A planar electronic acceptor motif contributing to NIR-II AIEgen with combined imaging and therapeutic applications.

Designing molecules with donor-acceptor-donor (D-A-D) architecture plays an important role in obtaining second near-infrared region (NIR-II, 1000-1700 nm) fluorescent dyes for biomedical applications; however, this always comes with a challenge due to very limited electronic acceptors. On the other hand, to endow NIR-II fluorescent dyes with combined therapeutic applications, trivial molecular design is indispensable. Herein, we propose a pyrazine-based planar electronic acceptor with a strong electron affinity, which can be used to develop NIR-II fluorescent dyes. By structurally attaching two classical triphenylamine electronic donors to it, a basic D-A-D module, namely Py-NIR, can be generated. The planarity of the electronic acceptor is crucial to induce a distinct NIR-II emission peaking at ∼1100 nm. The unique construction of the electronic acceptor can cause a twisted and flexible molecular conformation by the repulsive effect between the donors, which is essential to the aggregation-induced emission (AIE) property. The tuned intramolecular motions and twisted D-A pair brought by the electronic acceptor can lead to a remarkable photothermal conversion with an efficiency of 56.1% and induce a type I photosensitization with a favorable hydroxyl radical (OH˙) formation. Note that no additional measures are adopted in the molecular design, providing an ideal platform to realize NIR-II fluorescent probes with synergetic functions based on such an acceptor. Besides, the nanoparticles of Py-NIR can exhibit excellent NIR-II fluorescence imaging towards orthotopic 4T1 breast tumors in living mice with a high sensitivity and contrast. Combined with photothermal imaging and photoacoustic imaging caused by the thermal effect, the imaging-guided photoablation of tumors can be well performed. Our work has created a new opportunity to develop NIR-II fluorescent probes for accelerating biomedical applications.

What determines the batteries recycling behavior of e-bike citizens in Guangzhou?: Integrating place identity and environmental concern into the extended norm activation model.

Battery recycling is viewed in China as an important means of achieving primary sustainability goals and greater economic and environmental development. With the notice of high battery recycling intentions through relevant investigations, this study examine the influencing factors of these recycling behaviors of e-bikes citizens by incorporating the place identity and environmental concern into the Extended Normative Activation Model (NAM), which fill the research gap on how place identity and environmental concern affect the batteries recycling behavior. This study proposes that the consequence awareness, personal norms, and attitudes have mediating effect on place identity to the recycling behavior, and the environmental concern has moderating effect on consequence awareness, personal norms, and attitudes to the recycling behavior, respectively. Based on 1068 valid surveys, hypotheses were examined using partial least square structural equation modeling (PLS-SEM). The results show that personal norms and awareness of consequences positively impact e-bike users' intentions to recycle waste batteries, and environmental concerns have no moderating effect on attitude, recycling intention, personal norms, and recycling intention. Theoretical and practical implications are discussed at last.

Nomogram models for predicting overall and cancer-specific survival in early-onset gastric cancer patients: a population-based cohort study.

To develop nomogram models for predicting the overall survival (OS) and cancer-specific survival (CSS) of early-onset gastric cancer (EOGC) patients. A total of 1077 EOGC patients from the Surveillance, Epidemiology, and End Results (SEER) database were included, and an additional 512 EOGC patients were recruited from the Fourth Hospital of Hebei Medical University, serving as an external test set. Univariate and multivariate Cox regression analyses were performed to identify independent prognostic factors. Based on these factors, two nomogram models were established, and web-based calculators were developed. These models were validated using receiver operating characteristics (ROC) curve analysis, calibration curves, and decision curve analysis (DCA). Multivariate analysis identified gender, histological type, stage, N stage, tumor size, surgery, primary site, and lung metastasis as independent prognostic factors for OS and CSS in EOGC patients. Calibration curves and DCA curves demonstrated that the two constructed nomogram models exhibited good performance. These nomogram models demonstrated superior performance compared to the 7th edition of the AJCC tumor-node-metastasis (TNM) classification (internal validation set: 1-year OS: 0.831 vs 0.793, P = 0.072; 1-year CSS: 0.842 vs 0.816, P = 0.190; 3-year OS: 0.892 vs 0.857, P = 0.039; 3-year CSS: 0.887 vs 0.848, P = 0.018; 5-year OS: 0.906 vs 0.880, P = 0.133; 5-year CSS: 0.900 vs 0.876, P = 0.109). In conclusion, this study developed two nomogram models: one for predicting OS and the other for CSS of EOGC patients, offering valuable assistance to clinicians.

