Versatile Platinum Nanoparticles-Decorated Phage Nanozyme Integrating Recognition, Bacteriolysis, and Catalysis Capabilities for On-Site Detection of Foodborne Pathogenic Strains Vitality Based on Bioluminescence/Pressure Dual-Mode Bioassay.

Sensitive and on-site discrimination of live and dead foodborne pathogenic strains remains a significant challenge due to the lack of appropriate assay and signal probes. In this work, a versatile platinum nanoparticle-decorated phage nanozyme (P2@PtNPs) that integrated recognition, bacteriolysis, and catalysis was designed to establish the bioluminescence/pressure dual-mode bioassay for on-site determination of the vitality of foodborne pathogenic strains. Benefiting from the bacterial strain-level specificity of phage, the target Salmonella typhimurium (S.T) was specially captured to form sandwich complexes with P2@PtNPs on another phage-modified glass microbead (GM@P1). As the other part of the P2@PtNPs nanozyme, the introduced PtNPs could not only catalyze the decomposition of hydrogen peroxide to generate a significant oxygen pressure signal but also produce hydroxyl radicals around the target bacteria to enhance the bacteriolysis of phage and adenosine triphosphate release. It significantly improved the bioluminescence signal. The two signals corresponded to the total and live target bacteria counts, so the dead target could be easily calculated from the difference between the total and live target bacteria counts. Meanwhile, the vitality of S.T was realized according to the ratio of live and total S.T. Under optimal conditions, the application range of this proposed bioassay for bacterial vitality was 102-107 CFU/mL, with a limit of detections for total and live S.T of 30 CFU/mL and 40 CFU/mL, respectively. This work provides an innovative and versatile nanozyme signal probe for the on-site determination of bacterial vitality for food safety.

HuR promotes castration-resistant prostate cancer progression by altering ERK5 activation via posttranscriptional regulation of BCAT1.

BACKGROUND: Castration-resistant prostate cancer (CRPC) is refractory to hormone treatment, and the underlying mechanism has not been fully elucidated. This study aimed to clarify the role and mechanism of Human antigen R (HuR) as a therapeutic target for CRPC progression. METHODS: HuR was knocked out by Cas9 or inhibited by the HuR-specific inhibitor KH-3 in CRPC cell lines and in a mouse xenograft model. The effects of HuR inhibition on tumour cell behaviors and signal transduction were examined by proliferation, transwell, and tumour xenograft assays. Posttranscriptional regulation of BCAT1 by HuR was determined by half-life and RIP assays. RESULTS: HuR knockout attenuated the proliferation, migration, and invasion of PC3 and DU145 cells in vitro and inhibited tumour progression in vivo. Moreover, BCAT1 was a direct target gene of HuR and mediated the oncogenic effect of HuR on CRPC. Mechanistically, HuR directly interacted with BCAT1 mRNA and upregulated BCAT1 expression by increasing the stability and translation of BCAT1, which activated ERK5 signalling. Additionally, the HuR-specific inhibitor KH-3 attenuated CRPC progression by disrupting the HuR-BCAT1 interaction. CONCLUSIONS: We confirmed that the HuR/BCAT1 axis plays a crucial role in CRPC progression and suggest that inhibiting the HuR/BCAT1 axis is a promising therapeutic approach for suppressing CRPC progression.

Validation of Artificial Intelligence-based Bowel Preparation Assessment in Screening Colonoscopy.

