenous general anesthetic. However, its safety, particularly its effects on the heart, is not fully understood. In this study, we investigated the effects of esketamine exposure on zebrafish embryonic heart development. Zebrafish embryos were exposed to esketamine at concentrations of 1, 10, and 100 mg/L from 48 h post-fertilization (hpf) to 72 hpf. We found that after exposure, zebrafish embryos had an increased hatching rate, decreased heart rate, stroke volume, and cardiac output. When we exposed transgenic zebrafish of the Tg(cmlc2:EGFP) strain to esketamine, we observed ventricular dilation and thickening of atrial walls in developing embryos. Additionally, we further discovered the abnormal expression of genes associated with cardiac development, including nkx2.5, gata4, tbx5, and myh6, calcium signaling pathways, namely ryr2a, ryr2b, atp2a2a, atp2a2b, slc8a3, slc8a4a, and cacna1aa, as well as an increase in acetylcholine concentration. In conclusion, our findings suggest that esketamine may impair zebrafish larvae's cardiac development and function by affecting acetylcholine concentration, resulting in weakened cardiac neural regulation and subsequent effects on cardiac function. The insights garnered from this research advocate for a comprehensive safety assessment of esketamine in clinical applications.

Polymersomal Poly(I:C) Self-Magnifies Antitumor Immunity by Inducing Immunogenic Cell Death and Systemic Immune Activation.

Immunotherapy has emerged as a powerful weapon against lung cancer, yet only a fraction of patients respond to the treatment. Poly(I:C) (PIC) effectively triggers both innate and adaptive immunity. It can also induce immunogenic cell death (ICD) in tumor cells. However, its efficacy is hindered by its instability in vivo and limited cellular uptake. To address this, PIC is encapsulated in cRGD-functionalized polymersomes (t-PPIC), which significantly increases its stability and uptake, thus activating dendritic cells (DCs) and inducing apoptosis of lung tumor cells in vitro. In a murine LLC lung tumor model, systemic administration of t-PPIC effectively suppresses tumor growth and leads to survival benefits, with 40% of the mice becoming tumor-free. Notably, t-PPIC provokes stronger apoptosis and ICD in tumor tissue and elicits a more potent stimulation of DCs, recruitment of natural killer (NK) cells, and activation of CD8+ T cells, compared to free PIC and nontargeted PPIC controls. Furthermore, when combined with immune checkpoint inhibitors or radiotherapy, t-PPIC amplifies the antitumor immune response, resulting in complete regression in 60% of the mice. These compelling findings underscore the potential of integrin-targeted polymersomal PIC to enhance antitumor immunity by simultaneously inducing ICD and systemic immune activation.

VX-702 Ameliorates the Severity of Sepsis-Associated Acute Kidney Injury by Downregulating Inflammatory Factors in Macrophages.

Purpose: Sepsis-associated acute kidney injury (S-AKI) contributes to high mortality, but it is lack of specific treatments. We aimed to investigate the underlying mechanism of S-AKI and to identify target drugs to alleviate AKI. Methods: We establish a stable mouse model of S-AKI by Pseudomonas aeruginosa incision infection. Based on high-throughput sequencing and bioinformatics analysis, we investigated the underlying mechanism and selected the target drug (VX-702) for S-AKI. An in vitro model established by co-cultured of kidney tubular epithelial cell line (TCMK-1) cells with lipopolysaccharide (LPS)-induced leukemic monocyte/macrophage cells (RAW264.7), we explored the effect of VX-702 on S-AKI. Results: The data showed interleukin (IL)-6 and IL-1ß were the hub genes, and the mitogen-activated protein kinase (MAPK) signaling pathway was the main pathway involved in S-AKI. Administration of VX-702 by oral gavage decreased the elevated concentrations of IL-6, IL-1ß, serum creatinine, and blood urea nitrogen in mice with S-AKI. Moreover, VX-702 reduced the number of apoptotic cells in damaged kidney tissues. Cell viability was decreased, and the number of apoptotic cells was increased in TCMK-1 cells co-cultured with LPS-induced RAW264.7 cells compared to LPS-induced TCMK-1 cells. VX-702 treatment reversed this effect. VX-702 treatment reduced the levels of phosphorylated p38 MAPK and proinflammatory cytokines in RAW264.7 cells and the supernatant. VX-702 could bind IL-6, IL-1ß and MAPK, and affect the binding of IL-1ß and its receptor, as demonstrated by molecular docking. Conclusion: VX-702 ameliorated S-AKI by inhibiting the release of proinflammatory cytokines from macrophages, indicating its potential as a novel therapeutic for S-AKI treatment.

