Interleukin-33 Signaling Controls the Development of Iron-Recycling Macrophages.

Splenic red pulp macrophages (RPMs) contribute to erythrocyte homeostasis and are required for iron recycling. Heme induces the expression of SPIC transcription factor in monocyte-derived macrophages and promotes their differentiation into RPM precursors, pre-RPMs. However, the requirements for differentiation into mature RPMs remain unknown. Here, we have demonstrated that interleukin (IL)-33 associated with erythrocytes and co-cooperated with heme to promote the generation of mature RPMs through activation of the MyD88 adaptor protein and ERK1/2 kinases downstream of the IL-33 receptor, IL1RL1. IL-33- and IL1RL1-deficient mice showed defective iron recycling and increased splenic iron deposition. Gene expression and chromatin accessibility studies revealed a role for GATA transcription factors downstream of IL-33 signaling during the development of pre-RPMs that retained full potential to differentiate into RPMs. Thus, IL-33 instructs the development of RPMs as a response to physiological erythrocyte damage with important implications to iron recycling and iron homeostasis.

MARK4 controls ischaemic heart failure through microtubule detyrosination.

Myocardial infarction is a major cause of premature death in adults. Compromised cardiac function after myocardial infarction leads to chronic heart failure with systemic health complications and a high mortality rate1. Effective therapeutic strategies are needed to improve the recovery of cardiac function after myocardial infarction. More specifically, there is a major unmet need for a new class of drugs that can improve cardiomyocyte contractility, because inotropic therapies that are currently available have been associated with high morbidity and mortality in patients with systolic heart failure2,3 or have shown a very modest reduction of risk of heart failure4. Microtubule detyrosination is emerging as an important mechanism for the regulation of cardiomyocyte contractility5. Here we show that deficiency of microtubule-affinity regulating kinase 4 (MARK4) substantially limits the reduction in the left ventricular ejection fraction after acute myocardial infarction in mice, without affecting infarct size or cardiac remodelling. Mechanistically, we provide evidence that MARK4 regulates cardiomyocyte contractility by promoting phosphorylation of microtubule-associated protein 4 (MAP4), which facilitates the access of vasohibin 2 (VASH2)-a tubulin carboxypeptidase-to microtubules for the detyrosination of α-tubulin. Our results show how the detyrosination of microtubules in cardiomyocytes is finely tuned by MARK4 to regulate cardiac inotropy, and identify MARK4 as a promising therapeutic target for improving cardiac function after myocardial infarction.

miniSNV: accurate and fast single nucleotide variant calling from nanopore sequencing data.

Nanopore sequence technology has demonstrated a longer read length and enabled to potentially address the limitations of short-read sequencing including long-range haplotype phasing and accurate variant calling. However, there is still room for improvement in terms of the performance of single nucleotide variant (SNV) identification and computing resource usage for the state-of-the-art approaches. In this work, we introduce miniSNV, a lightweight SNV calling algorithm that simultaneously achieves high performance and yield. miniSNV utilizes known common variants in populations as variation backgrounds and leverages read pileup, read-based phasing, and consensus generation to identify and genotype SNVs for Oxford Nanopore Technologies (ONT) long reads. Benchmarks on real and simulated ONT data under various error profiles demonstrate that miniSNV has superior sensitivity and comparable accuracy on SNV detection and runs faster with outstanding scalability and lower memory than most state-of-the-art variant callers. miniSNV is available from https://github.com/CuiMiao-HIT/miniSNV.

Exploring the Origins and Evolution of Oxygenic and Anoxygenic Photosynthesis in Deeply Branched Cyanobacteriota.

