Evaluation of a plasma cell-free DNA methylation test for colorectal cancer diagnosis: a multicenter clinical study.

BACKGROUND: A blood-based diagnostic test is a promising strategy for colorectal cancer (CRC). The MethyDT test (IColohunter), which detects methylation levels of NTMT1 and MAP3K14-AS1, exhibited potential in discriminating CRC, but its clinical performance needs to be validated in large-scale populations. METHODS: A multicenter, double-blinded, cross-sectional study that enrolled 1194 participants was performed. Plasma samples were collected to detect methylation levels of NTMT1 and MAP3K14-AS1 using quantitative methylation-specific PCR with the MethyDT test, and the accuracy was further evaluated by Sanger sequencing. RESULTS: The sensitivities of the MethyDT test for detecting CRC, early stages of CRC (I and II), advanced adenoma (AA), and high-grade intraepithelial neoplasia (HGIN) were 91.2% (95% confidence interval [CI], 88.4-94.0), 87.4% (95% CI, 82.5-92.2), 43.5% (95% CI, 35.7-51.4), and 72.7% (95% CI, 57.5-87.9), respectively. The specificities for participants with non-AA, interfering diseases (ID), and no evidence of disease (NED) were 85.0% (95% CI, 78.8-91.3), 93.7% (95% CI, 91.4-95.9) and 97.3% (95% CI, 90.5-99.7), respectively, and its overall specificity for all-controls was 92.4% (95% CI, 90.3-94.4). The consistency of the MethyDT test with pathology for CRC was high with a kappa value of 0.830 (95% CI, 0.795-0.865). Additionally, the MethyDT test was comparable to Sanger sequencing for detecting methylation with kappa values > 0.97. CONCLUSIONS: The MethyDT test demonstrates excellent sensitivity and specificity for CRC and high consistency with Sanger sequencing for methylation, suggesting it may serve as a potential noninvasive diagnostic tool for the detection of CRC. TRIAL REGISTRATION: This clinical trial has been registered in ClinicalTrials.gov (NCT05508503).

Spiral-Locking Strategy for Efficient Narrowband Multiple Resonance Thermally Activated Delayed Fluorescence Emitters.

Multiple resonance thermally activated delayed fluorescence (MR-TADF) materials are applied in organic light-emitting diodes (OLEDs) due to their high efficiency and color purity. However, the inherent planar structure of MR emitters presents significant challenges, including concentration-induced emission quenching, spectral redshift and broadening. To address these issues, two orthorhombic asymmetric conformational materials, SBNO and SBNOS, have been developed. Both MR-TADF emitters incorporate a sterically hindered spiro-carbon bridge to minimize intermolecular chromophore interactions. Consequently, the spectra of the SBNOS-based devices exhibit only a 4 nm redshift and a 7 nm broadening of the full-width at half maximum (FWHM) across a doping ratio range of 1-100 wt%. The steric effect produces pure green OLEDs with a CIE y of 0.69 and enhances performance, achieving a maximum external quantum efficiency (EQEmax) of up to 32.7%. The referent BNO without spiro skeleton suffers from serious spectral redshift and broadening as well as a lower device efficiency. This research demonstrates a promising approach to developing MR-TADF devices that resist redshift and broadening while maintaining high color purity and efficiency.

Development and validation of a nomogram for sleep disorders among stroke patients.

