Intraductal photothermal ablation: a noninvasive approach for early breast cancer treatment and prevention.

Background: Innovative treatment strategies for early-stage breast cancer (BC) are urgently needed. Tumors originating from mammary ductal cells present an opportunity for targeted intervention. Methods: We explored intraductal therapy via natural nipple openings as a promising non-invasive approach for early BC. Using functional Near-infrared II (NIR-II) nanomaterials, specifically NIR-IIb quantum dots conjugated with Epep polypeptide for ductal cell targeting, we conducted in situ imaging and photothermal ablation of mammary ducts. Intraductal administration was followed by stimulation with an 808 nm laser. Results: This method achieved precise ductal destruction and heightened immunological responses in the microenvironment. The technique was validated in mouse models of triple-negative BC and a rat model of ductal carcinoma in situ, demonstrating promising therapeutic potential for localized BC treatment and prevention. Conclusion: Our study demonstrated the effectiveness of NIR-II nanoprobes in guiding non-invasive photothermal ablation of mammary ducts, offering a compelling avenue for early-stage BC therapy.

Identification of Hypoxia and Mitochondrial-related Gene Signature and Prediction of Prognostic Model in Lung Adenocarcinoma.

Background: The correlation between hypoxia and tumor development is widely acknowledged. Meanwhile, the foremost organelle affected by hypoxia is mitochondria. This study aims to determine whether they possess prognostic characteristics in lung adenocarcinoma (LUAD). For this purpose, a bioinformatics analysis was conducted to assess hypoxia and mitochondrial scores related genes, resulting in the successful establishment of a prognostic model. Methods: Using the single sample Gene Set Enrichment Analysis algorithm, the hypoxia and mitochondrial scores were computed. Differential expression analysis and weighted correlation network analysis were employed to identify genes associated with hypoxia and mitochondrial scores. Prognosis-related genes were obtained through univariate Cox regression, followed by the establishment of a prognostic model using least absolute shrinkage and selection operator Cox regression. Two independent validation datasets were utilized to verify the accuracy of the prognostic model using receiver operating characteristic and calibration curves. Additionally, a nomogram was employed to illustrate the clinical significance of this study. Results: 318 differentially expressed genes associated with hypoxia and mitochondrial scores were identified for the construction of a prognostic model. The prognostic model based on 16 genes, including PKM, S100A16, RRAS, TUBA4A, PKP3, KCTD12, LPGAT1, ITPRID2, MZT2A, LIFR, PTPRM, LATS2, PDIK1L, GORAB, PCDH7, and CPED1, demonstrates good predictive accuracy for LUAD prognosis. Furthermore, tumor microenvironments analysis and drug sensitivity analysis indicate an association between risk scores and certain immune cells, and a higher risk scores suggesting improved chemotherapy efficacy. Conclusion: The research established a prognostic model consisting of 16 genes, and a nomogram was developed to accurately predict the prognosis of LUAD patients. These findings may contribute to guiding clinical decision-making and treatment selection for patients with LUAD, ultimately leading to improved treatment outcomes.

A Strong Supramolecular Mechanophore with Controlled Mechanical Strength.

Supramolecular mechanophores typically exhibit much lower mechanical strengths than covalent counterparts, with strengths usually around 100 pN, which is significantly lower than the nN-scale strength of covalent bonds. Inspired by the slow dissociation kinetics of the cucurbit[7]uril (CB[7])-hexanoate-isoquinoline (HIQ) complex, we discovered that charge-dipole repulsion can be utilized to create strong supramolecular mechanophores. When activated at its -COO- state, the CB[7]-HIQ complex exhibits a high mechanical strength of ~700 pN, comparable to weak covalent bonds such as Au-S bonds or a thiol-maleimide adducts. The strength of the CB[7]-HIQ complex can also be tuned with pH in a gradual manner, with a minimum value of ~150 pN at its -COOH state, similar to an ordinary supramolecular conjugate. This research may pave the way for the development of supramolecular architectures that combine the advantages of covalent and supramolecular systems.

A pan-KRAS degrader for the treatment of KRAS-mutant cancers.