LncRNA KIFAP3-5:1 inhibits epithelial-mesenchymal transition of renal tubular cell through PRRX1 in diabetic nephropathy.

Long noncoding RNAs play an important role in several pathogenic processes in diabetic nephropathy, but the relationship with epithelial-mesenchymal transition in DN is unclear. Herein, we found that KIFAP3-5:1 expression was significantly down-regulated in DN plasma samples, db/db mouse kidney tissues and high glucose treated renal tubular epithelial cells compared to normal healthy samples and untreated cells. Overexpression of KIFAP3-5:1 improved renal fibrosis in db/db mice and rescued epithelial-mesenchymal transition of high glucose cultured renal tubular epithelial cells. The silence of KIFAP3-5:1 will exacerbate the progression of EMT. Mechanistically, KIFAP3-5:1 was confirmed to directly target to the -488 to -609 element of the PRRX1 promoter and negatively modulate PRRX1 mRNA and protein expressions. Furthermore, rescue assays demonstrated that the knockdown of PRRX1 counteracted the KIFAP3-5:1 low expression-mediated effects on EMT in hRPTECs cultured under high glucose. The plasma KIFAP3-5:1 of DN patients is highly correlated with the severity of renal dysfunction and plays an important role in the prediction model of DN diseases. These findings suggested that KIFAP3-5:1 plays a critical role in regulation of renal EMT and fibrosis through suppress PRRX1, and highlight the clinical potential of KIFAP3-5:1 to assist in the diagnosis of diabetic nephropathy.

Predicting the Pro-Inflammatory Effects of Oxidized Methyl Oleate Based on the Volatile Compounds.

The negative impact of lipid peroxidation on health is intimately tied to its oxidation products. In this study, methyl oleate was oxidized at 180℃ for 0, 2, 4, 8 and 12 h respectively. The free radicals and volatile components generated during the oxidation process were determined using electron spin resonance and headspace solid-phase microextraction (HS-SPME)-GC-MS. The pro-inflammatory effects of oxidized methyl oleate were evaluated in RAW264.7 cells. Then partial least-squares regression (PLSR) models were established for predicting the 3 pro-inflammatory genes expression based on the volatile components. The results revealed that the alkoxy radical content increased rapidly during oxidation from 4 h to 8 h, and the rate of oxidation of methyl oleate dropped after 8 h. A total of 27 volatile oxidation compounds were detected by HS-SPME-GC-MS. The content of most compounds, including aldehydes, esters, and acids, exhibited a pattern of initial increase and then decrease as the oxidation time increased. Similarly, the proinflammatory effects of oxidized methyl oleate peaked after 8 h of oxidation. The PLSR quantitative prediction models showed that the coefficient of determination (R2P) between the predicted and measured values of the 3 inflammatory gene expressions were 0.915, 0.946 and 0.951 respectively. The established PLSR model predicts the pro-inflammatory effects of oxidized methyl oleate well and provides a theoretical foundation for quick evaluation of the pro-inflammatory effects of oxidized lipids.

Potential Immune-Inflammatory Proteome Biomarkers for Guiding the Treatment of Patients with Primary Acute Angle-Closure Glaucoma Caused by COVID-19.

