Nuclear KRT19 is a transcriptional co-repressor promoting histone deacetylation and liver tumorigenesis.

BACKGROUND AND AIMS: Epigenetic reprogramming and escape from terminal differentiation are poorly understood enabling characteristics of liver cancer. Keratin 19 (KRT19), classically known to form the intermediate filament cytoskeleton, is a marker of stemness and worse prognosis in liver cancer. This study aimed to address the functional roles of KRT19 in liver tumorigenesis and to elucidate the underlying mechanisms. APPROACH AND RESULTS: Using multiplexed genome editing of hepatocytes in vivo, we demonstrated that KRT19 promoted liver tumorigenesis in mice. Cell fractionation revealed a previously unrecognized nuclear fraction of KRT19. Tandem affinity purification identified histone deacetylase 1 (HDAC1) and REST co-repressor 1 (RCOR1), components of the co-repressor of RE-1 silencing transcription factor (CoREST) complex as KRT19-interacting proteins. KRT19 knockout markedly enhanced histone acetylation levels. Mechanistically, KRT19 promotes CoREST complex formation by enhancing HDAC1 and RCOR1 interaction, thus increases the deacetylase activity. ChIP-seq revealed hepatocyte-specific genes, such as hepatocyte nuclear factor 4 alpha (HNF4A), as direct targets of KRT19-CoREST. In addition, we identified forkhead box P4 (FOXP4) as a direct activator of aberrant KRT19 expression in liver cancer. Furthermore, treatment of primary liver tumors and patient-derived xenografts in mice suggest that KRT19 expression has the potential to predict response to HDAC inhibitors especially in combination with Lenvatinib. CONCLUSIONS: Our data show that nuclear KRT19 acts as a transcriptional co-repressor through promoting the deacetylase activity of the CoREST complex, resulting in dedifferentiation of liver cancer. These findings reveal a previously unrecognized function of KRT19 in directly shaping the epigenetic landscape in cancer.

Preorganization Effects on Eu(III) Ion Coordination by Dipyridyl-Phenanthroline Ligands: A Combined Experimental and Theoretical Analysis.

Although 1,10-phenanthroline has been proven to hold a strong complexing capacity for f-block elements and their derivatives have been applied in many fields, research on more highly or completely rigid phenanthroline ligands is still rare due to the challenging syntheses. Here, we reported three tetradentate ligands 2,9-di(pyridin-2-yl)-1,10-phenanthroline (L1), 12-(pyridin-2-yl)-5,6-dihydroquinolino[8,7b][1,10]phenanthroline (L2), and 5,6,11,12-tetrahydrobenzo[2,1-b:3,4-b']bis([1,10]phenanthroline) (L3) with increasing preorganization on the side chain; among which, L3 is fully preorganized. Their complexation reactions with Eu(III) were systematically investigated by electrospray ionization mass spectrometry (ESI-MS), UV-vis titrations, and single-crystal structures. It is found that all three ligands form only 1:1 M/L complexes with Eu(III). The single-crystal structures revealed that the three ligands hold similar coordination modes, while their stability constants determined by UV-vis titrations were L3 (4.80 ± 0.01) > L2 (4.38 ± 0.01) > L1 (3.88 ± 0.01). This trend is supported not only by the thermodynamic stability of rigid ligands compared to free ligands but also by the conclusion that rigid ligands exhibit faster reaction rates (lower energy barrier) than free ligands kinetically. This work is helpful in providing theoretical guidance for the subsequent development of highly preorganized chelating ligands with strong coordination ability and high selectivity for f-block elements.

Epimerization effects on coordination behaviours of phenanthroline-based phosphine-oxide ligands with uranyl ions.

Epimers of the (1,10-phenanthroline-2,9-diyl)bis(ethyl(phenyl)phosphine oxide) (Et-Ph-BPPhen) ligand with two chiral centers (R,R/S,S and R,S) were synthesized. The configurational effects on the coordination ability and mechanism between these epimeric ligands and uranyl ions were thoroughly investigated. This work is helpful to reveal the effects of different conformations of epimeric ligands on their coordination properties.

