Photoacoustic/ultrasound dual-modality imaging for marker clip localization in neoadjuvant chemotherapy of breast cancer.

Significance: To ensure precise tumor localization and subsequent pathological examination, a metal marker clip (MC) is placed within the tumor or lymph node prior to neoadjuvant chemotherapy for breast cancer. However, as tumors decrease in size following treatment, detecting the MC using ultrasound imaging becomes challenging in some patients. Consequently, a mammogram is often required to pinpoint the MC, resulting in additional radiation exposure, time expenditure, and increased costs. Dual-modality imaging, combining photoacoustic (PA) and ultrasound (US), offers a promising solution to this issue. Aim: Our objective is to localize the MC without radiation exposure using PA/US dual-modality imaging. Approach: A PA/US dual-modality imaging system was developed. Utilizing this system, both phantom and clinical experiments were conducted to demonstrate that PA/US dual-modality imaging can effectively localize the MC. Results: The PA/US dual-modality imaging can identify and localize the MC. In clinical trials encompassing four patients and five MCs, the recognition rate was ∼80%. Three experiments to verify the accuracy of marker position recognition were successful. Conclusions: We effectively localized the MC in real time using PA/US dual-modality imaging. Unlike other techniques, the new method enables surgeons to pinpoint nodules both preoperatively and intraoperatively. In addition, it boasts non-radioactivity and is comparatively cost-effective.

Synthesis and antibacterial properties of fluorinated biodegradable cationic polyesters.

Antimicrobial peptide-mimicking antibacterial polymers represent a practical strategy to conquer the ever-growing threat of antimicrobial resistance. Herein, we report the syntheses and antibacterial performance of degradable amphiphilic cationic polyesters containing pendent quaternary ammonium motifs and hydrophobic alkyl or fluoroalkyl groups. These polyesters were conveniently prepared from poly(3-methylene-1,5-dioxepan-2-one) via highly efficient one-pot successive thiol-Michael addition reactions. The antibacterial activity of these polyesters against S. aureus and E. coli and their hemolytic activity toward red blood cells were evaluated; some of them showed moderate antibacterial activity and selectivity against Gram-positive S. aureus. The membrane disruption mechanism of these cationic polyesters was briefly explored by monitoring the bacteria killing kinetics and SEM observations. Moreover, the effects of cationic/hydrophobic ratio and the incorporation of fluoroalkyl groups on the antibacterial activity and selectivity of the polyesters were demonstrated.

Effects of diabetes mellitus and glycemic traits on cardiovascular morpho-functional phenotypes.

BACKGROUND: The effects of diabetes on the cardiac and aortic structure and function remain unclear. Detecting and intervening these variations early is crucial for the prevention and management of complications. Cardiovascular magnetic resonance imaging-derived traits are established endophenotypes and serve as precise, early-detection, noninvasive clinical risk biomarkers. We conducted a Mendelian randomization (MR) study to examine the association between two types of diabetes, four glycemic traits, and preclinical endophenotypes of cardiac and aortic structure and function. METHODS: Independent genetic variants significantly associated with type 1 diabetes, type 2 diabetes, fasting insulin (FIns), fasting glucose (FGlu), 2 h-glucose post-challenge (2hGlu), and glycated hemoglobin (HbA1c) were selected as instrumental variables. The 96 cardiovascular magnetic resonance imaging traits came from six independent genome-wide association studies. These traits serve as preclinical endophenotypes and offer an early indication of the structure and function of the four cardiac chambers and two aortic sections. The primary analysis was performed using MR with the inverse-variance weighted method. Confirmation was achieved through Steiger filtering and testing to determine the causal direction. Sensitivity analyses were conducted using the weighted median, MR-Egger, and MR-PRESSO methods. Additionally, multivariable MR was used to adjust for potential effects associated with body mass index. RESULTS: Genetic susceptibility to type 1 diabetes was associated with increased ascending aortic distensibility. Conversely, type 2 diabetes showed a correlation with a reduced diameter and areas of the ascending aorta, as well as decreased distensibility of the descending aorta. Genetically predicted higher levels of FGlu and HbA1c were correlated with a decrease in diameter and areas of the ascending aorta. Furthermore, higher 2hGlu levels predominantly showed association with a reduced diameter of both the ascending and descending aorta. Higher FIns levels corresponded to increased regional myocardial-wall thicknesses at end-diastole, global myocardial-wall thickness at end-diastole, and regional peak circumferential strain of the left ventricle. CONCLUSIONS: This study provides evidence that diabetes and glycemic traits have a causal relationship with cardiac and aortic structural and functional remodeling, highlighting the importance of intensive glucose-lowering for primary prevention of cardiovascular diseases.

