Enhanced charge-carrier dynamics and efficient solar-to-urea conversion on Si-based photocathodes.

Photoelectrochemical (PEC) coupling of CO2 and nitrate can provide a useful and green source of urea, but the process is affected by the photocathodes with poor charge-carrier dynamics and low conversion efficiency. Here, a NiFe diatomic catalysts/TiO2 layer/nanostructured n+p-Si photocathode is rationally designed, achieving a good charge-separation efficiency of 78.8% and charge-injection efficiency of 56.9% in the process of PEC urea synthesis. Compared with the electrocatalytic urea synthesis by using the same catalysts, the Si-based photocathode shows a similar urea yield rate (81.1 mg·h-1·cm-2) with a higher faradic efficiency (24.2%, almost twice than the electrocatalysis) at a lower applied potential under 1 sun illumination, meaning that a lower energy-consumption method acquires more aimed productions. Integrating the PEC measurements and characterization results, the synergistic effect of hierarchical structure is the dominating factor for enhancing the charge-carrier separation, transfer, and injection by the matched band structure and favorable electron-migration channels. This work provides a direct and efficient route of solar-to-urea conversion.

Molecular and Spatial Signatures of Mouse Embryonic Endothelial Cells at Single-Cell Resolution.

BACKGROUND: Mature endothelial cells (ECs) are heterogeneous, with subtypes defined by tissue origin and position within the vascular bed (ie, artery, capillary, vein, and lymphatic). How this heterogeneity is established during the development of the vascular system, especially arteriovenous specification of ECs, remains incompletely characterized. METHODS: We used droplet-based single-cell RNA sequencing and multiplexed error-robust fluorescence in situ hybridization to define EC and EC progenitor subtypes from E9.5, E12.5, and E15.5 mouse embryos. We used trajectory inference to analyze the specification of arterial ECs (aECs) and venous ECs (vECs) from EC progenitors. Network analysis identified candidate transcriptional regulators of arteriovenous differentiation, which we tested by CRISPR (clustered regularly interspaced short palindromic repeats) loss of function in human-induced pluripotent stem cells undergoing directed differentiation to aECs or vECs (human-induced pluripotent stem cell-aECs or human-induced pluripotent stem cell-vECs). RESULTS: From the single-cell transcriptomes of 7682 E9.5 to E15.5 ECs, we identified 19 EC subtypes, including Etv2+Bnip3+ EC progenitors. Spatial transcriptomic analysis of 15 448 ECs provided orthogonal validation of these EC subtypes and established their spatial distribution. Most embryonic ECs were grouped by their vascular-bed types, while ECs from the brain, heart, liver, and lung were grouped by their tissue origins. Arterial (Eln, Dkk2, Vegfc, and Egfl8), venous (Fam174b and Clec14a), and capillary (Kcne3) marker genes were identified. Compared with aECs, embryonic vECs and capillary ECs shared fewer markers than their adult counterparts. Early capillary ECs with venous characteristics functioned as a branch point for differentiation of aEC and vEC lineages. CONCLUSIONS: Our results provide a spatiotemporal map of embryonic EC heterogeneity at single-cell resolution and demonstrate that the diversity of ECs in the embryo arises from both tissue origin and vascular-bed position. Developing aECs and vECs share common venous-featured capillary precursors and are regulated by distinct transcriptional regulatory networks.

Therapeutic Inhibition of LincRNA-p21 Protects Against Cardiac Hypertrophy.