BACKGROUND: Precisely identifying high-risk sleep disorder patients and implementing suitable measures are important for decreasing the incidence of sleep disorders. In this study, a nomogram method was adopted to construct a tool to predict sleep disorders in stroke based on four factors: individual characteristics, treatment-related factors, psychological factors, and family-related factors. METHODS: A total of 450 stroke patients were continuously diagnosed at the Affiliated Hospital of Nantong University, and the data on participants were randomly distributed into a training set (n = 315) and a validation set (n = 135). Within the training set, using LASSO regression and random forest methods, five optimal predictors of sleep disorders were identified. Five optimal predictors were used to develop a model. The calibration, discrimination, generalization, and clinical applicability of the model were evaluated using calibration curves, receiver operating characteristic (ROC) curves, internal validation, and decision curve analysis (DCA). RESULTS: We found that the place of residence, average daily infusion time, the Hospital Anxiety and Depression Scale (HADS), the Type D Personality Scale-14 (DS14), and the Fatigue Severity Scale (FSS) were crucial factors associated with sleep disorders. The validation data showed an area under the curve (AUC) of 0.903 compared to 0.899 in the training set. There was an approach to the diagonal in the calibration curve of this model, and the results of DCA noted that it is clinically beneficial across a range of thresholds from 5 % to 99 %. CONCLUSION: A model was developed to predict sleep disorders among stroke patients to help hospital staff evaluate the risk among patients and screen high-risk patients.

TikTok and Bilibili as health information sources on gastroesophageal reflux disease: an assessment of content and its quality.

Gastroesophageal reflux disease (GERD) is a global chronic disease. Short video platforms make it easy for patients with GERD to obtain medical information. However, the quality of information from these videos remains uncertain. This study aimed to systematically assess videos related to GERD on TikTok and Bilibili. We conducted a search and gathered 241 Chinese videos related to GERD and recorded the essential information. Two independent evaluators assessed each video based on the completeness of six components of the GERD guidelines, and assessed the quality and reliability of the information in the videos using recognition tools. Finally, videos from different sources were compared. The uploaders of most videos were medical professionals (86.7%, n = 209). The content was mainly about symptoms and treatment. The quality of the videos information varied depending on the sources. Among videos posted on Bilibili, those posted by medical professionals had a lower content score for definition (P < 0.001). Videos produced by non-gastroenterologists had the highest mean modified DISCERN. (The DISCERN scoring tool was initially created for assessing written publications, but nowadays, it is frequently leveraged for appraising various health-related videos. Details can be found in the text) quality of the videos information was acceptable; however, the content varied significantly depending on the type of source used. Videos with broad content should be carefully screened to meet more needs.

Sinonasal Phosphaturic Mesenchymal Tumors Without Any Nasal Symptoms: A Case Report and Literature Review.

OBJECTIVE: We present a case of phosphaturic mesenchymal tumor (PMT) in the left ethmoid without any nasal symptoms in a 63-year-old woman. Initially diagnosed with postmenopausal osteoporosis, 2-year history of hypophosphatemia and a significantly higher uptake of Fluorine-18 (18F)-AlF-NOTA-octreotide (18F-OC) in the left ethmoid sinus, provided crucial information for accurate diagnosis. METHODS: We presented a case with chart review and conducted review of the literature. RESULTS: The patient endured 1-year history of weakness and bone pain but without any nasal symptoms before a tissue diagnosis was eventually reached. It is a challenging diagnosis to make-patients present with non-specific clinical symptoms and the culprit neoplasm is often tiny in size and difficult to detect. It emphasizes the importance of thorough patient history-taking and the whole-body functional imaging. CONCLUSIONS: Sinonasal PMTs are rare, and because of this most otolaryngologists are unfamiliar with its clinical presentation. This case highlights the importance of early diagnosis to enable prompt intervention and reduce the burden of associated symptoms.

Reconfigurable Five-In-One Carbon Nanotube Optoelectronic Transistor for Intelligent Computing and Communication.

Advances in artificial general intelligence (AGI) necessitate the integration of diverse functionalities to address complex tasks. Carbon nanotubes (CNTs), with their unique physical properties, have broad applications in emerging research fields, providing a foundation for next-generation devices that could overcome the limits of Moore's Law. This work demonstrates a novel intelligent device that integrates five functions─sensors, memory, neuromorphic computing, logic, and communication─using CNT field-effect transistors (CNFETs) compatible with CMOS processes. Through passivation and annealing techniques, we have significantly enhanced the optoelectronic performance of CNFETs, leading to the development of multifunctional optoelectronic synaptic transistors. These optimized CNFETs enable dual-mode weight-tunable synaptic functions, including long-term plasticity and multilevel storage. Additionally, a CNT-based neural network has achieved high recognition accuracy on the MNIST data set, showcasing the potential of in-memory computing. This research also innovates by integrating logic functions with optoelectronic communication capabilities, paving the way for next-generation intelligent computing and communication integrated systems.

