Recommendations of the Blue Ribbon Committee II for the Optimization of Surgical Education and Training in the United States: The Surgical Trainee Perspective.

OBJECTIVE: This study aims to appraise recommendations from an expert panel of surgical educators on optimizing surgical education and training in the setting of contemporary challenges. BACKGROUND: The Blue Ribbon Committee (BRC II), a group of surgical educators, was convened to make recommendations to optimize surgical training considering the current changes in the landscape of surgical education. Surgical trainees were recruited to assess their impressions of the recommendations. METHODS: A mixed-methods study design was employed, with a survey, followed by focus group interviews. Participating residents and fellows were recruited through a purposeful sampling approach. Descriptive statistics were applied to analyze the survey data, and a thematic data analysis on interview transcripts was employed. RESULTS: The majority of trainee respondents (n=16) thought that all of the subcommittee recommendations should be included in the final BRC II recommendations and paper. According to the interviews, overall, the feedback from the trainees was positive, with particular excitement around work-life integration, education support and faculty development, and funding pitfalls. Some themes about concerns included a lack of clarity about the recommendations, concern about some recommendations being in conflict with one another, and a disconnect between the initial BRC II survey and the subsequent recommendations. CONCLUSIONS: The residents gathered for this focus group were encouraged by the thought, effort, and intention that gathered the surgical leaders across the country to make the recommendations. While there were areas the trainees wanted clarity on, the overall opinion was in agreement with the recommendations.

Iron Chelator Deferiprone Restores Iron Homeostasis and Inhibits Retinal Neovascularization in Experimental Neovascular Age-Related Macular Degeneration.

Purpose: Retinal neovascularization is a significant feature of advanced age-related macular degeneration (AMD) and a major cause of blindness in patients with AMD. However, the underlying mechanism of this pathological neovascularization remains unknown. Iron metabolism has been implicated in various biological processes. This study was conducted to investigate the effects of iron metabolism on retinal neovascularization in neovascular AMD (nAMD). Methods: C57BL/6J and very low-density lipoprotein receptor (VLDLR) knockout (Vldlr-/-) mice, a murine model of nAMD, were used in this study. Bulk-RNA sequencing was used to identify differentially expressed genes. Western blot analysis was performed to test the expression of proteins. Iron chelator deferiprone (DFP) was administrated to the mice by oral gavage. Fundus fluorescein angiography was used to evaluate retinal vascular leakage. Immunofluorescence staining was used to detect macrophages and iron-related proteins. Results: RNA sequencing (RNA-seq) results showed altered transferrin expression in the retina and RPE of Vldlr-/- mice. Disrupted iron homeostasis was observed in the retina and RPE of Vldlr-/- mice. DFP mitigated iron overload and significantly reduced retinal neovascularization and vascular leakage. In addition, DFP suppressed the inflammation in Vldlr-/- retinas. The reduced signals of macrophages were observed at sites of neovascularization in the retina and RPE of Vldlr-/- mice after DFP treatment. Further, the IL-6/JAK2/STAT3 signaling pathway was activated in the retina and RPE of Vldlr-/- mice and reversed by DFP treatment. Conclusions: Disrupted iron metabolism may contribute to retinal neovascularization in nAMD. Restoring iron homeostasis by DFP could be a potential therapeutic approach for nAMD.

Utilizing machine learning to integrate single-cell and bulk RNA sequencing data for constructing and validating a novel cell adhesion molecules related prognostic model in gastric cancer.

