Optimization of Charge Extraction and Interconnecting Layers for Highly Efficient Perovskite/Organic Tandem Solar Cells with High Fill Factor.

Perovskite/organic tandem solar cells (POTSCs) have garnered significant attention due to their potential for achieving high photovoltaic (PV) performance. However, the reported power conversion efficiencies (PCEs) and fill factors (FFs) are still subpar due to the challenges associated with charge extraction in the organic bulk-heterojunction (BHJ) and significant energy losses in the interconnecting layers (ICLs). Here, a quaternary organic BHJ blend is developed to enhance the charge extraction in the organic subcell, contributing to an increased FF of ≥78% under 1 sun illumination and even more under lower illumination intensities. Meanwhile, energy losses in the ICLs are reduced via the incorporation of a self-assembly monolayer (SAM), (4-(3,6-Dimethyl-9H-carbazol-9-yl)butyl)phosphonic acid (Me-4PACz), in organic BHJ to form a MoOx/SAM interface and the thorough control of the MoOx thickness to suppress parasitic absorption. The resultant POTSCs achieve a remarkable PCE of 25.56% (certified: 24.65%), with a record FF of 83.62%, which is among the highest PCEs of POTSCs and the highest FF of all types of perovskite-based tandem solar cells (TSCs) till now. This work proves the optimization of charge extraction and ICLs are effective strategies to promote the performance of POTSCs to surpass other solution-processed perovskite-based TSCs in the near future.

Development of message passing-based graph convolutional networks for classifying cancer pathology reports.

BACKGROUND: Applying graph convolutional networks (GCN) to the classification of free-form natural language texts leveraged by graph-of-words features (TextGCN) was studied and confirmed to be an effective means of describing complex natural language texts. However, the text classification models based on the TextGCN possess weaknesses in terms of memory consumption and model dissemination and distribution. In this paper, we present a fast message passing network (FastMPN), implementing a GCN with message passing architecture that provides versatility and flexibility by allowing trainable node embedding and edge weights, helping the GCN model find the better solution. We applied the FastMPN model to the task of clinical information extraction from cancer pathology reports, extracting the following six properties: main site, subsite, laterality, histology, behavior, and grade. RESULTS: We evaluated the clinical task performance of the FastMPN models in terms of micro- and macro-averaged F1 scores. A comparison was performed with the multi-task convolutional neural network (MT-CNN) model. Results show that the FastMPN model is equivalent to or better than the MT-CNN. CONCLUSIONS: Our implementation revealed that our FastMPN model, which is based on the PyTorch platform, can train a large corpus (667,290 training samples) with 202,373 unique words in less than 3 minutes per epoch using one NVIDIA V100 hardware accelerator. Our experiments demonstrated that using this implementation, the clinical task performance scores of information extraction related to tumors from cancer pathology reports were highly competitive.

Application of galactosylated albumin for targeted delivery of triptolide to suppress hepatocellular carcinoma progression through inhibiting de novo lipogenesis.

Hepatocellular carcinoma (HCC) remains the fourth leading cause of cancer-associated death globally with a lack of efficient therapy. The pathogenesis of HCC is a complex and multistep process, highly reliant on de novo lipogenesis, from which tumor cells can incorporate fatty acids to satisfy the necessary energy demands of rapid proliferation and provide survival advantages. Triptolide (TP) is a bioactive ingredient exhibiting potent abilities of anti-proliferation and lipid metabolism regulation, but its clinical application is constrained because of its toxicity and non-specific distribution. The present study has developed galactosylated bovine serum albumin nanoparticles loaded with TP (Gal-BSA-TP NPs) to alleviate systemic toxicity and increase tumor-targeting and antitumor efficacy. Furthermore, Gal-BSA-TP NPs could inhibit de novo lipogenesis via the p53-SREBP1C-FASN pathway to deprive the fuel supply of HCC, offering a specific strategy for HCC treatment. In general, this study provided a biocompatible delivery platform for targeted therapy for HCC from the perspective of de novo lipogenesis.

Clinicopathological characteristics and survival analysis of different molecular subtypes of breast invasive ductal carcinoma achieving pathological complete response through neoadjuvant chemotherapy.