A time-resolved fluorescence immunoassay for rapid and precise automatic quality control of human papillomavirus type 68 VLPs in human papillomavirus vaccine.

The effectiveness and necessity of human papillomavirus (HPV) vaccination to prevent HPV infection and cervical cancer are increasingly recognized by people. The 15-valent HPV vaccine, which protects against almost high-risk types of HPV viruses identified by WHO, has attracted much attention. However, as the valence of vaccines increases, quality control in the HPV vaccine production process is facing more challenges. The precise quality control of the HPV type 68 virus-like particles (VLPs), one of the unique components of the 15-valent HPV vaccine that distinguishes it from existing vaccines, is the new requirement for vaccine manufacturers. Here we developed a novel time-resolved fluorescence immunoassay (TRFIA) for rapid and precise automatic quality control of HPV68 VLPs in HPV vaccine. Two murine monoclonal antibodies specifically targeting the HPV68 L1 protein were used to establish a classical sandwich assay. Except for pretreating the vaccine sample, the whole analysis process was performed by a fully automated machine, which saves detection time and gets rid of manual error. Multiple experiments established that the current novel TRFIA can efficiently and reliably analyses HPV68 VLPs. Present novel TRFIA has exhibited merits with speed, robustness, high sensitivity with a minimum detection value of 0.08 ng/mL, considerable accuracy, a wide detection range (up to 1000 ng/mL) and excellent specificity. It is also expected to provide a new detection method for quality control for each HPV type VLPs. To summarize, the novel TRFIA is of great interest for application in HPV vaccine quality control.

TWF1 induces autophagy and accelerates malignant phenotype in lung adenocarcinoma via inhibiting the cAMP signaling pathway.

Many studies have shown that the actin cytoskeleton plays an essential role in the initiation and progression of cancer. As an actin-binding protein, Twinfilin1 (TWF1) plays an important role in regulating cytoskeleton-related functions. However, little is known about the expression and function of TWF1 in human tumors. The present study aimed to investigate the functional roles and the underlying molecular mechanisms of TWF1 in human lung adenocarcinoma (LUAD). By using bioinformatics databases and tumor tissues, TWF1 expression was found to be higher in LUAD tissues than in adjacent tissues and poor survival was predicted in patients with LUAD. In vitro and in vivo assays indicated that downregulation of TWF1 expression suppressed LUAD cells invasion and migration. Further studies revealed that TWF1 interacted with p62 and was involved in the regulation of autophagy. The molecular mechanisms underlying TWF1 were investigated by RNA-seq analysis and a series of functional experiments. The results showed that downregulation of TWF1 suppressed LUAD progression through the cAMP signaling pathway. Therefore, overexpression of TWF1 in LUAD promoted migration, invasion, and autophagy through the cAMP signaling pathway.

Enhanced interface stability of ammine magnesium borohydride by in situ decoration of MgBr2·2NH3 nanoparticles.

A novel Mg(BH4)2·1.9NH3-MgBr2·2NH3 composite was demonstrated as a solid-state Mg2+ electrolyte. The in situ decoration of MgBr2·2NH3 nanoparticles with an average size of 3.7 nm on the surface of Mg(BH4)2·1.9NH3 improves the Mg2+ conductivity to 2.1 × 10-4 S cm-1 at 50 °C and offers long-term stability towards the Mg metal anode.

A custom-made time-resolved fluoroimmunoassay for the quantitation of the host cell protein of Vero in rabies vaccine.