BACKGROUND: Cell adhesion molecules (CAMs) play a vital role in cell-cell interactions, immune response modulation, and tumor cell migration. However, the unique role of CAMs in gastric cancer (GC) remains largely unexplored. METHODS: This study characterized the genetic alterations and mRNA expression of CAMs. The role of CD34, a representative molecule, was validated in 375 GC tissues. The activity of the CAM pathway was further tested using single-cell and bulk characterization. Next, data from 839 patients with GC from three cohorts was analyzed using univariate Cox and random survival forest methods to develop and validate a CAM-related prognostic model. RESULTS: Most CAM-related genes exhibited multi-omics alterations and were associated with clinical outcomes. There was a strong correlation between increased CD34 expression and advanced clinical staging (P = 0.026), extensive vascular infiltration (P = 0.003), and unfavorable prognosis (Log-rank P = 0.022). CD34 expression was also found to be associated with postoperative chemotherapy and tumor immunotherapy response. Furthermore, the CAM pathway was significantly activated and mediated poor prognosis. Additionally, eight prognostic signature genes (PSGs) were identified in the training cohort. There was a substantial upregulation of the expression of immune checkpoints and a pronounced infiltration of immune cells in GC tissues with high PSG score, which is consistent with the prediction of increased sensitivity to immunotherapy. Moreover, 9 compounds from the CTRPv2 database and 13 from the Profiling Relative Inhibition Simultaneously in Mixture (PRISM) database were identified as potential therapeutic drugs for patients with GC with high PSG score. CONCLUSION: Thorough understanding of CAM pathways regulation and the innovative PSG score model hold significant implications for medical diagnosis, potentially enhancing personalized treatment strategies and improving patient outcomes in GC management.

Genome-Wide Identification and Expression Analysis of SlNRAMP Genes in Tomato under Nutrient Deficiency and Cadmium Stress during Arbuscular Mycorrhizal Symbiosis.

Arbuscular mycorrhizal (AM) fungi are well known for enhancing phosphorus uptake in plants; however, their regulating roles in cation transporting gene family, such as natural resistance-associated macrophage protein (NRAMP), are still limited. Here, we performed bioinformatics analysis and quantitative expression assays of tomato SlNRAMP 1 to 5 genes under nutrient deficiency and cadmium (Cd) stress in response to AM symbiosis. These five SlNRAMP members are mainly located in the plasma or vacuolar membrane and can be divided into two subfamilies. Cis-element analysis revealed several motifs involved in phytohormonal and abiotic regulation in their promoters. SlNRAMP2 was downregulated by iron deficiency, while SlNRAMP1, SlNRAMP3, SlNRAMP4, and SlNRAMP5 responded positively to copper-, zinc-, and manganese-deficient conditions. AM colonization reduced Cd accumulation and expression of SlNRAMP3 but enhanced SlNRAMP1, SlNRAMP2, and SlNRMAP4 in plants under Cd stress. These findings provide valuable genetic information for improving tomato resilience to nutrient deficiency and heavy metal stress by developing AM symbiosis.

RAG1 and RAG2 non-core regions are implicated in leukemogenesis and off-target V(D)J recombination in BCR-ABL1-driven B-cell lineage lymphoblastic leukemia.

The evolutionary conservation of non-core RAG regions suggests significant roles that might involve quantitative or qualitative alterations in RAG activity. Off-target V(D)J recombination contributes to lymphomagenesis and is exacerbated by RAG2' C-terminus absence in Tp53-/- mice thymic lymphomas. However, the genomic stability effects of non-core regions from both Rag1c/c and Rag2c/c in BCR-ABL1+ B-lymphoblastic leukemia (BCR-ABL1+ B-ALL), the characteristics, and mechanisms of non-core regions in suppressing off-target V(D)J recombination remain unclear. Here, we established three mouse models of BCR-ABL1+ B-ALL in mice expressing full-length RAG (Ragf/f), core RAG1 (Rag1c/c), and core RAG2 (Rag2c/c). The Ragc/c (Rag1c/c and Rag2c/c) leukemia cells exhibited greater malignant tumor characteristics compared to Ragf/f cells. Additionally, Ragc/c cells showed higher frequency of off-target V(D)J recombination and oncogenic mutations than Ragf/f. We also revealed decreased RAG cleavage accuracy in Ragc/c cells and a smaller recombinant size in Rag1c/c cells, which could potentially exacerbate off-target V(D)J recombination in Ragc/c cells. In conclusion, these findings indicate that the non-core RAG regions, particularly the non-core region of RAG1, play a significant role in preserving V(D)J recombination precision and genomic stability in BCR-ABL1+ B-ALL.

Development and validation of a machine learning-based 18F-fluorodeoxyglucose PET/CT radiomics signature for predicting gastric cancer survival.