KRAS mutations are highly prevalent in a wide range of lethal cancers, and these mutant forms of KRAS play a crucial role in driving cancer progression and conferring resistance to treatment. While there have been advancements in the development of small molecules to target specific KRAS mutants, the presence of undruggable mutants and the emergence of secondary mutations continue to pose challenges in the clinical treatment of KRAS-mutant cancers. In this study, we developed a novel molecular tool called tumor-targeting KRAS degrader (TKD) that effectively targets a wide range of KRAS mutants. TKD is composed of a KRAS-binding nanobody, a cell-penetrating peptide selectively targeting cancer cells, and a lysosome-binding motif. Our data revealed that TKD selectively binds to KRAS in cancer cells and effectively induces KRAS degradation via a lysosome-dependent process. Functionally, TKD suppresses tumor growth with no obvious side effects and enhances the antitumor effects of PD-1 antibody and cetuximab. This study not only provides a strategy for developing drugs targeting "undruggable" proteins but also reveals that TKD is a promising therapeutic for treating KRAS-mutant cancers.

Development and validation of a social alienation predictive model for older maintenance hemodialysis patients based on latent profile analysis-a cross-sectional study.

BACKGROUND: Social alienation refers to the state of feeling isolated, helpless, and unsatisfied due to maintaining distance from others or avoiding social interaction and activities. This phenomenon is caused by a lack of social skills, social anxiety, physical health problems, and other reasons. Older maintenance hemodialysis patients are exposed to a higher risk of social alienation. However, previous studies have been performed using the total score of the scale, which does not allow the identification of the characteristics of various patient groups with different levels of social alienation. In contrast, latent profile analysis can classify individuals into different categories based on continuous observational indicators, which improves accuracy and provides a more objective assessment by accounting for the uncertainty of variables. Given the concealed nature of social alienation and the differences in characteristics and treatment measures between different profiles, developing a predictive model for social alienation in older maintenance hemodialysis patients holds significance. OBJECTIVE: To explore the latent profile analysis of social alienation in older maintenance hemodialysis patients and to develop and validate a predictive model for social alienation in this population. METHODS: A total of 350 older maintenance hemodialysis patients were selected as the study subjects using convenience sampling. A cross-sectional survey was conducted using a general information questionnaire, the Generalized Alienation Scale, and the Self-Perceived Burden Scale. Based on the results of the Generalized Alienation Scale, a latent profile analysis was performed, followed by univariate analysis and multinomial logistic regression to develop a predictive model. The effectiveness of the predictive model was evaluated in terms of its authenticity, reliability, and predictive ability. RESULTS: Three hundred nineteen valid questionnaires were collected. The social alienation of older maintenance hemodialysis patients based on latent profile analysis were divided into three profiles, which were named the low/medium/high-symptom groups, comprising 21%, 38.9%, and 40.1% of participants, respectively. Based on male, monthly social activity hours, Age-Adjusted Charlson Comorbidity Index, dialysis age, and Self-Perceived Burden Scale, a predictive model of social alienation for older maintenance hemodialysis patients was developed, and the Hosmer-Lemeshow tests showed no statistical significance (P > 0.05). The model has high predictive efficiency in authenticity, reliability and predictability. CONCLUSION: Older maintenance hemodialysis patients exhibited moderate to high levels of social alienation. The latent profile analysis based method was used to divide patients into low/medium/high-symptom profiles, and the predictive model demonstrates excellent authenticity, reliability, and predictability.

Challenges of COVID-19 Case Forecasting in the US, 2020-2021.