Safety, tolerability, and pharmacokinetics of mitoxantrone hydrochloride injection for tracing in patients with gastric cancer: a single-blind, single-center, phase I clinical trial.

Mitoxantrone Hydrochloride Injection for Tracing (MHI), a modified new drug marketed in China, has been approved by the National Medical Products Administration for lymph node tracing in thyroid cancer and sentinel lymph node biopsy in breast cancer. This single-center, single-blind, dose-escalation phase I clinical trial aimed to investigate the safety of MHI on lymph node tracing in gastric cancer. In this study, four dose groups (1.0 mL, 1.5 mL, 2.0 mL, and 3.0 mL) with 3 gastric cancer patients in each group were set. The safety, tolerability, pharmacokinetics and preliminary efficacy of different doses were investigated. Results showed that none of the patients experienced dose-limiting toxicity or developed serious adverse events or adverse drug reactions. Pharmacokinetic analyses revealed minimal absorption of the tracer, resulting in low and transient blood drug concentrations across all participants. The mean time to peak concentration was (0.561 ± 0.3728) h (with mean peak concentration (Cmax) of 10.300 ng/mL), (0.500 ± 0.0167) h (mean Cmax of 13.687 ng/mL), (0.494 ± 0.0096) h (mean Cmax of 30.933 ng/mL), and (0.661 ± 0.2791) h (mean Cmax of 21.067 ng/mL) in the 1.0 mL, 1.5 mL, 2.0 mL, and 3.0 mL dose groups, respectively. The mean lymph node staining rates were 21.0%, 24.7%, 32.5%, and 44.5%, and the mean metastatic lymph node staining rates were 20.6%, 36.1%, 42.4%, and 21.0% in each group. This study confirmed that MHI was safe, well-tolerated, and had low systemic effects when used for lymphatic tracing of gastric cancer, and the tracing effect was better in the 3 mL dose group. This trail was registered on the website of Centre for Drug Evaluation State Drug and Food Administration (http://www.chinadrugtrials.org.cn/index.html) with the name of clinical study of lymphatic tracer in lymph node tracing of gastric cancer, the code was CTR20201906.

Machine learning models for abstract screening task - A systematic literature review application for health economics and outcome research.

OBJECTIVE: Systematic literature reviews (SLRs) are critical for life-science research. However, the manual selection and retrieval of relevant publications can be a time-consuming process. This study aims to (1) develop two disease-specific annotated corpora, one for human papillomavirus (HPV) associated diseases and the other for pneumococcal-associated pediatric diseases (PAPD), and (2) optimize machine- and deep-learning models to facilitate automation of the SLR abstract screening. METHODS: This study constructed two disease-specific SLR screening corpora for HPV and PAPD, which contained citation metadata and corresponding abstracts. Performance was evaluated using precision, recall, accuracy, and F1-score of multiple combinations of machine- and deep-learning algorithms and features such as keywords and MeSH terms. RESULTS AND CONCLUSIONS: The HPV corpus contained 1697 entries, with 538 relevant and 1159 irrelevant articles. The PAPD corpus included 2865 entries, with 711 relevant and 2154 irrelevant articles. Adding additional features beyond title and abstract improved the performance (measured in Accuracy) of machine learning models by 3% for HPV corpus and 2% for PAPD corpus. Transformer-based deep learning models that consistently outperformed conventional machine learning algorithms, highlighting the strength of domain-specific pre-trained language models for SLR abstract screening. This study provides a foundation for the development of more intelligent SLR systems.