BACKGROUND AND AIMS: Accurate bowel preparation assessment is essential for determining colonoscopy screening intervals. Patients with suboptimal bowel preparation are at a high risk of missing >5mm adenomas, and should undergo an early repeat colonoscopy. In this study, we employed artificial intelligence (AI) to evaluate bowel preparation and validated the ability of the system in accurately identifying patients who are at high risk of missing >5mm adenoma due to inadequate bowel preparation. PATIENTS AND METHODS: This prospective, single-center, observational study was conducted at the Eighth Affiliated Hospital, Sun Yat-sen University from October 8, 2021, to November 9, 2022. Eligible patients underwent screening colonoscopy were consecutively enrolled. The AI assessed bowel preparation using e-Boston Bowel Preparation Scale (BBPS) while endoscopists evaluated using BBPS. If both BBPS and e-BBPS deemed preparation adequate, the patient immediately underwent a second colonoscopy, otherwise the patient underwent bowel re-cleansing before the second colonoscopy. RESULTS: Among the 393 patients, 72 ＞5mm adenomas were detected, while 27 ＞5mm adenomas were missed. In unqualified-AI patients, the >5mm AMR was significantly higher than in qualified-AI patients (35.71% vs 13.19%, p=0.0056, OR 0.2734, 95% CI 0.1139, 0.6565), as were the AMR (50.89% vs 20.79%, p<0.001, OR 0.2532, 95% CI 0.1583, 0.4052) and >5mm PMR (35.82% vs 19.48%, p=0.0152, OR 0.4335, 95% CI 0.2288, 0.8213). CONCLUSIONS: This study confirmed that patients classified as inadequate by AI showed unacceptable >5mm AMR, provided key evidence for implementing AI in guiding the bowel re-cleansing, potentially standardizing the future colonoscopy screening; ClincialTrials.gov, NCT05145712.

Ultrasensitive and Specific Phage@DNAzyme Probe-Triggered Fluorescent Click Chemistry for On-Site Detection of Foodborne Pathogens Using a Smartphone.

Rapid, specific, and on-site detection of virulent foodborne pathogenic strains plays a key role in controlling food safety. In this work, an ultrasensitive and specific Phage@DNAzyme signal probe was designed to detect foodborne pathogens. The proposed sensing probe was composed of the selected phage and functionalized DNAzyme, which realized the specific recognition of target foodborne pathogens at the strain level and the efficient catalysis of copper(II) based azide-alkyne cycloaddition (CuAAC) click reaction with fluorescent signal, respectively. As a proof of concept, the virulent Escherichia coli O157:H7 (E. coli O157:H7) as the representative analyte was first enriched and purified from the complex food samples by a 4-mercaptophenylboronic acid-modified gold slide. Following, the Phage@DNAzyme probes were specifically combined with the captured E. coli O157: H7 and catalyzed the click reaction between 3-azido-7-hydroxycoumarin and 3-butyn-1-ol with the assistance of Cu(II) to generate a visual fluorescent signal. Finally, the corresponding fluorescent signals were measured by a smartphone to quantify the target concentrations. Under optimized conditions, the bioassay exhibited a wide linear range from 102 to 108 CFU/mL and the detection limit was 50 CFU/mL (S/N = 3). It was further extended to the detection of another foodborne pathogen Salmonella typhimurium with satisfying sensing performances. This work gives a new path for developing rapid, specific, and on-site detection methods for trace levels of pathogenic strains in foods.

Supermode Bragg grating inscribed in a strongly coupled seven-core fiber and its responses to temperature and curvature.

A Bragg grating is successfully inscribed in a piece of strongly coupled seven-core fiber (SCF). There are two separate Bragg resonance notches observed in the transmission spectrum, corresponding to backward coupling of HE11-like and HE12-like supermodes of the SCF. The mode coupling mechanism of the Bragg grating is theoretically investigated via modeling and analyzing modal properties of the SCF. The theoretical results agree well with the experimental results. Since the SCF is spliced between two standard single mode fibers with central alignments at both ends, the transmission spectrum of the device also contains a set of interference fringe due to modal interference between the supermodes. The device's responses to temperature and curvature are experimentally measured, respectively. The obtained temperature sensitivities and curvature sensitivities of the supermode Bragg grating notches are 9.55 pm/°C and 9.55 pm/°C, -1.8 pm/m-1 and -112.3 pm/m-1, respectively. The obtained temperature sensitivity and curvature sensitivity of one of the interference spectrum dips are 11.8 pm/°C and -3909.8 pm/m-1, respectively. This device is potentially useful for simultaneous measurement of temperature and curvature.

Real-time artificial intelligence for endoscopic diagnosis of early esophageal squamous cell cancer (with video).