BACKGROUND: Cardiac hypertrophy is an adaptive response to pressure overload aimed at maintaining cardiac function. However, prolonged hypertrophy significantly increases the risk of maladaptive cardiac remodeling and heart failure. Recent studies have implicated long noncoding RNAs in cardiac hypertrophy and cardiomyopathy, but their significance and mechanism(s) of action are not well understood. METHODS: We measured lincRNA-p21 RNA and H3K27ac levels in the hearts of dilated cardiomyopathy patients. We assessed the functional role of lincRNA-p21 in basal and surgical pressure-overload conditions using loss-of-function mice. Genome-wide transcriptome analysis revealed dysregulated genes and pathways. We labeled proteins in proximity to full-length lincRNA-p21 using a novel BioID2-based system. We immunoprecipitated lincRNA-p21-interacting proteins and performed cell fractionation, ChIP-seq (chromatin immunoprecipitation followed by sequencing), and co-immunoprecipitation to investigate molecular interactions and underlying mechanisms. We used GapmeR antisense oligonucleotides to evaluate the therapeutic potential of lincRNA-p21 inhibition in cardiac hypertrophy and associated heart failure. RESULTS: lincRNA-p21 was induced in mice and humans with cardiomyopathy. Global and cardiac-specific lincRNA-p21 knockout significantly suppressed pressure overload-induced ventricular wall thickening, stress marker elevation, and deterioration of cardiac function. Genome-wide transcriptome analysis and transcriptional network analysis revealed that lincRNA-p21 acts in trans to stimulate the NFAT/MEF2 pathway. Mechanistically, lincRNA-p21 is bound to the scaffold protein KAP1. lincRNA-p21 cardiac-specific knockout suppressed stress-induced nuclear accumulation of KAP1, and KAP1 knockdown attenuated cardiac hypertrophy and NFAT activation. KAP1 positively regulates pathological hypertrophy by physically interacting with NFATC4 to promote the overactive status of NFAT/MEF2 signaling. GapmeR antisense oligonucleotide depletion of lincRNA-p21 similarly inhibited cardiac hypertrophy and adverse remodeling, highlighting the therapeutic potential of inhibiting lincRNA-p21. CONCLUSIONS: These findings advance our understanding of the functional significance of stress-induced long noncoding RNA in cardiac hypertrophy and demonstrate the potential of lincRNA-p21 as a novel therapeutic target for cardiac hypertrophy and subsequent heart failure.

The compensatory role of T cells from lymph nodes in mice with splenectomy.

The spleen is a vital organ for the immune system, while splenectomy may be necessary for various reasons. However, there is limited research on the impact of splenectomy on T cell function in peripheral lymph nodes as a compensatory mechanism in preventing infections. This study aimed to investigate the characteristics and function of CD8+ and CD4+ T cells in different peripheral lymph nodes during viral infection using a well-established splenectomy model. The results revealed that splenectomy caused an increase in CD8+GP33+ T cells in the mesenteric lymph nodes (MLN). Moreover, we demonstrated that splenectomy resulted in an increase of effector KLRG1+ T cells in the MLN. Additionally, the number of CD4+ cytotoxic T cells (CD4 CTLs) was also elevated in the peripheral lymph nodes of mice with splenectomy. Surprisingly, aged mice exhibited a stronger compensatory ability than adult mice, as evidenced by an increase in effector CD8+ T cells in all peripheral lymph nodes. These findings provide compelling evidence that T cells in MLN play a crucial role in protecting individuals with splenectomy against viral infections. The study offers new insights into understanding the changes in the immune system of individuals with splenectomy and highlights the potential compensatory mechanisms involved by T cells in peripheral lymph nodes.

In Vivo Dissection of Chamber-Selective Enhancers Reveals Estrogen-Related Receptor as a Regulator of Ventricular Cardiomyocyte Identity.

BACKGROUND: Cardiac chamber-selective transcriptional programs underpin the structural and functional differences between atrial and ventricular cardiomyocytes (aCMs and vCMs). The mechanisms responsible for these chamber-selective transcriptional programs remain largely undefined. METHODS: We nominated candidate chamber-selective enhancers (CSEs) by determining the genome-wide occupancy of 7 key cardiac transcription factors (GATA4, MEF2A, MEF2C, NKX2-5, SRF, TBX5, TEAD1) and transcriptional coactivator P300 in atria and ventricles. Candidate enhancers were tested using an adeno-associated virus-mediated massively parallel reporter assay. Chromatin features of CSEs were evaluated by performing assay of transposase accessible chromatin sequencing and acetylation of histone H3 at lysine 27-HiChIP on aCMs and vCMs. CSE sequence requirements were determined by systematic tiling mutagenesis of 29 CSEs at 5 bp resolution. Estrogen-related receptor (ERR) function in cardiomyocytes was evaluated by Cre-loxP-mediated inactivation of ERRα and ERRγ in cardiomyocytes. RESULTS: We identified 134 066 and 97 506 regions reproducibly occupied by at least 1 transcription factor or P300, in atria or ventricles, respectively. Enhancer activities of 2639 regions bound by transcription factors or P300 were tested in aCMs and vCMs by adeno-associated virus-mediated massively parallel reporter assay. This identified 1092 active enhancers in aCMs or vCMs. Several overlapped loci associated with cardiovascular disease through genome-wide association studies, and 229 exhibited chamber-selective activity in aCMs or vCMs. Many CSEs exhibited differential chromatin accessibility between aCMs and vCMs, and CSEs were enriched for aCM- or vCM-selective acetylation of histone H3 at lysine 27-anchored loops. Tiling mutagenesis of 29 CSEs identified the binding motif of ERRα/γ as important for ventricular enhancer activity. The requirement of ERRα/γ to activate ventricular CSEs and promote vCM identity was confirmed by loss of the vCM gene profile in ERRα/γ knockout vCMs. CONCLUSIONS: We identified 229 CSEs that could be useful research tools or direct therapeutic gene expression. We showed that chamber-selective multi-transcription factor, P300 occupancy, open chromatin, and chromatin looping are predictive features of CSEs. We found that ERRα/γ are essential for maintenance of ventricular identity. Finally, our gene expression, epigenetic, 3-dimensional genome, and enhancer activity atlas provide key resources for future studies of chamber-selective gene regulation.