Cyanobacteriota, the sole prokaryotes capable of oxygenic photosynthesis (OxyP), occupy a unique and pivotal role in Earth's history. While the notion that OxyP may have originated from Cyanobacteriota is widely accepted, its early evolution remains elusive. Here, by using both metagenomics and metatranscriptomics, we explore 36 metagenome-assembled genomes from hot spring ecosystems, belonging to two deep-branching cyanobacterial orders: Thermostichales and Gloeomargaritales. Functional investigation reveals that Thermostichales encode the crucial thylakoid membrane biogenesis protein, vesicle-inducing protein in plastids 1 (Vipp1). Based on the phylogenetic results, we infer that the evolution of the thylakoid membrane predates the divergence of Thermostichales from other cyanobacterial groups and that Thermostichales may be the most ancient lineage known to date to have inherited this feature from their common ancestor. Apart from OxyP, both lineages are potentially capable of sulfide-driven AnoxyP by linking sulfide oxidation to the photosynthetic electron transport chain. Unexpectedly, this AnoxyP capacity appears to be an acquired feature, as the key gene sqr was horizontally transferred from later-evolved cyanobacterial lineages. The presence of two D1 protein variants in Thermostichales suggests the functional flexibility of photosystems, ensuring their survival in fluctuating redox environments. Furthermore, all MAGs feature streamlined phycobilisomes with a preference for capturing longer-wavelength light, implying a unique evolutionary trajectory. Collectively, these results reveal the photosynthetic flexibility in these early-diverging cyanobacterial lineages, shedding new light on the early evolution of Cyanobacteriota and their photosynthetic processes.

Identification of target genes co-regulated by four key histone modifications of five key regions in hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is a cancer with high morbidity and mortality. Studies have shown that histone modification plays an important regulatory role in the occurrence and development of HCC. However, the specific regulatory effects of histone modifications on gene expression in HCC are still unclear. This study focuses on HepG2 cell lines and hepatocyte cell lines. First, the distribution of histone modification signals in the two cell lines was calculated and analyzed. Then, using the random forest algorithm, we analyzed the effects of different histone modifications and their modified regions on gene expression in the two cell lines, four key histone modifications (H3K36me3, H3K4me3, H3K79me2, and H3K9ac) and five key regions that co-regulate gene expression were obtained. Subsequently, target genes regulated by key histone modifications in key regions were screened. Combined with clinical data, Cox regression analysis and Kaplan-Meier survival analysis were performed on the target genes, and four key target genes (CBX2, CEBPZOS, LDHA, and UMPS) related to prognosis were identified. Finally, through immune infiltration analysis and drug sensitivity analysis of key target genes, the potential role of key target genes in HCC was confirmed. Our results provide a theoretical basis for exploring the occurrence of HCC and propose potential biomarkers associated with histone modifications, which may be potential drug targets for the clinical treatment of HCC.

Serum biomarker signature is predictive of the risk of hepatocellular cancer in patients with cirrhosis.

BACKGROUND: Inflammatory and metabolic biomarkers have been associated with hepatocellular cancer (HCC) risk in phases I and II biomarker studies. We developed and internally validated a robust metabolic biomarker panel predictive of HCC in a longitudinal phase III study. METHODS: We used data and banked serum from a prospective cohort of 2266 adult patients with cirrhosis who were followed until the development of HCC (n=126). We custom designed a FirePlex immunoassay to measure baseline serum levels of 39 biomarkers and established a set of biomarkers with the highest discriminatory ability for HCC. We performed bootstrapping to evaluate the predictive performance using C-index and time-dependent area under the receiver operating characteristic curve (AUROC). We quantified the incremental predictive value of the biomarker panel when added to previously validated clinical models. RESULTS: We identified a nine-biomarker panel (P9) with a C-index of 0.67 (95% CI 0.66 to 0.67), including insulin growth factor-1, interleukin-10, transforming growth factor ß1, adipsin, fetuin-A, interleukin-1 ß, macrophage stimulating protein α chain, serum amyloid A and TNF-α. Adding P9 to our clinical model with 10 factors including AFP improved AUROC at 1 and 2 years by 4.8% and 2.7%, respectively. Adding P9 to aMAP score improved AUROC at 1 and 2 years by 14.2% and 7.6%, respectively. Adding AFP L-3 or DCP did not change the predictive ability of the P9 model. CONCLUSIONS: We identified a panel of nine serum biomarkers that is independently associated with developing HCC in cirrhosis and that improved the predictive ability of risk stratification models containing clinical factors.