During the COVID-19 pandemic, forecasting COVID-19 trends to support planning and response was a priority for scientists and decision makers alike. In the United States, COVID-19 forecasting was coordinated by a large group of universities, companies, and government entities led by the Centers for Disease Control and Prevention and the US COVID-19 Forecast Hub (https://covid19forecasthub.org). We evaluated approximately 9.7 million forecasts of weekly state-level COVID-19 cases for predictions 1-4 weeks into the future submitted by 24 teams from August 2020 to December 2021. We assessed coverage of central prediction intervals and weighted interval scores (WIS), adjusting for missing forecasts relative to a baseline forecast, and used a Gaussian generalized estimating equation (GEE) model to evaluate differences in skill across epidemic phases that were defined by the effective reproduction number. Overall, we found high variation in skill across individual models, with ensemble-based forecasts outperforming other approaches. Forecast skill relative to the baseline was generally higher for larger jurisdictions (e.g., states compared to counties). Over time, forecasts generally performed worst in periods of rapid changes in reported cases (either in increasing or decreasing epidemic phases) with 95% prediction interval coverage dropping below 50% during the growth phases of the winter 2020, Delta, and Omicron waves. Ideally, case forecasts could serve as a leading indicator of changes in transmission dynamics. However, while most COVID-19 case forecasts outperformed a naïve baseline model, even the most accurate case forecasts were unreliable in key phases. Further research could improve forecasts of leading indicators, like COVID-19 cases, by leveraging additional real-time data, addressing performance across phases, improving the characterization of forecast confidence, and ensuring that forecasts were coherent across spatial scales. In the meantime, it is critical for forecast users to appreciate current limitations and use a broad set of indicators to inform pandemic-related decision making.

The application of a single-hand-operated hepatic pedicle clamping clamp in laparoscopic hepatectomy.

OBJECTIVE: In this paper, a single-hand-operated hepatic pedicle clamp was introduced, and its application value in laparoscopic liver tumor resection was preliminarily discussed. METHODS: The clinical data of 67 patients who underwent laparoscopic liver tumor resection at the First Affiliated Hospital of Wannan Medical College from March 2019 to October 2023 were retrospectively analyzed. The Pringle maneuver was performed with a hepatic pedicle clamp during the operation. The preoperative, intraoperative and postoperative clinical data were observed and recorded. RESULTS: Sixty-seven patients had a median block number, block time, intraoperative blood loss, and postoperative length of hospital stay of 4, 55 min, 400 ml, and 7 days, respectively. The average operation time was 304.9±118.4 min, the time required for each block was 3.2±2.4 s, and the time required for each removed block was 2.6±0.7 s. None of the patients developed portal vein thrombosis or hepatic artery aneurysm formation. CONCLUSION: The hepatic pedicle clamping clamp is simple to use in laparoscopic hepatectomy, optimizes the operation process, and has a reliable blocking effect. It is recommended for clinical application.

Exploring heterogeneity and dynamics of meteorological influences on US PM2.5: A distributed learning approach with spatiotemporal varying coefficient models.

Particulate matter (PM) has emerged as a primary air quality concern due to its substantial impact on human health. Many recent research works suggest that PM2.5 concentrations depend on meteorological conditions. Enhancing current pollution control strategies necessitates a more holistic comprehension of PM2.5 dynamics and the precise quantification of spatiotemporal heterogeneity in the relationship between meteorological factors and PM2.5 levels. The spatiotemporal varying coefficient model stands as a prominent spatial regression technique adept at addressing this heterogeneity. Amidst the challenges posed by the substantial scale of modern spatiotemporal datasets, we propose a pioneering distributed estimation method (DEM) founded on multivariate spline smoothing across a domain's triangulation. This DEM algorithm ensures an easily implementable, highly scalable, and communication-efficient strategy, demonstrating almost linear speedup potential. We validate the effectiveness of our proposed DEM through extensive simulation studies, demonstrating that it achieves coefficient estimations akin to those of global estimators derived from complete datasets. Applying the proposed model and method to the US daily PM2.5 and meteorological data, we investigate the influence of meteorological variables on PM2.5 concentrations, revealing both spatial and seasonal variations in this relationship.

Prognosis and immunotherapy efficacy in dMMR&MSS colorectal cancer patients and an MSI status predicting model.

