Downregulation of HNRNPA1 induced neoantigen generation via regulating alternative splicing.

BACKGROUND: Immunotherapies effectively treat human malignancies, but the low response and resistance are major obstacles. Neoantigen is an emerging target for tumor immunotherapy that can enhance anti-tumor immunity and improve immunotherapy. Aberrant alternative splicing is an important source of neoantigens. HNRNPA1, an RNA splicing factor, was found to be upregulated in the majority of tumors and play an important role in the tumor immunosuppressive microenvironment. METHODS: Whole transcriptome sequencing was performed on shHNRNPA1 SKOV3 cells and transcriptomic data of shHNRNPA1 HepG2, MCF-7M, K562, and B-LL cells were downloaded from the GEO database. Enrichment analysis was performed to elucidate the mechanisms underlying the activation of anti-tumor immunity induced by HNRNPA1 knockdown. mRNA alternative splicing was analyzed and neoantigens were predicted by JCAST v.0.3.5 and Immune epitope database. The immunogenicity of candidate neoantigens was calculated by Class I pMHC Immunogenicity and validated by the IFN-γ ELISpot assay. The effect of shHNRNPA1 on tumor growth and immune cells in vivo was evaluated by xenograft model combined with immunohistochemistry. RESULTS: HNRNPA1 was upregulated in a majority of malignancies and correlated with immunosuppressive status of the tumor immune microenvironment. Downregulation of HNRNPA1 could induce the activation of immune-related pathways and biological processes. Disruption of HNRNPA1 resulted in aberrant alternative splicing events and generation of immunogenic neoantigens. Downregulation of HNRNPA1 inhibited tumor growth and increased CD8+ T cell infiltration in vivo. CONCLUSION: Our study demonstrated that targeting HNRNPA1 could produce immunogenic neoantigens that elicit anti-tumor immunity by inducing abnormal mRNA splicing. It suggests that HNRNPA1 may be a potential target for immunotherapy.

Ultrafast evanescently coupled waveguide MUTC-PDs with high responsivity.

Novel evanescently coupled waveguide modified uni-traveling carrier photodiodes (MUTC-PDs) employing a thick multi-layer coupling waveguide are reported. To improve the optical-to-electrical (O/E) conversion efficiency, a thick multi-layer coupling waveguide with a gradually increased refractive index from the bottom layer to the absorption layer is utilized. The refractive index profile facilitates the upward transmission of incident light into the absorption region, thereby enhancing the evanescent coupling efficiency. Meanwhile, the coupling waveguide, with a total thickness of 1.75 µm, expands the mode field diameter, thereby reducing the input coupling loss. Additionally, the top layer of the coupling waveguide also serves as the drift layer. This configuration facilitates efficient light absorption within a short PD length, thus ensuring ultrawide bandwidth and high O/E conversion efficiency simultaneously. Without an additional spot size coupler or anti-reflection coating, the measured responsivity is as high as 0.38 A/W for the PD with an active area of 5 × 6 µm2. Meanwhile, an ultrawide 3-dB bandwidth of 153 GHz has been demonstrated.

Quantitative US fat fraction for noninvasive assessment of hepatic steatosis in suspected metabolic-associated fatty liver disease.

OBJECTIVES: To evaluate the agreement between quantitative ultrasound system fat fraction (USFF) and proton magnetic resonance spectroscopy (1H-MRS) and the diagnostic value of USFF in assessing metabolic-associated fatty liver disease (MAFLD). METHODS: The participants with or suspected of MAFLD were prospectively recruited and underwent 1H-MRS, USFF, and controlled attenuation parameter (CAP) measurements. The correlation between USFF and 1H-MRS was assessed using Pearson correlation coefficients. The USFF diagnostic performance for different grades of steatosis was evaluated using receiver operating characteristic curve analysis (ROC) and was compared with CAP, visual hepatic steatosis grade (VHSG). RESULTS: A total of 113 participants (mean age 44.79 years ± 13.56 (SD); 71 males) were enrolled, of whom 98 (86.73%) had hepatic steatosis (1H-MRS ≥ 5.56%). USFF showed a good correlation (Pearson r = 0.76) with 1H-MRS and showed a linear relationship, which was superior to the correlation between CAP and 1H-MRS (Pearson r = 0.61). The USFF provided high diagnostic performance for different grades of hepatic steatosis, with ROC from 0.84 to 0.98, and the diagnostic performance was better than that of the CAP and the VHSG. The cut-off values of the USFF were different for various grades of steatosis, and the cut-off values for S1, S2, and S3 were 12.01%, 19.98%, and 22.22%, respectively. CONCLUSIONS: There was a good correlation between USFF and 1H-MRS. Meanwhile, USFF had good diagnostic performance for hepatic steatosis and was superior to CAP and VHSG. USFF represents a superior method for noninvasive quantitative assessment of MAFLD. CRITICAL RELEVANCE STATEMENT: Quantitative ultrasound system fat fraction (USFF) accurately assesses liver fat content and has a good correlation with magnetic resonance spectroscopy (1H-MRS) for the assessment of metabolic-associated fatty liver disease (MAFLD), as well as for providing an accurate quantitative assessment of hepatic steatosis. KEY POINTS: Current diagnostic and monitoring modalities for metabolic-associated fatty liver disease have limitations. USFF correlated well with 1H-MRS and was superior to the CAP. USFF has good diagnostic performance for steatosis, superior to CAP and VHSG.