BACKGROUND: To investigate the prognostic differences following the achievement of a pathological complete response (pCR) through neoadjuvant chemotherapy across different molecular subtypes of breast invasive ductal carcinoma. METHODS: Data from the Surveillance, Epidemiology, and End Results (SEER) were identified for patients undergoing neoadjuvant chemotherapy who achieved pathological complete response for invasive ductal carcinoma of the breast between 2010 and 2019.Comparing the clinicopathological characteristics of patients across different molecular subtypes. Univariate and Cox multivariate analyses were utilized to identify independent predictors of overall survival (OS) and cancer-specific survival (CSS). The Kaplan-Meier method is used to compare OS and CSS among different molecular subtypes. After propensity score matching, subgroup analysis results were presented through forest plots. RESULTS: This study included 9,380 patients diagnosed with invasive ductal carcinoma, who were categorized into four molecular subtypes: 2,721 (29.01%) HR + /HER-2 + , 1,661 (17.71%) HR + /HER2-, 2,082 (22.20%) HR-/HER2 + , and 2,916 (31.08%) HR-/HER-2-. HR + /HER-2- subgroup exhibited a significantly higher proportion of patients under 50 years old than the other subtype groups (54.67% vs 40.2%, 50.35% and 51.82%, p < 0.01), and had a higher N2 + N3 stage (11.2% vs 7.24%, 8.69% and 7.48%, p < 0.01). Univariate and multivariate analysis revealed that molecular subtype was the independent risk factor for OS and CSS in patients(p < 0.05). The Kaplan-Meier curves indicated that the HR + /HER-2 + subtype had the highest OS and CSS(p < 0.05). Next, were the HR-/HER-2 + and HR-/HER-2- subtypes, with the HR + /HER-2- group having the lowest OS and CSS(p < 0.05). After propensity score matching, the OS and CSS of patients in the HR + /HER-2 + group remained higher compared to HR + /HER-2- group(p < 0.05). CONCLUSIONS: Patients with invasive ductal carcinoma of different molecular subtypes exhibit varying prognoses after achieving pCR to neoadjuvant chemotherapy. Those in the HR + /HER-2- group are younger, have a higher lymph node stage, and the lowest OS and CSS, whereas patients in the HR + /HER-2 + group have the highest OS and CSS.

Metallic 1T/1T' phase TMD nanosheets with enhanced chemisorption sites for ultrahigh-efficiency lead removal.

Two-dimensional (2D) materials, as adsorbents, have garnered great attention in removing heavy metal ions (HMIs) from drinking water due to their extensive exposed adsorption sites. Nevertheless, there remains a paucity of experimental research to remarkably unlock their adsorption capabilities and fully elucidate their adsorption mechanisms. In this work, exceptional lead ion (Pb2+) (a common HMI) removal capacity (up to 758 mg g-1) is achieved using our synthesized metallic 1T/1T' phase 2D transition metal dichalcogenide (TMD, including MoS2, WS2, TaS2, and TiS2) nanosheets, which hold tremendous activated S chemisorption sites. The residual Pb2+ concentration can be reduced from 2 mg L-1 to 2 µg L-1 within 0.5 min, meeting the drinking water standards following World Health Organization guideline (Pb2+ concentrations <10 µg L-1). Atomic-scale characterizations and calculations based on density functional theory unveil that Pb2+ bond to the top positions of transition metal atoms in a single-atom form through the formation of S-Pb bonds. Point-of-use (POU) devices fabricated by our reported metallic phase MoS2 nanosheets exhibit treatment capacity of 55 L-water g-1-adsorbent for feed Pb2+ concentration of 1 mg L-1, which is 1-3 orders of magnitude higher than other 2D materials and commercial activated carbon.

Circular RNA-encoded oncogenic PIAS1 variant blocks immunogenic ferroptosis by modulating the balance between SUMOylation and phosphorylation of STAT1.