BACKGROUND: Survival prognosis of patients with gastric cancer (GC) often influences physicians' choice of their follow-up treatment. This study aimed to develop a positron emission tomography (PET)-based radiomics model combined with clinical tumor-node-metastasis (TNM) staging to predict overall survival (OS) in patients with GC. METHODS: We reviewed the clinical information of a total of 327 patients with pathological confirmation of GC undergoing 18 F-fluorodeoxyglucose (18 F-FDG) PET scans. The patients were randomly classified into training (n = 229) and validation (n = 98) cohorts. We extracted 171 PET radiomics features from the PET images and determined the PET radiomics scores (RS) using the least absolute shrinkage and selection operator (LASSO) and random survival forest (RSF). A radiomics model, including PET RS and clinical TNM staging, was constructed to predict the OS of patients with GC. This model was evaluated for discrimination, calibration, and clinical usefulness. RESULTS: On multivariate COX regression analysis, the difference between age, carcinoembryonic antigen (CEA), clinical TNM, and PET RS in GC patients was statistically significant (p < 0.05). A radiomics model was developed based on the results of COX regression. The model had the Harrell's concordance index (C-index) of 0.817 in the training cohort and 0.707 in the validation cohort and performed better than a single clinical model and a model with clinical features combined with clinical TNM staging. Further analyses showed higher PET RS in patients who were older (p < 0.001) and those who had elevated CEA (p < 0.001) and higher clinical TNM (p < 0.001). At different clinical TNM stages, a higher PET RS was associated with a worse survival prognosis. CONCLUSIONS: Radiomics models based on PET RS, clinical TNM, and clinical features may provide new tools for predicting OS in patients with GC.

Radial extracorporeal shockwave promotes osteogenesis-angiogenesis coupling of bone marrow stromal cells from senile osteoporosis via activating the Piezo1/CaMKII/CREB axis.

Radial extracorporeal shockwave (r-ESW) and bone marrow stromal cells (BMSCs) have been reported to alleviate senile osteoporosis (SOP), but its regulatory mechanism remains unclear. In this study, we firstly isolated human BMSCs from bone marrow samples and treated with varying r-ESW doses. And we found that r-ESW could enhance the proliferation of SOP-BMSCs in a dose-dependent manner by EdU assay. Subsequently, the impact of r-ESW on the proliferation, apoptosis and multipotency of BMSCs was assessed. And the outcomes of flow cytometry, Alizarin red S (ARS), and tube formation test demonstrated that the optimal shockwave obviously boosted SOP-BMSCs osteogenesis and angiogenesis but exhibited no significant impact on cell apoptosis. Additionally, the signaling of Piezo1 and CaMKII/CREB was examined by Western blotting, qPCR and immunofluorescence. And the results showed that r-ESW promoted the expression of Piezo1, increased intracellular Ca2+ and activated the CaMKII/CREB signaling pathway. Then, the application of Piezo1 siRNA hindered the r-ESW-induced enhancement ability of osteogenesis coupling with angiogenesis of SOP-BMSCs. The use of the CaMKII/CREB signaling pathway inhibitor KN93 suppressed the Piezo1-induced increase in osteogenesis and angiogenesis in SOP-BMSCs. Finally, we also found that r-ESW might alleviate SOP in the senescence-accelerated mouse prone 6 (SAMP6) model by activating Piezo1. In conclusion, our research offers experimental evidence and an elucidated underlying molecular mechanism to support the use of r-ESW as a credible rehabilitative treatment for senile osteoporosis.

CRISPR/Cas12a trans-cleavage mediated photoelectrochemical biosensor based on zeolitic imidazolate framework-67 for ATP determination.

An efficient PEC biosensor is proposed for ATP detection based on exciton energy transfer from CdTe quantum dots (CdTe QDs) to Au nanoparticles (AuNPs), integrating CRISPR/Cas12a trans-cleavage activity and specific recognition of ZIF-67 to ATP. Exciton energy transfer between CdTe QDs and AuNPs system is firstly constructed as photoelectrochemical (PEC) sensing substrate. Then, the activator DNAs, used to activate CRISPR/Cas12a, are absorbed on the surface of ZIF-67. In the presence of ATP, the activator DNAs are released due to more efficient adsorption of ZIF-67 to ATP. The released activator DNA activates trans-cleavage activity of CRISPR/Cas12a to degrade ssDNA on the electrode, leading to the recovery of photocurrent due to the interrupted energy transfer. Benefiting from the specific recognition of ZIF-67 to ATP and CRISPR/Cas12a-modulated amplification strategy, the sensor is endowed with excellent specificity and high sensitivity.