Causal associations between sarcopenia-related traits and intervertebral disc degeneration: a two-sample mendelian randomization analysis.

BACKGROUND: Sarcopenia (SP) and intervertebral disc degeneration (IVDD) have a higher incidence in the elderly population. Previous studies have indicated a potential association between SP and IVDD. The objective of this study is to elucidate the potential causal relationship between sarcopenia-related traits and IVDD through Two-sample Mendelian randomization (MR) analysis. METHODS: We utilized a genome-wide association study conducted on the European population to collect aggregated data on sarcopenia and IVDD. Inverse variance weighting was primarily employed, supplemented by MR Egger, weighted median, simple model, and weighted model methods. Additionally, sensitivity analysis was performed to assess the robustness of the findings. RESULTS: Appendicular lean mass is positively associated with "Other intervertebral disc disorders" (OIDD) and "Prolapsed or slipped disc" (POSD) (OIDD: p = 0.002, OR = 1.120; POSD: p < 0.001, OR = 1.003), while grip strength (GS) is positively associated with POSD (left: p = 0.004, OR = 1.008; right: p < 0.001, OR = 1.010). It is worth mentioning that walking pace has significant causal relationship with "Low back pain" (LBP), "Lower back pain or/and sciatica" (LBPOAS), "Sciatica with lumbago" (SWL) and OIDD (LBP: p < 0.001, OR = 0.204; LBPOAS: p < 0.001, OR = 0.278; SWL: p = 0.003, OR = 0.249; OIDD: p < 0.001, OR = 0.256). CONCLUSION: The present study revealed the causal relationship between SP-related traits and IVDD and recommended to prevent and treat sarcopenia as a means of preventing IVDD in clinic practice.

Oxypeucedanin hydrate alleviates rheumatoid arthritis by inhibiting the TLR4-MD2/NF-κB/MAPK signaling axis.

Rheumatoid arthritis (RA) is an idiopathic and chronic autoimmune disease for which there are currently no effective treatments. Oxypeucedanin hydrate (OXH) is a natural coumarin known for its potent anti-inflammatory properties. However, further investigations are needed to determine its therapeutic efficacy in treating RA. In this study, we evaluate the anti-inflammatory activity of OXH by treating LPS-induced RAW264.7 macrophages. Our results show that OXH treatment reverses the changes in iNOS, COX-2, IL-1ß, IL-6, and TNF-α levels. Additionally, OXH reduces ROS production. Further analysis reveals that OXH suppresses the activation of the NF-κB/MAPK pathway. CETSA results show that OXH competes with LPS for binding to the TLR4/MD2 complex. MST experiments demonstrate the specific affinity of OXH for the TLR4/MD2 complex, with a Kd value of 33.7 µM. Molecular docking analysis suggests that OXH binds to the pocket of the TLR4/MD2 complex and interacts with specific amino acids, such as GLY-343, LYS-388, and PHE-345. Molecular dynamics simulations further confirm this conclusion. Finally, we investigate the potential of OXH in treating RA using a collagen-induced arthritis (CIA) model in rats. OXH effectively ameliorates the symptoms of CIA, including improving body weight, reducing swelling and redness, increasing talus volume, and decreasing bone erosion. OXH also decreases the mRNA levels of pro-inflammatory factors in synovial tissue. Transcriptome enrichment analysis and western blot analysis confirm that OXH suppresses the NF-κB/MAPK pathway, which is consistent with our in vitro findings.

A natural hydrogel complex improves intervertebral disc degeneration by correcting fatty acid metabolism and inhibiting nucleus pulposus cell pyroptosis.