BACKGROUND: The clinical response rate to immune checkpoint blockade (ICB) therapy in melanoma remains low, despite its widespread use. Circular non-coding RNAs (circRNAs) are known to play a crucial role in cancer progression and may be a key factor limiting the effectiveness of ICB treatment. METHODS: The circRNAs that were downregulated after coadministration compared with single administration of PD-1 inhibitor administration were identified through RNA-seq and Ribo-seq, and thus the circPIAS1 (mmu_circ_0015773 in mouse, has_circ_0008378 in human) with high protein coding potential was revealed. Fluorescence in situ hybridization (FISH) assays were conducted to determine the localization of circPIAS1 in human and mouse melanoma cells, as well as its presence in tumor and adjacent tissues of patients. Validation through dual-luciferase reporter assay and LC-MS/MS confirmed the ability of circPIAS1 to encode a novel 108 amino acid polypeptide (circPIAS1-108aa). Specific antisense oligonucleotides (ASOs) targeting the junction site of circPIAS1 were developed to reduce its intracellular levels. Proliferation changes in melanoma cells were assessed using CCK8, EdU, and colony formation assays. The impact of circPIAS1-108aa on the ferroptosis process of melanoma cells was studied through GSH, MDA, and C11-BODIPY staining assays. Western Blot, Immunoprecipitation (IP), and Immunoprecipitation-Mass Spectrometry (IP-MS) techniques were employed to investigate the impact of circPIAS1-108aa on the P-STAT1/SLC7A11/GPX4 signaling pathway, as well as its influence on the balance between STAT1 SUMOylation and phosphorylation. Additionally, a melanoma subcutaneous transplanted tumor mouse model was utilized to examine the combined effect of reducing circPIAS1 levels alongside PD-1 inhibitor. RESULTS: Compared with the group treated with PD-1 inhibitor alone, circPIAS1 was significantly down-regulated in the coadministration group and demonstrated higher protein coding potential. CircPIAS1, primarily localized in the nucleus, was notably upregulated in tumor tissues compared to adjacent tissues, where it plays a crucial role in promoting cancer cell proliferation. This circRNA can encode a unique polypeptide consisting of 108 amino acids, through which it exerts its cancer-promoting function and impedes the effectiveness of ICB therapy. Mechanistically, circPIAS1-108aa hinders STAT1 phosphorylation by recruiting SUMO E3 ligase Ranbp2 to enhance STAT1 SUMOylation, thereby reactivating the transduction of the SLC7A11/GPX4 signaling pathway and restricting the immunogenic ferroptosis induced by IFNγ. Furthermore, the combination of ASO-circPIAS1 with PD-1 inhibitor effectively inhibits melanoma growth and significantly enhances the efficacy of immune drugs in vivo. CONCLUSIONS: Our study uncovers a novel mechanism regarding immune evasion in melanoma driven by a unique 108aa peptide encoded by circPIAS1 in melanoma that dramatically hinders immunogenic ferroptosis triggered by ICB therapy via modulating the balance between SUMOylation and phosphorylation of STAT1. This work reveals circPIAS1-108aa as a critical factor limiting the immunotherapeutic effects in melanoma and propose a promising strategy for improving ICB treatment outcomes.

Higher 10-Year Survival with Breast-Conserving Therapy over Mastectomy for Women with Early-Stage (I-II) Breast Cancer: Analysis of the CDC Patterns of Care Data Base.

Background: Studies in the United States are scarce that assess the survival differences between breast-conserving surgery plus radiation (Breast-Conserving Therapy; BCT) and mastectomy groups using population-based data while accounting for sociodemographic and clinical factors that affect the survival of women with early-stage breast cancer (ESBC). Objective: To assess whether BCT provides superior long-term overall survival (OS) and breast cancer-specific survival (BCSS) compared with mastectomy in women with ESBC, while considering key factors that impact survival. Design: Cohort study. Methods: We analyzed data on women aged 20 years and older diagnosed with stage I-II breast cancer (BC) in 2004 who received either BCT or mastectomy. The data were collected by 5 state cancer registries through the Centers for Disease Control and Prevention-funded Patterns of Care study. Multivariable Cox proportional hazard models, accounting for sociodemographic and clinical factors, were used to calculate hazard ratios (HRs) with 95% confidence intervals (CI). Sensitivity analysis involved optimal caliper propensity score (PS) matching to address residual confounding. Results: Of the 3495 women, 41.5% underwent mastectomy. The 10-year OS and BCSS were 82.7% and 91.1% for BCT and 72.3% and 85.7% for mastectomy, respectively. Adjusted models showed that mastectomy recipients had a 22% higher risk of all-cause deaths (ACD) (HR = 1.22, 95% CI = [1.06, 1.41]) and a 26% higher risk of breast cancer-specific deaths (BCD) (HR = 1.26, 95% CI = [1.02, 1.55]) than BCT recipients. Sensitivity analysis demonstrated that mastectomy was associated with a higher risk of ACD (P < .05) but did not exhibit a statistically significant risk for BCD. Women with HR+/HER2+ (luminal B) or invasive ductal carcinoma BC who underwent mastectomy had higher risks of ACD and BCD compared with BCT recipients, while the hazards for ACD in triple-negative BC did not remain significant after adjusting for covariates. Conclusion: ESBC BCT recipients demonstrate superior OS and BCSS compared with mastectomy recipients.