Design, synthesis, and biological evaluation of pyrido[2,3-d]pyrimidin-7(8H)-one derivatives as potent USP1 inhibitors.

USP1 has emerged as a novel and potential target for drug discovery in single therapeutic agents or combination with chemotherapy and molecular targeted therapy. In this study, based on the disclosed structure of ML323 and KSQ-4279, we designed and synthesized a series of pyrido[2,3-d]pyrimidin-7(8H)-one derivatives as potent USP1 inhibitors by cyclization strategy and the systematic structure-activity relationship exploration was conducted. The representative compounds 1k, 1m and 2d displayed excellent USP1/UAF inhibition and exhibited strong antiproliferation effect in NCI-H1299 cells. Further flow cytometry analysis revealed that they could arrest breast cancer cells MDA-MB-436 in the S phase. Inhibition mechanism study of compound 1m indicated these derivatives acted as reversible and noncompetitive USP1 inhibitors. Of note, the combination of compound 1m with PARP inhibitor olaparib generated enhanced cell killing in olaparib-resistant MDA-MB-436/OP cells, and compound 1m exhibited excellent oral pharmacokinetic properties in mice. Overall, our efforts may provide a reliable basis for the development of novel USP1 inhibitor as a single therapeutic agent and in combination with PARP inhibitors.

Photosynthetic Bacteria-Hitchhiking 2D iMXene-mRNA Vaccine to Enable Photo-Immunogene Cancer Therapy.

Therapeutic mRNA vaccines have become powerful therapeutic tools for severe diseases, including infectious diseases and malignant neoplasms. mRNA vaccines encoding tumor-associated antigens provide unprecedented hope for many immunotherapies that have hit the bottleneck. However, the application of mRNA vaccines is limited because of biological instability, innate immunogenicity, and ineffective delivery in vivo. This study aims to construct a novel mRNA vaccine delivery nanosystem to successfully co-deliver a tumor-associated antigen (TAA) encoded by the Wilms' tumor 1 (WT1) mRNA. In this system, named PSB@Nb1.33C/mRNA, photosynthetic bacteria (PSB) efficiently delivers the iMXene-WT1 mRNA to the core tumor region using photo-driven and hypoxia-driven properties. The excellent photothermal therapeutic (PTT) properties of PSB and 2D iMxene (Nb1.33C) trigger tumor immunogenic cell death, which boosts the release of the WT1 mRNA. The released WT1 mRNA is translated, presenting the TAA and amplifying immune effect in vivo. The designed therapeutic strategy demonstrates an excellent ability to inhibit distant tumors and counteract postsurgical lung metastasis. Thus, this study provides an innovative and effective paradigm for tumor immunotherapy, i.e., photo-immunogene cancer therapy, and establishes an efficient delivery platform for mRNA vaccines, thereby opening a new path for the wide application of mRNA vaccines.

Highly reversible zinc metal anode enabled by strong Brønsted acid and hydrophobic interfacial chemistry.

Uncontrollable zinc (Zn) plating and hydrogen evolution greatly undermine Zn anode reversibility. Previous electrolyte designs focus on suppressing H2O reactivity, however, the accumulation of alkaline byproducts during battery calendar aging and cycling still deteriorates the battery performance. Here, we present a direct strategy to tackle such problems using a strong Brønsted acid, bis(trifluoromethanesulfonyl)imide (HTFSI), as the electrolyte additive. This approach reformulates battery interfacial chemistry on both electrodes, suppresses continuous corrosion reactions and promotes uniform Zn deposition. The enrichment of hydrophobic TFSI- anions at the Zn|electrolyte interface creates an H2O-deficient micro-environment, thus inhibiting Zn corrosion reactions and inducing a ZnS-rich interphase. This highly acidic electrolyte demonstrates high Zn plating/stripping Coulombic efficiency up to 99.7% at 1 mA cm-2 ( > 99.8% under higher current density and areal capacity). Additionally, Zn | |ZnV6O9 full cells exhibit a high capacity retention of 76.8% after 2000 cycles.