Host cell proteins (HCPs) are the process-specific and inevitable impurities during the manufacture via a host cell, which affect the safety or efficacy of the bio-product. However, the commercial HCP enzyme-linked immunosorbent assay (ELISA) kits may not apply to specific products such as rabies vaccine from Vero cells. More advanced and process-specific assay methods are needed in the quality control of rabies vaccine throughout the whole manufacturing process. Therefore, a novel time-resolved fluoroimmunoassay (TRFIA) for the detection of process-specific HCP of Vero cells in rabies vaccine was established in this study. Liquid chromatography coupled tandem mass spectrometry (LC-MS/MS) was used during the preparation of HCP antigen. Based on a sandwich-type immunoassay format, analytes in samples were captured by one antibody coating in the wells and "sandwiched" by another antibody labeled with europium chelates. Due to the complex composition of HCP, both the capture and detected antibodies are polyclonal antibodies from the same anti-HCP antibodies pool. Multiple experiments have identified the optimal conditions to allow the valid and reliable detection of HCP in rabies vaccine. The TRFIA had a satisfactory limit of detection value (0.011 µg/ml) under optimal conditions, with the linear range from 0.0375 to 2.4 µg/ml of HCP. The coefficient variations (CVs) were all < 10%, and the recoveries were in the range of 97.00-102.42%. All the test results of Vero cell protein reference substance were included in the expected concentration, which demonstrated that the present method was available for the test of HCP in rabies vaccine. Based on these results, the novel TRFIA to detect HCP appears to be important for application in modern vaccine quality control during the whole manufacturing process.

Bulk and single-cell characterisation of the immune heterogeneity of atherosclerosis identifies novel targets for immunotherapy.

BACKGROUND: Immune cells that infiltrate lesions are important for atherosclerosis progression and immunotherapies. This study was aimed at gaining important new insights into the heterogeneity of these cells by integrating the sequencing results of multiple samples and using an enhanced single-cell sequencing workflow to overcome the limitations of a single study. RESULTS: Integrative analyses identified 28 distinct subpopulations based on gene expression profiles. Further analysis demonstrated that these cells manifested high heterogeneity at the levels of tissue preferences, genetic perturbations, functional variations, immune dynamics, transcriptional regulators, metabolic changes, and communication patterns. Of the T cells, interferon-induced CD8+ T cells were involved in the progression of atherosclerosis. In contrast, proinflammatory CD4+ CD28null T cells predicted a poor outcome in atherosclerosis. Notably, we identified two subpopulations of foamy macrophages that exhibit contrasting phenotypes. Among them, TREM2- SPP1+ foamy macrophages were preferentially distributed in the hypoxic core of plaques. These glycolytic metabolism-enriched cells, with impaired cholesterol metabolism and robust pro-angiogenic capacity, were phenotypically regulated by CSF1 secreted by co-localised mast cells. Moreover, combined with deconvolution of the bulk datasets, we revealed that these dysfunctional cells had a higher proportion of ruptured and haemorrhagic lesions and were significantly associated with poor atherosclerosis prognoses. CONCLUSIONS: We systematically explored atherosclerotic immune heterogeneity and identified cell populations underlying atherosclerosis progression and poor prognosis, which may be valuable for developing new and precise immunotherapies.

Synthesis and Post-Functionalization of Poly(conjugated ester)s Based on 3-Methylene-1,5-dioxepan-2-one.

Poly(α-methylene ester)s are an attractive type of functional aliphatic polyesters that represent a platform for the fabrication of various biodegradable and biomedical polymers. Herein, we report the controlled ring-opening polymerization (ROP) of a seven-membered α-methylene lactone (3-methylene-1,5-dioxepan-2-one, MDXO) that was synthesized based on the Baylis-Hillman reaction. The chemoselective ROP of MDXO was catalyzed by diphenyl phosphate (DPP) at 60 °C or stannous octoate (Sn(Oct)2) at 130 °C, generating α-methylene-containing polyester (PMDXO) with a linear structure and easily tunable molar mass. The ring-opening copolymerization of MDXO with ε-caprolactone or 1,5-dioxepan-2-one was also performed under the catalysis of DPP or Sn(Oct)2 to afford copolymers with different compositions and sequence structures that are influenced by the kinds of monomers and catalysts. PMDXO is a slowly crystallizable polymer with a glass transition temperature of ca. -33 °C, and its melting temperature and enthalpy are significantly influenced by the thermal history. The thermal properties of the copolymers are dependent on their composition and sequence structure. Finally, the post-modification of PMDXO based on the thiol-Michael addition reaction was briefly explored using triethylamine as a catalyst. Given the optimized condition, PMDXO could be dually modified to afford biodegradable polyesters with different functionalities.

Advanced imaging modalities provide new insights into coronary artery calcification.