One-year outcomes of a novel venous stent for symptomatic iliofemoral venous obstruction: prospective cohort study.

BACKGROUND: A stent with characteristics of a hybrid design may have advantages in improving the patency of symptomatic iliofemoral vein obstruction. This study assessed the safety and effectiveness of the V-Mixtent Venous Stent in treating symptomatic iliofemoral outflow obstruction. METHODS: Eligible patients had a Clinical-Etiologic-Anatomic-Physiologic (CEAP) C classification of ≥ 3 or a Venous Clinical Severity Score (VCSS) pain score of ≥ 2. The primary safety endpoint was the rate of major adverse events within 30 days. The primary effectiveness endpoint was the 12-month primary patency rate. Secondary endpoints included changes in VCSS from baseline to 6 and 12 months, alterations in CEAP C classification, Chronic Venous Disease Quality of Life Questionnaire (CIVIQ-14) scores at 12 months, and stent durability measures. RESULTS: Between December 2020 and November 2021, 171 patients were enrolled across 15 institutions. A total of 185 endovenous stents were placed, with 91.81% of subjects receiving one stent and 8.19% receiving 2 stents. Within 30 days, only two major adverse events occurred (1.17%; 95% confidence interval [CI], 0.14-4.16%), below the literature-defined performance goal of 11% (P < .001). The 12-month primary patency rate (91.36%; 95% CI, 85.93-95.19%; P < .001) exceeded the literature-defined performance goal. VCSS changes from baseline demonstrated clinical improvement at 6 months (- 4.30 ± 3.66) and 12 months (- 4.98 ± 3.67) (P < .001). Significant reduction in symptoms, as measured by CEAP C classification and CIVIQ-14, was observed from pre-procedure to 12 months (P < .001). CONCLUSIONS: The 12-month outcomes confirm the safety and effectiveness of the V-Mixtent Venous Stent in managing symptomatic iliofemoral venous outflow obstruction, including clinical symptom improvement compared to before treatment.

NUSAP1 promotes pancreatic ductal adenocarcinoma progression by drives the epithelial-mesenchymal transition and reduces AMPK phosphorylation.

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) has a poor prognosis, and its molecular mechanisms are unclear. Nucleolar and spindle-associated protein 1 (NUSAP1), an indispensable mitotic regulator, has been reported to be involved in the development of several types of tumors. The biological function and molecular mechanism of NUSAP1 in PDAC remain controversial. This study explored the effects and mechanism of NUSAP1 in PDAC. METHODS: Differentially expressed genes (DEGs) were screened. A protein‒protein interaction (PPI) network was constructed to identify hub genes. Experimental studies and tissue microarray (TMA) analysis were performed to investigate the effects of NUSAP1 in PDAC and explore its mechanism. RESULTS: Network analysis revealed that NUSAP1 is an essential hub gene in the PDAC transcriptome. Genome heterogeneity analysis revealed that NUSAP1 is related to tumor mutation burden (TMB), loss of heterozygosity (LOH) and homologous recombination deficiency (HRD) in PDAC. NUSAP1 is correlated with the levels of infiltrating immune cells, such as B cells and CD8 T cells. High NUSAP1 expression was found in PDAC tissues and was associated with a poor patient prognosis. NUSAP1 promoted cancer cell proliferation, migration and invasion, drives the epithelial-mesenchymal transition and reduces AMPK phosphorylation. CONCLUSIONS: NUSAP1 is an essential hub gene that promotes PDAC progression and leads to a dismal prognosis by drives the epithelial-mesenchymal transition and reduces AMPK phosphorylation.

Complete response of recurrent perihilar cholangiocarcinoma following sintilimab combined with lenvatinib plus S-1: a case report and review of literature.