The inconsistency between mismatch repair (MMR) protein immunohistochemistry (IHC) and microsatellite instability PCR (MSI-PCR) methods has been widely reported. We aim to investigate the prognosis and the effect of immunotherapy in dMMR by IHC but MSS by MSI-PCR (dMMR&MSS) colorectal cancer (CRC) patients. A microsatellite instability (MSI) predicting model was established to help find dMMR&MSS patients. MMR and MSI states were detected by the IHC and MSI-PCR in 1622 CRC patients (ZS6Y-1 cohort). Logistic regression analysis was used to screen clinical features to construct an MSI-predicting nomogram. We propose a new nomogram-based assay to find patients with dMMR&MSS, in which the MSI-PCR assay only detects dMMR patients with MSS predictive results. We applied the new strategy to a random cohort of 248 CRC patients (ZS6Y-2 cohort). The consistency of MMR IHC and MSI-PCR in the ZS6Y-1 cohort was 95.7% (1553/1622). Both pMMR&MSS and dMMR&MSS groups experienced significantly shorter overall survival (OS) than those in dMMR by IHC and MSI-H by MSI-PCR (dMMR&MSI-H) group (hazard ratio [HR] = 2.429, 95% confidence interval [CI]: 1.89-3.116, p < .01; HR = 21.96, 95% CI: 7.24-66.61, p < .01). The dMMR&MSS group experienced shorter OS than the pMMR&MSS group, but the difference did not reach significance (log rank test, p = .0686). In the immunotherapy group, the progression-free survival of dMMR&MSS patients was significantly shorter than that of dMMR&MSI-H patients (HR = 13.83, 95% CI: 1.508-126.8, p < .05). The ZS6Y-MSI-Pre nomogram (C-index = 0.816, 95% CI: 0.792-0.841, already online) found 66% (2/3) dMMR&MSS patients in the ZS6Y-2 cohort. There are significant differences in OS and immunotherapy effect between dMMR&MSI-H and dMMR&MSS patients. Our prediction model provides an economical way to screen dMMR&MSS patients.

Clinical, pathologic and molecular findings in 2 Rottweiler littermates with appendicular osteosarcoma.

Appendicular osteosarcoma was diagnosed and treated in a pair of littermate Rottweiler dogs, resulting in distinctly different clinical outcomes despite similar therapy within the context of a prospective, randomized clinical trial (NCI-COTC021/022). Histopathology, immunohistochemistry, mRNA sequencing, and targeted DNA hotspot sequencing techniques were applied to both dogs' tumors to define factors that could underpin their differential response to treatment. We describe the comparison of their clinical, histologic and molecular features, as well as those from a companion cohort of Rottweiler dogs, providing new insight into potential prognostic biomarkers for canine osteosarcoma.

Testing region selection and prognostic analysis of MLH1 promoter methylation in colorectal cancer in China.

Background: MLH1 promoter methylation analysis is recommended in screening for Lynch syndrome (LS) in patients with MLH1-deficient colorectal cancer (CRC). The study aims to identify specific methylation regions in the MLH1 promoter and to evaluate the clinicopathologic characteristics of and prognosis for patients with MLH1 methylation. Methods: A total of 580 CRC cases were included. The DNA mismatch repair (MMR) protein expression was assessed by using immunohistochemistry (IHC). The methylation status of the Regions A, B, C, D, and E in the MLH1 promoter was tested by using bisulfite sequencing PCR. The specificities of the five regions were calculated. Associations between MLH1 methylation and clinicopathologic characteristics were evaluated. Kaplan-Meier analyses for overall survival (OS) were carried out. Results: In 580 CRC cases, the specificities of the methylation test in Regions D and E were both 97.8%. In the MLH1-deficient CRCs, the frequencies of MLH1 methylation and BRAFV600E mutation were 52.6% and 14.6%, respectively; BRAFV600E mutation occurred in 27.7% of patients with MLH1-methylated CRC. In the MMR-deficient patients, compared with MLH1 unmethylation, MLH1 methylation was more common in patients who were aged ≥50 years, female, had no family history of LS-related tumors, and had tumors located at the right colon. In the MMR-deficient patients, the MLH1-methylated cases had lower OS rates than the unmethylated cases with a family history of LS-related tumors (P = 0.047). Conclusions: Regions D and E in the MLH1 promoter are recommended for determining the MLH1 methylation status in screening for LS in MLH1-deficient CRC. In MMR-deficient patients, the MLH1-methylated cases had a worse OS than the unmethylated cases with a family history of LS-related cancer.