Coronary calcification plays a major role as a key surrogate measure of plaque burden, providing powerful risk stratification and influencing preventive therapy. Depending on its location and density, microcalcifications may directly result in plaque rupture and adverse clinical events. Although macroscopic calcifications are frequently linked to advanced and stable plaques, the fact that a small number of thrombotic events are caused by plaques that possess a substantial amount of calcification should not be overlooked. Early and accurate assessment of calcium content in atherosclerotic plaques potentially enhances the identification of high-risk patients requiring preventive treatments. Non-invasive imaging allows for the visualization, detection, and quantification of calcific lesions, whereas intravascular imaging has the unique advantage of providing real-time and accurate information during calcium modification interventions. Simultaneously, emerging molecular imaging modalities aid in the investigation of calcification activity. This review summarizes advanced techniques for coronary artery calcification imaging, including their merits and limitations, in addition to their potential applications in both experimental and clinical settings.

Ultrabright nanoparticle-labeled lateral flow immunoassay for detection of anti-SARS-CoV-2 neutralizing antibodies in human serum.

The level of anti-SARS-CoV-2 neutralizing antibodies (NAb) is an indispensable reference for evaluating the acquired protective immunity against SARS-CoV-2. Here, we established an ultrabright nanoparticles-based lateral flow immunoassay (LFIA) for one-step rapid semi-quantitative detection of anti-SARS-CoV-2 NAb in vaccinee's serum. Once embedded in polystyrene (PS) nanoparticles, the aggregation-induced emission (AIE) luminogen, AIE490, exhibited ultrabright fluorescence due to the rigidity of PS and severe inhibition of intramolecular motions. The ultrabright AIE490-PS nanoparticle was used as a fluorescent marker of LFIA. Upon optimized conditions including incubation time, concentrations of coated proteins and conjugated nanoparticles, amounts of antigens modified on the surface of nanoparticles, dilution rate of serum samples, and so on, the ultrabright nanoparticles-based LFIA could accurately identify 70 negative samples and 63 positive samples from human serum (p < 0.0001). The intra- and inter-assay precisions of the established method are above 13% and 16%, respectively. The established LFIA has tremendous practical value of generalization as a rapid semi-quantitative detection method of anti-SARS-CoV-2 NAb. Meanwhile, the AIE490-PS nanoparticle is also promising to detect many other analytes by altering the protein on the surface.

Dual-color quantum dot-loaded nanoparticles based lateral flow biosensor for the simultaneous detection of gastric cancer markers in a single test line.

A dual-color quantum dots-loaded nanoparticles (QPs) based lateral flow biosensor with single test line has been developed. Red and green emitted QPs were conjugated with antibodies and served as detecting probes in assays respectively, while the mixture of various antibodies were immobilized on nitrocellulose membranes as one detection line. Benefit from eliminating the heterogeneity caused by different position on the membrane, current biosensor achieved higher accuracy comparing with prevalent multi-lines or multi-strips lateral flow systems, which is of great significance for analyzing ratio-related diagnostics. The capability and reliability of the multiplex biosensor are also demonstrated by utilizing pepsinogen I (PG I) and pepsinogen II (PG II) as the model analytes. Under the optimal conditions, quantitative detection was achieved with ultra-low limits of detection at 6.9 pM (0.29 ng mL-1, PG I) and 15.7 pM (0.66 ng mL-1, PG II) respectively. The spectra crosstalk was negligible and no apparent cross-reaction was found in simultaneous detection. Furthermore, a good linear correlation of the QPs based lateral flow biosensor and commercial time-resolved fluoroimmunoassay was obtained in the detection of clinical samples, indicating the high reliability of the proposed biosensor.

Europium (III) chelate nanoparticle-based lateral flow immunoassay strips for rapid and quantitative detection of cystatin C in serum.

The concentration of Cys C in the patient's serum can reflect the level of glomerular filtration rate and indicate the occurrence of renal failure. The establishment of a simple and rapid analytical method to quantitatively monitor the concentration of Cys C in serum could help timely detection of renal failure. In this study, we have developed an Eu (III) chelate nanoparticles based lateral flow immunoassay to fulfill real-time monitoring of Cys C concentration in serum within 15 min. This method was performed as a sandwich immunoassay with a wide detection range (0.05-10 µg/mL) and a low limit of detection (24.54 ng/mL). The intra and inter-assay coefficients of variation were 8.31-8.61% and 8.92-9.95%, respectively. Furthermore, the application of this method was evaluated by comparing the determined results with those obtained by chemiluminescence immunoassay, exhibiting a satisfactory correlation (R2 = 0.9830). The developed LFIA method with satisfactory analytical performance has great potential for real-time monitoring of renal failure and self-detection for the high-risk population.

Differences in Culprit Lesions Between Premenopausal and Postmenopausal Women With Acute Coronary Syndrome: An Optical Coherence Tomography Study.

