Specific peptides targeting the myocardiocyte are prognostic markers for heart attack: Function of α-SMA protein.

Myocardial infarction (MI) is a serious cardiovascular disease that often results in a significant decline in heart function and associated complications. α-SMA (α-smooth muscle cell actin) is an important biomarker in the process of cardiac remodeling and repair, and its expression level is closely related to myocardial remodeling and prognosis. Therefore, the purpose of this study was to investigate the potential of nanoparticles containing cardiomyocyte targeting peptides in predicting prognosis and α-SMA protein expression after myocardial infarction, with a view to providing new therapeutic strategies and clinical guidelines. In this study, a novel targeting nanoparticle was constructed, using cardiomyocyte specific peptides as targeting ligands, and characterized by loading different drugs. Subsequently, a mouse model of myocardial infarction was used to systematically evaluate the effect of nanoparticles on α-SMA protein expression and prognosis prediction ability after MI. The expression level of α-SMA was analyzed by Western blot and immunohistochemistry, and the prognosis was evaluated by cardiac function assessment. The study found that nanoparticles containing cardiomyocyte targeting peptides significantly increased α-SMA expression levels and improved heart function in animal models of myocardial infarction. Compared with the control group, the application of targeted nanoparticles was closely related to the level of myocardial cell repair and fibrosis, and could effectively predict the prognosis after myocardial infarction. Therefore, nanoparticles containing cardiomyocyte targeting peptides can not only effectively improve the expression of α-SMA, but also serve as an important prognostic tool after myocardial infarction.

Advances of immune-checkpoint inhibition of CTLA-4 in pancreatic cancer.

Targeting checkpoints for immune cell activation has been acknowledged known as one of the most effective way to activate anti-tumor immune responses. Among them, drugs targeting cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) are approved for clinical treatment though several more are in advanced stages of development, which demonstrated durable response rates and manageable safety profile. However, its therapy efficacy is unsatisfactory in pancreatic cancer (PC), which can be limited by the overall condition of patients, the pathological type of PC, the expression level of tumor related genes, etc. To improve clinical efficiency, various researches have been conducted, and the efficacy of combination therapy showed significantly improvement compared to monotherapy. This review analyzed current strategies based on anti-CTLA-4 combination immunotherapy, providing totally new idea for future research.

New insights into the role of Klotho in inflammation and fibrosis: molecular and cellular mechanisms.

As the body's defense mechanism against damage and infection, the inflammatory response is a pathological process that involves a range of inflammatory cells and cytokines. A healthy inflammatory response helps the body repair by eliminating dangerous irritants. However, tissue fibrosis can result from an overly intense or protracted inflammatory response. The anti-aging gene Klotho suppresses oxidation, delays aging, and fosters development of various organs. Numerous investigations conducted in the last few years have discovered that Klotho expression is changed in a variety of clinical diseases and is strongly linked to the course and outcome of a disease. Klotho functions as a co-receptor for FGF and as a humoral factor that mediates intracellular signaling pathways such as transforming growth factor ß (TGF-ß), toll-like receptors (TLRs), nuclear factor-kappaB (NF-κB), renin -angiotensin system (RAS), and mitogen-activated protein kinase (MAPK). It also interferes with the phenotype and function of inflammatory cells, such as monocytes, macrophages, T cells, and B cells. Additionally, it regulates the production of inflammatory factors. This article aims to examine Klotho's scientific advances in terms of tissue fibrosis and the inflammatory response in order to provide novel therapy concepts for fibrotic and inflammatory disorders.

NMC-4 Ameliorates Depression-Like Behavior and Neuroinflammation Caused by Chronic Unpredictable Mild Stress.

Depression is a prevalent mental disorder, but the side effects of antidepressants also make depressed patients resistant. Effective and safe antidepressants should be developed from traditional herbs, with the aim of reducing the side effects of antidepressants and improving the efficacy of drugs. In this study, the new macamide compound-4 (NMC-4) was synthesized for the first time, addressing the problem of difficult extraction, isolation, and low content of natural macamide. NMC-4 was characterized using mass spectrometry, nuclear magnetic resonance, and infrared spectroscopy. The protective effect of NMC-4 against cell injury was demonstrated to be stronger than that of natural macamide (N-benzylhexadecanamide, XA) using a PC12 cell injury model. The study explored the effects of NMC-4 on chronic unpredictable mild stress (CUMS)-induced depressive symptoms. NMC-4 significantly improved depressive-like behaviors. NMC-4 ameliorated CUMS-induced depressive-like behaviors by mitigating neuroinflammation and modulating the NF-κB/Nrf2 and BDNF/PI3K/Akt pathways.