Primary acute angle-closure glaucoma (PAACG) is a sight-threatening condition that can lead to blindness. With the increasing incidence of COVID-19, a multitude of people are experiencing acute vision loss and severe swelling of the eyes and head. These patients were then diagnosed with acute angle closure, with or without a history of PACG. However, the mechanism by which viral infection causes PACG has not been clarified. This is the first study to explore the specific inflammatory proteomic landscape in SARS-CoV-2-induced PAACG. The expression of 92 inflammation-related proteins in 19 aqueous humor samples from PAACGs or cataract patients was detected using the Olink Target 96 Inflammation Panel based on a highly sensitive and specific proximity extension assay technology. The results showed that 76 proteins were significantly more abundant in the PAACG group than in the cataract group. Notably, the top eight differentially expressed proteins were IL-8, MCP-1, TNFRSF9, DNER, CCL4, Flt3L, CXCL10, and CD40. Generally, immune markers are related to inflammation, macrophage activation, and viral infection, revealing the crucial role of macrophages in the occurrence of PAACGs caused by SARS-CoV-2.

Thin-film lithium niobate circulator-free dispersion compensator in a time-lens system for femtosecond-pulse generation.

We demonstrate a circulator-free thin-film lithium niobate (TFLN) dispersion compensator based on the cascading 2 × 2 multimode interferometer (MMI) and two identical chirped Bragg gratings (CBGs). The cascaded MMI-CBG structure provides a dispersion value of 920 ps/nm/m over a 20 nm bandwidth covering 1537 to 1557 nm, featuring a compact footprint of 1 mm × 0.7 mm. Utilizing this device within a TFLN electro-optic time-lens system, we successfully generate 863-fs pulses at a 37 GHz repetition rate. Our compact, scalable, low-loss, and circulator-free dispersion compensator is the building block for the efficient generation of high-peak-power femtosecond laser pulses.

The role of immune cell signatures in the pathogenesis of ovarian-related diseases: a causal inference based on mendelian randomization.

BACKGROUND: Immune cells play a pivotal role in maintaining ovarian function. However, the specific contributions of different immune cell phenotypes to the pathogenesis of specific ovarian-related diseases remain poorly understood. We aim to investigate the correlation between 731 immunophenotypes and ovarian-related diseases. MATERIALS AND METHODS: Utilizing publicly available genetic data, we undertook a series of quality control measures to identify instrumental variables (IVs) associated with exposure. Subsequently, we conducted two-sample Mendelian randomization (MR) using inverse variance weighting to explore the causal relationships between 731 immune cell features and six ovarian-related diseases: ovarian cysts, ovarian dysfunction, premature ovarian failure (POF), polycystic ovary syndrome (PCOS), benign neoplasm of ovary, and malignant neoplasm of ovary at the genetic level. Sensitivity analyses, including leave-one-out and other MR analysis models, were performed. Finally, Bayesian colocalization (COLOC) analysis was employed to identify specific co-localized genes, thereby validating the MR results. RESULTS: At the significance level corrected by Bonferroni, four immune phenotypes, including CD25 on IgD- CD38- B cells, were associated with ovarian cysts; four immune phenotypes, including CD39+ CD4+ T cell Absolute Count, were associated with ovarian dysfunction; eight immune phenotypes, including SSC-A on HLA DR+ CD8+ T cells, were associated with POF; five immune phenotypes, including CD20- CD38- B cell Absolute Count, were associated with PCOS; five immune phenotypes, including CD4+ CD8dim T cell Absolute Count, were associated with benign ovarian tumors; and three immune phenotypes, including BAFF-R on IgD- CD38+ B cells, were associated with malignant ovarian tumors. Sensitivity analysis indicated robust results. COLOC analysis identified four immune cell co-localized variants (rs150386792, rs117936291, rs75926368, rs575687159) with ovarian diseases. CONCLUSION: Our study elucidates the close genetic associations between immune cells and six ovarian-related diseases, thereby providing valuable insights for future research endeavors and clinical applications.

CircRNA: An emerging star in plant research: A review.