How multidisciplinary clinics may mitigate socioeconomic barriers to care for chronic limb-threatening ischemia.

OBJECTIVE: Although multidisciplinary clinics improve outcomes in chronic limb-threatening ischemia (CLTI), their role in addressing socioeconomic disparities is unknown. Our institution treats patients with CLTI at both traditional general vascular clinics and a multidisciplinary Limb Preservation Program (LPP). The LPP is in a minority community, providing expedited care at a single facility by a consistent team. We compared outcomes within the LPP with our institution's traditional clinics and explored patients' perspectives on barriers to care to evaluate if the LPP might address them. METHODS: All patients undergoing index revascularization for CLTI from 2014 to 2023 at our institution were stratified by clinic type (LPP or traditional). We collected clinical and socioeconomic variables, including Area Deprivation Index (ADI). Patient characteristics were compared using χ2, Student t, or Mood median tests. Outcomes were compared using log-rank and multivariable Cox analysis. We also conducted semi-structured interviews to understand patient-perceived barriers. RESULTS: From 2014 to 2023, 983 limbs from 871 patients were revascularized; 19.5% of limbs were treated within the LPP. Compared with traditional clinic patients, more LPP patients were non-White (43.75% vs 27.43%; P < .0001), diabetic (82.29% vs 61.19%; P < .0001), dialysis-dependent (29.17% vs 13.40%; P < .0001), had ADI in the most deprived decile (29.38% vs 19.54%; P = .0061), resided closer to clinic (median 6.73 vs 28.84 miles; P = .0120), and had worse Wound, Ischemia, and foot Infection (WIfI) stage (P < .001). There were no differences in freedom from death, major adverse limb event (MALE), or patency loss. Within the most deprived subgroup (ADI >90), traditional clinic patients had earlier patency loss (P = .0108) compared with LPP patients. Multivariable analysis of the entire cohort demonstrated that increasing age, heart failure, dialysis, chronic obstructive pulmonary disease, and increasing WIfI stage were independently associated with earlier death, and male sex was associated with earlier MALE. Ten traditional clinic patients were interviewed via convenience sampling. Emerging themes included difficulty understanding their disease, high visit frequency, transportation barriers, distrust of the health care system, and patient-physician racial discordance. CONCLUSIONS: LPP patients had worse comorbidities and socioeconomic deprivation yet had similar outcomes to healthier, less deprived non-LPP patients. The multidisciplinary clinic's structure addresses several patient-perceived barriers. Its proximity to disadvantaged patients and ability to conduct multiple appointments at a single visit may address transportation and visit frequency barriers, and the consistent team may facilitate patient education and improve trust. Including these elements in a multidisciplinary clinic and locating it in an area of need may mitigate some negative impacts of socioeconomic deprivation on CLTI outcomes.

Enzyme-Instructed Photoactivatable Supramolecular Antigens on Cancer Cell Membranes for Precision-Controlled T-Cell-Based Cancer Immunotherapy.

Cancer immunotherapies based on cytotoxic CD8+ T lymphocytes (CTLs) are highly promising for cancer treatment. The specific interaction between T-cell receptors and peptide-MHC-I complexes (pMHC-I) on cancer cell membranes critically determines their therapeutic outcomes. However, the lack of appropriate endogenous antigens for MHC-I presentation disables tumor recognition by CTLs. By devising three antigen-loaded self-assembling peptides of pY-K(Ag)-ERGD, pY-K(Ag)-E, and Y-K(Ag)-ERGD to noncovalently generate light-activatable supramolecular antigens at tumor sites in different manners, we report pY-K(Ag)-ERGD as a promising candidate to endow tumor cells with pMHC-I targets on demand. Specifically, pY-K(Ag)-ERGD first generates low-antigenic supramolecular antigens on cancer cell membranes, and a successive light pulse allows antigen payloads to efficiently release from the supramolecular scaffold, directly producing antigenic pMHC-I. Intravenous administration of pY-K(Ag)-ERGD enables light-controlled tumor inhibition when combined with adoptively transferred antigen-specific CTLs. Our strategy is feasible for broadening tumor antigen repertoires for T-cell immunotherapies and advancing precision-controlled T-cell immunotherapies.