FUS reads histone H3K36me3 to regulate alternative polyadenylation.

Complex organisms generate differential gene expression through the same set of DNA sequences in distinct cells. The communication between chromatin and RNA regulates cellular behavior in tissues. However, little is known about how chromatin, especially histone modifications, regulates RNA polyadenylation. In this study, we found that FUS was recruited to chromatin by H3K36me3 at gene bodies. The H3K36me3 recognition of FUS was mediated by the proline residues in the ZNF domain. After these proline residues were mutated or H3K36me3 was abolished, FUS dissociated from chromatin and bound more to RNA, resulting in an increase in polyadenylation sites far from stop codons genome-wide. A proline mutation corresponding to a mutation in amyotrophic lateral sclerosis contributed to the hyperactivation of mitochondria and hyperdifferentiation in mouse embryonic stem cells. These findings reveal that FUS is an H3K36me3 reader protein that links chromatin-mediated alternative polyadenylation to human disease.

Morphologic and Functional Assessment of Photoreceptors in Laser Induced Retinopathy Using Adaptive Optics-SLO and Microperimetry.

PURPOSE: To assess the cone photoreceptors morphology and associated retinal sensitivity in laser-induced retinopathy (LIR) using adaptive optics Scanning Laser Ophthalmoscopy (AO-SLO) and microperimetry (MP). DESIGN: Cohort study. METHODS: This study included 13 patients (15 eyes) with LIR and 38 age-matched healthy volunteers (38 eyes). Participants underwent comprehensive evaluations including AO-SLO, MP, and spectral-domain OCT. Lesion morphology, cone density, dispersion and regularity in AO-SLO were assessed and correlated with visual function. RESULTS: In AO-SLO images, LIR lesions were predominantly characterized by hyporeflective regions, suggesting potential cone loss at the fovea, accompanied by the presence of sizable clumps of hyperreflective material within these lesions. The average size of lesions in affected eyes was 97,128±107,478µm², ranging from 6,705 to 673,348µm². Compared to the healthy contralateral eye and control group, LIR demonstrated significantly reduced cone density, increased cone dispersion, and notably decreased cone regularity in all four quadrants at 3° eccentricity (all P values <0.05). Lesion morphology in AO-SLO correlated with EZ defects observed in OCT, showing a positive correlation in size (r = 0.84, P<0.001) but not with retinal sensitivities (P = 0.09). Similarly, cone density at 3° eccentricity did not correlate with retinal sensitivities (P = 0.13). CONCLUSIONS AND RELEVANCE: The study provides crucial insights into the morphological and functional impacts of LIR on cone photoreceptors, revealing significant morphological changes in cones that do not consistently align with functional outcomes. This research highlights the need for continued exploration into the relationship between retinal structure and function in LIR, and the importance of heightened public awareness and preventive strategies to mitigate the risk of LIR.

Flexural Performance and Stress Calculation of External Prestressed Fiber-Reinforced Polymer-Bar-Strengthened One-Way Concrete Slabs.

External prestressing is widely employed in structural strengthening engineering due to its numerous advantages. However, external prestressed steel bars are prone to corrosion when exposed to the service environment. This paper is dedicated to examining the use of fiber-reinforced polymer (FRP) bars as external prestressing materials to strengthen one-way concrete slabs. Five one-way concrete slabs were strengthened with externally prestressed FRP bars with different prestress levels and different amounts of FRP bars, while one non-strengthened slab was used for comparison. The effects of strengthening on the flexural behavior, specifically the cracking load, ultimate load, stiffness and failure mode, were analyzed systematically. Moreover, the ductility and cost-benefit optimizing properties of the reinforcing design were discussed. The results show that external prestressed FRP bars significantly improve the cracking load, ultimate load and stiffness of one-way concrete slabs. The absence of a bond between the concrete and FRP bars overcomes the brittleness of the FRP bars, while the strengthened slabs exhibit satisfactory ductility and a higher post-yield stiffness and bearing capacity. Additionally, the cost/benefit ratio is optimized by increasing the prestress level, while a higher number of prestressed FRP bars is beneficial to ductility. Finally, a method for calculating the stress in prestressed FRP bars at ultimate loads was proposed. Irrespective of the prestressing material, this method is applicable to both strengthened beams and one-way slabs.