Long-term developments in seasonal hypoxia and response to climate change: A three-decade modeling study in the Ariake Sea, Japan.

Hypoxia in the Ariake Sea, Japan, is steadily increasing in both duration and spatial coverage. Hypoxia, defined as dissolved oxygen (DO) below 3 mg/L, is strongly associated with the amplified frequency of extreme rainfall events driven by climate change, which poses a mounting threat to marine ecosystems on a global scale. In this study, we employed a general three-dimensional (3-D) hydrodynamic coastal model and a phytoplankton-based ecosystem model to identify the potential cause of seasonal hypoxic events over three decades. The results indicated a substantial decrease in bottom DO levels from 1992 to 2021, with the rate of increase in hypoxic area being 8 km2/yr (95 % CI: -0.38, 16.2) and the anoxic area increasing from almost non-existent to 100 km2. Notably, among various environmental drivers, increased river discharge was identified as a pivotal factor in the occurrence of hypoxia. Large-scale river discharge events can potentially increase water stratification, leading to the formation of hypoxia. River discharge volume and the duration of bottom hypoxia in the Ariake Sea were correlated. The duration of hypoxia was strongly associated with river discharge magnitude, with correlation coefficients ranging from 0.56 to 0.82 across six observational stations. Furthermore, analysis of varied simulated environmental factors over multiple years revealed diverse responses to climate change, indicating that the Ariake Sea is prone to experiencing a decline in its physical and water quality conditions.

Cryo-EM structure of human HCN3 channel and its regulation by cAMP.

HCN channels are important for regulating heart rhythm and nerve activity and have been studied as potential drug targets for treating depression, arrhythmia, nerve pain, and epilepsy. Despite possessing unique pharmacological properties, HCN channels share common characteristics in that they are activated by hyperpolarization and modulated by cAMP and other membrane lipids. However, the mechanisms of how these ligands bind and modulate HCN channels are unclear. In this study, we solved structures of full-length human HCN3 using cryo-EM and captured two different states, including a state without any ligand bound and a state with cAMP bound. Our structures reveal the novel binding sites for cholesteryl hemisuccinate in apo state and show how cholesteryl hemisuccinate and cAMP binding cause conformational changes in different states. These findings explain how these small modulators are sensed in mammals at the molecular level. The results of our study could help to design more potent and specific compounds to influence HCN channel activity and offer new therapeutic possibilities for diseases that lack effective treatment.

Interventions for Postextubation Dysphagia in Critically Ill Patients: A Systematic Review and Meta-analysis.

OBJECTIVE: This review evaluates the efficacy and safety of dysphagia interventions for patients with prolonged endotracheal intubation (⩾48 h) in critical care units. DATA SOURCES: We systematically searched PubMed, Cochrane Library, Medline, Embase, OVID, CINAHL, Wanfang (China), CNKI (China), and ProQuest Dissertations for studies published up to December 31, 2023. STUDY SELECTION: Inclusion criteria encompassed randomized controlled trials (RCTs), quasi-randomized trials, and cohort studies comparing dysphagia rehabilitation - such as swallowing stimulation, swallowing and respiratory muscle exercise, and neuromuscular electrical stimulation - with standard care or no treatment. The primary outcomes assessed were dysphagia severity, time to resume oral intake, and incidence of aspiration and aspiration pneumonia. DATA EXTRACTION: Detailed information on study design, setting, participant demographics, interventions, and outcomes was systematically extracted. DATA SYNTHESIS: Our analysis included ten studies with a total of 1031 participants. The findings demonstrate a significant reduction in dysphagia severity, time to oral intake and the risk of aspiration pneumonia, and an improvement in quality of life among patients receiving swallowing therapy. However, no substantial difference was found in nutritional status. Limited data availability necessitated a descriptive presentation of outcomes like the risk of aspiration, ICU/hospital stay duration, pharyngeal/oral residue severity, and intervention-related adverse events. CONCLUSION: The current evidence for the effectiveness of dysphagia interventions in critically ill patients with prolonged endotracheal intubation is limited. There is a pressing need for future research, particularly high-quality RCTs employing standardized outcome measures, to substantiate these findings.