VEGF-A in serum protects against memory impairment in APP/PS1 transgenic mice by blocking neutrophil infiltration.

Activation of innate immunity in the brain is a prominent feature of Alzheimer's disease (AD). The present study investigated the regulation of innate immunity by wild-type serum injection in a transgenic AD mouse model. We found that treatment with wild-type mouse serum significantly reduced the number of neutrophils and microglial reactivity in the brains of APP/PS1 mice. Mimicking this effect, neutrophil depletion via Ly6G neutralizing antibodies resulted in improvements in AD brain functions. Serum proteomic analysis identified vascular endothelial growth factor-A (VEGF-A) and chemokine (C-X-C motif) ligand 1 (CXCL1) as factors enriched in serum samples, which are crucial for neutrophil migration and chemotaxis, leukocyte migration, and cell chemotaxis. Exogenous VEGF-A reversed amyloid ß (Aß)-induced decreases in cyclin-dependent kinase 5 (Cdk5) and increases in CXCL1 in vitro and blocked neutrophil infiltration into the AD brain. Endothelial Cdk5 overexpression conferred an inhibitory effect on CXCL1 and neutrophil infiltration, thereby restoring memory abilities in APP/PS1 mice. Our findings uncover a previously unknown link between blood-derived VEGF signaling and neutrophil infiltration and support targeting endothelial Cdk5 signaling as a potential therapeutic strategy for AD.

GATA4 Regulates Developing Endocardium Through Interaction With ETS1.

BACKGROUND: The pioneer transcription factor (TF) GATA4 (GATA Binding Protein 4) is expressed in multiple cardiovascular lineages and is essential for heart development. GATA4 lineage-specific occupancy in the developing heart underlies its lineage specific activities. Here, we characterized GATA4 chromatin occupancy in cardiomyocyte and endocardial lineages, dissected mechanisms that control lineage specific occupancy, and analyzed GATA4 regulation of endocardial gene expression. METHODS: We mapped GATA4 chromatin occupancy in cardiomyocyte and endocardial cells of embryonic day 12.5 (E12.5) mouse heart using lineage specific, Cre-activated biotinylation of GATA4. Regulation of GATA4 pioneering activity was studied in cell lines stably overexpressing GATA4. GATA4 regulation of endocardial gene expression was analyzed using single cell RNA sequencing and luciferase reporter assays. RESULTS: Cardiomyocyte-selective and endothelial-selective GATA4 occupied genomic regions had features of lineage specific enhancers. Footprints within cardiomyocyte- and endothelial-selective GATA4 regions were enriched for NKX2-5 (NK2 homeobox 5) and ETS1 (ETS Proto-Oncogene 1) motifs, respectively, and both of these TFs interacted with GATA4 in co-immunoprecipitation assays. In stable NIH3T3 cell lines expressing GATA4 with or without NKX2-5 or ETS1, the partner TFs re-directed GATA4 pioneer binding and augmented its ability to open previously inaccessible regions, with ETS1 displaying greater potency as a pioneer partner than NKX2-5. Single-cell RNA sequencing of embryonic hearts with endothelial cell-specific Gata4 inactivation identified Gata4-regulated endocardial genes, which were adjacent to GATA4-bound, endothelial regions enriched for both GATA4 and ETS1 motifs. In reporter assays, GATA4 and ETS1 cooperatively stimulated endothelial cell enhancer activity. CONCLUSIONS: Lineage selective non-pioneer TFs NKX2-5 and ETS1 guide the activity of pioneer TF GATA4 to bind and open chromatin and create active enhancers and mechanistically link ETS1 interaction to GATA4 regulation of endocardial development.

Recognizing Functional Groups of MES/APG Mixed Surfactants for Enhanced Solubilization toward Benzo[a]pyrene.