The degeneration of intervertebral discs is strongly associated with the occurrence of pyroptosis in nucleus pulposus (NP) cells. This pyroptosis is characterized by abnormal metabolism of fatty acids in the degenerative pathological state, which is further exacerbated by the inflammatory microenvironment and degradation of the extracellular matrix. In order to address this issue, we have developed a fibrin hydrogel complex (FG@PEV). This intricate formulation amalgamates the beneficial attributes of platelet extravasation vesicles, contributing to tissue repair and regeneration. Furthermore, this complex showcases exceptional stability, gradual-release capabilities, and a high degree of biocompatibility. In order to substantiate the biological significance of FG@PEV in intervertebral disc degeneration (IVDD), we conducted a comprehensive investigation into its potential mechanism of action through the integration of RNA-seq sequencing and metabolomics analysis. Furthermore, these findings were subsequently validated through experimentation in both in vivo and in vitro models. The experimental results revealed that the FG@PEV intervention possesses the capability to reshape the inflammatory microenvironment within the disc. It also addresses the irregularities in fatty acid metabolism of nucleus pulposus cells, consequently hindering cellular pyroptosis and slowing down disc degeneration through the regulation of extracellular matrix synthesis and degradation. As a result, this injectable gel system represents a promising and innovative therapeutic approach for mitigating disc degeneration.

A review of distribution and functions of extracellular DNA in the environment and wastewater treatment systems.

Extracellular DNA referred to DNA fragments existing outside the cell, originating from various cell release mechanisms, including active secretion, cell lysis, and phage-mediated processes. Extracellular DNA serves as a vital environmental biomarker, playing crucial ecological and environmental roles in water bodies. This review is summarized the mechanisms of extracellular DNA release, including pathways involving cell lysis, extracellular vesicles, and type IV secretion systems. Then, the extraction and detection methods of extracellular DNA from water, soil, and biofilm are described and analyzed. Finally, we emphasize the role of extracellular DNA in microbial community systems, including its significant contributions to biofilm formation, biodiversity through horizontal gene transfer (HGT), and electron transfer processes. This review offers a comprehensive insight into the sources, distribution, functions, and impacts of extracellular DNA within aquatic environments, aiming to foster further exploration and understanding of extracellular DNA dynamics in aquatic environments as well as other environments.

Urinary proteomics for noninvasive monitoring of biomarkers of chronic mountain sickness in a young adult population using data-independent acquisition (DIA)-based mass spectrometry.

Different populations exhibit varying pathophysiological responses to plateau environments. Therefore, it is crucial to identify molecular markers in body fluids with high specificity and sensitivity to aid in determination. Proteomics offers a fresh perspective for investigating protein changes linked to diseases. We utilize urine as a specific biomarker for early chronic mountain sickness (CMS) detection, as it is a simple-to-collect biological fluid. We collected urine samples from three groups: plains health, plateau health and CMS. Using DIA's proteomic approach, we found differentially expressed proteins between these groups, which will be used as a basis for future studies to identify protein markers. Compared with the healthy plain population, 660 altering proteins were identified in plateau health, which performed the resistance to altitude response function by boosting substance metabolism and reducing immune stress function. Compared to the healthy plateau population, the CMS group had 140 different proteins identified, out of which 8 were potential biomarkers for CMS. Our study has suggested that CMS may be closely related to increased thyroid hormone levels, oxidative damage to the mitochondria, impaired cell detoxification function and inhibited hydrolase activity. SIGNIFICANCE: Our team has compiled a comprehensive dataset of urine proteomics for AMS disease. We successfully identified differentially expressed proteins between healthy and AMS groups using the DIA proteomic approach. We discovered that 660 proteins were altered in plateau health compared to the healthy plain population, resulting in a heightened resistance to altitude response function by boosting substance metabolism and reducing immune stress function. Additionally, we pinpointed 140 different proteins in the AMS group compared to the healthy plateau population, with 8 showing potential as biomarkers for AMS. Our findings suggest that the onset of AMS may be closely linked to increased thyroid hormone levels, oxidative damage to the mitochondria, impaired cell detoxification function and inhibited hydrolase activity.

The impact of frailty on clinical outcomes of older patients undergoing enhanced recovery after lumbar fusion surgery: A prospective cohort study.