Umbilical cord blood-derived neutrophils possess higher viability than peripheral blood derived neutrophils.

Neutrophils, a primary type of immune cell, play critical roles in numerous biological processes. Both umbilical cord blood (UCB) and peripheral blood are rich in neutrophils. UCB is more abundant than peripheral blood, with cells generally at a more immature stage. However, comparative data between these two cell sources is lacking. This study aims to elucidate differences between UCB-derived neutrophils (UCBN) and peripheral blood-derived neutrophils (PBN). UCBN and PBN were isolated from fresh human umbilical cord blood and peripheral blood, respectively. Transcriptomic profiling was performed and compared against neutrophil RNA from three different donors. Bioinformatics analysis was employed to compare cell phenotypes. A cytokine cocktail (IFN-ß, IFN-γ, and LPS) was used to activate UCBN and PBN in vitro. A united multi-omic approach, combining transcriptomic and proteomic analysis, was followed by experimental validation through flow cytometry, cell killing assays, and proteome profiler array to verify cell functions. Transcriptomic analysis revealed that the most upregulated genes in freshly isolated umbilical cord blood neutrophils (UCBN) compared to peripheral blood neutrophils (PBN) predominantly involve neutrophil activation and cell-killing functions. Validation through flow cytometry and cell-killing experiments demonstrated that highly viable UCBN exhibited significantly stronger ovarian tumor cell-killing activity in vitro compared to PBN. Both transcriptomic and proteomic analyses indicated that the primary upregulated genes in activated UCBN are chiefly involved in biological processes related to the regulation of cytokine secretion. Integrative multi-omic analysis, including a proteome profiler array, confirmed that UCBN indeed secrete elevated levels of cytokines. In conclusion: UCBN shows higher viability and cellular activity compared with PBN, particularly in tumor cell-killing and cytokine secretion.

Interoperator reproducibility of quantitative ultrasound analysis of hepatic steatosis in participants with suspected MASLD: A prospective study.

OBJECTIVES: To evaluate the reproducibility of tissue attenuation imaging (TAI) and tissue scatter distribution imaging (TSI) measurements in adults with suspected metabolic dysfunction-associated steatotic liver disease (MASLD) between radiologists with varying experience. MATERIALS AND METHODS: Participants with suspected MASLD were prospectively recruited. TAI and TSI were performed for each participant by two radiologists with different levels of experience. Interoperability reliability was assessed on the basis of Bland-Altman analysis and intraclass correlation coefficients (ICCs). The study determined and compared the diagnostic performance of TAI and TSI with clinical prediction models using proton magnetic resonance spectroscopy (1H-MRS) as a reference. RESULTS: A total of 180 participants (women, n = 56; men, n = 124, mean age, 46.98 ± 14.92 years; mean BMI, 25.81 ± 4.47) were enrolled from August 2022 to September 2022. Bland-Altman plots showed only slight deviation in the TAI and TSI results of the two radiologists; there was good interoperator reproducibility for TAI (ICC = 0.92) and TSI (ICC = 0.86). Senior and junior radiologists performed examinations labeled as TAI-1 and TSI-1, and TAI-2 and TSI-2, respectively. The areas under the curves (AUCs) of TAI-1, TAI-2, TSI-1, and TAI-2 for the detection of ≥5 % hepatic steatosis were 0.90, 0.96, 0.91 and 0.96, respectively. According to ROC analysis, the diagnostic performance of both radiologists for TAI and TSI was statistically similar and superior to that of the clinical prediction model. CONCLUSIONS: TAI and TSI have good reproducibility between radiologists with different levels of experience. Meanwhile, both TAI and TSI demonstrated good diagnostic performance for hepatic steatosis (≥5%), surpassing that of clinical prediction models.

Senolytic drugs dasatinib and quercetin combined with Carboplatin or Olaparib reduced the peritoneal and adipose tissue metastasis of ovarian cancer.