A piezoresistive-based 3-axial MEMS tactile sensor and integrated surgical forceps for gastrointestinal endoscopic minimally invasive surgery.

In robotic-assisted surgery (RAS), traditional surgical instruments without sensing capability cannot perceive accurate operational forces during the task, and such drawbacks can be largely intensified when sophisticated tasks involving flexible and slender arms with small end-effectors, such as in gastrointestinal endoscopic surgery (GES). In this study, we propose a microelectromechanical system (MEMS) piezoresistive 3-axial tactile sensor for GES forceps, which can intuitively provide surgeons with online force feedback during robotic surgery. The MEMS fabrication process facilitates sensor chips with miniaturized dimensions. The fully encapsulated tactile sensors can be effortlessly integrated into miniature GES forceps, which feature a slender diameter of just 3.5 mm and undergo meticulous calibration procedures via the least squares method. Through experiments, the sensor's ability to accurately measure directional forces up to 1.2 N in the Z axis was validated, demonstrating an average relative error of only 1.18% compared with the full-scale output. The results indicate that this tactile sensor can provide effective 3-axial force sensing during surgical operations, such as grasping and pulling, and in ex vivo testing with a porcine stomach. The compact size, high precision, and integrability of the sensor establish solid foundations for clinical application in the operating theater.

Enhancing Colorectal Cancer Immunotherapy: The Pivotal Role of Ferroptosis in Modulating the Tumor Microenvironment.

Colorectal cancer (CRC) represents a significant challenge in oncology, with increasing incidence and mortality rates worldwide, particularly among younger adults. Despite advancements in treatment modalities, the urgent need for more effective therapies persists. Immunotherapy has emerged as a beacon of hope, offering the potential for improved outcomes and quality of life. This review delves into the critical interplay between ferroptosis, an iron-dependent form of regulated cell death, and immunotherapy within the CRC context. Ferroptosis's influence extends beyond tumor cell fate, reshaping the tumor microenvironment (TME) to enhance immunotherapy's efficacy. Investigations into Ferroptosis-related Genes (OFRGs) reveal their pivotal role in modulating immune cell infiltration and TME composition, closely correlating with tumor responsiveness to immunotherapy. The integration of ferroptosis inducers with immunotherapeutic strategies, particularly through novel approaches like ferrotherapy and targeted co-delivery systems, showcases promising avenues for augmenting treatment efficacy. Furthermore, the expression patterns of OFRGs offer novel prognostic tools, potentially guiding personalized and precision therapy in CRC. This review underscores the emerging paradigm of leveraging ferroptosis to bolster immunotherapy's impact, highlighting the need for further research to translate these insights into clinical advancements. Through a deeper understanding of the ferroptosis-immunotherapy nexus, new therapeutic strategies can be developed, promising enhanced efficacy and broader applicability in CRC treatment, ultimately improving patient outcomes and quality of life in the face of this formidable disease.

Apolipoprotein A-I: Potential Protection Against Intestinal Injury Induced by Dietary Lipid.

The intestinal barrier system protects the human body from harmful factors, by continuously renewing the intestinal epithelium, tight junctions and enteric microbes. However, dietary fat can harm the intestinal epithelial barrier enhancing gut permeability. In recent years, Apolipoprotein A-I has attracted much attention because of its anti-inflammatory properties. Numerous studies have demonstrated that Apolipoprotein A-I can regulate mucosal immune cells, inhibit the progression of inflammation, promote epithelial proliferation and repair, and maintain physical barrier function; it can also regulate angiogenesis, thereby improving local circulation. This article is intended to elucidate the mechanism by which Apolipoprotein A-I improves intestinal barrier damage caused by dietary fat and to review the role of Apolipoprotein A-I in maintaining intestinal homeostasis.