Perihilar cholangiocarcinoma is a refractory malignancy with an unfavorable prognosis and a high probability of recurrence. Systemic chemotherapy is critical for palliative treatment, but effective therapeutic strategies for perihilar cholangiocarcinoma after first-line chemotherapy failure are scarce. Here, we introduced a sustained benefit following sintilimab combined with lenvatinib plus S-1 in a patient with recurrent perihilar cholangiocarcinoma. A 52-year-old female patient was admitted to our hospital due to yellow skin and sclera, and further radiological examination revealed perihilar cholangiocarcinoma. The patient underwent surgery and histopathological results confirmed moderately differentiated adenocarcinoma with metastatic lymph nodes. Postoperative adjuvant chemotherapy with gemcitabine and S-1 was given. One year after surgery, the patient experienced hepatic recurrence. Then, she received radiofrequency ablation combined with gemcitabine and cisplatin. Unfortunately, radiological assessment revealed progressive disease with multiple liver metastases after treatment. Subsequently, she received sintilimab combined with lenvatinib plus S-1 and the lesions were completely regressed following 14 cycles of combination therapy. The patient recovered well without disease recurrence at the last follow-up. Sintilimab combined with lenvatinib plus S-1 may be an alternative therapeutic option for chemotherapy-refractory perihilar cholangiocarcinoma, and further evaluation in a larger number of patients is needed.

CD39hi identifies an exhausted tumor-reactive CD8+ T cell population associated with tumor progression in human gastric cancer.

The ectonucleotidase CD39 has been regarded as a promising immune checkpoint in solid tumors. However, the expression of CD39 by tumor-infiltrating CD8+ T cells as well as their potential roles and clinical implications in human gastric cancer (GC) remain largely unknown. Here, we found that GC-infiltrating CD8+ T cells contained a fraction of CD39hi cells that constituted about 6.6% of total CD8+ T cells in tumors. These CD39hi cells enriched for GC-infiltrating CD8+ T cells with features of exhaustion in transcriptional, phenotypic, metabolic and functional profiles. Additionally, GC-infiltrating CD39hiCD8+ T cells were also identified for tumor-reactive T cells, as these cells expanded in vitro were able to recognize autologous tumor organoids and induced more tumor cell apoptosis than those of expanded their CD39int and CD39-CD8+ counterparts. Furthermore, CD39 enzymatic activity controlled GC-infiltrating CD39hiCD8+ T cell effector function, and blockade of CD39 efficiently enhanced their production of cytokines IFN-γ and TNF-α. Finally, high percentages of GC-infiltrating CD39hiCD8+ T cells correlated with tumor progression and independently predicted patients' poor overall survival. These findings provide novel insights into the association of CD39 expression level on CD8+ T cells with their features and potential clinical implications in GC, and empowering those exhausted tumor-reactive CD39hiCD8+ T cells through CD39 inhibition to circumvent the suppressor program may be an attractive therapeutic strategy against GC.

Cooperative Catalysis-Enabled (4 + 3) Cycloaddition of 2-Indolylmethanols with In Situ-Generated ortho-Naphthoquinone Methides.

A cooperative catalysis-enabled (4 + 3) cycloaddition of 2-indolylmethanols with ortho-naphthoquinone methides (o-NQMs), which were in situ-generated from enynones, has been established in the presence of silver/Brønsted acid cocatalysts. In the reaction pathway, the key o-NQM intermediates were formed through Ag(I)-catalyzed cyclization of enynones, while the indole-based carbocation intermediates were generated via Brønsted acid-catalyzed dehydration of 2-indolylmethanols. By this approach, a wide range of seven-membered cyclohepta[b]indoles were synthesized in good yields with high efficiency under mild reaction conditions, which serves as a useful strategy toward constructing indole-fused seven-membered rings. Moreover, the catalytic asymmetric version of this (4 + 3) cycloaddition has been realized under the cooperative catalysis of Ag(I) with chiral phosphoric acid, which offered chiral cyclohepta[b]indole with a good enantioselectivity (75% ee). This work not only represents the first cooperative catalysis-enabled (4 + 3) cycloaddition of 2-indolylmethanols but also provides a good example for o-NQM-involved cycloadditions, which will contribute to the chemistry of 2-indolylmethanols and enrich the research contents of cooperative catalysis.

Neutrophils impaired by anti-galectin-3 antibodies elicit inflammation of endothelial cells to aggregate the development of lupus cutaneous vasculitis.