Benzo[a]pyrene is difficult to remove from soil due to its high octanol/water partition coefficient. The use of mixed surfactants can increase solubility but with the risk of secondary soil contamination, and the compounding mechanism is still unclear. This study introduced a new approach using environmentally friendly fatty acid methyl ester sulfonate (MES) and alkyl polyglucoside (APG) to solubilize benzo[a]pyrene. The best result was obtained when the ratio of MES/APG was 7:1 under 6 g/L total concentration, with an apparent solubility (Sw) of 8.58 mg/L and a molar solubilization ratio (MSR) of 1.31 for benzo[a]pyrene, which is comparable to that of Tween 80 (MSR, 0.95). The mechanism indicates that the hydroxyl groups (-OH) in APG form "O-H···OSO2-" hydrogen bonding with the sulfonic acid group (-SO3-) of MES, which reduces the electrostatic repulsion between MES molecules, thus facilitating the formation of large and stable micelles. Moreover, the strong solubilizing effect on benzo[a]pyrene should be ascribed to the low polarity of ester groups (-COOCH3) in MES. Functional groups capable of forming hydrogen bonds and having low polarity are responsible for the enhanced solubilization of benzo[a]pyrene. This understanding helps choose suitable surfactants for the remediation of PAH-contaminated soils.

The effect of different pterygium surgery techniques on the ocular surface parameters in different durations: a systematic review and meta-analysis.

PURPOSE: To evaluate the effects of different pterygium surgery techniques on ocular surface (OS) in different follow-up periods. METHODS: PubMed, Cochrane Library, Web of Science, China National Knowledge Infrastructure, Wan Fang, and China Biology Medicine disc were searched for studies reporting pre- and post-operative OS parameters in pterygium. RESULTS: A total of 33 articles were finally included. Three OS parameters showed relatively consistent changing trends after surgery including ocular surface disease index (OSDI), tear film break-up time (BUT), and score of corneal fluorescein staining (SCFS). They worsened significantly at 1w post-operation and then gradually improved: OSDI and BUT showed obvious improvement in 1 m post-operation (SMD = - 0.58, 95%CI = [- 1.04, - 0.13]; SMD = 0.42, 95%CI = [0.06, 0.78]); SCFS was restored to preoperative levels in 3 m after surgery (SMD = - 0.54, 95%CI = [- 1.16, 0.07]). Another parameter, Schirmer test without anesthesia (SIT), presented transient increase at 1w post-operation (SMD = 0.87, 95%CI = [0.27, 1.47]) and presented a relatively stable improvement after 1 m post-operation (SMD = 0.52, 95%CI = [0.16, 0.89]). All parameters in amniotic membrane graft (AMT) showed better improvement in early stage and they showed non-inferior improvements in the long term compared with conjunctival autograft (CAG). Limbal-conjunctival autograft (LCAG) made excellent improvement to OS in the long term while pterygium excision (PE) showed the worst OS. The type of pterygium (primary and secondary), diabetes mellitus (DM) status, and fixation method had certain effects on the results. CONCLUSIONS: OS of pterygium is deteriorated at 1w post-operation then gradually improved to preoperative levels after 1 m post-operation. Among various surgery techniques, LCAG had the best improvement to OS which especially displayed in the long-term outcomes.

Trends and outcomes of outpatient total shoulder arthroplasty after its removal from CMS's inpatient-only list.

BACKGROUND: In January 2021, the US Medicare program approved reimbursement of outpatient total shoulder arthroplasties (TSA), including anatomic and reverse TSAs. It remains unclear whether shifting TSAs from the inpatient to outpatient setting has affected clinical outcomes. Herein, we describe the rate of outpatient TSA growth and compare inpatient and outpatient TSA complications, readmissions, and mortality. METHODS: Medicare fee-for-service claims for 2019-2022Q1 were analyzed to identify the trends in outpatient TSAs and to compare 90-day postoperative complications, all-cause hospital readmissions, and mortality between outpatients and inpatients. Outpatient cases were defined as those discharged on the same day of the surgery. To reduce the COVID-19 pandemic's impact and selection bias, we excluded 2020Q2-Q4 data and used propensity scores to match 2021-2022Q1 outpatients with inpatients from the same period (the primary analysis) and from 2019-2020Q1 (the secondary analysis), respectively. We performed both propensity score-matched and -weighted multivariate analyses to compare outcomes between the two groups. Covariates included sociodemographics, preoperative diagnosis, comorbid conditions, the Hierarchical Condition Category risk score, prior year hospital/skilled nursing home admissions, annual surgeon volume, and hospital characteristics. RESULTS: Nationally, the proportion of outpatient TSAs increased from 3% (619) in 2019Q1 to 22% (3456) in 2021Q1 and 38% (6778) in 2022Q1. A total of 55,166 cases were identified for the primary analysis (14,540 outpatients and 40,576 inpatients). Overall, glenohumeral osteoarthritis was the most common indication for surgery (70.8%), followed by rotator cuff pathology (14.6%). The unadjusted rates of complications (1.3 vs 2.4%, P < .001), readmissions (3.7 vs 6.1%, P < .001), and mortality (0.2 vs 0.4%, P = .024) were significantly lower among outpatient TSAs than inpatient TSAs. Using 1:1 nearest matching, 12,703 patient pairs were identified. Propensity score-matched multivariate analyses showed similar rates of postoperative complications, hospital readmissions, and mortality between outpatients and inpatients. Propensity score-weighted multivariate analyses resulted in similar conclusions. The secondary analysis showed a lower hospital readmission rate in outpatients (odds ratio: 0.8, P < .001). CONCLUSIONS: There has been accelerated growth in outpatient TSAs since 2019. Outpatient and inpatient TSAs have similar rates of postoperative complication, hospital readmission, and mortality.