The segmentation and intelligent recognition of structural surfaces in borehole images based on the U2-Net network.

Structural planes decrease the strength and stability of rock masses, severely affecting their mechanical properties and deformation and failure characteristics. Therefore, investigation and analysis of structural planes are crucial tasks in mining rock mechanics. The drilling camera obtains image information of deep structural planes of rock masses through high-definition camera methods, providing important data sources for the analysis of deep structural planes of rock masses. This paper addresses the problems of high workload, low efficiency, high subjectivity, and poor accuracy brought about by manual processing based on current borehole image analysis and conducts an intelligent segmentation study of borehole image structural planes based on the U2-Net network. By collecting data from 20 different borehole images in different lithological regions, a dataset consisting of 1,013 borehole images with structural plane type, lithology, and color was established. Data augmentation methods such as image flipping, color jittering, blurring, and mixup were applied to expand the dataset to 12,421 images, meeting the requirements for deep network training data. Based on the PyTorch deep learning framework, the initial U2-Net network weights were set, the learning rate was set to 0.001, the training batch was 4, and the Adam optimizer adaptively adjusted the learning rate during the training process. A dedicated network model for segmenting structural planes was obtained, and the model achieved a maximum F-measure value of 0.749 when the confidence threshold was set to 0.7, with an accuracy rate of up to 0.85 within the range of recall rate greater than 0.5. Overall, the model has high accuracy for segmenting structural planes and very low mean absolute error, indicating good segmentation accuracy and certain generalization of the network. The research method in this paper can serve as a reference for the study of intelligent identification of structural planes in borehole images.

Disruption of Communication: Recent Advances in Antibiofilm Materials with Anti-Quorum Sensing Properties.

Biofilm contamination presents a significant threat to public health, the food industry, and aquatic/marine-related applications. In recent decades, although various methods have emerged to combat biofilm contamination, the intricate and persistent nature of biofilms makes complete eradication challenging. Therefore, innovative alternative solutions are imperative for addressing biofilm formation. Instead of solely focusing on the eradication of mature biofilms, strategically advantageous measures involve the delay or prevention of biofilm formation on surfaces. Quorum sensing, a communication system enabling bacteria to coordinate their behavior based on population density, plays a pivotal role in biofilm formation for numerous microbial species. Materials possessing antibiofilm properties that target quorum sensing have gained considerable attention for their potential to prevent biofilm formation. This Review consolidates recent research progress on the utilization of materials with antiquorum sensing properties for combating biofilm formation. These materials can be categorized into three distinct types: (i) antibiofilm nanomaterials, (ii) antibiofilm surfaces, and (iii) antibiofilm hydrogels with antiquorum sensing capabilities. Finally, the Review concludes with a brief discussion of current challenges and outlines potential avenues for future research.

Lower doses of carvedilol in Japanese heart failure patients with reduced ejection fraction could show the potential to be non-inferior to higher doses in US patients: An international collaborative observational study.

The Japanese national guidelines recommend significantly lower doses of carvedilol for heart failure with reduced ejection fraction (HFrEF) management than the US guidelines. Using real-world data, we determined whether initial and target doses of carvedilol in Japanese patients (JPNs) differ from those in US patients (USPs), especially in Asian Americans (ASA) and Caucasians (CA), and investigated differences in outcomes. We collected data from the electronic medical records, including demographics, carvedilol dosing, tolerability, cardiac functional indicators like EF, cardiovascular events including all-cause deaths, and laboratory values from the University of California, San Diego Health and Osaka University. JPNs had significantly lower doses (mg/day) of carvedilol initiation (66 USPs composed of 38 CAs and 28 ASAs, 17.1±16.2; 93 JPNs, 4.3±4.2, p<0.001) and one year after initiation (33.0±21.8; 11.2±6.5, p<0.001), and a significantly lower relative rate (RR) of dose discontinuation and reduction than USPs (RR: 0.406, 95% confidence interval (CI): 0.181-0.911, p<0.05). CAs showed the highest reduction rate (0.184), and ASAs had the highest discontinuation rate (0.107). A slight mean difference with narrow 95% CI ranges straddling zero was observed between the two regions in the change from the baseline of each cardiac functional indicator (LVEF, -0.68 [-5.49-4.12]; LVDd, -0.55 [-3.24-2.15]; LVDd index, -0.25 [-1.92-1.43]; LVDs, -0.03 [-3.84-3.90]; LVDs index, -0.04 [-2.38-2.30]; heart rate, 1.62 [-3.07-6.32]). The event-free survival showed no difference (p = 0.172) among the races. Conclusively, despite JPNs exhibiting markedly lower carvedilol doses, their dose effectiveness has the potential to be non-inferior to that in USPs. Dose de-escalation, not discontinuation, could be an option in some Asian and ASA HFrEF patients intolerable to high doses of carvedilol.