Chemotherapy and targeted drugs-induced senescent ovarian cancer cells that accumulate in peritoneal adipose tissue contribute significantly to chronic inflammation, disrupt homeostasis, and may fuel various aspects of cancer progression. However, the pro-senescence effects of chemotherapy and targeted drugs on adipose derived stem cells (ADSCs) within peritoneal adipose tissue remain poorly understood. In this study, we show that the first-line chemotherapy and targeted drugs can induce the cellular senescence of ADSCs in vitro and increase the aging of peritoneal adipose tissue in vivo. These treatments significantly promoted the dysregulation of glucose and lipid metabolism, including insulin resistance and liver lipid accumulation. Our study shows that dasatinib and quercetin, as senolytics, effectively restore glucose homeostasis in mice with ovarian cancer and significantly reduce adipose tissue aging. Importantly, combining these drugs with Carboplatin or Olaparib results in a marked decrease in both peritoneal and adipose tissue metastasis of ovarian cancer cells. Mechanistically, we revealed that there is crosstalk between ovarian cancer cells and senescent ADSCs. The crosstalk increases inflammatory cytokines and chemokines production in ADSCs and notably upregulates chemokine receptors on cancer cells. Collectively, these data indicate that senescent ADSCs induced by chemotherapy and targeted therapy drugs impair adipose tissue function. However, the senolytic drugs dasatinib and quercetin, can significantly ameliorate organ aging and damage induced by these treatments. Notably, dasatinib and quercetin combined with Carboplatin or Olaparib reduced the peritoneal and adipose tissue metastasis of ovarian cancer, ultimately benefiting the mice undergoing chemotherapy and targeted therapy.

Erratum to "Bladder-embedded ectopic intrauterine device with calculus".

[This corrects the article DOI: 10.1515/med-2020-0173.].

Dysphagia Pattern in Early to Moderate Parkinson's Disease Caused by Abnormal Pharyngeal Kinematic Function.

Airway invasion is common in patients with Parkinson's disease (PD) and can cause serious complications. However, a PD-related dysphagic pattern has not been clearly elucidated. In this study, 53 patients with early to moderate PD were enrolled to undergo a videofluoroscopic study of swallowing evaluation (VFSS) and a battery of neuropsychological assessments. A set of VFSS variables (three visuoperceptual, nine temporal, and six spatial) were measured. The main effects of bolus viscosity and volume on airway invasion were calculated. Statistical analyses were performed to determine key kinematic factors of airway invasion for swallowing each bolus type. Airway invasion frequency was significantly higher for liquid boluses (liquid vs. pudding P < 0.001; liquid vs. honey P = 0.006). Laryngeal vestibule closure reaction time (LVCrt) was the key kinematic factor of airway invasion for 3 ml liquid swallow (P = 0.040), anterior displacement of hyoid bone was the key kinematic factor for both 5 ml and 10 ml liquid swallows (P = 0.010, 0.034, respectively). Male sex and advanced Hoehn and Yahr stage were significantly related to reduced anterior displacement of hyoid bone. These results reveal the dysphagic pattern related to PD, demonstrating that prolonged LVCrt and reduced anterior displacement of hyoid bone are two crucial kinematic factors contributing to airway invasion during the liquid swallow. In addition, hyoid bone dysfunction was correlated with disease severity and male sex. Our findings warrant further investigation of the pathophysiological mechanism of dysphagia in PD and would guide clinical intervention.

Structure-based discovery of a new series of nucleoside-derived ring-opening PRMT5 inhibitors.

The ubiquitous methyltransferases employing SAM as the methyl donor have emerged as potential targets in many disease treatments, especially in anticancer. Therefore, developing SAM-competitive inhibitors of methyltransferases is of great interest to the drug research. To explore this direction, herein, we rationally designed a series of nucleoside derivatives as potent PRMT5 inhibitors with novel scaffold. The representative compounds A2 and A8 exhibited highly potent PRMT5 inhibition activity as well as good selectivity over other PRMTs and PKMTs. Further cellular experiments revealed that compounds A2 and A8 potently reduced the level of sDMA and inhibited the proliferation of Z-138 and MOLM-13 cell lines by inducing apoptosis. Moreover, compounds A8 which had favorable pharmacokinetic properties exhibited potent antitumor efficacy without the loss of body weight in a subcutaneous MOLM-13 xenograft model. In summary, our efforts provided a series of novel nucleoside analogs as potent PRMT5 inhibitors and may also offer a new strategy to develop SAM analogs as other methyltransferases' inhibitors.

Establishing and validation of the VBV score for assessing Lung ground-glass nodules based on high-resolution computed tomography.