A Preoperative Risk Assessment Tool for Predicting Adverse Outcomes among Total Shoulder Arthroplasty Patients.

BACKGROUND: With the increased utilization of Total Shoulder Arthroplasty (TSA) in the outpatient setting, understanding the risk factors associated with complications and hospital readmissions becomes a more significant consideration. Prior developed assessment metrics in the literature either consisted of hard-to-implement tools or relied on postoperative data to guide decision-making. This study aimed to develop a preoperative risk assessment tool to help predict the risk of hospital readmission and other postoperative adverse outcomes. METHODS: We retrospectively evaluated the 2019-2022(Q2) Medicare fee-for-service inpatient and outpatient claims data to identify primary anatomic or reserve TSAs and to predict postoperative adverse outcomes within 90 days post-discharge, including all-cause hospital readmissions, postoperative complications, emergency room visits, and mortality. We screened 108 candidate predictors, including demographics, social determinants of health, TSA indications, prior 12-month hospital and skilled nursing home admissions, comorbidities measured by hierarchical conditional categories, and prior orthopedic device-related complications. We used two approaches to reduce the number of predictors based on 80% of the data: 1) the Least Absolute Shrinkage and Selection Operator (LASSO) logistic regression and 2) the machine-learning-based cross-validation approach, with the resulting predictor sets being assessed in the remaining 20% of the data. A scoring system was created based on the final regression models' coefficients, and score cutoff points were determined for low, medium, and high-risk patients. RESULTS: A total of 208,634 TSA cases were included. There was a 6.8% hospital readmission rate with 11.2% of cases having at least one postoperative adverse outcome. Fifteen covariates were identified for predicting hospital readmission with the area under the curve (AUC) of 0.70, and 16 were selected to predict any adverse postoperative outcome (AUC=0.75). The LASSO and machine learning approaches had similar performance. Advanced age and a history of fracture due to orthopedic devices are among the top predictors of hospital readmissions and other adverse outcomes. The score range for hospital readmission and an adverse postoperative outcome was 0 to 48 and 0 to 79, respectively. The cutoff points for the low, medium, and high-risk categories are 0-9, 10-14, ≥15 for hospital readmissions, and 0-11, 12-16, ≥17 for the composite outcome. CONCLUSION: Based on Medicare fee-for-service claims data, this study presents a preoperative risk stratification tool to assess hospital readmission or adverse surgical outcomes following TSA. Further investigation is warranted to validate these tools in a variety of diverse demographic settings and improve their predictive performance.

Racial and Gender Disparities in Utilization of Outpatient Total Shoulder Arthroplasties.