BACKGROUND AND AIMS: Endoscopic diagnosis of early esophageal squamous cell cancer (ESCC) is complicated and dependent on operators' experience. This study aimed to develop an artificial intelligence (AI) model for automatic diagnosis of early ESCC. METHODS: Non-magnifying and magnifying endoscopic images of normal/noncancerous lesions, early ESCC, and advanced esophageal cancer (AEC) were retrospectively obtained from Qilu Hospital of Shandong University. A total of 10,988 images from 5075 cases were chosen for training and validation. Another 2309 images from 1055 cases were collected for testing. One hundred and four real-time videos were also collected to evaluate the diagnostic performance of the AI model. The diagnostic performance of the AI model was compared with endoscopists by magnifying images and the assistant efficiency of the AI model for novices was evaluated. RESULTS: The AI diagnosis for non-magnifying images showed a per-patient accuracy, sensitivity, and specificity of 99.5%, 100%, 99.5% for white light imaging, and 97.0%, 97.2%, 96.4% for optical enhancement/iodine straining images. Regarding diagnosis for magnifying images, the per-patient accuracy, sensitivity, and specificity were 88.1%, 90.9%, and 85.0%. The diagnostic accuracy of the AI model was similar to experts (84.5%, P = 0.205) and superior to novices (68.5%, P = 0.005). The diagnostic performance of novices was significantly improved by AI assistance. When it comes to the diagnosis for real-time videos, the AI model showed acceptable performance as well. CONCLUSIONS: The AI model could accurately recognize early ESCC among noncancerous mucosa and AEC. It could be a potential assistant for endoscopists, especially for novices.

Robust superhydrophobic cotton fabric based on dual-sized silica particles with self-healing nature.

Improving the durability of wear-resistant superhydrophobic surfaces is crucial for their practical use. To tackle this, research is now delving into self-healing superhydrophobic surfaces. In our study, we developed superhydrophobic cotton fabrics by embedding nano-silica particles, micro-silica powder, and polydimethylsiloxane (PDMS) using a dipping method. This innovative design grants the SiO2/PDMS cotton fabric remarkable superhydrophobicity, reflected by a water contact angle of 155°. Moreover, the PDMS was stored in the amorphous areas of cellulose of cotton fabrics, attaching to the fiber surface and playing a role in connecting micro-blocks and nano-particles. This causes a self-diffusion of PDMS molecules in these fabrics, allowing the surface to regain its superhydrophobicity even after abrasion damage. Impressively, this self-healing property can be renewed at least 8 times, showcasing the fabric's resilience. Moreover, these superhydrophobic cotton fabrics exhibit outstanding self-cleaning abilities and repel various substances such as blood, milk, cola, and tea. This resilience, coupled with its simplicity, low cost-effectiveness, and eco-friendliness, makes this coating highly promising for applications across construction, chemical, and medical fields. Our study also delves into understanding the self-healing mechanism of the SiO2/PDMS cotton fabric, offering insights into their long-term performance and potential advancements in this field.

A microfluidic chip platform based on Pt nanozyme and magnetized phage composite probes for dual-mode detecting and imaging pathogenic bacteria viability.

The detection of pathogen viability is critically important to evaluate its infectivity. In the study, an integrated microfluidic chip based on dual-mode analytical strategy was developed to rapidly realize detection of bacteria activity (with Salmonella typhimurium, S.T, as a model analyte). Firstly, the composite probes, including deactivated phage modified magnetic beads and nano Pt-antimicrobial peptide (AMP) which can specifically recognize Gram-negative bacteria as nanozyme were prepared. When the composite probes are introduced into the chip together with target bacteria, after enrichment, oscillating and magnetic separation, they will conjugate with S.T and produce a magnetic sandwich complex. The complex can catalyze tetramethylbenzidine (TMB)-H2O2 to produce visible colorimetric signals which is correspondent to the total S.T content. Simultaneously, PtNPs in the complex can produce hydroxyl radical oxidation (∙OH) by decomposing H2O2. Under the synergistic action of ∙OH and AMP, the captured live S.T can be lysed to release ATP and emit bioluminescence signals which corresponds to the live S.T concentration. Therefore, the chip can simultaneously detect and image S.T at different viability in one test. The dual-mode assay demonstrated high sensitivity (≤33 CFU/mL), high specificity (identifying strain), signal amplification (5 folds) and short time (≤40min). The chip array can detect four samples in one test and exhibited advantages of high-integration, -sensitivity, -specificity and miniaturization, which are suitable to rapidly detect and image pathogen's viability in trace level. The replacement of phage probes can detect other bacteria. It has a wide prospect in pathogens screening.