Breast-preserving treatment leads to higher 10-year survival in early-stage breast cancer This study compared the long-term survival outcomes of breast-conserving therapy (BCT) and mastectomy for early-stage breast cancer. Analyzing data from over 3400 women diagnosed in 2004, researchers found that BCT recipients had higher 10-year overall and breast cancer-specific survival rates compared with mastectomy recipients. Adjusted models showed a 22% higher risk of all-cause death.

The Role of the SIRT1-mTOR Signaling Pathway in Regulating Autophagy in Sevoflurane-Induced Apoptosis of Fetal Rat Brain Neurons.

BACKGROUND: Isoflurane is a commonly used general anesthetic widely employed in clinical surgeries. Recent studies have indicated that isoflurane might induce negative impacts on the nervous system, notably by triggering neuronal apoptosis. This process is pivotal to the development and emergence of neurological disorders; its misregulation could result in functional deficits and the initiation of diseases within nervous system. However, the potential molecular mechanism of isoflurane on the neuronal apoptosis remains fully unexplored. This study aims to investigate the regulatory role of the sirtuin 1-mechanistic target of rapamycin (SIRT1-mTOR) signaling pathway in autophagy during isoflurane-induced apoptosis of fetal rat brain neuronal cells. METHODS: Terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) assay, real-time quantitative polymerase chain reaction (qPCR), and Western blot were utilized to evaluate the apoptotic status of hippocampal tissue cells in fetal mice after sevoflurane exposure. Our further investigation was commenced with flow cytometry, immunofluorescence, qPCR, and Western blot to determine the impact of autophagy on sevoflurane-induced apoptosis in these neurons. On the other hand, we conducted an additional set of analyses, including flow cytometric analysis, qPCR, and Western blot, to further elucidate the neuroprotective potential of autophagy in neural cells of fetal mice subjected to sevoflurane-induced apoptosis. RESULTS: Our findings indicated that a 3% sevoflurane treatment led to a significant rise in apoptosis among fetal rat hippocampal tissue cells and neurons. Levels of apoptosis-associated proteins, cleaved-caspase-3 and Bcl-2 associated X protein (Bax), were found to be markedly higher, coinciding with an enhancement in autophagy as evidenced by increased microtubule-associated proteins 1A/1B-light chain 3 (LC3) and decreased p62 expression. Concurrently, there was a notable up-regulation of sirtuin 1 (SIRT1) and a down-regulation of mechanistic target of rapamycin (mTOR) expression. In conclusion, our research elucidated the pivotal function of cellular autophagy in an apoptosis induced by sevoflurane in fetal rat nerve cells. Through experimental manipulation, we observed that interference with SIRT1 resulted in a reduction of both cleaved-caspase-3 and Bax levels. This intervention also beget a diminished expression of the autophagy-associated factor LC3 and an up-regulation of p62. Furthermore, inhibition against mTOR reversed the effects induced by SIRT1 interference, suggesting a complex interplay amid these regulatory pathways. CONCLUSIONS: SIRT1 possesses a capacity to modulate apoptosis in the hippocampal neurons of fetal rats triggered by sevoflurane, with mTOR functioning as an inhibitory factor within this signaling pathway.

Effect of remimazolam on intra-operative hypotension: Systematic review and meta-analysis of randomised controlled trials.

