Enhanced removal of ciprofloxacin and associated antibiotic-resistant genes from wastewater using a biological aeration filters in combination with Fe3O4-modified zeolite.

Antibiotics release into the water environment through sewage discharge is a significant environmental concern. In the present study, we investigated the removal of ciprofloxacin (CIP) in simulated sewage by biological aeration filter (BAF) equipped with Fe3O4-modified zeolite (Fe3O4@ZF). Fe3O4@ZF were prepared with impregnation method, and the Fe3O4 particles were successfully deposited on the surface of ZF in an amorphous form according to the results of XPS and XRD analysis. The modification also increased the specific surface area (from 16.22 m²/g to 22 m²/g) and pore volume (from 0.0047 cm³/g to 0.0063 cm³/g), improving the adsorption efficiency of antibiotics. Fe3O4 modified ZF improved the treatment performance significantly, and the removal efficiency of CIP in BAF-Fe3O4@ZF was 79%±2.4%. At 10ml/L CIP, the BAF-Fe3O4@ZF reduced the relative abundances of antibiotics resistance genes (ARGs) int, mexA, qnrB and qnrS in the effluent by 57.16%, 39.59%, 60.22%, and 20.25%, respectively, which effectively mitigate the dissemination risk of ARGs. The modification of ZF increased CIP-degrading bacteria abundance, such as Rhizobium and Deinococcus-Thermus, and doubled bacterial ATP activity, promoting CIP degradation. This study offers a viable, efficient method to enhance antibiotic treatment and prevent leakage via sewage discharge.

[Determination of 11 nutrients in liquid milk by ultra-performance liquid chromatography-tandem mass spectrometry].

OBJECTIVE: To establish an ultra-performance liquid chromatography-tandem mass spectrometry(UPLC-MS/MS) method for simultaneous determination of 11 nutritional components(thiamine, riboflavin, nicotinamide, nicotinic acid, pantothenic acid, pyridoxine, pyridoxal, pyridoxamine, biotin, choline, L-carnitine) in liquid milk. METHODS: Milk samples were shaken with 20 mmol/L ammonium formate solution and heated in a water bath at 100 ℃ for 30 min, then incubated with papain and acid phosphatase at 45 ℃ for 16 h, the lower liquid was collected after centrifugation for analysis. UPLC separation was performed on an ACQUITY~(TM) HSS T3(3.0 mm×150 mm, 1.8 µm) column, 2 mmol/L ammonium formate(containing 0.1% formic acid) solution and acetonitrile(containing 0.1% formic acid) were used as mobile phase. Quantitative detection was performed by internal standard method. RESULTS: 11 nutritional components can be effectively separated and detected in 12 min, and the linear correlation coefficients(R~2) were all above 0.995. The limits of detection(LODs) were between 0.05 and 0.50 µg/L, and the limits of quantification(LOQs) were between 0.20 and 1.25 µg/L. The recovery rates of three-level addition were 85.6%-119.3%, and the precision RSDs were between 3.68% and 7.82%(n=6). Based on the detection of 60 liquid milk samples from 5 different animals, it was found that the contents of 11 nutrients in liquid milk from different milk sources were significantly different, but pyridoxine could not be detected. CONCLUSION: The method can quantitatively detect 11 water-soluble nutrients, including free and bound forms, by effective enzymolysis. It is sensitive, reproducible and can meet the needs of quantitative detection.

Unexpected submucosal lesion with malignant potential.

The inverted hyperplastic polyp (IHP) is known as hyperplastic gastric mucosa growth into submucosa and endoscopically presented as sessile or pedunculated submucosa lesion. It occurs in between 3.1% to 20.1% of cases, while its malignant transformation rate is just 0.02%. A male underwent esophagogastroduodenoscopy (EGD) and discovered a submucosal lesion with a pinhole-like orifice in the fundus. And endoscopic ultrasound (EUS) showed it was a heterogenous hypoechoic lesion located in the submucosa. After endoscopic resection, the pathological findings and immunohistochemical staining revealed it was inverted hyperplastic polyp (IHP) with adenocarcinoma. The measurement of the cancerous IHP depth of invasion is controversial. Thus, how to define the depth of lesion invasion in this patient needs to be seriously considered. To manage IHP with adenocarcinoma better, the depth of lesion invasion cancerous IHP needs to be seriously considered.