Behind the pattern: General surgery residsent autonomy in robotic surgery.

Objective: Robotic surgery is increasingly utilized and common in general surgery training programs. This study sought to better understand the factors that influence resident operative autonomy in robotic surgery. We hypothesized that resident seniority, surgeon work experience, surgeon robotic-assisted surgery (RAS) case volume, and procedure type influence general surgery residents' opportunities for autonomy in RAS as measured by percentage of resident individual console time (ICT). Methods: General surgery resident ICT data for robotic cholecystectomy (RC), inguinal hernia (RIH), and ventral hernia (RVH) operations performed on the dual-console Da Vinci surgical robotic system between July 2019 and June 2021 were extracted. Cases with postgraduate year (PGY) 2-5 residents participating as a console surgeon were included. A sequential explanatory mixed-methods approach was undertaken to explore the ICT results and we conducted secondary qualitative interviews with surgeons. Descriptive statistics and thematic analysis were applied. Results: Resident ICT data from 420 robotic cases (IH 200, RC 121, and VH 99) performed by 20 junior residents (PGY2-3), 18 senior residents (PGY4-5), and 9 attending surgeons were extracted. The average ICT per case was 26.8 % for junior residents and 42.4 % for senior residents. Compared to early-career surgeons, surgeons with over 10 years' work experience gave less ICT to junior (18.2 % vs. 32.0 %) and senior residents (33.9 % vs. 56.6 %) respectively. Surgeons' RAS case volume had no correlation with resident ICT (r = 0.003, p = 0.0003). On average, residents had the most ICT in RC (45.8 %), followed by RIH (36.7 %) and RVH (28.6 %). Interviews with surgeons revealed two potential reasons for these resident ICT patterns: 1) Surgeon assessment of resident training year/experience influenced decisions to grant ICT; 2) Surgeons' perceived operative time pressure inversely affected resident ICT. Conclusions: This study suggests resident ICT/autonomy in RC, RIH, and RVH are influenced by resident seniority level, surgeon work experience, and procedure type, but not related to surgeon RAS case volume. Design and implementation of an effective robotic training program must consider the external pressures at conflict with increased resident operative autonomy and seek to mitigate them.

Therapeutic options for different metastatic sites arising from renal cell carcinoma: A review.

Renal cell carcinoma (RCC) stands among the top 10 malignant neoplasms with the highest fatality rates. It exhibits pronounced heterogeneity and robust metastatic behavior. Patients with RCC may present with solitary or multiple metastatic lesions at various anatomical sites, and their prognoses are contingent upon the site of metastasis. When deliberating the optimal therapeutic approach for a patient, thorough evaluation of significant risk factors such as the feasibility of complete resection, the presence of oligometastases, and the patient's functional and physical condition is imperative. Recognizing the nuanced differences in RCC metastasis to distinct organs proves advantageous in contemplating potential treatment modalities aimed at optimizing survival outcomes. Moreover, discerning the metastatic site holds promise for enhancing risk stratification in individuals with metastatic RCC. This review summarizes the recent data pertaining to the current status of different RCC metastatic sites and elucidates their role in informing clinical management strategies across diverse metastatic locales of RCC.

Prognostic value and association of the age-adjusted Charlson Comorbidity Index with sarcopenia within patients with gastric cancer after radical resection.