BACKGROUND: The widespread utilization of chest High-resolution Computed Tomography (HRCT) has prompted detection of pulmonary ground-glass nodules (GGNs) in otherwise asymptomatic individuals. We aimed to establish a simple clinical risk score model for assessing GGNs based on HRCT. METHODS: We retrospectively analyzed 574 GGNs in 574 patients undergoing HOOK-WIRE puncture and pulmonary nodule surgery from January 2014 to November 2018. Clinical characteristics and imaging features of the GGNs were assessed. We analyzed the differences between malignant and benign nodules using binary logistic regression analysis and constructed a simple risk score model, the VBV Score, for predicting the malignancy status of GGNs. Then, we validated this model via other 1200 GGNs in 1041 patients collected from three independent clinical centers in 2022. RESULTS: For the exploratory phase of this study, out of the 574 GGNs, 481 were malignant and 93 were benign. Vacuole sign, air bronchogram, and intra-nodular vessel sign were important indicators of malignancy in GGNs. Then, we derived a VBV Score = vacuole sign + air bronchogram + intra-nodular vessel sign, to predict the malignancy of GGNs, with a sensitivity, specificity, and accuracy of 95.6%, 80.6%, and 93.2%, respectively. We also validated it on other 1200 GGNs, with a sensitivity, specificity, and accuracy of 96.0%, 82.6%, and 95.0%, respectively. CONCLUSIONS: Vacuole sign, air bronchogram, and intra-nodular vessel sign were important indicators of malignancy in GGNs. VBV Score showed good sensitivity, specificity, and accuracy for differentiating benign and malignant pulmonary GGNs.

Prognostic Nomograms for Patients with Primary Sarcomatoid Carcinoma of The Urinary Bladder: Based on The SEER Database.

PURPOSE: The present study aimed to develop nomograms based on the SEER database to predict the prognosis for patients with primary sarcomatoid carcinoma of the urinary bladder (SCUB). MATERIALS AND METHODS: Patients with primary SCUB were identified in the Surveillance, Epidemiology, and End Results (SEER) database, between 1975 and 2017. Univariate and multivariable Cox analysis were conducted to identify the independent prognostic factors for developing the overall survival (OS) and cancer-specific survival (CSS) nomograms. Then, concordance index (C-index), receiver operating characteristic (ROC) curve and calibration curve were used to evaluate the accuracy of the nomogram model. In addition, the model was further compared with TNM staging system. RESULTS: A total of 238 eligible patients with primary SCUB were selected from the SEER database. As suggested by Cox-analysis, age, sex, T stage, M stage, tumor size, and surgery type of primary site were identified as the independent factors for predicting both OS and CSS. We developed OS and CSS nomograms with a favorable C-index by using these prognostic factors. The C-indexes of the OS and CSS nomogram in the present study were 0.738 (0.701-0.775) and 0.763 (0.724-0.802), which were superior to those of the AJCC TNM staging with 0.621 (0.576-0.666) and 0.637 (0.588-0.686) respectively, showing better discriminatory ability. Subsequently, the ROC curves showed that the 1-, 3- and 5-year AUCs (area under the curve) of OS nomogram (i.e., 0.793, 0.807 and 0.793) were higher than those of the TNM stage((i.e., 0.659, 0.676, 0.659). Similarly, as for CSS model, them ((i.e., 0.823, 0.804 and 0.804) were aslo exceed those of TNM stage((i.e., 0.683, 0.682, 0.682). Furthermore, the calibration curves indicated a good consistency between the predictive survival and the actual survival. Finally, patients were stratified by risk, and Kaplan-Meier survival curve suggested that the prognosis of the low-risk group was significantly better than that of the high-risk group. CONCLUSION: We developed nomograms with the SEER database, which could help predict the prognosis of SCUB individuals more accurately.

Activating the Basal Planes and Oxidized Oxygens in Layer-Structured Na0.6 CoO2 for Boosted OER Activity.

With the CoO2 slabs consisting of Co4 O4 cubane structure, layered Nax CoO2 are considered promising candidates for oxygen evolution reaction (OER) in alkaline media given their earth-abundant and structural advantages. However, due to the strong adsorption of intermediates on the large basal planes, Nax CoO2 cannot meet the activity demands. Here, a novel one-pot synthesis strategy is proposed to realize the high solubility of iron in Nax CoO2 in an air atmosphere. The optimist Na0.6 Co0.9 Fe0.1 O2 exhibits enhanced OER activity compared to their pristine and other reported Fe-doped Nax CoO2 counterparts. Such an enhancement is mainly ascribed to the abundant active sites on the activated basal planes and the participation of oxidized oxygen as active sites independently, which breaks the scaling relationship limit in the OER process. This work is expected to contribute to the understanding of the modification mechanism of Fe-doped cobalt-based oxides and the exploitation of layer-structured oxides for energy application.