BACKGROUND: Frailty is recognized as a surrogate for physiological age and has been established as a valid and independent predictor of postoperative morbidity, mortality, and complications. ERAS can enhance surgical safety by minimizing stress responses in frail patients, enabling surgeons to discharge patients earlier. However, the question of whether and to what extent the frailty impacts the post-ERAS outcomes in older patients remains. MATERIALS AND METHODS: An evidence-based ERAS program was implemented in our center from January 2019. This is a prospective cohort study of patients aged ≥75 years who underwent open transforaminal lumbar interbody fusion (TLIF) for degenerative spine disease from April 2019 to October 2021. Frailty was assessed with the Fried frailty scale (FP scale), and patients were categorized as non/prefrail (FP 0-2) or frail (FP ≥ 3). The preoperative variables, operative data, postoperative outcomes and follow-up information were compared between the two groups. Univariate and multivariate logistic regression analyses were used to identify risk factors for 90-day major complications and prolonged length of hospital stay (LOS) after surgery. RESULTS: A total of 245 patients (age of 79.8 ± 3.4 yr) who had a preoperative FP score recorded and underwent scheduled TLIF surgery were included in the final analysis. Comparisons between non-frail and prefrail/frail patients revealed no significant difference in age, sex, and surgery-related variables. Even after adjusting for multiple comparisons, the association between Fried frailty and ADL-dependency, IADL-dependency, and malnutrition remained significant. Preoperative frailty was associated with increased rates of postoperative adverse events. A higher CCI grade was an independent predictor for 90-day major complications, while Fried frailty and MNA-SF scores <12 were predictive of poor postoperative recovery. CONCLUSION: Frail older patients had more adverse post-ERAS outcomes after TLIF compared to non/prefrail older patients. Continued research and multidisciplinary collaboration will be essential to refine and optimize protocols for surgical care in frail older adults.

Comparison of perioperative and functional outcomes of single-incision versus standard multi-incision robot-assisted laparoscopic radical prostatectomy: a prospective, controlled, nonrandomized trial.

To compare perioperative and functional outcomes between improved (port-free) single-site robot-assisted laparoscopic radical prostatectomy (pf-ssRARP) and standard multi-port robot-assisted radical prostatectomy (MPRARP). A total of 372 consecutive patients underwent RARAP using the da Vinci Si® robotic surgical system. Group I (n = 210) included patients undergoing pf-ssRARP and Group II (n = 162) included patients undergoing MPRARP. Demographics and perioperative data including postoperative recovery outcomes were recorded and compared between the two groups. Overall mean operative time was significantly shorter with the pf-ssRARP compared to the MPRARP (p < 0.05). The length of hospitalization after the pf-ssRARP was shorter (p < 0.05). In Group I, the positive surgical margin rate was 15.2%; while in Group II, the positive margin rate was 33.3% (p < 0.05). The rate of instant urinary continence was significantly higher in Group I than in Group II (p < 0.05). The percentage of urinary continence was higher in the pf-ssRARP than in the MPRARP, at 6 months post-surgery (p < 0.05) and 9 months post-surgery (p < 0.05). There was no significant difference in the proportion of erectile function in the pf-ssRARP and MPRARP groups at the time of reaching the endpoint of this study (p > 0.05). The two groups were comparable in terms of total hospitalization costs (p < 0.05). The improved (port-free) single-site robot-assisted laparoscopic radical prostatectomy is a practical and easy technique to implement in clinical practice. Extraperitoneal implementation of the modified technique requires only a small incision, no special PORT, no additional auxiliary foramen creation, increased postoperative aesthetics and reduced hospitalization costs, and a high percentage of early postoperative urinary control recovery.

Advances in the study of plant-derived extracellular vesicles in the skeletal muscle system.