Enzymatic-related network of catalysis, polyamine, and tumors for acetylpolyamine oxidase: from calculation to experiment.

The regulation of enzymes and development of polyamine analogs capable of controlling the dynamics of endogenous polyamines to achieve anti-tumor effects is one of the biggest challenges in polyamine research. However, the root of the problem remains unsolved. This study represents a significant milestone as it unveils, for the first time, the comprehensive catalytic map of acetylpolyamine oxidase that includes chemical transformation and product release kinetics, by utilizing multiscale simulations with over six million dynamical snapshots. The transportation of acetylspermine is strongly exothermic, and high binding affinity of enzyme and reactant is observed. The transfer of hydride from polyamine to FAD is the rate-limiting step, via an H-shift coupled electron transfer mechanism. The two products are released in a detour stepwise mechanism, which also impacts the enzymatic efficiency. Inspired by these mechanistic insights into enzymatic catalysis, we propose a novel strategy that regulates the polyamine level and catalytic progress through the action of His64. Directly suppressing APAO by mutating His64 further inhibited growth and migration of tumor cells and tumor tissue in vitro and in vivo. Therefore, the network connecting microcosmic and macroscopic scales opens up new avenues for designing polyamine compounds and conducting anti-tumor research in the future.

Assessing the Role of BN-Embedding Position in B2N2-Perylenes.

Incorporating heteroatoms can effectively modulate the molecular optoelectronic properties. However, the fundamental understanding of BN doping effects in BN-embedded polycyclic aromatic hydrocarbons (PAHs) is underexplored, lacking rational guidelines to modulate the electronic structures through BN units for advanced materials. Herein, a concise synthesis of novel B2N2-perylenes with BN doped at the bay area is achieved to systematically explore the doping effect of BN position on the photophysical properties of PAHs. The shift of BN position in B2N2-perylenes alters the π electron conjugation, aromaticity and molecular rigidness significantly, achieving substantially higher electron transition abilities than those with BN doped in the nodal plane. It is further clarified that BN position dominates the photophysical properties over BN orientation. The revealed guideline here may apply generally to novel BN-PAHs, and aid the advancement of BN-PAHs with highly-emissive performance.

The identification and classification of candidate genes during the zygotic genome activation in the mammals.

Zygotic genome activation (ZGA) is a critical event in early embryonic development, and thousands of genes are involved in this delicate and sophisticated biological process. To date, however, only a handful of these genes have revealed their core functions in this special process, and therefore the roles of other genes still remain unclear. In the present study, we used previously published transcriptome profiling to identify potential key genes (candidate genes) in minor ZGA and major ZGA in both human and mouse specimens, and further identified the conserved genes across species. Our results showed that 887 and 760 genes, respectively, were thought to be specific to human and mouse in major ZGA, and the other 135 genes were considered to be orthologous genes. Moreover, the conserved genes were most enriched in rRNA processing in the nucleus and cytosol, ribonucleoprotein complex biogenesis, ribonucleoprotein complex assembly and ribosome large subunit biogenesis. The findings of this first comprehensive identification and characterization of candidate genes in minor and major ZGA provide relevant insights for future studies on ZGA.

Development and Comprehensive Benchmark of a High-Quality AMBER-Consistent Small Molecule Force Field with Broad Chemical Space Coverage for Molecular Modeling and Free Energy Calculation.