Analyzing infections caused by 11 respiratory pathogens in children: Pre- and post-COVID-19 pandemic trends in China.

With the lifting of coronavirus disease 2019 (COVID-19) restrictions in December 2022 in China, the population was widely infected with COVID-19. We aim to analyzed changes in the epidemiological characteristics of other respiratory pathogens in children before and after the COVID-19 pandemic. We conducted a retrospective analysis of 44 704 children with acute respiratory infections who underwent 11 respiratory pathogen tests based on multiplex polymerase chain reaction between February and December in both 2022 and 2023. The total pathogen detection rate (24861, 74.80% vs. 6423, 56.01%; p = 0.000) and detection rates of coinfection (4059, 12.21% vs. 676, 5.89%; p = 0.000) in 2023 was significantly higher than that in 2022. The detection rates of influenza A (2567, 7.72% vs. 222, 1.94%; p = 0.000), influenza B (383, 1.15% vs. 37, 0.32%; p = 0.000), human parainfluenza virus (2175, 6.54% vs. 602, 5.25%; p = 0.000), human metapneumovirus (1354, 4.07% vs. 346, 3.01%; p = 0.000), respiratory syncytial virus (3148, 9.47% vs. 870, 7.59%; p = 0.000), and Mycoplasma pneumonia (MP; 9494, 28.56% vs. 1790, 15.61%; p = 0.000) in 2023 were significantly higher than those in 2022, whereas the detection rates of human adenovirus (1124, 3.38% vs. 489, 4.26%; p = 0.000) and human bocavirus (629, 1.89% vs. 375, 3.27%; p = 0.000) were significantly lower than those in 2022. Chlamydia, human rhinovirus, and human coronavirus showed similar detection rates between 2023 and 2022. In 2023, the influenza virus and human parainfluenza virus regained seasonal characteristic, an outbreak of MP infection occurred, the epidemic season of respiratory syncytial virus changed, and the proportion of children with acute respiratory infection aged 0-28 days and over 3 years old increased. Influenza B, metapneumovirus, and human bocavirus were detected in children aged 0-28 days in 2023, but not in 2022. After the COVID-19 pandemic, we should be alert to the increase of respiratory diseases and the change of epidemic season and susceptible age.

A prediction model of dementia conversion for mild cognitive impairment by combining plasma pTau181 and structural imaging features.

AIMS: The early stages of Alzheimer's disease (AD) are no longer insurmountable. Therefore, identifying at-risk individuals is of great importance for precise treatment. We developed a model to predict cognitive deterioration in patients with mild cognitive impairment (MCI). METHODS: Based on the Alzheimer's Disease Neuroimaging Initiative (ADNI) database, we constructed models in a derivation cohort of 761 participants with MCI (138 of whom developed dementia at the 36th month) and verified them in a validation cohort of 353 cognitively normal controls (54 developed MCI and 19 developed dementia at the 36th month). In addition, 1303 participants with available AD cerebrospinal fluid core biomarkers were selected to clarify the ability of the model to predict AD core features. We assessed 32 parameters as candidate predictors, including clinical information, blood biomarkers, and structural imaging features, and used multivariable logistic regression analysis to develop our prediction model. RESULTS: Six independent variables of MCI deterioration were identified: apolipoprotein E ε4 allele status, lower Mini-Mental State Examination scores, higher levels of plasma pTau181, smaller volumes of the left hippocampus and right amygdala, and a thinner right inferior temporal cortex. We established an easy-to-use risk heat map and risk score based on these risk factors. The area under the curve (AUC) for both internal and external validations was close to 0.850. Furthermore, the AUC was above 0.800 in identifying participants with high brain amyloid-ß loads. Calibration plots demonstrated good agreement between the predicted probability and actual observations in the internal and external validations. CONCLUSION: We developed and validated an accurate prediction model for dementia conversion in patients with MCI. Simultaneously, the model predicts AD-specific pathological changes. We hope that this model will contribute to more precise clinical treatment and better healthcare resource allocation.

Extracorporeal shock wave therapy (ESWT) favors healing of diabetic foot ulcers: A systematic review and meta-analysis.