USP47 deficiency in mice modulates tumor infiltrating immune cells and enhances antitumor immune responses in prostate cancer.

This study investigates the role of USP47, a deubiquitinating enzyme, in the tumor microenvironment and its impact on antitumor immune responses. Analysis of TCGA database revealed distinct expression patterns of USP47 in various tumor tissues and normal tissues. Prostate adenocarcinoma showed significant downregulation of USP47 compared to normal tissue. Correlation analysis demonstrated a positive association between USP47 expression levels and infiltrating CD8+ T cells, neutrophils, and macrophages, while showing a negative correlation with NKT cells. Furthermore, using Usp47 knockout mice, we observed a slower tumor growth rate and reduced tumor burden. The absence of USP47 led to increased infiltration of immune cells, including neutrophils, macrophages, NK cells, NKT cells, and T cells. Additionally, USP47 deficiency resulted in enhanced activation of cytotoxic T lymphocytes (CTLs) and altered T cell subsets within the tumor microenvironment. These findings suggest that USP47 plays a critical role in modulating the tumor microenvironment and promoting antitumor immune responses, highlighting its potential as a therapeutic target in prostate cancer.

WS2 ribbon arrays with defined chirality and coherent polarity.

One-dimensional transition metal dichalcogenides exhibiting an enhanced bulk photovoltaic effect have the potential to exceed the Shockley-Queisser limit efficiency in solar energy harvest within p-n junction architectures. However, the collective output of these prototype devices remains a challenge. We report on the synthesis of single-crystalline WS2 ribbon arrays with defined chirality and coherent polarity through an atomic manufacturing strategy. The chirality of WS2 ribbon was defined by substrate couplings into tunable armchair, zigzag, and chiral species, and the polarity direction was determined by the ribbon-precursor interfacial energy along a coherent direction. A single armchair ribbon showed strong bulk photovoltaic effect and the further integration of ~1000 aligned ribbons with coherent polarity enabled upscaling of the photocurrent.

Glycolytic lactate in diabetic kidney disease.

Lactate elevation is a well-characterized biomarker of mitochondrial dysfunction, but its role in diabetic kidney disease (DKD) is not well defined. Urine lactate was measured in patients with type 2 diabetes (T2D) in 3 cohorts (HUNT3, SMART2D, CRIC). Urine and plasma lactate were measured during euglycemic and hyperglycemic clamps in participants with type 1 diabetes (T1D). Patients in the HUNT3 cohort with DKD had elevated urine lactate levels compared with age- and sex-matched controls. In patients in the SMART2D and CRIC cohorts, the third tertile of urine lactate/creatinine was associated with more rapid estimated glomerular filtration rate decline, relative to first tertile. Patients with T1D demonstrated a strong association between glucose and lactate in both plasma and urine. Glucose-stimulated lactate likely derives in part from proximal tubular cells, since lactate production was attenuated with sodium-glucose cotransporter-2 (SGLT2) inhibition in kidney sections and in SGLT2-deficient mice. Several glycolytic genes were elevated in human diabetic proximal tubules. Lactate levels above 2.5 mM potently inhibited mitochondrial oxidative phosphorylation in human proximal tubule (HK2) cells. We conclude that increased lactate production under diabetic conditions can contribute to mitochondrial dysfunction and become a feed-forward component to DKD pathogenesis.

A simple and economical method for unbiasedly quantifying the alveolar size of entire mouse lung tissue utilizing Hematoxylin and Eosin Staining.