Biomolecular simulations have become an essential tool in contemporary drug discovery, and molecular mechanics force fields (FFs) constitute its cornerstone. Developing a high quality and broad coverage general FF is a significant undertaking that requires substantial expert knowledge and computing resources, which is beyond the scope of general practitioners. Existing FFs originate from only a limited number of groups and organizations, and they either suffer from limited numbers of training sets, lower than desired quality because of oversimplified representations, or are costly for the molecular modeling community to access. To address these issues, in this work, we developed an AMBER-consistent small molecule FF with extensive chemical space coverage, and we provide Open Access parameters for the entire modeling community. To validate our FF, we carried out benchmarks of quantum mechanics (QM)/molecular mechanics conformer comparison and free energy perturbation calculations on several benchmark data sets. Our FF achieves a higher level of performance at reproducing QM energies and geometries than two popular open-source FFs, OpenFF2 and GAFF2. In relative binding free energy calculations for 31 protein-ligand data sets, comprising 1079 pairs of ligands, the new FF achieves an overall root-mean-square error of 1.19 kcal/mol for ΔΔG and 0.92 kcal/mol for ΔG on a subset of 463 ligands without bespoke fitting to the data sets. The results are on par with those of the leading commercial series of OPLS FFs.

LY6/PLAUR domain containing 3 (LYPD3) maintains melanoma cell stemness and mediates an immunosuppressive microenvironment.

BACKGROUND: Malignant melanoma is a highly heterogeneous skin cancer with the highest mortality rate among dermatological cancers. Catenins form functional networks in the nucleus to regulate gene expression and determine cell fate. Dysregulation of catenin expression correlates with the malignant characteristics of the tumor. We aimed to investigate the regulatory mechanisms of catenins in melanoma and to further define the function of catenin-related molecular signaling in the tumor microenvironment. METHODS: In this study, a bioinformatics approach combined with experimental validation was used to explore the potential tumor biology mechanisms of catenin-related signaling. RESULTS: Melanoma patients can be divided into two catenin clusters. Patients defined by high Junction Plakoglobin (JUP), Plakophilin 1 (PKP1), Plakophilin 3 (PKP3) levels (C2) had shorter survival time than other patients (C1). We demonstrated that JUP regulates Anterior Gradient 2 (AGR2)/LY6/PLAUR Domain Containing 3 (LYPD3) to maintain melanoma stemness and promotes glycolysis. We also found that LYPD3 was co-expressed with S100A9 and associated with immunosuppressive tumor microenvironment (TME). CONCLUSION: The JUP/AGR2/LYPD3 signaling axis plays an important role in the malignant features of melanoma. Targeting the JUP/AGR2/LYPD3 signaling axis can help develop promising drugs.

Association between choroidopathy and photoreceptors during the early stage of diabetic retinopathy: a cross-sectional study.

PURPOSE: To explore the role of choroidopathy in diabetic retinopathy (DR) by investigating the correlation between alterations of choroidal vessel and photoreceptors during the early stage of DR. METHODS: We performed a cross-sectional comparison of diabetic patients without DR (NDR group; n=16) and those with mild nonproliferative diabetic retinopathy (NPDR group; n=39). Optical coherence tomography (OCT) images of choroidal vessel alterations and photoreceptor structures were evaluated using the choroidal vascularity index (CVI) and adjusted ellipsoid zone (EZ) reflectivity, respectively. To evaluate the function of cone photoreceptors, the fundamental, harmonic amplitudes, the parameters S and Rmp3 were calculated from the electroretinogram (ERG). These factors were compared between groups. The correlation between the CVI and parameters describing the function and structure of the photoreceptors was evaluated. RESULTS: The significant decrease was observed in the CVI in the NPDR group compared to the NDR group (0.67 ± 0.04 vs. 0.70 ± 0.06; p = 0.028), but not in the adjusted EZ reflectivity or ERG parameters. In NPDR group and merging the 2 groups, CVI was moderately positively correlated with the fundamental amplitude obtained by the flicker ERG (NPDR only: r = 0.506; p = 0.001; merge the 2 groups: r = 0.423; p = 0.001), which was regulated by the response of the cone photoreceptors. The CVI was positively and moderately correlated with the logS (NPDR only: r = 0.462; p = 0.003; merge the 2 groups: r = 0.355; p = 0.008), indicating the sensitivity of cone cell light transduction. CONCLUSION: Compared to eyes without DR, CVI decreased representing choroidal vascular changes in eyes with mild NPDR. These changes may be related to the functional impairment of cone photoreceptors, especially phototransduction sensitivity, as the DR develops.