BACKGROUND: Hypotension is common during anaesthesia. Increasing number of studies have reported that remimazolam may be associated with lower incidence of intra-operative hypotension compared with other anaesthetics. However, the results remain controversial. OBJECTIVE: This study aimed to evaluate the influence of remimazolam on intra-operative hypotension and its related outcomes (hypoxaemia, bradycardia and time to awake). DESIGN: A systematic review of randomised controlled trials (RCTs) with meta-analyses. DATA SOURCES: PubMed, Cocharane and Embase databases were searched to identify eligible RCTs published up to June 2024. ELIGIBILITY CRITERIA: RCTs published in English were eligible for inclusion. The study patients were 18 years or older who were administered with remimazolam and other positive control agents in either the pre-operative or intra-operative period. The incidence of intra-operative hypotension was identified in these studies. RESULTS: This study evaluated 34 trials including 4847 individuals. Basing on moderate-certainty evidence, we found that remimazolam administration reduced the incidence of intra-operative hypotension [risk ratio (RR) = 0.48, 95% confidence interval (95% CI): 0.41 to 0.57] and bradycardia (16 studies, n = 2869, RR = 0.40, 95% CI: 0.29 to 0.54). No difference was observed in the incidence of hypoxaemia (RR = 0.70, 95% CI: 0.48 to 1.01) and time to awake (MD = -0.91, 95% CI: -2.42 to 0.60). The remarkable association between remimazolam and hypotension remained robust and significant, regardless of general anaesthesia or procedural sedation (P < 0.01, I2 = 82%). No significant difference was found between different control drugs (P = 0.97, I2 = 82%). CONCLUSION: Moderate-quality evidence shows that remimazolam administration to patients undergoing general anaesthesia or procedural sedation decreases the incidence of intra-operative hypotension and bradycardia.

Glycemic Control in Diabetic Patients Improved Overall Lung Cancer Survival across Diverse Populations.

BACKGROUND: The consequence of diabetes on lung cancer overall survival (OS) is debated. This retrospective study used two large lung cancer databases to assess comprehensively diabetes effects on lung cancer OS in diverse demographic populations, including health disparity. METHODS: The University of Texas MD Anderson Cancer Center database (32,643 lung cancer cases with 11,973 diabetics) was extracted from electronic health records (EHRs) using natural language processing (NLP). Associations were between diabetes and lung cancer prognostic features [age, sex, race, body mass index (BMI), insurance status, smoking, stage, and histopathology]. Hemoglobin A1C (HgbA1c) and glucose levels assessed glycemic control. Validation was with a Louisiana cohort (17,768 lung cancer cases with 4,746 diabetics) enriched for health disparity cases. Kaplan-Meier analysis, log-rank test, multivariable Cox proportional hazard models, and survival tree analyses were employed. RESULTS: Lung cancer patients with diabetes exhibited marginally elevated OS or no statistically-significant difference versus non-diabetic patients. When examining OS for two glycemic levels (HgbA1c > 7.0 or glucose > 154 mg/dL versus HgbA1c > 9.0 or glucose > 215 mg/dL), a statistically significant improvement in OS occurred in lung cancers with controlled versus uncontrolled glycemia (P < 0.0001). This improvement spanned gender, age, smoking status, insurance status, stage, race, BMI, histopathology and therapy. Survival tree analysis revealed that obese and morbidly obese patients with controlled glycemia or no known diabetes had higher lung cancer OS than comparison groups. CONCLUSION: These findings indicate a need for optimal glycemic control to improve lung cancer OS in diverse populations with diabetes.

Causal relationship between key genes and metabolic dysfunction-associated fatty liver disease risk mediated by immune cells: A Mendelian randomization and mediation analysis.

AIM: Non-invasive diagnostics for metabolic dysfunction-associated fatty liver disease (MAFLD) remain challenging. We aimed to identify novel key genes as non-invasive biomarkers for MAFLD, elucidate causal relationships between biomarkers and MAFLD and determine the role of immune cells as potential mediators. MATERIALS AND METHODS: Utilizing published transcriptome data of patients with biopsy-proven MAFLD, we applied linear models for microarray data, least absolute shrinkage and selector operation (LASSO) regressions and receiver operating characteristic (ROC) curve analyses to identify and validate biomarkers for MAFLD. Using the expression quantitative trait loci database and a cohort of 778 614 Europeans, we used Mendelian randomization to analyse the causal relationships between key biomarkers and MAFLD. Additionally, mediation analysis was performed to examine the involvement of 731 immunophenotypes in these relationships. RESULTS: We identified 31 differentially expressed genes, and LASSO regression showed three hub genes, IGFBP2, PEG10, and P4HA1, with area under the receiver operating characteristic (AUROC) curve of 0.807, 0.772 and 0.791, respectively, for identifying MAFLD. The model of these three genes had an AUROC of 0.959 and 0.800 in the development and validation data sets, respectively. This model was also validated using serum-based enzyme-linked immunosorbent assay data from MAFLD patients and control subjects (AUROC: 0.819, 95% confidence interval: 0.736-0.902). PEG10 was associated with an increased MAFLD risk (odds ratio = 1.106, p = 0.032) via inverse variance-weighted analysis, and about 30% of this risk was mediated by the percentage of CD11c + CD62L- monocytes. CONCLUSIONS: The MAFLD panels have good diagnostic accuracy, and the causal link between PEG10 and MAFLD was mediated by the percentage of CD11c + CD62L- monocytes.