Efficient and Stable Red Perovskite Light-Emitting Diodes via Thermodynamic Crystallization Control.

Efficient and stable red perovskite light-emitting diodes (PeLEDs) demonstrate promising potential in high-definition displays and biomedical applications. Although significant progress has been made in device performance, meeting commercial demands remains a challenge in the aspects of long-term stability and high external quantum efficiency (EQE). Here, an in situ crystallization regulation strategy is developed for optimizing red perovskite films through ingenious vapor design. Mixed vapor containing dimethyl sulfoxide and carbon disulfide (CS2) is incorporated to conventional annealing, which contributes to thermodynamics dominated perovskite crystallization for well-aligned cascade phase arrangement. Additionally, the perovskite surface defect density is minimized by the CS2 molecule adsorption. Consequently, the target perovskite films exhibit smooth exciton energy transfer, reduced defect density, and blocked ion migration pathways. Leveraging these advantages, spectrally stable red PeLEDs are obtained featuring emission at 668, 656, and 648 nm, which yield record peak EQEs of 30.08%, 32.14%, and 29.04%, along with prolonged half-lifetimes of 47.7, 60.0, and 43.7 h at the initial luminances of 140, 250, and 270 cd m-2, respectively. This work provides a universal strategy for optimizing perovskite crystallization and represents a significant stride toward the commercialization of red PeLEDs.

Antibiotic Resistance of Helicobacter pylori in Mainland China: A Focus on Geographic Differences Through Systematic Review and Meta-Analysis.

BACKGROUND: Empirical treatment needs to be supported by regional data, but knowledge of interregional differences is currently lacking in China. This study aimed to summarize and map the primary and secondary antibiotic resistance of Helicobacter pylori in different regions of mainland China. METHODS: PubMed, EMBASE, Web of Science, China National Knowledge Infrastructure and Wanfang databases were systematically reviewed for studies published between 1 January 2000 and 15 July 2023. Data related to primary and secondary H. pylori antibiotic resistance rates were included. Random-effects models were used to synthesize the pooled resistance rates. RESULTS: Ultimately, 74 studies were included in the final analysis. A total of 16 provinces reported resistance data. The overall resistance rates of H. pylori in mainland China were 30.72% (95% CI 27.53%-33.99%) to clarithromycin, 70.14% (95% CI 29.53%-37.46%) to metronidazole and 32.98% (95% CI 28.73%-37.37%) to levofloxacin; for amoxicillin, tetracycline, and furazolidone, the rates were 2.41% (95% CI 1.43%-3.60%), 2.53% (95% CI 1.19%-4.28%) and 1.54% (95% CI 0.28%-3.62%), respectively. Spatial and temporal differences were observed. The resistance rates increased after treatment failure; however, secondary resistance to amoxicillin, tetracycline and furazolidone were still low across the vast majority of study regions. CONCLUSION: Surveillance of the updated prevalence of antibiotic resistance of H. pylori for different regions is warranted, which should factor into clinical decision making and guideline recommendations.

Efficacy of a real-time intelligent quality-control system for the detection of early upper gastrointestinal neoplasms: a multicentre, single-blinded, randomised controlled trial.