Caerin 1.9-Titanium Plates Aid Implant Healing and Inhibit Bacterial Growth in New Zealand Rabbit Mandibles.

OBJECTIVES: With rising rates of maxillofacial fracture, postoperative infection following rigid internal fixation is an important issue that requires immediate resolution. It is important to explore an alternative antibacterial method apart from conventional antibiotics. A controlled experiment was conducted to evaluate the effectiveness of a caerin 1.9 peptide-coated titanium plate in reducing mandibular infection in New Zealand (NZ) rabbits, aiming to minimise the risk of post-metallic implantation infection. METHODS: Twenty-two NZ rabbits were randomly divided into 3 groups. The experiment group received caerin 1.9 peptide-coated titanium plates and mixed oral bacteria exposure. The control group received normal titanium plates with mixed oral bacteria exposure. The untreated group served as a control to prove that bacteria in the mouth can cause infection. Weight, temperature, hepatic function, and C-reactive protein levels were measured. Wound and bone conditions were evaluated. Further analysis included local infection, anatomic conditions, histology, and bacterial load. RESULTS: No significant differences were found in temperature, weight, blood alanine aminotransferase, and C-reactive protein levels amongst the 3 groups. The experiment group showed the lowest amount of bacterial RNA in wounds. Additionally, the experiment group had higher peripheral lymphocyte counts compared to the control group and lower neutrophil counts on the third and seventh day postoperatively. Histologic analysis revealed lower levels of inflammatory cell infiltration, bleeding, and areas of necrosis in the experimental group compared with the controls. CONCLUSIONS: A caerin 1.9-coated titanium plate is able to inhibit bacterial growth in a NZ rabbit mandibular mixed bacteria infection model and is worth further investigation.

Tesla valve-assisted biosensor for dual-mode and dual-target simultaneous determination of foodborne pathogens based on phage/DNAzyme co-modified zeolitic imidazolate framework-encoded probes.

Sensitive and accurate detection of multiplex foodborne pathogens is crucial for food safety. In this work, a dual-mode and dual-target biosensor regulated by a Tesla valve was established for simultaneously determining Escherichia coli O157:H7 (E. coli) and Salmonella typhimurium (S. T). Two zeolitic imidazolate framework (ZIF-8) signal probes decorated with electroactive materials (ferrocene or methylene blue), DNAzyme, and different phages were synthesized to specifically recognize the targets and generate fluorescent/electrochemical dual-mode signals. In the presence of bacteria, they were captured and enriched on two individual working electrodes through the modified 4-mercaptophenylboric acid. The encoded signal probes added on different working electrodes could be conjugated with the corresponding target bacteria depending on the specificity of phages. Under the acidic condition, the DNAzyme could catalyze click chemistry for fluorescent signals. Simultaneously, the released ferrocene and methylene blue from ZIF-8 could generate electrochemical signals at different potentials. Benefiting from the flow regulation feature of the Tesla valve, the triggered fluorescent and electrochemical signals in the two individual electrodes would not influence each other, achieving simultaneous dual-mode and dual-target determination of foodborne pathogens. It depicted good linearity ranged 10-107 CFU mL-1. And the corresponding detection of limits were 5 CFU mL-1 and 8 CFU mL-1 for two bacteria, respectively. A low false positive was realized through the dual-mode strategy. The proposed biosensor can not only on-site, specifically, and sensitively determine E. coli and S. T, but also provide the wide prospect in rapid screening of other foodborne pathogens.

Efficient uranium(VI) adsorbing bioinspired nano-sized hydroxyapatite composites: synthesis, tuning, and adsorption mechanism.