PURPOSE: The association between the age-adjusted Charlson Comorbidity Index (ACCI) and sarcopenia in patients with gastric cancer (GC) remains ambiguous. This study aimed to investigate the association between the ACCI and sarcopenia and the prognostic value in patients with GC after radical resection. In addition, this study aimed to develop a novel prognostic scoring system based on these factors. METHODS: Univariate and multivariate Cox regression analyses were used to determine prognostic factors in patients undergoing radical GC resection. Based on the ACCI and sarcopenia, a new prognostic score (age-adjusted Charlson Comorbidity Index and Sarcopenia [ACCIS]) was established, and its prognostic value was assessed. RESULTS: This study included 1068 patients with GC. Multivariate analysis revealed that the ACCI and sarcopenia were independent risk factors during the prognosis of GC (P = 0.001 and P < 0.001, respectively). A higher ACCI score independently predicted sarcopenia (P = 0.014). A high ACCIS score was associated with a greater American Society of Anesthesiologists score, higher pathologic TNM (pTNM) stage, and larger tumor size (all P < 0.05). Multivariate analysis demonstrated that the ACCIS independently predicted the prognosis for patients with GC (P < 0.001). By incorporating the ACCIS score into a prognostic model with sex, pTNM stage, tumor size, and tumor differentiation, we constructed a nomogram to predict the prognosis accurately (concordance index of 0.741). CONCLUSION: The ACCI score and sarcopenia are significantly correlated in patients with GC. The integration of the ACCI score and sarcopenia markedly enhances the accuracy of prognostic predictions in patients with GC.

Locationally activated PRP via an injectable dual-network hydrogel for endometrial regeneration.

Enhancing the effectiveness of platelet-rich plasma (PRP) for endometrial regeneration is challenging, due to its limited mechanical properties and burst release of growth factors. Here, we proposed an injectable interpenetrating dual-network hydrogel that can locationally activate PRP within the uterine cavity, sustained release growth factors and further address the insufficient therapeutic efficacy. Locational activation of PRP is achieved using the dual-network hydrogel. The phenylboronic acid (PBA) modified methacrylated hyaluronic acid (HAMA) dispersion chelates Ca2+ by carboxy groups and polyphenol groups, and in situ crosslinked with PRP-loaded polyvinyl alcohol (PVA) dispersion by dynamic borate ester bonds thus establishing the soft hydrogel. Subsequently, in situ photo-crosslinking technology is employed to enhance the mechanical performance of hydrogels by initiating free radical polymerization of carbon-carbon double bonds to form a dense network. The PRP-hydrogel significantly promoted the endometrial cell proliferation, exhibited strong pro-angiogenic effects, and down-regulated the expression of collagen deposition genes by inhibiting the TGF-ß1-SMAD2/3 pathway in vitro. In vivo experiments using a rat intrauterine adhesion (IUA) model showed that the PRP-hydrogel significantly promoted endometrial regeneration and restored uterine functionality. Furthermore, rats treated with the PRP-hydrogel displayed an increase in the number of embryos, litter size, and birth rate, which was similar to normal rats. Overall, this injectable interpenetrating dual-network hydrogel, capable of locational activation of PRP, suggests a new therapeutic approach for endometrial repair.

The Blue Ribbon Committee II Report and Recommendations on Surgical Education and Training in the United States: 2024.

OBJECTIVE: An expert panel made recommendations to optimize surgical education and training based on the effects of contemporary challenges. BACKGROUND: The inaugural Blue Ribbon Committee (BRC I) proposed sweeping recommendations for surgical education and training in 2004. In light of those findings, a second BRC (BRC II) was convened to make recommendations to optimize surgical training considering the current landscape in medical education. METHODS: BRC II was a panel of 67 experts selected on the basis of experience and leadership in surgical education and training. It was organized into subcommittees which met virtually over the course of a year. They developed recommendations, along with the Steering Committee, based on areas of focus and then presented them to the entire BRC II. The Delphi Method was chosen to obtain consensus, defined as>80% agreement amongst the panel. Cronbach alpha was computed to assess the internal consistency of three Delphi rounds. RESULTS: Of 50 recommendations, 31 obtained consensus in the following aspects of surgical training (# consensus recommendation /# proposed): Workforce (1/5), Medical Student Education (3/8), Work Life Integration (4/6), Resident Education (5/7), Goals, Structure and Financing of Training (5/8), Education Support and Faculty Development (5/6), Research Training (7/9), and Educational Technology and Assessment (1/1). The internal consistency was good in Rounds 1 and 2 and acceptable in Round 3. CONCLUSIONS: BRC II used the Delphi approach to identify and recommend 31 priorities for surgical education in 2024. We advise establishing a multidisciplinary surgical educational group to oversee, monitor and facilitate implementation of these recommendations.