The H3.3 K36M oncohistone disrupts the establishment of epigenetic memory through loss of DNA methylation.

Histone H3.3 is frequently mutated in cancers, with the lysine 36 to methionine mutation (K36M) being a hallmark of chondroblastomas. While it is known that H3.3K36M changes the cellular epigenetic landscape, it remains unclear how it affects the dynamics of gene expression. Here, we use a synthetic reporter to measure the effect of H3.3K36M on silencing and epigenetic memory after recruitment of KRAB: a member of the largest class of human repressors, commonly used in synthetic biology, and associated with H3K9me3. We find that H3.3K36M, which decreases H3K36 methylation, leads to a decrease in epigenetic memory and promoter methylation weeks after KRAB release. We propose a new model for establishment and maintenance of epigenetic memory, where H3K36 methylation is necessary to convert H3K9me3 domains into DNA methylation for stable epigenetic memory. Our quantitative model can inform oncogenic mechanisms and guide development of epigenetic editing tools.

Achieving Ideal and Environmentally Stable n-Type Charge Transport in Polymer Field-Effect Transistors.

Realizing ideal charge transport in field-effect transistors (FETs) of conjugated polymers is crucial for evaluating device performance, such as carrier mobility and practical applications of conjugated polymers. However, the current FETs using conjugated polymers as the active layers generally show certain non-ideal transport characteristics and poor stability. Here, ideal charge transport of n-type polymer FETs is achieved on flexible polyimide substrates by using an organic-inorganic hybrid double-layer dielectric. Deposited conjugated polymer films show highly ordered structures and low disorder, which are supported by grazing-incidence wide-angle X-ray scattering, near-edge X-ray absorption fine structure, and molecular dynamics simulations. Furthermore, the organic-inorganic hybrid double-layer dielectric provides low interfacial defects, leading to excellent charge transport in FETs with high electron mobility (1.49 ± 0.46 cm2  V-1  s-1 ) and ideal reliability factors (102 ± 7%). Fabricated polymer FETs show a self-encapsulation effect, resulting in high stability of the FET charge transport. The polymer FETs still work with high mobility above 1 cm2  V-1  s-1 after storage in air for more than 300 days. Compared with state-of-the-art conjugated polymer FETs, this work simultaneously achieves ideal charge transport and environmental stability in n-type polymer FETs, facilitating rapid device optimization of high-performance polymer electronics.

Hyperoside alleviates photoreceptor degeneration by preventing cell senescence through AMPK-ULK1 signaling.

Vision loss and blindness are frequently caused by photoreceptor degeneration, for example in age-related macular degeneration and retinitis pigmentosa. However, there is no effective medicine to treat these photoreceptor degeneration-related diseases. Cell senescence is a common phenotype in many diseases; however, few studies have reported whether it occurs in photoreceptor degeneration diseases. Herein, we identified that cell senescence is associated with photoreceptor degeneration induced by N-methyl-N-nitrosourea (MNU, a commonly used photoreceptor degeneration model), presented as increased senescence-associated ß-galactosidase activity, DNA damage, oxidative stress and inflammation-related cytokine Interleukin 6 (IL6), and upregulation of cyclin p21 or p16. These results suggested that visual function might be protected using anti-aging treatment. Furthermore, Hyperoside is reported to help prevent aging in various organs. In this study, we showed that Hyperoside, delivered intravitreally, alleviated photoreceptor cell senescence and ameliorated the functional and morphological degeneration of the retina in vivo and in vitro. Importantly, Hyperoside attenuated the MNU-induced injury and aging of photoreceptors via AMPK-ULK1 signaling inhibition. Taken together, our results demonstrated that Hyperoside can prevent MNU-induced photoreceptor degeneration by inhibiting cell senescence via the AMPK-ULK1 pathway.