Mechanism and origin of enantioselectivity for organocatalyzed asymmetric heteroannulation of alkynes in the construction of axially chiral C2-arylquinoline.

Axially chiral C2-arylquinoline has been successfully constructed via asymmetric heteroannulation of alkynes catalyzed by chiral phosphoric acid with high yield and high enantioselectivity. Inspired by this intriguing work, theoretical calculations have been carried out, and the detailed reaction mechanism has been elaborated, in which the whole reaction can be divided into steps including hydrogen transfer, C-N bonding, annulation reaction and the final dehydration processes. The initial hydrogen-transfer reaction has two possible pathways, while the subsequent C-N bonding process has eight possible pathways. Then, after the annulation reaction and the final dehydration processes, the major product and byproduct were formed. QTAIM and IGMH analyses were used to illustrate the role of weak intermolecular interactions in the catalytic process, and the distortion/interaction and EDA analyses provided a deeper understanding of the origin of enantioselectivity. The calculated results are consistent with the experimental results. This work would provide valuable insights into asymmetric reactions catalyzed by chiral phosphoric acid.

NCI SEER-Linked Virtual Tissue Repository Pilot.

BACKGROUND: The Surveillance, Epidemiology, and End Results (SEER) Program with the National Cancer Institute tested whether population-based cancer registries can serve as honest brokers to acquire tissue and data in the SEER-Linked Virtual Tissue Repository (VTR) Pilot. METHODS: We collected formalin-fixed, paraffin-embedded tissue and clinical data from patients with pancreatic ductal adenocarcinoma (PDAC) and breast cancer (BC) for two studies comparing cancer cases with highly unusual survival (≥5 years for PDAC and ≤30 months for BC) to pair-matched controls with usual survival (≤2 years for PDAC and ≥5 years for BC). Success was defined as the ability for registries to acquire tissue and data on cancer cases with highly unusual outcomes. RESULTS: Of 98 PDAC and 103 BC matched cases eligible for tissue collection, sources of attrition for tissue collection were tissue being unavailable, control paired with failed case, second control that was not requested, tumor necrosis ≥20%, and low tumor cellularity. In total, tissue meeting the study criteria was obtained for 70 (71%) PDAC and 74 (72%) BC matched cases. For patients with tissue received, clinical data completeness ranged from 59% for CA-19-9 after treatment to >95% for margin status, whether radiation therapy and chemotherapy were administered, and comorbidities. CONCLUSIONS: The VTR Pilot demonstrated the feasibility of using SEER cancer registries as honest brokers to provide tissue and clinical data for secondary use in research. Studies using this program should oversample by 45% to 50% to obtain sufficient sample size and targeted population representation and involve subspecialty matter expert pathologists for tissue selection.

Reporting tumor genomic test results to SEER registries via linkages.