AIMS: To investigate the efficacy and safety of extracorporeal shockwave therapy(ESWT) for diabetic foot ulcers(DFUs). METHODS: Search in PubMed, EMBASE, the Cochrane Controlled Register of Trials (CENTAL), and Web of Science for randomized controlled trials (RCTs) published before August 8, 2023. All identified studies were screened following the selection criteria. Finally, we employed the STATA 14.0 software for conducting a meta-analysis to evaluate the efficacy and safety of ESWT. RESULTS: A total of ten RCTs with moderate methodological quality were included for data analysis. The findings showed that ESWT was significantly associated with significantly complete healed ulcers (risk ratio [RR]: 1.57, 95 % confidence interval [CI]:1.26 to 1.95) and lower rate of unchanged ulcers (RR: 0.25, 95 %CI: 0.14 to 0.42) compared to controls. Subgroup analysis further revealed that ESWT was better than both hyperbaric oxygen therapy (HOT) and the standard of care (SOC). Moreover, ESWT also significantly improved the average transcutaneous partial oxygen pressure (TcPO2) (mean difference[MD]: 1.71, 95 %CI: 1.22 to 2.19, p < 0.001). However, the rate of ≥ 50 % improved ulcers and treatment-emergent adverse events (TEAEs) were not significantly different between the ESWT and controls. CONCLUSIONS: ESWT has shown promising efficacy and a favorable safety profile in the treatment of DFUs.

Ferroptosis-targeting drugs in breast cancer.

In 2020, breast cancer surpassed lung cancer as the most common cancer in the world for the first time. Due to the resistance of some breast cancer cell lines to apoptosis, the therapeutic effect of anti-breast cancer drugs is limited. According to recent report, the susceptibility of breast cancer cells to ferroptosis affects the progress, prognosis and drug resistance of breast cancer. For instance, roblitinib induces ferroptosis of trastuzumab-resistant human epidermal growth factor receptor 2 (HER2)-positive breast cancer cells by diminishing fibroblast growth factor receptor 4 (FGFR4) expression, thereby augmenting the susceptibility of these cells to HER2-targeted therapies. In tamoxifen-resistant breast cancer cells, Fascin exacerbates their resistance by repressing solute carrier family 7 member 11 (SLC7A11) expression, which in turn heightens their responsiveness to tamoxifen. In recent years, Chinese herbs extracts and therapeutic drugs have been demonstrated to elicit ferroptosis in breast cancer cells by modulating a spectrum of regulatory factors pertinent to ferroptosis, including SLC7A11, glutathione peroxidase 4 (GPX4), acyl-CoA synthetase long chain family member 4 (ACSL4), and haem oxygenase 1 (HO-1). Here, we review the roles and mechanisms of Chinese herbal extracts and therapeutic drugs in regulating ferroptosis in breast cancer, providing potential therapeutic options for anti-breast cancer.

Arrested development: the dysfunctional life history of medulloblastoma.

Medulloblastoma is a heterogeneous embryonal tumor of the cerebellum comprised of four distinct molecular subgroups that differ in their developmental origins, genomic landscapes, clinical presentation, and survival. Recent characterization of the human fetal cerebellum at single-cell resolution has propelled unprecedented insights into the cellular origins of medulloblastoma subgroups, including those underlying previously elusive groups 3 and 4. In this review, the molecular pathogenesis of medulloblastoma is examined through the lens of cerebellar development. In addition, we discuss how enhanced understanding of medulloblastoma origins has the potential to refine disease modeling for the advancement of treatment and outcomes.

Soybean oil induces neuroinflammatory response through brain-gut axis under high-fat diet.

Neuroinflammation is considered the principal pathogenic mechanism underlying neurodegenerative diseases, and the incidence of brain disorders is closely linked to dietary fat consumption and intestinal health. To investigate this relationship, 60 8-week-old C57BL/6J mice were subjected to a 20-week dietary intervention, wherein they were fed lard and soybean oil, each at 15% and 35% fat energy. At a dietary fat energy level of 35%, inflammation was observed in both the soybean oil and lard groups. Nevertheless, inflammation was more pronounced in the mice that were administered soybean oil. The process by which nerve cell structure is compromised, inflammatory factors are upregulated, brain antioxidant capacity is diminished, and the TLR4/MyD88/NF-κB p65 inflammatory pathway is activated resulting in damage to the brain-gut barrier. This, in turn, leads to a reduction in the abundance of Akkermansia and unclassified_f_Lachnospiraceae, as well as an increase in Dubosiella abundance, ultimately resulting in brain inflammation and damage. These results suggested that soybean oil induces more severe neuroinflammation compared to lard. Our study demonstrated that, at a dietary fat energy level of 35%, compared to soybean oil, lard could be the healthier option, the outcomes would help provide a reference basis for the selection of residents' daily dietary oil.