BACKGROUND: Utilization in outpatient total shoulder arthroplasties (TSAs) has increased significantly in recent years. It remains largely unknown whether utilization of outpatient TSA differs across gender and racial groups. This study aimed to quantify racial and gender disparities both nationally and by geographic regions. METHODS: 168,504 TSAs were identified using Medicare fee-for-service (FFS) inpatient and outpatient claims data and beneficiary enrollment data from 2020 to 2022Q4. The percentage of outpatient cases, defined as cases discharged on the same day of surgery, was evaluated by racial and gender groups and by different census divisions. A multivariate logistics regression model controlling for patient socio-demographic information (white vs. non-white race, age, gender, and dual eligibility for both Medicare and Medicaid), hierarchical condition category (HCC) score, hospital characteristics, year fixed effects, and patient residency state fixed effects was performed. RESULTS: The TSA volume per 1000 beneficiaries was 2.3 for the White population compared to 0.8, 0.6 and 0.3 for the Black, Hispanic, and Asian population, respectively. A higher percentage of outpatient TSAs were in White patients (25.6%) compared to Black patients (20.4%) (p < 0.001). The Black TSA patients were also younger, more likely to be female, more likely to be dually eligible for Medicaid, and had higher HCC risk scores. After controlling for patient socio-demographic characteristics and hospital characteristics, the odds of receiving outpatient TSAs were 30% less for Black than the White group (OR 0.70). Variations were observed across different census divisions with South Atlantic (0.67, p < 0.01), East North Central (0.56, p < 0.001), and Middle Atlantic (0.36, p < 0.01) being the four regions observed with significant racial disparities. Statistically significant gender disparities were also found nationally and across regions, with an overall odds ratio of 0.75 (p < 0.001). DISCUSSION: Statistically significant racial and gender disparities were found nationally in outpatient TSAs, with Black patients having 30% (p < 0.001) fewer odds of receiving outpatient TSAs than white patients, and female patients with 25% (p < 0.001) fewer odds than male patients. Racial and gender disparities continue to be an issue for shoulder arthroplasties after the adoption of outpatient TSAs.

The investigation of the binding ability between sodium dodecyl sulfate and Cu (II) in urban stormwater runoff.

The simultaneous presence of heavy metals and surfactants in runoff induces complexation and ecological harm during migration. However, interactions between these pollutants are often overlooked in past studies. Thus, investigating heavy metal-surfactant complexes in runoff is imperative. In this work, Cu (II) and sodium dodecyl sulfate (SDS) were selected to investigate the interaction between heavy metals and surfactants due to the higher detected frequency in runoff. Through 1H NMR and FTIR observation of hydrogen atom nuclear displacement and functional group displacement of SDS, the change of SDS and Cu (II) complexation was obtained, and then the complexation form of Cu (II) and SDS was verified. The results showed that solution pH values and ionic strength had significant effects on the complexation of Cu (II). When the pH values increase from 3.0 to 6.0, the complexation efficiency of SDS with Cu (II) increased by 12.12% at low concentration of SDS, which may be attributed to the excessive protonation in the aqueous solution at acidic condition. The increase of ionic strength would inhibit the complexation reaction efficiency by 19.57% and finally reached the platform with concentration of NaNO3 was 0.10 mmol/L, which was mainly due to the competitive relationship between Na (I) and Cu (II). As a general filtering material in stormwater treatment measures, natural zeolite could affect the interaction between SDS and Cu (II) greatly. After the addition of SDS, the content of free Cu (II) in the zeolite-SDS-Cu (II) three-phase mixed system was significantly reduced, indicating that SDS had a positive effect on the removal of Cu (II) from runoff. This study is of great significance for investigating the migration and transformation mechanism of SDS and Cu (II) in the future and studying the control technology of storm runoff pollution.

Occurrence and ecological risk of PAHs in urban road runoff in Beijing.

The occurrence and ecological risks of 16 polycyclic aromatic hydrocarbons (PAHs) in different types of urban road runoff in Beijing during two typical rainfall events were studied. The average concentration of PAHs in road runoff particulate was in the order of Guanyuanqiao Road (ring road, 15,175 ng/L) > Huayuanqiao Road (primary road, 4,792 ng/L) > Dongcheng Alley (alley, 4,774 ng/L) > Nansihuan Viaduct (viaduct, 770 ng/L), much higher than dissolved PAHs. The total concentration of ∑16PAHs decreased with runoff scouring. Rainfall conditions and the accumulation of PAHs in the early rainfall period show a significant impact on PAHs pollution. The event mean concentration range of PAHs is 674-21,596 ng/L, following in the order of ring road > primary road > alley > viaduct. The proportion of four-ring PAHs was the highest. The first flush effect of PAHs is found in both rainfall events, and the effect of different ring PAHs is relatively similar. The content of PAHs is positively correlated with the amount of total organic carbon and suspended substance in runoff (r2> 0.72). The ecological risk assessment indicated that PAHs in road runoff except viaduct road corresponded to high risk.

A Universal Approach for Sustainable Urea Synthesis via Intermediate Assembly at the Electrode/Electrolyte Interface.

Electrocatalytic C-N coupling process is indeed a sustainable alternative for direct urea synthesis and co-upgrading of carbon dioxide and nitrate wastes. However, the main challenge lies in the unactivated C-N coupling process. Here, we proposed a strategy of intermediate assembly with alkali metal cations to activate C-N coupling at the electrode/electrolyte interface. Urea synthesis activity follows the trend of Li+

Variation in Ischemic Stroke Payments in the USA: A Medicare Beneficiary Study.