BACKGROUND: Precision medicine has become a mainstay of cancer care in recent years. The National Cancer Institute (NCI) Surveillance, Epidemiology, and End Results (SEER) Program has been an authoritative source of cancer statistics and data since 1973. However, tumor genomic information has not been adequately captured in the cancer surveillance data, which impedes population-based research on molecular subtypes. To address this, the SEER Program has developed and implemented a centralized process to link SEER registries' tumor cases with genomic test results that are provided by molecular laboratories to the registries. METHODS: Data linkages were carried out following operating procedures for centralized linkages established by the SEER Program. The linkages used Match*Pro, a probabilistic linkage software, and were facilitated by the registries' trusted third party (an honest broker). The SEER registries provide to NCI limited datasets that undergo preliminary evaluation prior to their release to the research community. RESULTS: Recently conducted genomic linkages included OncotypeDX Breast Recurrence Score, OncotypeDX Breast Ductal Carcinoma in Situ, OncotypeDX Genomic Prostate Score, Decipher Prostate Genomic Classifier, DecisionDX Uveal Melanoma, DecisionDX Preferentially Expressed Antigen in Melanoma, DecisionDX Melanoma, and germline tests results in Georgia and California SEER registries. CONCLUSIONS: The linkages of cancer cases from SEER registries with genomic test results obtained from molecular laboratories offer an effective approach for data collection in cancer surveillance. By providing de-identified data to the research community, the NCI's SEER Program enables scientists to investigate numerous research inquiries.

Methylation of T and B Lymphocytes in Autoimmune Rheumatic Diseases.

The role of abnormal epigenetic modifications, particularly DNA methylation, in the pathogenesis of autoimmune rheumatic diseases (ARDs) has garnered increasing attention. Lymphocyte dysfunction is a significant contributor to the pathogenesis of ARDs. Methylation is crucial for maintaining normal immune system function, and aberrant methylation can hinder lymphocyte differentiation, resulting in functional abnormalities that disrupt immune tolerance, leading to the excessive expression of inflammatory cytokines, thereby exacerbating the onset and progression of ARDs. Recent studies suggest that methylation-related factors have the potential to serve as biomarkers for monitoring the activity of ARDs. This review summarizes the current state of research on the impact of DNA and RNA methylation on the development, differentiation, and function of T and B cells and examines the progress of these epigenetic modifications in studies of six specific ARDs: systemic lupus erythematosus, rheumatoid arthritis, Sjögren's syndrome, systemic sclerosis, juvenile idiopathic arthritis, and ankylosing spondylitis. Additionally, we propose that exploring the interplay between RNA methylation and DNA methylation may represent a novel direction for understanding the pathogenesis of ARDs and developing novel treatment strategies.

Intranasal administration of insulin on the incidence of postoperative delirium in middle-aged patients undergoing elective on-pump cardiac surgery (INIPOD-MOPS): a prospective double-blinded randomized control study protocol.

BACKGROUND: Delirium, marked by acute cognitive decline, poses a life-threatening issue among older individuals, especially after cardiac surgery, with prevalence ranging from 15 to 80%. Postoperative delirium is linked to increased morbidity and mortality. Although clinical trials suggest preventability, there is limited research on intranasal insulin (INI) for cardiac surgery-related delirium. INI has shown promise in managing cognitive disorders. It rapidly elevates brain hormone levels, enhancing memory even in non-impaired individuals. While effective in preventing delirium in gastrointestinal surgery, its impact after cardiac surgery remains understudied, especially for middle-aged patients. METHOD: This is a prospective randomized, double-blind, single-center controlled trial. A total of 76 eligible participants scheduled for elective on-pump cardiac surgery will be enrolled and randomly assigned in a 1:1 ratio to either receive Intranasally administered insulin (INI) or intranasally administered normal saline. The primary outcome of our study is the incidence of postoperative delirium (POD). Secondary outcomes include duration of ICU, postoperative hospital length of stay, all in-hospital mortality, the change in MMSE scores pre- and post-operation, and incidence of postoperative cognitive dysfunction at 1 month, 3 months, and 6 months after operation. Moreover, we will subjectively and objectively evaluate perioperative sleep quality to investigate the potential impact of nasal insulin on the development of delirium by influencing sleep regulation. DISCUSSION: Our study will aim to assess the impact of intranasal administration of insulin on the incidence of postoperative delirium in middle-aged patients undergoing on-pump elective cardiac surgery. If intranasal insulin proves to be more effective, it may be considered as a viable alternative for preventing postoperative delirium. TRIAL REGISTRATION: ChiCTR ChiCTR2400081444. Registered on March 1, 2024.

Enhanced CO2 Reduction on a Cu-Decorated Single-Atom Catalyst via an Inverse Sandwich M-Graphene-Cu Structure.