Fe-single-atom catalysts boosting electrochemiluminescence via bipolar electrode integrated with its peroxidase-like activity for bioanalysis.

Multifunctional single-atom catalysts (SACs) have been extensively investigated as outstanding signal amplifiers in bioanalysis field. Herein, a type of Fe single-atom catalysts with Fe-nitrogen coordination sites in nitrogen-doped carbon (Fe-N/C SACs) was synthesized and demonstrated to possess both catalase and peroxidase-like activity. Utilizing Fe-N/C SACs as dual signal amplifier, an efficient bipolar electrode (BPE)-based electrochemiluminescence (ECL) immunoassay was presented for determination of prostate-specific antigen (PSA). The cathode pole of the BPE-ECL platform modified with Fe-N/C SACs is served as the sensing side and luminol at the anode as signal output side. Fe-N/C SACs could catalyze decomposition of H2O2 via their high catalase-like activity and then increase the Faraday current, which can boost the ECL of luminol due to the electroneutrality in a closed BPE system. Meanwhile, in the presence of the target, glucose oxidase (GOx)-Au NPs-Ab2 was introduced through specific immunoreaction, which catalyzes the formation of H2O2. Subsequently, Fe-N/C SACs with peroxidase-like activity catalyze the reaction of H2O2 and 4-chloro-1-naphthol (4-CN) to generate insoluble precipitates, which hinders electron transfer and then inhibits the ECL at the anode. Thus, dual signal amplification of Fe-N/C SACs was achieved by increasing the initial ECL and inhibiting the ECL in the presence of target. The assay exhibits sensitive detection of PSA linearly from 1.0 pg/mL to 100 ng/mL with a detection limit of 0.62 pg/mL. The work demonstrated a new ECL enhancement strategy of SACs via BPE system and expands the application of SACs in bioanalysis field.

Esophageal cancer screening, early detection and treatment: Current insights and future directions.

Esophageal cancer ranks among the most prevalent malignant tumors globally, primarily due to its highly aggressive nature and poor survival rates. According to the 2020 global cancer statistics, there were approximately 604000 new cases of esophageal cancer, resulting in 544000 deaths. The 5-year survival rate hovers around a mere 15%-25%. Notably, distinct variations exist in the risk factors associated with the two primary histological types, influencing their worldwide incidence and distribution. Squamous cell carcinoma displays a high incidence in specific regions, such as certain areas in China, where it meets the cost-effectiveness criteria for widespread endoscopy-based early diagnosis within the local population. Conversely, adenocarcinoma (EAC) represents the most common histological subtype of esophageal cancer in Europe and the United States. The role of early diagnosis in cases of EAC originating from Barrett's esophagus (BE) remains a subject of controversy. The effectiveness of early detection for EAC, particularly those arising from BE, continues to be a debated topic. The variations in how early-stage esophageal carcinoma is treated in different regions are largely due to the differing rates of early-stage cancer diagnoses. In areas with higher incidences, such as China and Japan, early diagnosis is more common, which has led to the advancement of endoscopic methods as definitive treatments. These techniques have demonstrated remarkable efficacy with minimal complications while preserving esophageal functionality. Early screening, prompt diagnosis, and timely treatment are key strategies that can significantly lower both the occurrence and death rates associated with esophageal cancer.

Topological Nature of Radiation Asymmetry in Bilayer Metagratings.

Manipulating radiation asymmetry of photonic structures is of particular interest in many photonic applications such as directional optical antenna, high efficiency on-chip lasers, and coherent light control. Here, we proposed a term of pseudopolarization to reveal the topological nature of radiation asymmetry in bilayer metagratings. Robust pseudopolarization vortex with an integer topological charge exists in P-symmetry metagrating, allowing for tunable directionality ranging from -1 to 1 in synthetic parameter space. When P-symmetry breaking, such vortex becomes pairs of C points due to the conservation law of charge, leading to the phase difference of radiation asymmetry from π/2 to 3π/2. Furthermore, topologically enabled coherent perfect absorption is robust with customized phase difference at will between two counterpropagating external light sources. This Letter can not only enrich the understanding of two particular topological photonic behaviors, i.e., bound state in the continuum and unidirectional guided resonance, but also provide a topological view on radiation asymmetry, opening an unexplored avenue for asymmetric light manipulation in on-chip laser, light-light switch, and quantum emitters.