INTRODUCTION: The growing cost of stroke care has created the need for outcome-oriented and cost-saving payment models. Identifying imbalances in the current reimbursement model is an essential step toward designing impactful value-based reimbursement strategies. This study describes the variation in reimbursement fees for ischemic stroke management across the USA. METHODS: This Medicare Fee-For-Service claims study examines USA beneficiaries who suffered an ischemic stroke from 2021Q1 to 2022Q2 identified using the Medicare-Severity Diagnosis-Related Groups (MS-DRGs). Demographic national and regional US data were extracted from the Census Bureau. The MS-DRG codes were grouped into four categories according to treatment modality and clinical complexity. Our primary outcome of interest was payments made across individual USA and US geographic regions, assessed by computing the mean incremental payment in cases of comparable complexity. Differences between states for each MS-DRG were statistically evaluated using a linear regression model of the logarithmic transformed payments. RESULTS: 227,273 ischemic stroke cases were included in our analysis. Significant variations were observed among all DRGs defined by medical complexity, treatment modality, and states (p < 0.001). Differences in mean payment per case with the same MS-DRG vary by as high as 500% among individual states. Although higher payment rates were observed in MS-DRG codes with major comorbidities or complexity (MCC), the variation was more expressive for codes without MCC. It was not possible to identify a standard mean incremental fee at a state level. At a regional level, the Northeast registered the highest fees, followed by the West, Midwest, and South, which correlate with poverty rates and median household income in the regions. CONCLUSIONS: The payment variability observed across USA suggests that the current reimbursement system needs to be aligned with stroke treatment costs. Future studies may go one step further to evaluate accurate stroke management costs to guide policymakers in introducing health policies that promote better care for stroke patients.

Ferroptosis-associated lncRNA prognostic signature predicts prognosis and immune response in laryngeal squamous carcinoma.

In order to construct a prognostic model of ferroptosis-related lncRNA associated with laryngeal carcinoma and to investigate its prognostic value, RNA sequencing, genomic mutation, and clinical data of laryngeal squamous carcinoma patients were collected from the TCGA database. Patients were randomly divided into train and test groups. Cox regression analysis and lasso regression analysis were performed on the data of patients in the training group, and their independent prognostic effect was validated in the test group and the whole cohort. Data from 123 laryngeal squamous carcinoma patients in the TCGA database were collected. According to previous literature, 484 ferroptosis-related genes were collected, and 912 ferroptosis-related lncRNAs were obtained by co-expression. Cox models suggested six lncRNAs involved in ferroptosis (AC083862.2, CYTOR, AC114296.1, LINC02768, GATA2-AS1, CTB-178M22.2). Patients were divided into high-risk and low-risk groups based on median risk scores. Kapkan-Meier survival curve results showed a statistical difference in survival between the high- and low-risk groups. Receiver operating characteristic curves and principal component analysis demonstrated the high accuracy of the model. Univariate and multifactorial Cox regression analyses and column plots demonstrated risk scores as independent prognostic factors. The distribution of prognostic marker risk scores was correlated with clinical staging. Immune infiltration studies suggested the model was associated with immune checkpoints and multiple immune functions. GATA2-AS1 was able to promote cell proliferation, cell migration, and cell invasion. This study identified six lncRNAs associated with ferroptosis in laryngeal squamous carcinoma as prognostic predictors, which may be promising biomarkers involved in the treatment of laryngeal squamous carcinoma.

Predictive Values of ADAMTS13, TBIL, and D-D for Prognosis of Patients with Thrombotic Thrombocytopenic Purpura.