National centralized drug procurement and health care expenditure of households-micro-evidence from CFPS.

Objective: This paper utilizes data from the China Family Panel Studies (CFPS) to evaluate the impact of the "4 + 7" National Centralized Drug Procurement (NCDP) on Per Capita Household Health Care Expenditure (PCHHCE). Methods: The study applies the Differences-in-Differences (DID) methodology to analyze the effects of NCDP. Various robustness tests were conducted, including the Permutation test, Propensity Score Matching, alterations in regression methodologies, and consideration of individual fixed effects. Results: Research indicates that the implementation of NCDP led to a reduction of 10.6% in PCHHCE. The results remained consistent across all robustness tests. Additionally, the research identifies diversity in NCDP effects among various household characteristics, with a more significant impact on households residing in rural regions of China, enrolled in Basic Medical Insurance for urban and rural residents and urban workers, and having an income bracket of 25-75%. Conclusion: These findings carry policy implications for the future expansion and advancement of NCDP in China. The study highlights the effectiveness of NCDP in reducing healthcare expenditures and suggests potential areas for policy improvement and further research.

A brief model evaluated outcomes after liver transplantation based on the matching of donor graft and recipient.

BACKGROUND: A precise model for predicting outcomes is needed to guide perioperative management. With the developments of liver transplantation (LT) discipline, previous models may become inappropriate or noncomprehensive. Thus, we aimed to develop a novel model integrating variables from donors and recipients for quick assessment of transplant outcomes. METHODS: The risk model was based on Cox regression in a randomly selected derivation cohort and verified in a validation cohort. Perioperative data and overall survival were compared between stratifications grouped by X-tile. Receiver operating characteristic curve and decision curve analysis were used to compare the models. Violin and raincloud plots were generated to present post-LT complications distributed in different stratifications. RESULTS: Overall, 528 patients receiving LT from 2 centers were included with 2/3 in the derivation cohort and 1/3 in the validation cohort. Cox regression analysis showed that cold ischemia time (CIT) (P=0.012) and the Model for End-Stage Liver Disease (MELD) (P=0.007) score were predictors of survival. After comparison with the logarithmic models, the primitive algorithms of CIT and MELD were defined as the CIT-MELD Index (CMI). CMI was stratified by X-tile (grade 1 ≤1.06, 1.06< grade 2 ≤1.87, grade 3 >1.87). In both cohorts, CMI performed better in calculating transplant outcomes than the balance of risk score, including perioperative incidents and prevalence of complications. CONCLUSIONS: Model integrating variables from graft and recipient made the prediction more accurate and available. CMI provided new sight in outcome evaluation and risk factor management of LT.

FDGNet: Frequency Disentanglement and Data Geometry for Domain Generalization in Cross-Scene Hyperspectral Image Classification.

Cross-scene hyperspectral image classification (HSIC) poses a significant challenge in recognizing hyperspectral images (HSIs) from different domains. The current mainstream approaches based on domain adaptation (DA) methods need to access target data when aligning distributions between domains, limiting the applicability of the model. In contrast, recent domain generalization (DG) methods aim to directly generalize to unseen domains, eliminating the requirements for target data during training. Nonetheless, most DG-based methods overly focus on randomizing sample styles, leading to semantically compromised samples. In addition, broadening the source distribution without ensuring reasonable support may result in undesired extended distributions. To address these issues, we propose a novel DG network with frequency disentanglement and data geometry (FDGNet) for cross-scene HSIC. Specifically, we first develop a spectral-spatial encoder based on frequency disentanglement (FDSS encoder), which facilitates synthesized domains to preserve their semantic consistency while simulating interdomain gaps with the source domain. Second, to avoid the generation of unrealistic samples, we incorporate data geometry into adversarial training. This helps diversify new domains while keeping the data geometry of extended domains in an explainable support. To improve the learning of domain-invariant representation, we propose an intermediate domain sampling strategy based on the class-wise perceptual manifold. This strategy synthesizes reliable intermediate domains by sampling from class-wise manifold flows estimated over the source and extended domains. Extensive experiments and analysis on three public HSI datasets yield the superiority of our proposed FDGNet. The codes will be available from the website: https://github.com/Qba-heu/FDGNet.