OBJECTIVES: To investigate whether the interplay of anti-galectin-3 antibodies (anti-Gal3 Abs) with neutrophils contributes to the development of lupus cutaneous vasculitis. METHODS: Enzyme-linked immunosorbent assay was used to determine the serum level of anti-Gal3 Abs in lupus patients. Flow cytometry, quantitative PCR and western blot were performed to investigate the expression of cell surface receptors, proinflammatory cytokines and signalling molecules in neutrophils stimulated by serum from lupus patients or healthy controls (HCs) or anti-Gal3 Ab, respectively. Immunofluorescence was performed to visualise the formation of neutrophil extracellular traps (NETs). Human umbilical vein endothelial cells were co-cultured with the supernatants from neutrophils stimulated by anti-Gal3 Ab, and cytokine production was measured at mRNA and protein levels. Immunohistochemistry was adopted to reveal the distribution of Gal3, cytokines and myeloperoxidase within lupus skin lesions. RESULTS: Serum levels of anti-Gal3 Abs were negatively correlated with peripheral counts of neutrophils. Anti-Gal3 Abs positive sera from SLE patients accelerated neutrophil death, altered cell phenotype and promoted formation of NETs with the involvement of p38 MAPK pathway. Supernatants collected from neutrophils co-cultured with anti-Gal3 Ab provoked endothelial cells to produce cytokines such as IL-1, ICAM-1, SELE and particularly IL-6. Consistently, IL-6 was higher in SLE patients with anti-Gal3 Ab positive sera and enriched in the area of vascular inflammation together with enhanced expression of Gal3 protein and infiltration of neutrophils. CONCLUSIONS: Overall, these findings suggested that neutrophils were crucial mediators in anti-Gal3 Ab induced lupus cutaneous vasculitis.

Small-Intensity Rainfall Triggers Greater Contamination of Rubber-Derived Chemicals in Road Stormwater Runoff from Various Functional Areas in Megalopolis Cities.

Rubber-derived chemicals (RDCs) originating from tire and road wear particles are transported into road stormwater runoff, potentially threatening organisms in receiving watersheds. However, there is a lack of knowledge on time variation of novel RDCs in runoff, limiting initial rainwater treatment and subsequent rainwater resource utilization. In this study, we investigated the levels and time-concentration profiles of 35 target RDCs in road stormwater runoff from eight functional areas in the Greater Bay Area, South China. The results showed that the total concentrations of RDCs were the highest on the expressway compared with other seven functional areas. N-(1,3-Dimethylbutyl)-N'-phenyl-p-phenylenediamine (6PPD), 6PPD-quinone, benzothiazole, and 1,3-diphenylguanidine were the top four highlighted RDCs (ND-228840 ng/L). Seasonal and spatial differences revealed higher RDC concentrations in the dry season as well as in less-developed regions. A lag effect of reaching RDC peak concentrations in road stormwater runoff was revealed, with a lag time of 10-90 min on expressways. Small-intensity rainfall triggers greater contamination of rubber-derived chemicals in road stormwater runoff. Environmental risk assessment indicated that 35% of the RDCs posed a high risk, especially PPD-quinones (risk quotient up to 2663). Our findings contribute to a better understanding of managing road stormwater runoff for RDC pollution.

G3BP2 promotes tumor progression and gemcitabine resistance in PDAC via regulating PDIA3-DKC1-hENT in a stress granules-dependent manner.