The production of large amounts of uranium-containing wastewater and its potential hazards has stimulated green and efficient material removal of uranium (VI). Inspired by the natural mineralization of bone, a facile and eco-friendly biomimetic synthesis of nano-hydroxyapatite (HAP) was carried out using chitosan (CS) as a template. It was found that the reaction temperature and the amount of precursors influence the particle size, crystallinity and specific surface area of the CS/HAP nanorods, and consequently their U(VI) adsorption efficiency. Moreover, the synthesized CS/HAP-40 with smaller particle size, lower crystallinity, and larger specific surface area show a more efficient U(VI) removal compared with CS/HAP-55 and CS/HAP-55-AT. It has a maximum adsorption capacity of 294.12 mg·g-1 of the CS/HAP-40. Interestingly, the U(VI) removal mechanism of CS/HAP-40 in acidic (pH = 3) and alkaline (pH = 8) aqueous solutions was found to be different. As one of the main results, the U(VI) adsorption mechanisms at pH 8 could be surface complexation and ion exchange. On the contrary, three different mechanisms could be observed at pH 3: dissolution-precipitation to form chernikovite, surface complexation, and ion exchange.

Quantitative evaluation of viability- and apoptosis-related genes in Ascaris suum eggs under different culture-temperature conditions.

Ascaris suum eggs are inactivated by composting conditions; however, it is difficult to find functional changes in heat-treated A. suum eggs. Here, unembryonated A. suum eggs were incubated at 20°C, 50°C, and 70°C in vitro, and the gene expression levels related to viability, such as eukaryotic translation initiation factor 4E (IF4E), phosphofructokinase 1 (PFK1), and thioredoxin 1 (TRX1), and to apoptosis, such as apoptosis-inducing factor 1 (AIF1) and cell death protein 6 (CDP6), were evaluated by real-time quantitative RT-PCR. No prominent morphological alterations were noted in the eggs at 20°C until day 10. In contrast, the eggs developed rapidly, and embryonated eggs and hatched larvae began to die, starting on day 2 at 50°C and day 1 at 70°C. At 20°C, IF4E, PFK1, and TRX1 mRNA expression was significantly increased from days 2-4; however, AIF1 and CDP6 mRNA expression was not changed significantly. IF4E, PFK1, and TRX1 mRNA expression was markedly decreased from day 2 at 50° and 70°C, whereas AIF1 and CDP6 mRNA expression was significantly increased. The expressions of HSP70 and HSP90 were detected for 9-10 days at 20°C, for 3-5 days at 50°C, and for 2 days at 70°C. Taken together, incremental heat increases were associated with the rapid development of A. suum eggs, decreased expression of genes related to viability, and earlier expression of apoptosis-related genes, and finally these changes of viability- and apoptosis-related genes of A. suum eggs were associated with survival of the eggs under temperature stress.

A Modified Cuff Technique for Mouse Cervical Heterotopic Heart Transplantation Model.

Cardiac allograft rejection limits the long-term survival of patients after heart transplantation. A mouse heart transplantation model is ideal for investigating the mechanism of cardiac allograft rejection in preclinical studies because of their high homology with human genes. This understanding would help develop unique approaches to improving patients' long-term survival treated with cardiac allografts. In a mouse model, abdominal donor heart implantation is commonly performed with an end-to-side anastomosis to the recipient's aorta and inferior vena cava using stitches. In this model, the donor's heart is implanted by end-to-end anastomosis to the recipient's carotid artery and jugular vein by the modified-Cuff technique. The transplantation surgery is performed without stitching and thus may increase the survival of the recipient since there is no interference with the blood supply and venous reflux of the lower body. This mouse model would help investigate the mechanisms underlying the immunological and pathological (acute/chronic) rejection of cardiac allografts.

A Rat Orthotopic Renal Transplantation Model for Renal Allograft Rejection.

Renal allograft rejection limits the long-term survival of patients after renal transplantation. Rat orthotopic renal transplantation is an essential model to investigate the mechanism of renal allograft rejection in pre-clinical studies and could aid in the development of novel approaches to improve the long-term survival of renal allografts. Donor kidney implantation in rat orthotopic renal transplantation is commonly performed by end-to-side anastomosis to recipients' aorta and inferior vena cava. In this model, the donor's kidney was implanted using end-to-end anastomosis to the recipients' renal artery and renal vein. The donor's ureter was anastomosed to the recipient's bladder in an end-to-side 'tunnel' method. This model contributes to better healing of ureter-bladder anastomosis and increases the recipients' survival by avoiding interference with blood supply and venous reflux of the lower body. This model can be used to investigate the mechanisms of acute and chronic immune and pathologic rejection of renal allografts. Here, the study describes the detailed protocols of this orthotopic renal transplantation between rats.