Propofol improves survival in a murine model of sepsis via inhibiting Rab5a-mediated intracellular trafficking of TLR4.

BACKGROUND: Propofol is a widely used anesthetic and sedative, which has been reported to exert an anti-inflammatory effect. TLR4 plays a critical role in coordinating the immuno-inflammatory response during sepsis. Whether propofol can act as an immunomodulator through regulating TLR4 is still unclear. Given its potential as a sepsis therapy, we investigated the mechanisms underlying the immunomodulatory activity of propofol. METHODS: The effects of propofol on TLR4 and Rab5a (a master regulator involved in intracellular trafficking of immune factors) were investigated in macrophage (from Rab5a-/- and WT mice) following treatment with lipopolysaccharide (LPS) or cecal ligation and puncture (CLP) in vitro and in vivo, and peripheral blood monocyte from sepsis patients and healthy volunteers. RESULTS: We showed that propofol reduced membrane TLR4 expression on macrophages in vitro and in vivo. Rab5a participated in TLR4 intracellular trafficking and both Rab5a expression and the interaction between Rab5a and TLR4 were inhibited by propofol. We also showed Rab5a upregulation in peripheral blood monocytes of septic patients, accompanied by increased TLR4 expression on the cell surface. Propofol downregulated the expression of Rab5a and TLR4 in these cells. CONCLUSIONS: We demonstrated that Rab5a regulates intracellular trafficking of TLR4 and that propofol reduces membrane TLR4 expression on macrophages by targeting Rab5a. Our study not only reveals a novel mechanism for the immunomodulatory effect of propofol but also indicates that Rab5a may be a potential therapeutic target against sepsis.

Lack of clinical benefit from preoperative short-term parenteral nutrition on the clinical prognosis of patients treated with radical gastrectomy for gastric cancer: a two-center retrospective study based on propensity score matching analysis.

Background: Preoperative nutritional support studies for patients undergoing gastrointestinal (GI) surgery mostly focused on enteral nutrition (EN) or long-term (≥7 days) parenteral nutrition (PN). Some studies also found that preoperative short-term PN could improve the postoperative short-term nutritional status of tumor patients. But whether short-term PN support (1-6 days) before surgery can improve the prognosis of patients undergoing surgery for gastric cancer (GC) remains unclear. Therefore, we focused on assessing the effect of preoperative short-term PN on the outcomes of patients undergoing radical surgery for GC. Methods: A retrospective analysis of 1,155 patients who underwent radical gastrectomy for GC between July 2014 and February 2019 was conducted. According to whether patients received short-term (1-6 days) PN support before surgery, patients were divided into non-PN group and PN group. After 1:1 propensity score matching (PSM), two groups of patients with similar baseline clinical characteristics were obtained. The incidence of various complications and overall survival (OS) rate were compared between the two groups, and logistic regression analysis for complications, Cox regression analysis for OS, and subgroup analysis were performed. Results: Each group had 478 patients after PSM, and the clinical characteristics were balanced. There were no significant differences in overall postoperative complications (pre-PSM: P=0.495; post-PSM: P>0.99), postoperative length of stay (LOS; pre-PSM: P=0.092; post-PSM: P=0.460), or readmission rate within 30 days (pre-PSM: P=0.496; post-PSM: P=0.793) between the two groups before and after PSM. The OS of PN group before matching was lower than that of non-PN group (P=0.023), but this difference was not significant after matching (P=0.950), but the PN group's hospitalization expenses were substantially greater than those of the control group (post-PSM: P<0.001). Preoperative short-term PN support was not an independent factor in the incidence of postoperative complications (P>0.99) and OS (P=0.949). Subgroup analyses failed to identify those patients who might benefit from preoperative short-term PN support. Conclusions: Preoperative short-term PN support may have no significant benefit on short-term postoperative complications or the long-term OS of patients with GC but increase hospitalization costs. It thus should not be the first choice of treatment for these patients.