Alveolar, the smallest structural and functional units within the respiratory system, play a crucial role in maintaining lung function. Alveolar damage is a typical pathological hallmark of respiratory diseases. Nevertheless, there is currently no simple, rapid, economical, and unbiased method for quantifying alveolar size for entire lung tissue. Here, firstly, we conducted lung sample slicing based on the size, shape, and distribution of airway branches of different lobes. Next, we performed HE staining on different slices. Then, we provided an unbiased quantification of alveolar size using free software ImageJ. Through this protocol, we demonstrated that C57Bl/6 mice exhibit varying alveolar sizes among different lobes. Collectively, we provided a simple and unbiased method for a more comprehensive quantification of alveolar size in mice, which holds promise for a broader range of respiratory research using mouse models.

Impact of Obesity on Midurethral Sling Failure in a Highly Hispanic Population.

IMPORTANCE: Mixed data exist in the literature regarding the impact of obesity on midurethral sling (MUS) failure rates. OBJECTIVE: The aim of this study was to evaluate the impact of obesity and Hispanic ethnicity on MUS failure. STUDY DESIGN: This was a retrospective cohort study of females who underwent MUS surgery, alone or with concomitant prolapse repair, with at least 1 year of follow-up. Body mass index (BMI) classes were categorized as normal (<25 kg/m2), overweight (25-29.9 kg/m2), obese (30-39.9 kg/m2), and severe obesity (≥40 kg/m2). The primary outcome was MUS failure, defined as a composite of subjectively unchanged or worsened symptoms or need for additional procedures. Secondary outcomes included risk factors related to MUS failure and the effect of ethnicity on MUS failure rates. RESULTS: A total of 322 women were included for analysis. The mean age was 52.3 years. Increasing BMI was associated with higher MUS failure, with multivariate logistic regression showing a 5% increased risk for each 1 kg/m2 BMI increase. Failure rates were significantly different between normal BMI and severe obesity (16.7% vs 36.4%, P = 0.04). After adjusting for other variables, transobturator slings had a higher risk of failure compared with retropubic slings, whereas surgeon training and patient ethnicity did not affect failure rates. CONCLUSIONS: We found that increasing BMI was associated with higher MUS failures, with significantly higher failure rates in the severely obese population. Although MUS remains the standard of care for treatment of SUI, based on our findings, counseling should be individualized to the patient, taking into account each patient's unique characteristics.

A G-quadruplex-binding platinum complex induces cancer mitochondrial dysfunction through dual-targeting mitochondrial and nuclear G4 enriched genome.

BACKGROUND: G-quadruplex DNA (G4) is a non-canonical structure forming in guanine-rich regions, which play a vital role in cancer biology and are now being acknowledged in both nuclear and mitochondrial (mt) genome. However, the impact of G4-based targeted therapy on both nuclear and mt genome, affecting mt function and its underlying mechanisms remain largely unexplored. METHODS: The mechanisms of action and therapeutic effects of a G4-binding platinum(II) complex, Pt-ttpy, on mitochondria were conducted through a comprehensive approaches with in vitro and in vivo models, including ICP-MS for platinum measurement, PCR-based genetic analysis, western blotting (WB), confocal microscope for mt morphology study, extracellular flux analyzer, JC1 and Annexin V apoptosis assay, flow cytometry and high content microscope screening with single-cell quantification of both ROS and mt specific ROS, as well as click-chemistry for IF study of mt translation. Decipher Pt-ttpy effects on nuclear-encoded mt related genes expression were undertaken via RNA-seq, Chip-seq and CUT-RUN assays. RESULTS: Pt-ttpy, shows a highest accumulation in the mitochondria of A2780 cancer cells as compared with two other platinum(II) complexes with no/weak G4-binding properties, Pt-tpy and cisplatin. Pt-ttpy induces mtDNA deletion, copy reduction and transcription inhibition, hindering mt protein translation. Functional analysis reveals potent mt dysfunction without reactive oxygen species (ROS) induction. Mechanistic study provided first evidence that most of mt ribosome genes are highly enriched in G4 structures in their promoter regions, notably, Pt-ttpy impairs most nuclear-encoded mt ribosome genes' transcription through dampening the recruiting of transcription initiation and elongation factors of NELFB and TAF1 to their promoter with G4-enriched sequences. In vivo studies show Pt-ttpy's efficient anti-tumor effects, disrupting mt genome function with fewer side effects than cisplatin. CONCLUSION: This study underscores Pt-ttpy as a G4-binding platinum(II) complex, effectively targeting cancer mitochondria through dual action on mt and nuclear G4-enriched genomes without inducing ROS, offering promise for safer and effective platinum-based G4-targeted cancer therapy.