Background: Oesophagogastroduodenoscopy (OGD) quality and identification of the early upper gastrointestinal (UGI) neoplasm play an important role in detecting the UGI neoplasm. However, the optimal method for quality control in daily OGD procedures is currently lacking. We aimed to evaluate the efficacy of a real-time intelligent quality-control system (IQCS), which combines OGD quality control with lesion detection of early UGI neoplasms. Methods: We performed a multicentre, single-blinded, randomised controlled trial at 6 hospitals in China. Patients aged 40-80 years old who underwent painless OGD were screened for enrolment in this study. Patients with a history of advanced UGI cancer, stenosis, or obstruction in UGI tract were excluded. Eligible subjects were randomly assigned (1:1) to either the routine or IQCS group to undergo standard OGD examination and OGD examination aided by IQCS, respectively. Patients were masked to the randomisation status. The primary outcome was the detection of early UGI neoplasms. All analyses were done on a per-protocol basis. This trial is registered with ClinicalTrials.gov, NCT04720924. Findings: Between January 16, 2021 and December 23, 2022, 1840 patients were randomised (IQCS group: 919, routine group: 921). The full analysis set consisted of 914 in the IQCS group and 915 in the routine group. The early UGI neoplasms detection rate in the IQCS group (6.1%, 56/914) was significantly higher than in the routine group (2.3%, 21/915; P = 0.0001). The IQCS group had fewer blind spots (2.3 vs. 6.2, P < 0.0001). The IQCS group had higher stomach cleanliness on cardia or fundus (99.5% vs. 87.9%, P < 0.0001), body (98.9% vs. 88.0%, P < 0.0001), angulus (99.8% vs. 88.4%, P < 0.0001) and antrum or pylorus (100.0% vs. 87.4%, P < 0.0001). The inspection time (576.2 vs. 574.5s, P = 0.91) and biopsy rate (57.2% vs. 56.6%, P = 0.83) were not different between the groups. The early UGI neoplasms detection rate in the IQCS group increased in both non-academic centres (RR = 3.319, 95% CI 1.277-9.176; P = 0.0094) and academic centres (RR = 2.416, 95% CI 1.301-4.568; P = 0.0034). The same improvements were observed for both less-experienced endoscopists (RR = 2.650, 95% CI 1.330-5.410; P = 0.0034) and experienced endoscopists (RR = 2.710, 95% CI 1.226-6.205; P = 0.010). No adverse events or serious adverse events were reported in the two groups. Interpretation: The IQCS improved the OGD quality and increased early UGI neoplasm detection in different hospital types and endoscopist experiences. IQCS could play an important role in primary basic hospitals and non-expert endoscopists to improve the diagnostic accuracy of early UGI neoplasms. The effectiveness of IQCS in real-world clinical settings needs a larger population validation. Funding: Key R&D Program of Shandong Province, China (Major Scientific and Technological Innovation Project), National Natural Science Foundation of China, the Taishan Scholars Program of Shandong Province, the National Key Research and Development Program of China, and the Shandong Provincial Natural Science Foundation.

Hyperspectral imaging facilitating resect-and-discard strategy through artificial intelligence-assisted diagnosis of colorectal polyps: A pilot study.

BACKGROUND AND AIMS: The resect-and-discard strategy for colorectal polyps based on accurate optical diagnosis remains challenges. Our aim was to investigate the feasibility of hyperspectral imaging (HSI) for identifying colorectal polyp properties and diagnosis of colorectal cancer in fresh tissues during colonoscopy. METHODS: 144,900 two dimensional images generated from 161 hyperspectral images of colorectal polyp tissues were prospectively obtained from patients undergoing colonoscopy. A residual neural network model was trained with transfer learning to automatically differentiate colorectal polyps, validated by histopathologic diagnosis. The diagnostic performances of the HSI-AI model and endoscopists were calculated respectively, and the auxiliary efficiency of the model was evaluated after a 2-week interval. RESULTS: Quantitative HSI revealed histological differences in colorectal polyps. The HSI-AI model showed considerable efficacy in differentiating nonneoplastic polyps, non-advanced adenomas, and advanced neoplasia in vitro, with sensitivities of 96.0%, 94.0%, and 99.0% and specificities of 99.0%, 99.0%, and 96.5%, respectively. With the assistance of the model, the median negative predictive value of neoplastic polyps increased from 50.0% to 88.2% (p = 0.013) in novices. CONCLUSION: This study demonstrated the feasibility of using HSI as a diagnostic tool to differentiate neoplastic colorectal polyps in vitro and the potential of AI-assisted diagnosis synchronized with colonoscopy. The tool may improve the diagnostic performance of novices and facilitate the application of resect-and-discard strategy to decrease the cost.

Development and validation of a predictive model for submucosal fibrosis in patients with early gastric cancer undergoing endoscopic submucosal dissection: experience from a large tertiary center.