Plant-derived extracellular vesicles (PDEV) constitute nanoscale entities comprising lipids, proteins, nucleic acids and various components enveloped by the lipid bilayers of plant cells. These vesicles play a crucial role in facilitating substance and information transfer not only between plant cells but also across different species. Owing to its safety, stability, and the abundance of raw materials, this substance has found extensive utilization in recent years within research endeavors aimed at treating various diseases. This article provides an overview of the pathways and biological characteristics of PDEV, along with the prevalent methods employed for its isolation, purification, and storage. Furthermore, we comprehensively outline the therapeutic implications of diverse sources of PDEV in musculoskeletal system disorders. Additionally, we explore the utilization of PDEV as platforms for engineering drug carriers, aiming to delve deeper into the significance and potential contributions of PDEV in the realm of the musculoskeletal system.

FeS2-modified MXene nanocomposite platform for efficient PTT/CDT/TDT integration through enhanced GSH consumption.

Hypoxic microenvironment and glutathione (GSH) accumulation in tumours limit the efficacy of cytotoxic reactive oxygen species (ROS) anti-tumour therapy. To address this challenge, we increased the consumption of GSH and the production of ROS through a novel nanoplatform with the action of inorganic nanoenzymes. In this study, we prepared mesoporous FeS2 using a simple template method, efficiently loaded AIPH, and assembled Ti3C2/FeS2-AIPH@BSA (TFAB) nanocomposites through self-assembly with BSA and 2D Ti3C2. The constructed TFAB nanotherapeutic platform enhanced chemodynamic therapy (CDT) by generating toxic hydroxyl radicals (˙OH) via FeS2, while consuming GSH to reduce the loss of generated ˙OH via glutathione oxidase-like (GSH-OXD). In addition, TFAB is able to stimulate the decomposition of AIPH under 808 nm laser irradiation to produce oxygen-independent biotoxic alkyl radicals (˙R) for thermodynamic therapy (TDT). In conclusion, TFAB represents an innovative nanoplatform that effectively addresses the limitations of free radical-based treatment strategies. Through the synergistic therapeutic strategy of photothermal therapy (PTT), CDT, and TDT within the tumor microenvironment, TFAB nanoplatforms achieve controlled AIPH release, ROS generation, intracellular GSH consumption, and precise temperature elevation, resulting in enhanced intracellular oxidative stress, significant apoptotic cell death, and notable tumor growth inhibition. This comprehensive treatment strategy shows great promise in the field of tumor therapy.

Real-world effectiveness of a new powered stapling system with gripping surface technology on the intraoperative clinical and economic outcomes of gastrectomy for gastric cancer.

BACKGROUND: Surgical staplers have been widely used to facilitate surgeries, and this study aimed to examine the real-world effectiveness of a new powered stapling system with Gripping Surface Technology (GST) on intraoperative outcomes of gastrectomy for gastric cancer. METHOD: The data were extracted from the Fourth Hospital of Hebei Medical University's (FHHMU) medical records system. Participants (N = 121 patients) were classified into the GST (n = 59) or non-GST group (n = 62), based on the use of the GST system. The intraoperative outcomes such as bleeding were assessed by reviewing video records. T-tests, Chi-square tests, and Mann-Whitney-U tests were used to compare the baseline characteristics between groups. Multivariate logistic regression was conducted for adjusting outcomes to study the effect of variables. RESULTS: Compared with the non-GST group, the GST group had significantly lower risks for intraoperative bleeding, intraoperative anastomosis intervention rate, intraoperative suture, and intraoperative pression (aORs: 0.0853 (p < 0.0001), 0.076 (p = 0.0003), 0.167 (p = 0.0012), and 0.221 (p = 0.0107), respectively). The GST group also consumed one fewer cartridge than the non-GST group (GST:5 vs non-GST: 6, p = 0.0241). CONCLUSION: The use of the GST system was associated with better intraoperative outcomes and lower cartridge consumption in Chinese real-world settings.

N-Heterocyclic Carbene-Derived 1,3,5-Trimethylenebenzene: On-Surface Synthesis and Electronic Structure.