Study on fingerprint and quantitative analysis of Verbena officinalis water extract by LC-MS and HPLC.

Verbena officinalis L. as a medical plant has been used to treat many diseases. However, the quality control underlying V. officinalis remains to be studied. HPLC fingerprint analysis and the qualitative and quantitative analysis of water extract from V. officinalis were carried out, and it was found that the quality varies according to habitat and batch. Verbenalin could be a crucial component in the quality evaluation of V. officinalis. This study contributes to better understanding of quality control for V. officinalis.

Bevel-edge epitaxy of ferroelectric rhombohedral boron nitride single crystal.

Within the family of two-dimensional dielectrics, rhombohedral boron nitride (rBN) is considerably promising owing to having not only the superior properties of hexagonal boron nitride1-4-including low permittivity and dissipation, strong electrical insulation, good chemical stability, high thermal conductivity and atomic flatness without dangling bonds-but also useful optical nonlinearity and interfacial ferroelectricity originating from the broken in-plane and out-of-plane centrosymmetry5-23. However, the preparation of large-sized single-crystal rBN layers remains a challenge24-26, owing to the requisite unprecedented growth controls to coordinate the lattice orientation of each layer and the sliding vector of every interface. Here we report a facile methodology using bevel-edge epitaxy to prepare centimetre-sized single-crystal rBN layers with exact interlayer ABC stacking on a vicinal nickel surface. We realized successful accurate fabrication over a single-crystal nickel substrate with bunched step edges of the terrace facet (100) at the bevel facet (110), which simultaneously guided the consistent boron-nitrogen bond orientation in each BN layer and the rhombohedral stacking of BN layers via nucleation near each bevel facet. The pure rhombohedral phase of the as-grown BN layers was verified, and consequently showed robust, homogeneous and switchable ferroelectricity with a high Curie temperature. Our work provides an effective route for accurate stacking-controlled growth of single-crystal two-dimensional layers and presents a foundation for applicable multifunctional devices based on stacked two-dimensional materials.

Characterization of phospholipidome in milk, yogurt and cream, and phospholipid differences related to various dairy processing methods.

Milk phospholipids have multiple health benefits, but the deficiency of detailed phospholipid profiles in dairy products brings obstacles to intake calculation and function evaluation of dairy phospholipids. In present study, 306 phospholipid molecular species were identified and quantified among 207 milk, yogurt and cream products using a HILIC-ESI-Q-TOF MS and a HILIC-ESI-QQQ MS. The phospholipid profiles of five mammals' milk show that camel milk contains the most abundant phosphatidylethanolamine, phosphatidylserine and sphingomyelin; cow, yak and goat milk have similar phospholipidomes, while buffalo milk contains abundant phosphatidylinositol. Fewer plasmalogens but more lyso-glycerolphospholipids were found in ultra-high-temperature (UHT) sterilized milk than in pasteurized milk, and higher proportions of lyso-glycerolphospholipid/total phospholipid were observed in both cream and skimmed/semi-skimmed milk than whole milk, indicating that UHT and skimming processes improve glycerolphospholipid degradation and phospholipid nutrition loss. Meanwhile, more diacyl-glycerolphospholipids and less of their degradation products make yogurt a better phospholipid resource than whole milk.

[Changes in fingerprint and chromaticity values of Mori Cortex during stir-frying process].