The highly active and selective electrochemical CO2 reduction reaction (CO2RR) can be exploited to produce valuable chemicals and fuels and is also crucial for achieving clean energy goals and environmental remediation. Decorated single-atom catalysts (D-SACs), which feature synergistic interactions between the active metal site (M) and an axially decorated ligand, have been extensively explored for the CO2RR. Very recently, novel double-atom catalysts (DACs) featuring inverse sandwich structures were theoretically proposed and identified as promising CO2RR electrocatalysts. However, the experimental synthesis of DACs remains a challenge. To facilitate the fabrication and to realize the potential of these novel DACs, we designed a D-SAC system, denoted as M1@gra+Cuslab. This system features a graphene layer with a vacancy-anchored SAC, all stacked on a Cu(111) surface, thereby embodying a Cu slab-supported inverse sandwich M-graphene-Cu structure. Using density functional theory calculations, we evaluated the stability, selectivity, and activity of 27 M1@gra+Cuslab systems (M = Sc, Ti, V, Cr, Mn, Fe, Co, Ni, Cu, Zn, Y, Zr, Nb, Mo, Ru, Rh, Pd, Ag, Cd, Hf, Ta, W, Re, Os, Ir, Pt, or Au) and showed five M1@gra+Cuslab (M = Co, Ni, Cu, Rh, or Pd) systems exhibit optimal characteristics for the CO2RR and can potentially outperform their SAC and DAC counterparts. This study offers a new strategy for developing highly efficient CO2RR D-SACs with an inverse sandwich structural moiety.

Designing photothermal catalytic systems in multi-component MOFs for enhanced conversion of carbon dioxide.

We integrated a pair of donor-acceptor photothermal units, a Lewis acidic site, and a nucleophilic catalytic site into a multi-component metal-organic framework, resulting in an efficient photothermal catalytic system for the conversion of CO2 to cyclic carbonates.

Activation and polarization of striatal microglia and astrocytes are involved in bradykinesia and allodynia in early-stage parkinsonian mice.

In addition to the cardinal motor symptoms, pain is a major non-motor symptom of Parkinson's disease (PD). Neuroinflammation in the substantia nigra pars compacta and dorsal striatum is involved in neurodegeneration in PD. But the polarization of microglia and astrocytes in the dorsal striatum and their contribution to motor deficits and hyperalgesia in PD have not been characterized. In the present study, we observed that hemiparkinsonian mice established by unilateral 6-OHDA injection in the medial forebrain bundle exhibited motor deficits and mechanical allodynia. In these mice, both microglia and astrocytes in the dorsal striatum were activated and polarized to M1/M2 microglia and A1/A2 astrocytes as genes specific to these cells were upregulated. These effects peaked 7 days after 6-OHDA injection. Meanwhile, striatal astrocytes in parkinsonian mice also displayed hyperpolarized membrane potentials, enhanced voltage-gated potassium currents, and dysfunction in inwardly rectifying potassium channels and glutamate transporters. Systemic administration of minocycline, a microglia inhibitor, attenuated the expression of genes specific to M1 microglia and A1 astrocytes in the dorsal striatum (but not those specific to M2 microglia and A2 astrocytes), attenuated the damage in the nigrostriatal dopaminergic system, and alleviated the motor deficits and mechanical allodynia in parkinsonian mice. By contrast, local administration of minocycline into the dorsal striatum of parkinsonian mice mitigated only hyperalgesia. This study suggests that M1 microglia and A1 astrocytes in the dorsal striatum may play important roles in the development of pathophysiology underlying hyperalgesia in the early stages of PD.

Chaperone solvent-assisted assembly of polymers at the interface of two immiscible liquids.

The assembly of polymers at liquid-liquid interfaces offers a promising strategy for fabricating two-dimensional polymer films. However, a significant challenge arises when the polymers lack inherent interfacial traction. In response, we introduce an approach termed chaperone solvent-assisted assembly. This approach utilizes a target polymer, X, along with three solvents: α, ß, and γ. α and ß are poor solvents for X and immiscible with each other, while γ is a good solvent for X and miscible with both α and ß, thus serving as the chaperone solvent. The cross-interface diffusion of γ induces the assembly of interfacially nonactive X at the α-ß interface, and this mechanism is verified through systematic in situ and ex situ studies. We show that chaperone solvent-assisted assembly is versatile and reliable for the interfacial assembly of polymers, including those that are interfacially nonactive. Several practical applications based on chaperone solvent-assisted assembly are also demonstrated.