1,3,5-Trimethylenebenzene (1,3,5-TMB), a 3-fold-symmetric triradical with a high-spin ground state, is an attractive platform for investigating the unique spin properties of π-conjugated triangular triradicals. Here, we report the on-surface synthesis of N-heterocyclic carbene (NHC)-derived 1,3,5-TMB (N-TMB) via surface-assisted C-C and C-N coupling reactions on Au(111). The chemical and electronic structures of N-TMB on the Au(111) surface are revealed with atomic precision using scanning tunneling microscopy and noncontact atomic force microscopy, combined with density functional theory (DFT) calculations. It is demonstrated that there is substantial charge transfer between N-TMB and the substrate, resulting in a positively charged N-TMB on Au(111). DFT calculations at the UB3LYP/def2-TZVP level of theory and multireference method, e.g., CASSCF/NEVPT2, indicate that N-TMB possesses a doublet ground state with reduced Cs symmetry in the gas phase, contrasting the quartet ground state of 1,3,5-TMB with D3h symmetry, and exhibits a doublet-quartet energy gap of -0.80 eV. The incorporation of NHC structures and the extended π-conjugation promote the spin-orbital overlaps in N-TMB, leading to Jahn-Teller distortion and the formation of a robust doublet state. Our results not only demonstrate the fabrication of polyradicals based on NHC but also shed light on the effect of NHC and π-conjugation on the electronic structure and spin coupling, which opens up new possibilities for precisely regulating the spin-spin exchange coupling of organic polyradicals.

Efficacy and safety of ciprofol for sedation in outpatient gynecological procedures: a phase III multicenter randomized trial.

Objective: Ciprofol (also known as cipepofol and HSK3486), is a compound similar to propofol in chemical structure and hypnotic effect. Herein we evaluated the efficacy and safety of ciprofol for sedation in outpatient gynecological procedures. Methods: This phase III multicenter randomized trial with a non-inferiority design was conducted in nine tertiary hospitals. We enrolled 135 women aged 18-65 years who were scheduled for ambulatory gynecological procedures. Patients were randomly assigned to receive either ciprofol (0.4 mg/kg for induction and 0.2 mg/kg for maintenance) or propofol (2.0 mg/kg for induction and 1.0 mg/kg for maintenance) sedation in a 2:1 ratio. Patients and investigators for data collection and outcome assessment were blinded to study group assignments. The primary outcome was the success rate of sedation, defined as completion of procedure without remedial anesthetics. The non-inferiority margin was set at -8%. Secondary outcomes included time to successful induction, time to full awake, time to meet discharge criteria, and satisfaction with sedation assessed by patients and doctors. We also monitored occurrence of adverse events and injection pain. Results: A total of 135 patients were enrolled; 134 patients (90 patients received ciprofol sedation and 44 patients propofol sedation) were included in final intention-to-treat analysis. The success rates were both 100% in the two groups (rate difference, 0.0%; 95% CI, -4.1 to 8.0%), i.e., ciprofol was non-inferior to propofol. When compared with propofol sedation, patients given ciprofol required more time to reach successful induction (median difference [MD], 2 s; 95% CI, 1 to 7; p < 0.001), and required more time to reach full awake (MD, 2.3 min; 95% CI, 1.4 to 3.1; p < 0.001) and discharge criteria (MD, 2.3 min; 95% CI, 1.5 to 3.2; p < 0.001). Fewer patients in the ciprofol group were dissatisfied with sedation (relative risk, 0.21; 95% CI, 0.06 to 0.77; p = 0.024). Patients given ciprofol sedation had lower incidences of treat-emergent adverse events (34.4% [31/90] vs. 79.5% [35/44]; p < 0.001) and injection pain (6.7% [6/90] vs. 61.4% [27/44]; p < 0.001). Conclusion: Ciprofol for sedation in ambulatory gynecological procedures was non-inferior to propofol, with less adverse events and injection pain. Clinical trial registration: ClinicalTrials.gov, identifier NCT04958746.