CircRNAs are a class of covalently closed non-coding RNA formed by linking the 5' terminus and the 3' terminus after reverse splicing. CircRNAs are widely found in eukaryotes, and they are highly conserved, with spatio-temporal expression specificity and stability. CircRNAs can act as miRNA sponges to regulate the expression of downstream target genes, regulating the transcription of parental genes and some can even be translated into peptides or proteins. Research on circRNAs in plants is still in its infancy compared to that in animals. With the deepening of research, the results of a variety of plant circRNAs suggest that they play an important role in growth and development, and tolerance towards abiotic stresses such as salt, drought, low temperature, high temperature and other adverse environments. In this review paper, we elaborated the molecular characteristics, mechanism of action, function and bioinformatics databases of plant circRNAs, combined with the progress of circRNA research in animals, discussed the potential mechanism of action of plant circRNAs, and proposed the unsolved problems and prospects for future application of plant circRNAs.

Association of weight-adjusted waist index with hyperuricemia and gout among middle-aged and older adults in America: a cross-sectional analysis of NHANES 2007-2014.

OBJECTIVES: The weight-adjusted waist circumference index (WWI), a novel obesity indicator, gives better accuracy in assessing both muscle and fat mass. Our goal was to evaluate the relationship between WWI and the occurrence of hyperuricemia/gout among middle-aged and older adults in America. METHODS: We analyzed the National Health and Nutrition Examination Survey (NHANES) data from the 2007-2014 cycles. Logistic regression analyses, subgroup analyses, and restricted cubic splines (RCS) were performed to evaluate the association between WWI and hyperuricemia/gout prevalence. RESULTS: A total of 5332 adults aged 50 years and above were included in this study. The prevalence of hyperuricemia and gout was 23.20% and 6.70% respectively. The fourth quartile of WWI was associated with a 56% higher risk for hyperuricemia, compared with the first quartile (OR = 1.56, 95% CI 1.07-2.27, P trend < 0.001). A similar association was found between continuous WWI increase and OR of hyperuricemia in the fully adjusted model (OR = 1.35, 95% CI = 1.13-1.61, P < 0.05). However, WWI was not significantly associated with the prevalence of gout. The RCS model suggested a significant linear relationship between WWI and the risk of hyperuricemia/gout. Stratification analysis showed that the positive associations of WWI with the risk of hyperuricemia were more pronounced in participants who were women, aged 50-59, smokers, no physical activity, non-diabetes, hypertension, and hyperlipidemia. CONCLUSIONS: Our findings suggest a positive correlation between WWI and hyperuricemia among middle-aged and older adults in America. Employing WWI as a tool for hyperuricemia prevention may be meaningful. Key Points • Weight-adjusted waist circumference index is a new obesity evaluation index. • Weight-adjusted waist circumference index is associated with hyperuricemia not gout. • The association is more pronounced in participants who were women, aged 50-59, smokers, no physical activity, non-diabetes, hypertension, and hyperlipidemia.

Identification and analysis of short-term and long-term salt-associated lncRNAs in the leaf of Avicennia marina.

As a highly salt-resistant mangrove, Avicennia marina can thrive in the hypersaline water. The leaves of Avicennia marina play a crucial role in salinity stress adaptability by secreting salt. Although the functions of long non-coding RNAs (lncRNAs) in leaves remain unknown, they have emerged as regulators in leaf development, aging and salt response. In this study, we employed transcriptomic data of both short-term and long-term salt treated leaves to identify salt-associated lncRNAs of leaf tissue. As a result, 687 short-term and 797 long-term salt-associated lncRNAs were identified. Notably, both short-term and long-term salt-associated lncRNAs exhibited slightly longer lengths and larger exons, but smaller introns compared with salt-non-associated lncRNAs. Furthermore, salt-associated lncRNAs also displayed higher tissue-specificity than salt-non-associated lncRNAs. Most of the salt-associated lncRNAs were common to short- and long-term salt treatments. And about one fifth of the downregulated salt-associated lncRNAs identified both in two terms were leaf tissue-specific lncRNAs. Besides, these leaf-specific lncRNAs were found to be involved in the oxidation-reduction and photosynthesis processes, as well as several metabolic processes, suggesting the noticeable functions of salt-associated lncRNAs in regulating salt responses of Avicennia marina leaves.