BACKGROUND: Differences in culprit lesion characteristics remain unclear between premenopausal and postmenopausal women with acute coronary syndrome (ACS). Optical coherence tomography (OCT) enables high-resolution in vivo identification of plaques. We investigated potential differences in culprit lesions between premenopausal and postmenopausal women with ACS by means of OCT. METHODS: We included 191 ACS patients who had undergone preinterventional OCT and stratified them into 2 groups according to their menopausal status: premenopausal (n = 97) and postmenopausal (n = 94). The characteristics of culprit lesions were compared between the 2 groups. RESULTS: Multivessel lesions were more commonly noted on angiography in the postmenopausal group than in the premenopausal group (40.21% vs 72.34%; P < 0.0001). On OCT, the most common type of culprit plaque was the fibrous plaque in the premenopausal group and the lipid plaque in the postmenopausal group. Compared with the premenopausal group, plaque rupture was more common in the postmenopausal group (39.18% vs 55.32%; P = 0.0254); culprit lesions had more vulnerable features, including macrophage accumulation (58.76% vs 87.23%; P < 0.0001), microchannel (38.14% vs 84.04%; P < 0.0001), cholesterol crystals (30.93% vs 62.77%; P < 0.0001), lipid-rich plaque (32.99% vs 58.51%; P < 0.0001), thin-cap fibroatheroma (3.09% vs 21.28%; P = 0.0001), and calcium (20.62% vs 44.68%; P = 0.0004); maximum lipid arc was larger (121.06 ± 110.99° vs 220.12 ± 115.47°, P < 0.0001); and lipid length was longer (5.78 ± 5.29 mm vs 12.90 ± 8.97 mm; P < 0.0001). CONCLUSIONS: Compared with premenopausal women with ACS, postmenopausal women with ACS had more vulnerable culprit lesions. These finding suggest potential optimised lipid-lowering therapy for postmenopausal women with ACS.

Rapid Monitoring of Vancomycin Concentration in Serum Using Europium (III) Chelate Nanoparticle-Based Lateral Flow Immunoassay.

Establishing personalized medication plans for patients to maximize therapeutic efficacy and minimize the toxicity of vancomycin (VAN) requires rapid, simple, and accurate monitoring of VAN concentration in body fluid. In this study, we have developed a simple and rapid analytical method by integrating Eu (III) chelate nanoparticles (CN-EUs) and lateral flow immunoassay (LFIA) to achieve the real-time monitoring of VAN concentration in serum within 15 min. This approach was performed on nitrocellulose (NC) membrane assembled LFIA strips via indirect competitive immunoassay and exhibited a wide linear range of detection (0.1-80 µg*ml-1) with a low limit of detection (69.2 ng*ml-1). The coefficients of variation (CV) of the intra- and inter-assay in the detection of VAN were 7.12-8.53% and 8.46-11.82%, respectively. The dilution test and specificity indicated this method had a stability that was not affected by the serum matrix and some other antibiotics. Furthermore, the applicability of the proposed method was assessed by comparing the determined results with those measured by LC-MS/MS, showing a satisfactory correlation (R 2 = 0.9713). The proposed CN-EUs-based LFIA manifested promising analytical performance, which showed potential value in the real-time monitoring of VAN and could help optimize the clinical use of more antibiotics.

A chemiluminescence immunoassay for precise automatic quality control of glycoprotein in human rabies vaccine.

Currently, quality control of glycoprotein in the human rabies vaccine is based on enzyme-linked immunosorbent assay (ELISA). However, ELISA does not match the needs of a modernised quality control system. For a long time, human rabies virus vaccine manufacturers have been devoted to seeking a detection platform that is sensitive, accurate, automatic, and feasible for practical applications. Therefore, our team invested major efforts into establishing a fully automated micromagnetic particle (MMP)-based chemiluminescence immunoassay (CLIA) platform. For vaccine quality control, MMP-coupled rabies virus glycoprotein monoclonal antibodies (S037) were used to capture the rabies virus. Another rabies virus glycoprotein antibody (S053) labelled with acridinium ester was added as a signal tracer. After pretreating the vaccine sample, the entire analysis was performed using a fully automated machine, which had a limited detection time (only 30 min) and eliminated manual error. Multiple experiments have identified the optimal conditions allowing valid and reliable assessment of vaccine potency. The CLIA platform has exhibited merits in terms of speed, robustness, high sensitivity (with a minimum detection value of 0.45 mIU/mL), considerable accuracy, and a wide linear range of detection (9.4-1200 mIU/mL). Furthermore, the results showed that the CLIA platform is consistent with the National Institutes of Health test and time-resolved fluorescent immunoassay (TRFIA) in quantitative analysis, and had a better analytic performance than TRFIA. Therefore, the CLIA platform presented here may be important for application in modern vaccine quality control.