This study aims to reveal the dynamics of the HPLC fingerprint, chromaticity values, and main chemical components of Mori Cortex during the stir-frying process. The fingerprints of raw and processed products of Mori Cortex were established. The content of mulberroside A, oxyresveratrol, kuwanon G, and kuwanon H in the samples and the chromaticity values of the samples were determined. Furthermore, the similarity evaluation of fingerprints and the correlation analysis between fingerprints and chromaticity values were carried out. The results showed that the fingerprints of raw and processed products of Mori Cortex had high similarity, and the overall changes in the content of the main chemical components in the stir-frying process were similar. According to the experience, when the stir-frying is moderate, the total chromaticity value difference |ΔE~*_(ab)| is above 1.5. With the extension of stir-frying time, the L~* and E~*_(ab) values keep decreasing, and the a~* value keeps increasing. The results of the correlation analysis between fingerprints and chromaticity values showed that peaks 1(5-hydroxy maltol), 2(mulberroside A), 3, 4, 6, 7, 11(oxyresveratrol), 14, 17(kuwanon G), and 18(kuwanon H) had significant correlations with the chromaticity values. Quantitative analysis of the four components with higher content showed that the content of the four components decreased to varying degrees when the stir-frying was excessive. In addition, 5-hydroxy maltol was produced after stir-frying of Mori Cortex, and the fingerprint and chromaticity values showed regular changes during the stir-frying process. The chromaticity can be included in the evaluation of the stir-frying process of Mori Cortex, which provides a reference for standardizing the quality of stir-fried Mori Cortex.

Human Biomonitoring of Environmental Chemicals among Elderly in Wuhan, China: Prioritizing Risks Using EPA's ToxCast Database.

In line with the "healthy aging" principle, we aim to assess the exposure map and health risks of environmental chemicals in the elderly. Blood samples from 918 elderly individuals in Wuhan, China, were analyzed using the combined gas/liquid-mass spectrometry technology to detect levels of 118 environmental chemicals. Cluster analysis identified exposure profiles, while risk indexes and bioanalytical equivalence percentages were calculated using EPA's ToxCast database. The detection rates for 87 compounds exceeded 70%. DEHP, DiBP, naphthalene, phenanthrene, DnBP, pyrene, anthracene, permethrin, fluoranthene, and PFOS showed the highest concentrations. Fat-soluble pollutants varied across lifestyles. In cluster 2, which was characterized by higher concentrations of fat-soluble substances, the proportion of smokers or drinkers was higher than that of nonsmokers or nondrinkers. Pesticides emerged as the most active environmental chemicals in peroxisome proliferator-activated receptor gamma antagonist, thyroid hormone receptor (TR) antagonist, TR agonist, and androgen receptor (AR) agonist activity assays. Additionally, PAEs and polycyclic aromatic hydrocarbons played significant roles as active contaminants for the corresponding targets of AR antagonists and estrogen receptor alpha. We proposed a list of priority pollutants linked to endocrine-disrupting toxic effects in the elderly, which may provide the groundwork for further research into environmental etiology.

Prevalence of synthetic phenolic antioxidants in food contact materials from China and their implications for human dietary exposure through take-away food.

The application of disposable tableware has increased substantially in recent times due to the rapidly growing food delivery business in China. Synthetic phenolic antioxidants (SPAs) are widely used in food contact materials (FCMs) to delay the process of oxidation; however, their compositions, concentrations, and potential health hazards remain unclear. Therefore, FCMs comprised of five materials obtained from 19 categories (n = 118) in China were analyzed for SPAs concentrations. FCMs have been found to contain a variety of SPAs, with ∑SPAs concentrations ranging from 44.18 to 69,485.12 µg/kg (median: 2615.63 µg/kg). The predominant congeners identified in the sample include 2,4-di-tert-butylphenol (2,4-DTBP), 2,6-di-tert-butylphenol (2,6-DTBP), and 2,6-di-tert-butyl-p-benzoquinone (BHT-Q) with a median concentration of 885.75, 555.45 and of 217.44 µg/kg, respectively. Milky tea paper cups, instant noodle buckets, milky teacups, and disposable cups showed high levels of SPAs. 2,2'-methylenebis(4-methyl-6-tert-butylphenol) (AO 2246) was predominantly detected in polyethylene and polyethylene terephthalate-based products. The migration test identified disposable plastic cups and bowls as the predominant FCMs and 2,4-DTBP as the dominant SPA. The exposure risk of SPAs decreased with age. In children, the estimated daily intake of ∑SPAs from FCMs was determined to be 17.56 ng/kg body weight/day, which was 8.3 times higher than that of phthalic acid esters. The current findings indicate the potential ingestion risk of SPAs during the daily life application of multiple FCM categories.