BACKGROUND: Submucosal fibrosis is associated with adverse events of endoscopic submucosal dissection (ESD). The present study mainly aimed to establish a predictive model for submucosal fibrosis in patients with early gastric cancer (EGC) undergoing ESD. METHODS: Eligible patients with EGC, identified at Qilu Hospital of Shandong University from April 2013 to December 2023, were retrospectively included and randomly split into a training set and a validation set in a 7:3 ratio. Logistic regression analyses were used to pinpoint the risk factors for submucosal fibrosis. A nomogram was developed and confirmed using receiver operating characteristic (ROC) curves, calibration plots, Hosmer-Lemeshow (H-L) tests, and decision curve analysis (DCA) curves. Besides, a predictive model for severe submucosal fibrosis was further conducted and tested. RESULTS: A total of 516 cases in the training group and 220 cases in the validation group were recruited. The nomogram for submucosal fibrosis contained the following items: tumour location (long axis), tumour location (short axis), ulceration, and biopsy pathology. ROC curves showed high efficiency with an area under the ROC of 0.819 in the training group, and 0.812 in the validation group. Calibration curves and H-L tests indicated good consistency. DCA proved the nomogram to be clinically beneficial. Furthermore, the four items were also applicable for a nomogram predicting severe fibrosis, and the model performed well. CONCLUSION: The predictive models, initially constructed in this study, were validated as convenient and feasible for endoscopists to predict submucosal fibrosis and severe fibrosis in patients with EGC undergoing ESD.

Tetracycline Three Times Daily Versus Four Times Daily in Bismuth-Containing Quadruple Therapy as the First-Line Treatment of Helicobacter pylori Infection: A Multicenter, Noninferiority, Randomized Controlled Trial.

BACKGROUND: Current guidelines recommend bismuth-containing quadruple therapy for patients newly diagnosed with Helicobacter pylori (H. pylori) infection. We aimed to compare the efficacy and safety of tetracycline administered three times daily versus four times daily in bismuth-containing quadruple therapy for first-line treatment of H. pylori infection. METHODS: This multicenter, noninferiority, randomized controlled study, conducted in China, recruited treatment-naïve adults with H. pylori infection, randomized 1:1 into two treatment groups to receive either of the following bismuth-containing quadruple therapies: esomeprazole 20 mg twice-daily; bismuth 220 mg twice-daily; amoxicillin 1000 mg twice-daily; and tetracycline 500 mg three times daily (TET-T) versus 500 mg four times daily (TET-F). At least 6 weeks post-treatment, a 13C-urea breath test was performed to evaluate H. pylori eradication. RESULTS: In total, 406 patients were randomly assigned to the two treatment groups. Intention-to-treat eradication rates were 91.63% (186/203; 95% confidence interval [CI] 87.82%-95.44%) versus 90.15% (183/203; 95% CI 86.05%-94.25%) (p = 0.0005) and per-protocol eradication rates were 95.34% (184/193; 95% CI 92.36%-98.31%) versus 95.72% (179/187; 95% CI 92.82%-98.62%) (p = 0.0002) for the TET-T and TET-F group, respectively. TET-T-treated patients had a lower incidence of adverse effects than TET-F-treated patients (21.61% vs. 31.63%, p = 0.024), with no significant differences in compliance to treatment between the groups. CONCLUSION: As a first-line therapy for H. pylori infection, the eradication rate of the TET-T therapy was noninferior to that of the TET-F therapy while significantly reducing the incidence of adverse reactions. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT05431075.

Artificial Intelligence-Generated Patient Education Materials for Helicobacter pylori Infection: A Comparative Analysis.