Effect of soybean proteins and peptides on the growth and adhesive ability of Limosilactobacillus Reuteri DSM17938.

Limosilactobacillus reuteri DSM17938 is one of the most pivotal probiotics, whose general beneficial effects on the intestinal microbiota are well recognized. Enhancing their growth and metabolic activity can effectively regulate the equilibrium of intestinal microbiota, leading to improved physical health. A common method to promote the growth of Lactobacillus is the addition of prebiotics. Current research suggests that proteins and their hydrolysates from different sources with potential prebiotic activity can also promote the growth of probiotics. In this study, soybean proteins and peptides were effective in promoting the growth, organic acid secretion, and adhesive properties of Limosilactobacillus reuteri DSM17938 to Caco-2 cells. These results illustrate the feasibility of soybean proteins and peptides as prebiotics, providing theoretical and practical advantages for their application.

Electron transferring with oxygen defects on Ni-promoted Pd/Al2O3 catalysts for low-temperature lean methane combustion.

Methane (CH4) is the second most consequential greenhouse gas after CO2, with a substantial global warming potential. The CH4 catalytic combustion offers an efficient method for the elimination of CH4. However, improving the catalytic performance of Pd-based materials for low-temperature CH4 combustion remains a big challenge. In this study, we synthesized an enhanced Pd/5NiAlOx catalyst that demonstrated superior catalytic activity and improved water resistance compared to the Pd/Al2O3 catalyst. Specifically, the T90 was decreased by over 100 °C under both dry and wet conditions. Introducing Ni resulted in an enormously enhanced number of oxygen defects on the obtained 5NiAlOx support. This defect-rich support facilitates the anchoring of PdO through increased electron transfer, thereby inhibiting the production of high-valence Pd(2+δ)+ and stimulating the generation of unsaturated Pd sites. Pd0 can effectively activate surface oxygen and PdO plays a significant role in activating CH4, resulting in high activity for Pd/5NiAlOx. On the other hand, the increased water resistance of Pd/5NiAlOx was mainly due to the generation of *OOH species and the lower accumulation of surface -OH species during the reaction process.

Honeycomb effect elimination in differential phase fiber-bundle-based endoscopy.

Fiber-bundle-based endoscopy, with its ultrathin probe and micrometer-level resolution, has become a widely adopted imaging modality for in vivo imaging. However, the fiber bundles introduce a significant honeycomb effect, primarily due to the multi-core structure and crosstalk of adjacent fiber cores, which superposes the honeycomb pattern image on the original image. To tackle this issue, we propose an iterative-free spatial pixel shifting (SPS) algorithm, designed to suppress the honeycomb effect and enhance real-time imaging performance. The process involves the creation of three additional sub-images by shifting the original image by one pixel at 0, 45, and 90 degree angles. These four sub-images are then used to compute differential maps in the x and y directions. By performing spiral integration on these differential maps, we reconstruct a honeycomb-free image with improved details. Our simulations and experimental results, conducted on a self-built fiber bundle-based endoscopy system, demonstrate the effectiveness of the SPS algorithm. SPS significantly improves the image quality of reflective objects and unlabeled transparent scattered objects, laying a solid foundation for biomedical endoscopic applications.

Minor (≤ 10%) Ground-Glass Opacity Component in Clinical Stage I Non-Small Cell Lung Cancer: Associations With Pathologic Characteristics and Clinical Outcomes.