ITGB6 promotes pancreatic fibrosis and aggravates the malignant process of pancreatic cancer via JAK2/STAT3 signaling pathway.

Integrin ß6 (ITGB6) is upregulated in multiple tumor types and elevated ITGB6 levels have been detected in patients with chronic pancreatitis. However, the role of ITGB6 in pancreatic fibrosis and cancer remains to be elucidated. In the present study, ITGB6 expression was assessed using western blotting and qRT-PCR. Besides, cell proliferation, cycling, migration, and invasion were evaluated using CCK-8, flow cytometry, wound healing, and transwell assays, respectively. The expression of fibrosis and JAK2/STAT3 signaling markers was detected by western blotting and immunofluorescence analysis. Moreover, nude mice were subcutaneously injected with co-cultured cell suspensions to establish an in vivo model. The results showed that ITGB6 was highly expressed in pancreatic cancer tissues and TGF-ß-induced pancreatic stellate cells (PSCs). Inhibition of ITGB6 expression in PSCs resulted in clear inhibition of activated PSC proliferation, migration, and fibrogenesis. Additionally, reduced ITGB6 expression inhibits the JAK2/STAT3 signaling pathway. Interestingly, activators of the JAK2/STAT3 signaling pathway reversed the effects of ITGB6 disruption on PSCs. Activated PSCs notably promoted the proliferation, invasion, and migration of pancreatic cancer cells in a co-culture assay. In contrast, activated PSCs with low ITGB6 expression failed to significantly affect the malignancy of pancreatic cancer cells. Moreover, in vivo results showed that interference with ITGB6 inhibited the activation of PSCs and promoted the development of pancreatic cancer. Silencing ITGB6 inhibited the proliferation, migration, and fibrosis-like effects of activated PSCs and indirectly inhibited the metastasis and malignant process of pancreatic cancer by inhibiting the JAK2/STAT3 signaling pathway. Therefore, ITGB6 is a potential candidate target for pancreatic cancer prevention and treatment.

Comparative transcriptomics of the chilling stress response in two Asian mangrove species, Bruguiera gymnorhiza and Rhizophora apiculata.

Low temperatures largely determine the geographic limits of plant species by reducing survival and growth. Inter-specific differences in the geographic distribution of mangrove species have been associated with cold tolerance, with exclusively tropical species being highly cold-sensitive and subtropical species being relatively cold-tolerant. To identify species-specific adaptations to low temperatures, we compared the chilling stress response of two widespread Indo-West Pacific mangrove species from Rhizophoraceae with differing latitudinal range limits-Bruguiera gymnorhiza (L.) Lam. ex Savigny (subtropical range limit) and Rhizophora apiculata Blume (tropical range limit). For both species, we measured the maximum photochemical efficiency of photosystem II (Fv/Fm) as a proxy for the physiological condition of the plants and examined gene expression profiles during chilling at 15 and 5 °C. At 15 °C, B. gymnorhiza maintained a significantly higher Fv/Fm than R. apiculata. However, at 5 °C, both species displayed equivalent Fv/Fm values. Thus, species-specific differences in chilling tolerance were only found at 15 °C, and both species were sensitive to chilling at 5 °C. At 15 °C, B. gymnorhiza downregulated genes related to the light reactions of photosynthesis and upregulated a gene involved in cyclic electron flow regulation, whereas R. apiculata downregulated more RuBisCo-related genes. At 5 °C, both species repressed genes related to CO2 assimilation. The downregulation of genes related to light absorption and upregulation of genes related to cyclic electron flow regulation are photoprotective mechanisms that likely contributed to the greater photosystem II photochemical efficiency of B. gymnorhiza at 15 °C. The results of this study provide evidence that the distributional range limits and potentially the expansion rates of plant species are associated with differences in the regulation of photosynthesis and photoprotective mechanisms under low temperatures.