BACKGROUND: The aim of the study was to investigate the levels of a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13 (ADAMTS13), total bilirubin (TBIL), and D-dimer (D-D) in thrombotic thrombocytopenic purpura (TTP) and their values for predicting the prognosis. METHODS: The clinical data of 89 TTP patients admitted from March 2018 to December 2021 were collected for retrospective analysis. They were assigned to remission group (n = 61) and death group (n = 28) according to clinical outcomes. General clinical data were compared between the two groups. Predictors with non-zero coefficients were screened by LASSO regression analysis, and influencing factors were identified by logistic regression analysis. Then the risk factors were incorporated to construct a nomogram model, which was validated subsequently. Bivariate Pearson's correlation analysis was employed to analyze the correlations. The receiver operating characteristic curves were plotted to analyze the values of ADAMTS13, TBIL, and D-D for predicting the prognosis of TTP. RESULTS: TBIL ≥ 72.74 µmol/L, D-D ≥ 4.17 mg/L, PLASMIC score < 6 points, and absence of plasma exchange (PEx) were risk factors affecting the prognosis, and ADAMTS13 ≤ 25.04% was a protective factor for the prognosis of TTP patients (p < 0.05). ADAMTS13, TBIL, and D-D were significantly associated with death (p < 0.05). The areas under the curves of TBIL, ADAMTS13, D-D and their combination were 0.796 (95% confidence interval CI: 0.729 - 0.860), 0.721 (95% CI: 0.648 - 0.788), 0.820 (95% CI: 0.756 - 0.880), and 0.872 (95% CI: 0.823 - 0.920), respectively. CONCLUSIONS: TBIL, D-D, ADAMTS13, PLASMIC score, and absence of PEx are factors influencing the prognosis of TTP patients, among which TBIL, D-D, and ADAMTS13 are of high predictive values.

Effects of diet and gender on the pharmacokinetics of oral lenvatinib: A clinical trial in healthy Chinese participants.

OBJECTIVE: Lenvatinib is a tyrosine kinase inhibitor that helps prevent angiogenesis. In this study, we investigated the potential influencing factors on lenvatinib pharmacokinetics to provide a reference for clinical application. MATERIALS AND METHODS: All healthy participants received a single dose of 4 mg lenvatinib mesylate capsules with a high-fat meal or fasted conditions. Lenvatinib plasma concentrations were determined via high-performance liquid chromatography-mass spectrometry/mass spectrometry, and the pharmacokinetic parameters were calculated using WinNonlin 8.1 software. A mixed effect model analysis was adopted to explore the influence factor for the pharmacokinetic parameters of lenvatinib. RESULTS: After a single oral dose of 4 mg lenvatinib mesylate, the pharmacokinetic parameters for the fasted and fed groups were as follows: tmax was 2.0 hours and 4.5 hours, Cmax was 53.60 ng/mL and 45.54 ng/mL, AUC0-t was 597.44 h×ng/mL and 561.51 h×ng/mL, CL was 6.82 L/h and 7.26 L/h, and Vd was 82.82 L and 94.04 L, respectively. Compared with those in the fasted group, decreased Cmax and increased tmax were observed in the fed group. The geometric mean ratios of fed/fasted for Cmax, AUC0-t, and AUC0-∞ were 86.9%, 94.0%, and 93.9%, respectively, and the pharmacokinetics of lenvatinib were significantly influenced by food intake. Gender influenced the pharmacokinetics of lenvatinib; females had higher Cmax and AUC0-t levels after 4 mg lenvatinib. Lenvatinib was well tolerated in healthy Chinese subjects. CONCLUSION: High-fat diet altered the pharmacokinetic profile of lenvatinib, but not sufficient to significantly impact its clinical efficacy. Therefore, lenvatinib is suitable for administration under fasted or fed conditions.

Clinical observation of tear film breakup time with a novel smartphone-attachable technology.

PURPOSE: To demonstrate the practicability of a portable instrument in assessing tear film breakup time (TFBUT): a lens attachment for smartphones (LAS). METHODS: By applying LAS in combination with the iPhone 12 pro, and a recordable slit-lamp microscope, we obtained TFBUT videos from 58 volunteers. The comparison between the conventional slit-lamp microscope and LAS by an experienced ophthalmologist. Moreover, we also invited an ophthalmic postgraduate student and an undergraduate student with no clinical experience to assess TFBUT in those videos. The inter-observer reliability was assessed using intraclass correlation coefficients (ICC). RESULTS: The TFBUT of 116 eyes in total was recorded. Reliability indexes were adequate. The Spearman's correlation analysis and the intraclass correlation coefficient suggested a strong correlation between the 2 modalities (Right eye: Spearman's r = 0.929, 95% confidence interval (CI) = 0.847-0.963, ICC = 0.978, p < 0.001; Left eye: Spearman's r = 0.931, 95% CI = 0.866-0.964, ICC = 0.985, p < 0.001;). Between instruments, the majority of TFBUT measurements showed good agreement on Bland Altman plot. A high concordance was observed in TFBUT, when assessed by an ophthalmologist and an ophthalmic postgraduate student (Left eye: LAS ICC = 0.951, p < 0.001; Left eye: slit-lamp microscope ICC = 0.944, p < 0.001). CONCLUSIONS: Compared with the conventional slit-lamp microscope, the LAS has sufficient validity for evaluating TFBUT in clinics or at home.