Radiating blood flow signal: A new ultrasound feature of thyroid carcinoma.

OBJECTIVE: To summary radiating blood flow signals and evaluate their diagnostic value in differentiating benign and malignant thyroid nodules. MATERIALS AND METHODS: We retrospectively recruited consecutive patients undergoing US at 4 hospitals from 2018 to 2022. In a training dataset, the correlations of US features with malignant thyroid nodules were assessed by multivariate logistic analysis. Multivariate logistic regression models involving the ACR TI-RADS score, radiating blood flow signals and their combination were built and validated internally and externally. The AUC with 95% asymptotic normal confidence interval as well as sensitivity, specificity, negative predictive value (NPV), and positive predictive value (PPV) with 95% exact binomial confidence intervals were calculated. RESULTS: Among 2475 patients (1818 women, age: 42.47 ± 11.57; 657 men, age: 42.16 ± 11.69), there were 3187 nodules (2342 malignant nodules and 845 benign nodules). Radiating blood flow signals were an independent risk factor for diagnosing thyroid carcinoma. In the training set, the AUC of the model using the combination of radiating blood flow signals and the ACR TI-RADS score (0.95 95 % CI: [0.94, 0.97]; P < 0.001) was significantly higher than that of the ACR TI-RADS model (0.91 [0.89, 0.93]). In the two internal validation sets and the external validation set, the AUCs of the combination model were 0.97 [0.96, 0.98], 0.92 [0.88, 0.96], and 0.91 [0.86, 0.95], respectively, and were all significantly higher than that of the ACR TI-RADS score (0.92 [0.90, 0.95], 0.86 [0.81, 0.91], 0.84 [0.79, 0.89]; P < 0.001). CONCLUSION: Radiating blood flow is a new US feature of thyroid carcinomas that can significantly improve the diagnostic performance vs. the ACR TI-RADS score.

ML365 ameliorates postoperative cognitive impairment in aged mice by inhibiting NLRP3 inflammasome activation in the hippocampus.

The aim of this study was to examine the effects of ML365, a two-pore potassium channel (K2P) inhibitor, on postoperative cognitive impairment (POCD). A mouse model of POCD was constructed by subjecting aged C57BL/6 mice to exploratory laparotomy. Changes in cognitive function were assessed using the Morris water maze test. Western blotting and qPCR were used to detect hippocampal NLRP3, Caspase-1 and IL-1ß expression levels on days 3 and 7 post-surgery. Apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC) expression level was also assessed by western blotting. Pathological changes and nerve damage in the hippocampal CA1 and CA3 regions were detected by H&E staining, while the concentration of malondialdehyde (MDA) in the plasma was measured. We found that pretreatment with ML365 (administered intraperitoneally at a dose of 10 mg/kg) 30 min prior to exploratory laparotomy effectively ameliorated POCD in mice. ML365 pretreatment also reduced NLRP3, Caspase-1, ASC and IL-1ß expression levels in the hippocampus, improved POCD-induced pathological changes in the hippocampal CA1 and CA3 areas of aged mice, and decreased levels of plasma MDA and oxidative stress. Together, our findings indicate that ML365 can alleviate POCD in mice by inhibiting NLRP3 inflammasome activation in the hippocampus.