Construction of a Novel MitochondriaAssociated Gene Model for Assessing ESCC Immune Microenvironment and Predicting Survival.

Esophageal squamous cell carcinoma (ESCC) is among the most common malignant tumors of the digestive tract, with the sixth highest fatality rate worldwide. The ESCC-related dataset, GSE20347, was downloaded from the Gene Expression Omnibus (GEO) database, and weighted gene coexpression network analysis was performed to identify genes that are highly correlated with ESCC. A total of 91 transcriptome expression profiles and their corresponding clinical information were obtained from The Cancer Genome Atlas database. A mitochondria-associated risk (MAR) model was constructed using the least absolute shrinkage and selection operator Cox regression analysis and validated using GSE161533. The tumor microenvironment and drug sensitivity were explored using the MAR model. Finally, in vitro experiments were performed to analyze the effects of hub genes on the proliferation and invasion abilities of ESCC cells. To confirm the predictive ability of the MAR model, we constructed a prognostic model and assessed its predictive accuracy. The MAR model revealed substantial differences in immune infiltration and tumor microenvironment characteristics between high- and low-risk populations and a substantial correlation between the risk scores and some common immunological checkpoints. AZD1332 and AZD7762 were more effective for patients in the low-risk group, whereas Entinostat, Nilotinib, Ruxolutinib, and Wnt.c59 were more effective for patients in the high-risk group. Knockdown of TYMS significantly inhibited the proliferation and invasive ability of ESCC cells in vitro. Overall, our MAR model provides stable and reliable results and may be used as a prognostic biomarker for personalized treatment of patients with ESCC.

Stranski-Krastanov Growth of Two-Dimensional Covalent Organic Framework Films.

Insights into the formation mechanisms of two-dimensional covalent organic frameworks (2D COFs) at both the in-plane and interlayer levels are essential for improving material quality and synthetic methodology. Here, we report the controllable preparation of 2D COF films via on-surface synthesis and investigate the growth mechanism using atomic force microscopy. Monolayer, bilayer, and layer-plus-island multilayer COF films were successfully constructed on hexagonal boron nitride in a controlled manner. The porphyrin-based COF films grow in the Stranski-Krastanov mode, i.e., a uniform bilayer COF film can be formed through layer-by-layer growth in the initial stage followed by island growth starting from the third layer. Furthermore, fluorescence quenching caused by π-π stacking interactions between 2D COF neighboring layers was revealed. These results provide new perspectives on the synthesis of high-quality 2D COF films with controllable thickness and morphology, paving the way for a diverse range of applications.

Ambient Synthesis of Porphyrin-Based Fe-Covalent Organic Frameworks for Efficient Infected Skin Wound Healing.

Reactive oxygen species (ROS) have emerged as a promising treatment option for antibacterial and biofilm eradication. However, their therapeutic efficacy is significantly hampered by the unique microenvironments of diabetic wounds. In this study, we designed and synthesized porphyrin-based Fe covalent organic frameworks (Fe-COF) through a Schiff base condensation reaction. Subsequently, Fe-COF were encapsulated with hyaluronic acid (HA) through electrostatic adsorption, resulting in a novel formulation named HA-Fe-COF for diabetic wound healing. HA-Fe-COF were engineered to respond to hyaluronidase in the infected wound, leading to the controlled release of Fe-COF. Those released Fe-COF served a dual role as photosensitizers, generating singlet oxygen and localized heating when exposed to dual light sources. Additionally, they acted as peroxidase-like nanozymes, facilitating the production of ROS through enzymatic reactions. This innovative approach enabled a synergistic therapeutic effect combining photodynamic, photothermal, and chemodynamic modalities. Furthermore, the sustained release of HA from HA-Fe-COF promoted angiogenesis, collagen deposition, and re-epithelialization during the diabetic wound healing process. This "all-in-one" strategy offers a novel approach for the development of antimicrobial and biofilm eradication strategies that minimize damage to healthy tissues in vivo.