Controlling bacterial growth and inactivation using thin film-based surface acoustic waves.

Formation of bacterial films on structural surfaces often leads to severe contamination of medical devices, hospital equipment, implant materials, etc., and antimicrobial resistance of microorganisms has indeed become a global health issue. Therefore, effective therapies for controlling infectious and pathogenic bacteria are urgently needed. Being a promising active method for this purpose, surface acoustic waves (SAWs) have merits such as nanoscale earthquake-like vibration/agitation/radiation, acoustic streaming induced circulations, and localised acoustic heating effect in liquids. However, only a few studies have explored controlling bacterial growth and inactivation behaviour using SAWs. In this study, we proposed utilising piezoelectric thin film-based SAW devices on a silicon substrate for controlling bacterial growth and inactivation with and without using ZnO micro/nanostructures. Effects of SAW powers on bacterial growth for two types of bacteria, i.e., E. coli and S. aureus, were evaluated. Varied concentrations of ZnO tetrapods were also added into the bacterial culture to study their effects and the combined antimicrobial effects along with SAW agitation. Our results showed that when the SAW power was below a threshold (e.g., about 2.55 W in this study), the bacterial growth was apparently enhanced, whereas the further increase of SAW power to a high power caused inactivation of bacteria. Combination of thin film SAWs with ZnO tetrapods led to significantly decreased growth or inactivation for both E. coli and S. aureus, revealing their effectiveness for antimicrobial treatment. Mechanisms and effects of SAW interactions with bacterial solutions and ZnO tetrapods have been systematically discussed.

Acoustofluidic Diversity Achieved by Multiple Modes of Acoustic Waves Generated on Piezoelectric-Film-Coated Aluminum Sheets.

Excitation of multiple acoustic wave modes on a single chip is beneficial to implement diversified acoustofluidic functions. Conventional acoustic wave devices made of bulk LiNbO3 substrates generally generate few acoustic wave modes once the crystal-cut and electrode pattern are defined, limiting the realization of acoustofluidic diversity. In this paper, we demonstrated diversity of acoustofluidic behaviors using multiple modes of acoustic waves generated on piezoelectric-thin-film-coated aluminum sheets. Multiple acoustic wave modes were excited by varying the ratios between IDT pitch/wavelength and substrate thickness. Through systematic investigation of fluidic actuation behaviors and performances using these acoustic wave modes, we demonstrated fluidic actuation diversities using various acoustic wave modes and showed that the Rayleigh mode, pseudo-Rayleigh mode, and A0 mode of Lamb wave generally have better fluidic actuation performance than those of Sezawa mode and higher-order modes of Lamb wave, providing guidance for high-performance acoustofluidic actuation platform design. Additionally, we demonstrated diversified particle patterning functions, either on two sides of acoustic wave device or on a glass sheet by coupling acoustic waves into the glass using the gel. The pattern formation mechanisms were investigated through finite element simulations of acoustic pressure fields under different experimental configurations.

Exploring the mechanism of improving the pressure fluctuation of double suction centrifugal pump by impeller stagger.

BACKGROUND: The pressure fluctuation in the volute can be effectively reduced when the impeller of the double-suction pump is staggered, but the mechanism of this reduction is still unclear. At the same time, the traditional analysis method cannot realize the visualization of pressure fluctuation. OBJECTIVE: The purpose of this article is to explore the spatial distribution, propagation, and attenuation law of pressure fluctuation, and on this basis, to research the reason why staggered impeller reduce pressure fluctuation. METHODS: A new method called Pulse tracking network (PTN) was used in this article. Compared with the traditional method, which only analyzes the pressure fluctuation at scattered points, this method greatly improves the spatial resolution of the pressure fluctuation. In particular, the phase analysis is a major highlight of the method. RESULTS: Staggered impeller significantly reduced the pressure fluctuation intensity dominated by blade passing frequency. At the same time, the propagation of the pressure fluctuation in the volute changed from radial to circumferential in the volute cross-section. CONCLUSIONS: Staggered impeller can effectively reduce pressure fluctuation, and the circumferential propagation caused by it is considered to be the main reason for it.

Tutorial on phantoms for photoacoustic imaging applications.