Analysis of shared ceRNA networks and related-hub genes in rats with primary and secondary photoreceptor degeneration.

Introduction: Photoreceptor degenerative diseases are characterized by the progressive death of photoreceptor cells, resulting in irreversible visual impairment. However, the role of competing endogenous RNA (ceRNA) in photoreceptor degeneration is unclear. We aimed to explore the shared ceRNA regulation network and potential molecular mechanisms between primary and secondary photoreceptor degenerations. Methods: We established animal models for both types of photoreceptor degenerations and conducted retina RNA sequencing to identify shared differentially expressed long non-coding RNAs (lncRNAs), microRNAs (miRNAs), and messenger RNAs (mRNAs). Using ceRNA regulatory principles, we constructed a shared ceRNA network and performed function enrichment and protein-protein interaction (PPI) analyses to identify hub genes and key pathways. Immune cell infiltration and drug-gene interaction analyses were conducted, and hub gene expression was validated by quantitative real-time polymerase chain reaction (qRT-PCR). Results: We identified 37 shared differentially expressed lncRNAs, 34 miRNAs, and 247 mRNAs and constructed a ceRNA network consisting of 3 lncRNAs, 5 miRNAs, and 109 mRNAs. Furthermore, we examined 109 common differentially expressed genes (DEGs) through functional annotation, PPI analysis, and regulatory network analysis. We discovered that these diseases shared the complement and coagulation cascades pathway. Eight hub genes were identified and enriched in the immune system process. Immune infiltration analysis revealed increased T cells and decreased B cells in both photoreceptor degenerations. The expression of hub genes was closely associated with the quantities of immune cell types. Additionally, we identified 7 immune therapeutical drugs that target the hub genes. Discussion: Our findings provide new insights and directions for understanding the common mechanisms underlying the development of photoreceptor degeneration. The hub genes and related ceRNA networks we identified may offer new perspectives for elucidating the mechanisms and hold promise for the development of innovative treatment strategies.

Boosting the Cell Performance of the SiO/Cu and SiO/PPy Anodes via In-Situ Reduction/Oxidation Coating Strategies.

Silicon monoxide (SiO) has attracted great attention due to its high theoretical specific capacity as an alternative material for conventional graphite anode, but its poor electrical conductivity and irreversible side reactions at the SiO/electrolyte interface seriously reduce its cycling stability. Here, to overcome the drawbacks, the dicharged SiO anode coated with Cu coating layer is elaborately designed by in-situ reduction method. Compared with the pristine SiO anode of lithium-ion battery (293 mAh g-1 at 0.5 A g-1 after 200 cycles), the obtained SiO/Cu composite presents superior cycling stability (1206 mAh g-1 at 0.5 A g-1 after 200 cycles). The tight combination of Cu particles and SiO significantly improves the conductivity of the composite, effectively inhibits the side-reaction between the active material and electrolyte. In addition, polypyrrole-coated SiO composites are further prepared by in-situ oxidation method, which delivers a high reversible specific capacity of 1311 mAh g-1 at 0.5 A g-1 after 200 cycles. The in-situ coating strategies in this work provide a new pathway for the development and practical application of high-performance silicon-based anode.

27­Gauge vitrectomy vs. 25­gauge vitrectomy in the management of proliferative diabetic retinopathy with preoperative intravitreal injection of conbercept.