BACKGROUND: Patient education contributes to improve public awareness of Helicobacter pylori. Large language models (LLMs) offer opportunities to revolutionize patient education transformatively. This study aimed to assess the quality of patient educational materials (PEMs) generated by LLMs and compared with physician sourced. MATERIALS AND METHODS: Unified instruction about composing a PEM about H. pylori at a sixth-grade reading level in both English and Chinese were given to physician and five LLMs (Bing Copilot, Claude 3 Opus, Gemini Pro, ChatGPT-4, and ERNIE Bot 4.0). The assessments of the completeness and comprehensibility of the Chinese PEMs were conducted by five gastroenterologists and 50 patients according to three-point Likert scale. Gastroenterologists were asked to evaluate both English and Chinese PEMs and determine the accuracy and safety. The accuracy was assessed by six-point Likert scale. The minimum acceptable scores were 4, 2, and 2 for accuracy, completeness, and comprehensibility, respectively. The Flesch-Kincaid and Simple Measure of Gobbledygook scoring systems were employed as readability assessment tools. RESULTS: Accuracy and comprehensibility were acceptable for English PEMs of all sources, while completence was not satisfactory. Physician-sourced PEM had the highest accuracy mean score of 5.60 and LLM-generated English PEMs ranged from 4.00 to 5.40. The completeness score was comparable between physician-sourced PEM and LLM-generated PEMs in English. Chinese PEMs from LLMs proned to have lower score in accuracy and completeness assessment than English PEMs. The mean score for completeness of five LLM-generated Chinese PEMs was 1.82-2.70 in patients' perspective, which was higher than gastroenterologists' assessment. Comprehensibility was satisfactory for all PEMs. No PEM met the recommended sixth-grade reading level. CONCLUSION: LLMs have potential in assisting patient education. The accuracy and comprehensibility of LLM-generated PEMs were acceptable, but further optimization on improving completeness and accounting for a variety of linguistic contexts are essential for enhancing the feasibility.

Sensing of Liver-Derived Nicotinamide by Intestinal Group 2 Innate Lymphoid Cells Links Liver Cirrhosis and Ulcerative Colitis Susceptibility.

The correlation between liver disease and the progression of ulcerative colitis (UC) has remained elusive. In this study, it demonstrates that liver injury is intricately linked to the heightened severity of UC in patients, and causes more profound intestinal damage during DSS-induced colitis in mice. Metabolomics analysis of plasma from liver cirrhosis patients shows liver injury compromising nicotinamide supply for NAD+ biosynthesis in the intestine. Subsequent investigation identifies intestinal group 2 innate lymphoid cells (ILC2s) are responsible for liver injury-exacerbated colitis. Reconstitution of ILC2s or the restoration of NAD+ metabolism proves effective in relieving liver injury-aggravated experimental colitis. Mechanistically, the NAD+ salvage pathway regulates gut ILC2s in a cell-intrinsic manner by supporting the generation of succinate, which fuels the electron transport chain to sustaining ILC2s function. This research deepens the understanding of cellular and molecular mechanisms in liver disease-UC interplay, identifying a metabolic target for innovative treatments in liver injury-complicated colitis.

Twisted Structure and Multiple Charge-Transfer Channels Endow Thermally Activated Delayed Fluorescence Devices with Small Efficiency Roll-Off and Low Concentration Dependence.

Despite the rapid development of thermally activated delayed fluorescent (TADF) materials, developing organic light-emitting diodes (OLEDs) with small efficiency roll-off remains a formidable challenge. Herein, we have designed a TADF molecule (mClSFO) based on the spiro fluorene skeleton. The highly twisted structure and multiple charge-transfer channels effectively suppress aggregation-caused quenching (ACQ) and endow mClSFO with excellent exciton dynamic properties to reduce efficiency roll-off. Fast radiative rate (kr) and rapid reverse intersystem crossing (RISC) rate (kRISC) of 1.6 × 107 s-1 and 1.07 × 106 s-1, respectively, are obtained in mClSFO. As a result, OLEDs based on mClSFO obtain impressive maximum external quantum efficiency (EQEmax) exceeding 20% across a wide doping concentration range of 10-60 wt%. 30 wt% doped OLED exhibits an EQEmax of 23.1% with a small efficiency roll-off, maintaining an EQE of 18.6% at 1000 cd m-2. The small efficiency roll-off and low concentration dependence observed in the TADF emitter underscore its significant potential.