Comparison of the similarity between two quantum images.

Comparing the similarity between digital images is an important subroutine in various image processing algorithms. In this study, we present three quantum algorithms for comparing the similarity between two quantum images. These algorithms are applied to binary, grey and color images for the first time. Without considering the image preparation, the proposed algorithms achieve exponential acceleration than the existing quantum and classical methods in all three cases. At the end of this paper, an experiment based on the real quantum computer of IBMQ and simulations verify the effectiveness of the algorithms.

The efficacy of conservative management after conization in patients with stage IA1 microinvasive cervical carcinoma.

OBJECTIVE: To investigate the efficacy of conization followed by conservative management for treating stage IA1 microinvasive carcinoma of the uterine cervix. DESIGN/SETTING: Retrospective study. POPULATION: Seventy-five patients treated for stage IA1 microinvasive carcinoma of the cervix. Patients underwent conization followed by hysterectomy (Group 1, 53 patients), or were followed by conservative management (Group 2, 22 patients). METHODS: Medical and histopathological record review. RESULTS: For Group 1, pathology results showed that 30 had no residual tumor, one had cervical intraepithelial neoplasia (CIN) I, 11 had CIN III/cervical carcinoma in situ (CIS), nine had microinvasive carcinomas, and one had an invasive carcinoma (outcome for one patient not recorded). For Group 2, secondary procedures involved only cervical smears for 12 (48%) patients, of whom nine had normal cytology, one had low-grade squamous intraepithelial lesion and two had high-grade squamous intraepithelial lesions. For 13 (52%) patients in Group 2, secondary procedures involved repeat conization on whom six had no residual tumor, one had CIN II, four CIN III/CIS, and two microinvasive carcinoma and a negative resection margin. Therefore, conization followed by conservative management was an effective treatment for 90.9% (20/22) of Group 2. In neither group was recurrence recorded. There was no relation between lymphovascular invasion and follow-up cytology or pathology results, or between resection margin status and follow-up examination results. CONCLUSION: Conization alone with careful follow-up appears to be an effective and safe treatment for patients with stage IA1 microinvasive carcinoma of the uterine cervix, regardless of resection margins status or lymphovascular invasion.

Quantitative Evaluation of Viability- and Apoptosis-Related Genes in Ascaris suum Eggs under Different Culture-Temperature Conditions

Ascaris suum eggs are inactivated by composting conditions; however, it is difficult to find functional changes in heat-treated A. suum eggs. Here, unembryonated A. suum eggs were incubated at 20degrees C, 50degrees C, and 70degrees C in vitro, and the gene expression levels related to viability, such as eukaryotic translation initiation factor 4E (IF4E), phosphofructokinase 1 (PFK1), and thioredoxin 1 (TRX1), and to apoptosis, such as apoptosis-inducing factor 1 (AIF1) and cell death protein 6 (CDP6), were evaluated by real-time quantitative RT-PCR. No prominent morphological alterations were noted in the eggs at 20degrees C until day 10. In contrast, the eggs developed rapidly, and embryonated eggs and hatched larvae began to die, starting on day 2 at 50degrees C and day 1 at 70degrees C. At 20degrees C, IF4E, PFK1, and TRX1 mRNA expression was significantly increased from days 2-4; however, AIF1 and CDP6 mRNA expression was not changed significantly. IF4E, PFK1, and TRX1 mRNA expression was markedly decreased from day 2 at 50degrees C and 70degrees C, whereas AIF1 and CDP6 mRNA expression was significantly increased. The expressions of HSP70 and HSP90 were detected for 9-10 days at 20degrees C, for 3-5 days at 50degrees C, and for 2 days at 70degrees C. Taken together, incremental heat increases were associated with the rapid development of A. suum eggs, decreased expression of genes related to viability, and earlier expression of apoptosis-related genes, and finally these changes of viability- and apoptosis-related genes of A. suum eggs were associated with survival of the eggs under temperature stress.