Background: The presence of a ground-glass opacity (GGO) component is a favorable prognostic factor in non-small cell lung cancer (NSCLC), although the prognostic impact of a very small GGO component remains poorly investigated. Objective: To investigate the impact of a minor (≤10%) GGO component on the prognosis of clinical stage I NSCLC in comparison with pure-solid nodules. Methods: This retrospective study included 382 patients (mean age, 61 years; 210 men, 172 women) who underwent surgical resection between January 1, 2015 and December 31, 2015 for clinical stage I NSCLC appearing on preoperative chest CT as a nodule with a consolidation-to-tumor (CTR) ratio ≥0.9 and <1.0. Two radiologists independently assigned nodules to a minor-GGO (≥0.9 CTR <1.0) or pure-solid (CTR=1.0) groups. Recurrence-free survival (RFS) and cancer-specific survival (CSS) were assessed by Kaplan-Meier curves and compared between groups using log-rank tests. Cox proportional hazards models were used to assess associations with outcomes. Results: The two radiologists agreed for all nodules' classification into the minor-GGO (n=106) or pure-solid (n=276) groups. The mean CTR of the minor-GGO group was 0.93±0.02 (range, 0.90-0.97). Minor-GGO nodules, in comparison with pure-solid nodules, showed greater solid component diameter (2.68 vs 2.16 cm, p<.001) and total nodule diameter (2.89 vs 2.16 cm, p<.001). The minor-GGO group, in comparison with the pure-solid group, showed lower frequencies of visceral pleural invasion (6.6% vs 17.0%, P=.009), pathologic lymph node involvement (4.7% vs 20.3%, P<.001), and epidermal growth factor mutation (71.6% vs 39.9%; P<.001). The minor-GGO group, in comparison with the pure-solid group, showed better 5-year RFS (83.4% vs 55.0%; P<.001) and better 5-year CSS (92.4% vs 76.4%, P=.004). In multivariable analysis adjusting for patient, imaging, pathologic, and genetic factors, a minor-GGO component was independently associated with a decreased likelihood of recurrence (HR=0.37, P=.001) but not with the likelihood of CSS. Conclusion: Among patients with clinical stage I NSCLC, cancers with a minor-GGO component were associated with a better prognosis versus those with a pure-solid appearance. Clinical Impact: Radiologists encountering predominantly solid nodules on CT should carefully assess images for even a minor-GGO component given the favorable prognosis.

JinLiDa granules alleviates cardiac hypertrophy and inflammation in diabetic cardiomyopathy by regulating TP53.

BACKGROUND: JinLiDa granules (JLD) is a traditional Chinese medicine (TCM) used to treat type 2 diabetes mellitus with Qi and Yin deficiency. Clinical evidence has shown that JLD can alleviate diabetic cardiomyopathy, but the exact mechanism is not yet clear. PURPOSE: The purpose of this study was to examine the potential role and mechanism of JLD in the treatment of diabetic cardiomyopathy through network pharmacological analysis and basic experiments. METHODS: The targets of JLD associated with diabetic cardiomyopathy were examined by network pharmacology. Protein interaction analysis was performed on the targets, and the associated pathways were searched by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. Diabetic mice were treated with low or high doses of JLD by gavage, and AC16 and H9C2 cardiomyocytes exposed to high-glucose conditions were treated with JLD. The analysis results were verified by various experimental techniques to examine molecular mechanisms. RESULTS: Network pharmacological analysis revealed that JLD acted on the tumor suppressor p53 (TP53) during inflammation and fibrosis associated with diabetic cardiomyopathy. The results of basic experiments showed that after JLD treatment, ventricular wall thickening in diabetic mouse hearts was attenuated, cardiac hypertrophy and myocardial inflammation were alleviated, and the expression of cardiac hypertrophy- and inflammation-related factors in cardiomyocytes exposed to a high-glucose environment was decreased. Cardiomyocyte morphology also improved after JLD treatment. TP53 expression and the tumor necrosis factor (TNF) and transforming growth factor beta-1 (TGFß1) signaling pathways were significantly altered, and inhibiting TP53 expression effectively alleviated the activation of the TNF and TGFß1 signaling pathways under high glucose conditions. Overexpression of TP53 activated these signaling pathways. CONCLUSIONS: JLD acted on TP53 to regulate the TNF and TGFß1 signaling pathways, effectively alleviating cardiomyocyte hypertrophy and inflammation in high glucose and diabetic conditions. Our study provides a solid foundation for the future treatment of diabetic cardiomyopathy with JLD.