Molecular Imaging and Non-molecular Imaging of Atherosclerotic Plaque Thrombosis.

Thrombosis in the context of atherosclerosis typically results in life-threatening consequences, including acute coronary events and ischemic stroke. As such, early detection and treatment of thrombosis in atherosclerosis patients is essential. Clinical diagnosis of thrombosis in these patients is typically based upon a combination of imaging approaches. However, conventional imaging modalities primarily focus on assessing the anatomical structure and physiological function, severely constraining their ability to detect early thrombus formation or the processes underlying such pathology. Recently, however, novel molecular and non-molecular imaging strategies have been developed to assess thrombus composition and activity at the molecular and cellular levels more accurately. These approaches have been successfully used to markedly reduce rates of atherothrombotic events in patients suffering from acute coronary syndrome (ACS) by facilitating simultaneous diagnosis and personalized treatment of thrombosis. Moreover, these modalities allow monitoring of plaque condition for preventing plaque rupture and associated adverse cardiovascular events in such patients. Sustained developments in molecular and non-molecular imaging technologies have enabled the increasingly specific and sensitive diagnosis of atherothrombosis in animal studies and clinical settings, making these technologies invaluable to patients' health in the future. In the present review, we discuss current progress regarding the non-molecular and molecular imaging of thrombosis in different animal studies and atherosclerotic patients.

Molecular and Nonmolecular Imaging of Macrophages in Atherosclerosis.

Atherosclerosis is a major cause of ischemic heart disease, and the increasing medical burden associated with atherosclerotic cardiovascular disease has become a major public health concern worldwide. Macrophages play an important role in all stages of the dynamic progress of atherosclerosis, from its initiation and lesion expansion increasing the vulnerability of plaques, to the formation of unstable plaques and clinical manifestations. Early imaging can identify patients at risk of coronary atherosclerotic disease and its complications, enabling preventive measures to be initiated. Recent advances in molecular imaging have involved the noninvasive and semi-quantitative targeted imaging of macrophages and their related molecules in vivo, which can detect atheroma earlier and more accurately than conventional imaging. Multimodal imaging integrates vascular structure, function, and molecular imaging technology to achieve multi-dimensional imaging, which can be used to comprehensively evaluate blood vessels and obtain clinical information based on anatomical structure and molecular level. At the same time, the rapid development of nonmolecular imaging technologies, such as intravascular imaging, which have the unique advantages of having intuitive accuracy and providing rich information to identify macrophage inflammation and inform targeted personalized treatment, has also been seen. In this review, we highlight recent methods and research hotspots in molecular and nonmolecular imaging of macrophages in atherosclerosis that have enormous potential for rapid clinical application.

Fluoride-Triggered Self-Degradation of Poly(2,4-disubstitued 4-hydroxybutyric acid) Derivatives.

Self-immolative polymers are a special kind of degradable polymers that depolymerize into small molecules through a cascade of reactions upon stimuli-triggered cleavage of the polymer chain ends. This work reports the design and synthesis of a fluoride-triggered self-immolative polyester. A 2,4-disubstitued 4-hydroxy butyrate is first confirmed to quickly cyclize in solution to form a γ-butyrolactone derivative. Then, the Passerini three component reaction (P-3CR) of an AB dimer (A: aldehyde, B: carboxylic acid) with tert-butyl isocyanide or oligo(ethylene glycol) isocyanide affords two poly(2,4-disubstitued 4-hydroxybutyrate) derivatives (P2 and P3). Two silyl ether end-capped polymers (P4 and P5) are abtained from P2 and P3, and their degradation in solution is examined by NMR spectrum and size exclusion chromatography. Polymers P4 and P5 are stable in the absence of tetrabutylammonium fluoride (TBAF), while in the presence of TBAF, the molar masses of P4 and P5 gradually decrease with time together with the increase of the amount of formed 2,4-disubstitued γ-butyrolactone. The depolymerization mechanism is proposed. The first step is the fast removal of the silyl ether by fluoride. Then, the released hydroxyl group initiates the quick head-to-tail depolymerization of the polyester via intramolecular cyclization.