Small-gauge vitrectomy has become popular due to its notable advantages, including less trauma, shortened convalescence and improved manoeuvrability. The aim of the present study was to compare the surgical outcomes of 27-gauge (27-G) vitrectomy with those of 25-gauge (25-G) vitrectomy in the management of proliferative diabetic retinopathy (PDR) with preoperative intravitreal injection of conbercept. The data of 48 consecutive patients with PDR (48 eyes) were retrospectively collected. The patients underwent conbercept intravitreal injection and pars plana vitrectomy with a 27-G group (23 eyes) or 25-G group (25 eyes) vitrectomy system. The operating time, suturing rate, endodiathermy rate, postoperative best-corrected visual acuity (BCVA), intraocular pressure (IOP) and complications were recorded. The mean postoperative BCVA at final follow-up was significantly improved compared with that at the baseline in both groups (P<0.001 for both). The differences in the mean BCVA changes between the two groups were not significant (P>0.99), and no differences were observed in the final central foveal thickness (P=0.51) between the two groups. The final IOP remained stable compared with that at the baseline in the 27-G group (P=0.36) and the 25-G group (P=0.05). The suturing rate was significantly decreased in the 27-G group compared with the 25-G group (P=0.04). There were no significant differences between the two groups in terms of the operating time (P=0.18), rate of endodiathermy use (P>0.99), iatrogenic retinal breaks (P=0.42) or postoperative recurrent vitreous haemorrhage (P>0.99). In addition, no case of ocular hypotony was observed in either group. In conclusion, 27-G vitrectomy was as efficient and safe as 25-G vitrectomy in the management of PDR in terms of operating time and complications. With reference to the literature, preoperative conbercept injection appears to assist in decreasing the incidence of intraoperative and postoperative complications.

Socioeconomic determinants of racial disparities in survival outcomes among patients with renal cell carcinoma.

PURPOSE: Racially driven outcomes in cancer are challenging to study. Studies evaluating the impact of race in renal cell carcinoma (RCC) outcomes are inconsistent and unable to disentangle socioeconomic disparities from inherent biological differences. We therefore seek to investigate socioeconomic determinants of racial disparities with respect to overall survival (OS) when comparing Black and White patients with RCC. METHODS: We queried the National Cancer Database (NCDB) for patients diagnosed with RCC between 2004 and 2017 with complete clinicodemographic data. Patients were examined across various stages (all, cT1aN0M0, and cM1) and subtypes (all, clear cell, or papillary). We performed Cox proportional hazards regression with adjustment for socioeconomic and disease factors. RESULTS: There were 386,589 patients with RCC, of whom 46,507 (12.0%) were Black. Black patients were generally younger, had more comorbid conditions, less likely to be insured, in a lower income quartile, had lower rates of high school completion, were more likely to have papillary RCC histology, and more likely to be diagnosed at a lower stage of RCC than their white counterparts. By stage, Black patients demonstrated a 16% (any stage), 22.5% (small renal mass [SRM]), and 15% (metastatic) higher risk of mortality than White patients. Survival differences were also evident in histology-specific subanalyses. Socioeconomic factors played a larger role in predicting OS among patients with SRMs than in patients with metastasis. CONCLUSIONS: Black patients with RCC demonstrate worse survival outcomes compared to White patients across all stages. Socioeconomic disparities between races play a significant role in influencing survival in RCC.

P-doping boosting electronic properties and ionic kinetics of MnV2O6 for high-performance lithium-ion batteries.

Vanadate electrodes are potential candidates for lithium-ion batteries (LIBs) due to their large theoretical specific capacity. However, their practical application suffers from limitations of poor conductivity, inferior ion kinetics, and severe volume changes upon cycling. Herein, a doping strategy is realized to prepare phosphorus (P)-doped MnV2O6 (PMVO) nanosheets to enhance the electrochemical activity and structural stability. On combining experimental and computation results, it is found that the PMVO structure enhances the electrical conductivity, reduces the adsorption energy of lithium ions, increases the structural stability, and facilitates rapid surface diffusion kinetics. As expected, the desirable electrode of PMVO delivers a reversible capacity of 812.7 mA h g-1 at 200 mA g-1 and shows excellent coulombic efficiency, as well as an extraordinary energy density of 472.1 W h kg-1. Meanwhile, an excellent rate performance (from 0.1 to 5.0 and return to 0.1 A g-1; 779.6 to 319.6 and return to 811.9 mA h g-1) could be achieved. The strategy proposed here may aid in further development of doped vanadate electrodes for high-performance LIBs.