Significance: Photoacoustic imaging (PAI) is an emerging technology that holds high promise in a wide range of clinical applications, but standardized methods for system testing are lacking, impeding objective device performance evaluation, calibration, and inter-device comparisons. To address this shortfall, this tutorial offers readers structured guidance in developing tissue-mimicking phantoms for photoacoustic applications with potential extensions to certain acoustic and optical imaging applications. Aim: The tutorial review aims to summarize recommendations on phantom development for PAI applications to harmonize efforts in standardization and system calibration in the field. Approach: The International Photoacoustic Standardization Consortium has conducted a consensus exercise to define recommendations for the development of tissue-mimicking phantoms in PAI. Results: Recommendations on phantom development are summarized in seven defined steps, expanding from (1) general understanding of the imaging modality, definition of (2) relevant terminology and parameters and (3) phantom purposes, recommendation of (4) basic material properties, (5) material characterization methods, and (6) phantom design to (7) reproducibility efforts. Conclusions: The tutorial offers a comprehensive framework for the development of tissue-mimicking phantoms in PAI to streamline efforts in system testing and push forward the advancement and translation of the technology.

Flexible surface acoustic wave technology for enhancing transdermal drug delivery.

Transdermal drug delivery provides therapeutic benefits over enteric or injection delivery because its transdermal routes provide more consistent concentrations of drug and avoid issues of drugs affecting kidneys and liver functions. Many technologies have been evaluated to enhance drug delivery through the relatively impervious epidermal layer of the skin. However, precise delivery of large hydrophilic molecules is still a great challenge even though microneedles or other energized (such as electrical, thermal, or ultrasonic) patches have been used, which are often difficult to be integrated into small wearable devices. This study developed a flexible surface acoustic wave (SAW) patch platform to facilitate transdermal delivery of macromolecules with fluorescein isothiocyanates up to 2000 kDa. Two surrogates of human skin were used to evaluate SAW based energized devices, i.e., delivering dextran through agarose gels and across stratum corneum of pig skin into the epidermis. Results showed that the 2000 kDa fluorescent molecules have been delivered up to 1.1 mm in agarose gel, and the fluorescent molecules from 4 to 2000 kDa have been delivered up to 100 µm and 25 µm in porcine skin tissue, respectively. Mechanical agitation, localised streaming, and acousto-thermal effect generated on the skin surface were identified as the main mechanisms for promoting drug transdermal transportation, although micro/nanoscale acoustic cavitation induced by SAWs could also have its contribution. SAW enhanced transdermal drug delivery is dependent on the combined effects of wave frequency and intensity, duration of applied acoustic waves, temperature, and drug molecules molecular weights.

Ultrastrong, flexible thermogalvanic armor with a Carnot-relative efficiency over 8.

Body heat, a clean and ubiquitous energy source, is promising as a renewable resource to supply wearable electronics. Emerging tough thermogalvanic device could be a sustainable platform to convert body heat energy into electricity for powering wearable electronics if its Carnot-relative efficiency (ηr) reaches ~5%. However, maximizing both the ηr and mechanical strength of the device are mutually exclusive. Here, we develop a rational strategy to construct a flexible thermogalvanic armor (FTGA) with a ηr over 8% near room temperature, yet preserving mechanical robustness. The key to our design lies in simultaneously realizing the thermosensitive-crystallization and salting-out effect in the elaborately designed ion-transport highway to boost ηr and improve mechanical strength. The FTGA achieves an ultrahigh ηr of 8.53%, coupling with impressive mechanical toughness of 70.65 MJ m-3 and substantial elongation (~900%) together. Our strategy holds sustainable potential for harvesting body heat and powering wearable electronics without recharging.

Non-Abelian Holonomy in Degenerate Non-Hermitian Systems.

Non-Abelian holonomy, a noncommutative process that measures the parallel transport of non-Abelian gauge fields, has so far been realized in degenerate Hermitian systems with degenerate eigenstates or nondegenerate non-Hermitian systems with exceptional points. Here, we introduce non-Abelian holonomy into degenerate non-Hermitian systems possessing degenerate exceptional points and degenerate energy topologies. The interplay between energy degeneracy and energy topology around exceptional points leads to a non-Abelian holonomy with multiple energy levels and multiple degenerate levels simultaneously, going beyond that in degenerate Hermitian systems with a single energy level, or in nondegenerate non-Hermitian systems with a single degenerate level. We exploit an on-chip photonic platform to experimentally demonstrate the holonomy induced non-Abelian phenomenon, including the switching of eigenstates associated with different degenerate exceptional points and sequence-dependent holonomic outcomes. Our work shifts the paradigm of non-Abelian holonomy and adds new degrees of freedom for non-Abelian applications.