HA2-FimA DNA Vaccine Treats Experimental Periodontitis.

PURPOSE: To study the therapeutic effect of hemagglutinin-2 and fimbrial (HA2-FimA) vaccine on experimental periodontitis in rats. MATERIALS AND METHODS: The first batch of rats was divided into two groups and immunised with pure water or pVAX1-HA2-FimA at the age of 6, 7, and 9 weeks. After sacrificing the animals, total RNA was extracted from the spleens for RNA high-throughput sequencing (RNA-Seq) analysis. The second batch of rats was divided into four groups (A, B, C, D), and an experimental periodontitis rat model was established by suturing silk thread around the maxillary second molars of rats in groups B, C, and D for 4 weeks. The rats were immunised with pure water, pVAX1-HA2-FimA vaccine, empty pVAX1 vector, and pure water at 10, 11, and 13 weeks of age, respectively. Secretory immunoglobulin A (SIgA) antibodies and cathelicidin antimicrobial peptide (CAMP) levels in saliva were measured by enzyme-linked immunosorbent assay (ELISA). All rats were euthanised at 17 weeks of age, and alveolar bone loss was examined using micro-computed tomography (Micro-CT). RESULTS: Through sequencing analysis, six key genes, including Camp, were identified. Compared with the other three groups, the rats in the periodontitis+pVAX1-HA2-FimA vaccine group showed higher levels of SIgA and CAMP (p < 0.05). Micro-CT results showed significantly less alveolar bone loss in the periodontitis+pVAX1-HA2-FimA vaccine group compared to the periodontitis+pVAX1 group and periodontitis+pure water group (p < 0.05). CONCLUSION: HA2-FimA DNA vaccine can increase the levels of SIgA and CAMP in the saliva of experimental periodontitis model rats and reduce alveolar bone loss.

Prototype Learning for Medical Time Series Classification via Human-Machine Collaboration.

Deep neural networks must address the dual challenge of delivering high-accuracy predictions and providing user-friendly explanations. While deep models are widely used in the field of time series modeling, deciphering the core principles that govern the models' outputs remains a significant challenge. This is crucial for fostering the development of trusted models and facilitating domain expert validation, thereby empowering users and domain experts to utilize them confidently in high-risk decision-making contexts (e.g., decision-support systems in healthcare). In this work, we put forward a deep prototype learning model that supports interpretable and manipulable modeling and classification of medical time series (i.e., ECG signal). Specifically, we first optimize the representation of single heartbeat data by employing a bidirectional long short-term memory and attention mechanism, and then construct prototypes during the training phase. The final classification outcomes (i.e., normal sinus rhythm, atrial fibrillation, and other rhythm) are determined by comparing the input with the obtained prototypes. Moreover, the proposed model presents a human-machine collaboration mechanism, allowing domain experts to refine the prototypes by integrating their expertise to further enhance the model's performance (contrary to the human-in-the-loop paradigm, where humans primarily act as supervisors or correctors, intervening when required, our approach focuses on a human-machine collaboration, wherein both parties engage as partners, enabling more fluid and integrated interactions). The experimental outcomes presented herein delineate that, within the realm of binary classification tasks-specifically distinguishing between normal sinus rhythm and atrial fibrillation-our proposed model, albeit registering marginally lower performance in comparison to certain established baseline models such as Convolutional Neural Networks (CNNs) and bidirectional long short-term memory with attention mechanisms (Bi-LSTMAttns), evidently surpasses other contemporary state-of-the-art prototype baseline models. Moreover, it demonstrates significantly enhanced performance relative to these prototype baseline models in the context of triple classification tasks, which encompass normal sinus rhythm, atrial fibrillation, and other rhythm classifications. The proposed model manifests a commendable prediction accuracy of 0.8414, coupled with macro precision, recall, and F1-score metrics of 0.8449, 0.8224, and 0.8235, respectively, achieving both high classification accuracy as well as good interpretability.