Sensitive dual-signal detection and effective removal of tetracycline antibiotics in honey based on a hollow triple-metal organic framework nanozymes.

In this work, a colorimetric/fluorescent dual-signal mode sensor is proposed for the sensitive, selective and accurate detection and removal of tetracycline antibiotics (TCs). A triple-metal MOF of NiCoFe is successfully synthesized and controllable adjusted the shape of the hollow structure for the first time, and then modified with TCs aptamer. The as-prepared triple-atom MOF (apt-NiCoFe-MOF-74) exhibits well-defined hollow morphology, high crystallinity, and high surface areas endow their alluring adsorption and removal performances for TCs. More attractively, this triple-metal MOF show a good peroxidase-like activity and strong fluorescence property at 540 nm of apt-NiCoFe-MOF-74 when excitation wavelength was 370 nm. Inspire by this, a dual-signal output biosensor is constructed and the linear absorbance response is well correlated with wide range and low LOD for TCs. The biosensor provided an universal method with satisfactory sensitivity and accuracy for TCs analysis in real food samples.

TSP50 Attenuates DSS-Induced Colitis by Regulating TGF-ß Signaling Mediated Maintenance of Intestinal Mucosal Barrier Integrity.

The integrity of the intestinal mucosal barrier is crucial for protecting the intestinal epithelium against invasion by commensal bacteria and pathogens, thereby combating colitis. The investigation revealed that the absence of TSP50 compromised the integrity of the intestinal mucosal barrier in murine subjects. This disruption facilitated direct contact between intestinal bacteria and the intestinal epithelium, thereby increasing susceptibility to colitis. Mechanistic analysis indicated that TSP50 deficiency in intestinal stem cells (ISCs) triggered aberrant activation of the TGF-ß signaling pathway and impeded the differentiation of goblet cells in mice, leading to impairment of mucosal permeability. By inhibiting the TGF-ß pathway, the functionality of the intestinal mucosal barrier is successfully restored and mitigated colitis in TSP50-deficient mice. In conclusion, TSP50 played a crucial role in maintaining the intestinal mucosal barrier function and exhibited the preventive effect against the development of colitis by regulating the TGF-ß signaling pathway.

Fabrication of Au nanoclusters confined on hydroxy double salt-based intelligent biosensor for on-site monitoring of urease and its inhibitors.

Sensitive and convenient sensing of urease and its inhibitors is exceptionally urgent in clinical diagnosis and new drug development. In this study, the gold nanoclusters (AuNCs) and hydroxyl double salt (HDS) were composited by a simple confinement effect to prepare highly fluorescent AuNCs@HDS composites to monitor urease and its drug inhibitors. HDS was used as a matrix to confine AuNCs (AuNCs@HDS), facilitating the emission intensity of AuNCs. However, acidic conditions (low pH) can disrupt the structure of HDS to break the confinement effect, and quench the fluorescence of AuNCs. Therefore, a sensing platform for pH-related enzyme urease detection was constructed based on the sensitive response of AuNCs@HDS to pH. This sensing platform had a linear response range of 0.5-22.5 U/L and a low limit of detection (LOD) of 0.19 U/L for urease. Moreover, this sensing platform was also applied to monitor urease inhibitors and urease in human saliva samples. Additionally, a portable hydrogel kit combined with a smartphone was developed for urease detection to achieve portable, low-cost, instrument-free, and on-site monitoring of urease.