Pancreatic ductal adenocarcinoma (PDAC) is distinguished by its aggressive malignancy, limited treatment avenues and a tendency towards chemotherapy resistance, underscoring the critical need for advanced research to uncover new therapeutic approaches. Stress granules (SGs) that is implicated in cellular self-protection mechanism, along with its associated family molecules have shown pro-cancer effects and are closely related to tumor chemotherapy resistance. In this study we investigated the relationship between Ras GTPase-activating protein-binding proteins 2 (G3BP2), a core component of SGs, and the malignancy of PDAC as well as its resistance to the chemotherapy drug gemcitabine. Analyzing TCGA dataset revealed that the expression of G3BP1 and G3BP2 was significantly upregulated in PDAC compared with adjacent normal pancreatic tissues, and the high expression of G3BP2 rather than G3BP1 was significantly associated with poorer overall survival (OS) in PDAC patients. We demonstrated that knockdown of G3BP2 inhibited the proliferation and invasion of PANC-1 and CFPAC-1 cells in vitro and in vivo. By analyzing the differentially expressed genes in G3BP2 knockdown and overexpressed PANC-1 cells, we identified DKC1 that was associated with RNA stability and regulation as the target of G3BP2. We demonstrated that G3BP2 bound to PDIA3 mRNA and recruited them into SGs, increasing the stability of PDIA3 mRNA and attenuating its translation efficiency, thereby promoting DKC1 expression. Furthermore, DKC1 could bind to hENT mRNA and inhibited its expression, which enhanced gemcitabine resistance of PDAC. Therefore, we propose a novel mechanism wherein G3BP2 facilitates PDAC's resistance to chemotherapy by modulating PDIA3-DKC1-hENT in a SGs-dependent way, suggesting G3BP2 SGs a protentional therapeutic target for the treatment in PDAC.

SMAD4 endows TGF-ß1-induced highly invasive tumor cells with ferroptosis vulnerability in pancreatic cancer.

Pancreatic ductal adenocarcinoma (PDAC) is an extremely aggressive malignancy prone to recurrence and metastasis. Studies show that tumor cells with increased invasive and metastatic potential are more likely to undergo ferroptosis. SMAD4 is a critical molecule in the transforming growth factor ß (TGF-ß) pathway, which affects the TGF-ß-induced epithelial-mesenchymal transition (EMT) status. SMAD4 loss is observed in more than half of patients with PDAC. In this study, we investigated whether SMAD4-positive PDAC cells were prone to ferroptosis because of their high invasiveness. We showed that SMAD4 status almost determined the orientation of transforming growth factor ß1 (TGF-ß1)-induced EMT via the SMAD4-dependent canonical pathway in PDAC, which altered ferroptosis vulnerability. We identified glutathione peroxidase 4 (GPX4), which inhibited ferroptosis, as a SMAD4 down-regulated gene by RNA sequencing. We found that SMAD4 bound to the promoter of GPX4 and decreased GPX4 transcription in PDAC. Furthermore, TGF-ß1-induced high invasiveness enhanced sensitivity of SMAD4-positive organoids and pancreas xenograft models to the ferroptosis inducer RAS-selective lethal 3 (RSL3). Moreover, SMAD4 enhanced the cytotoxic effect of gemcitabine combined with RSL3 in highly invasive PDAC cells. This study provides new ideas for the treatment of PDAC, especially SMAD4-positive PDAC.

Relationship between social support and self-care ability among patients with breast cancer during rehabilitation: The multiple mediating roles of resilience and depression.

AIMS: To identify the multiple mediating effects of resilience and depression between social support and self-care ability among patients with breast cancer during rehabilitation to provide reference for developing and implementing targeted interventions. DESIGN: A cross-sectional study reported according to the STROBE checklist. METHODS: A convenience sample of 320 patients with breast cancer during rehabilitation was recruited from one hospital in China. Data were collected from April to August 2022 using a self-report questionnaire, including the demographic and clinical information, Appraisal of Self-Care Agency Scale-Revised, Multidimensional Scale of Perceived Social Support, Connor-Davidson Resilience Scale-10 item, and Patient Health Questionnaire-9. The mediation analysis was conducted using the SPSS Process macro. RESULTS: Self-care ability was positively associated with social support (ß = .229) and resilience (ß = .290), and negatively associated with depression (ß = -.208). The relationship between social support and self-care ability was mediated by resilience and depression, respectively, and together in serial. The multiple mediating effects accounted for 34.0% of the total effect of social support on self-care ability. CONCLUSION: Our findings identify resilience and depression as multiple mediators between social support and self-care ability and highlight the important roles of social support, resilience and depression in improving self-care ability. RELEVANCE TO CLINICAL PRACTICE: Healthcare providers should pay great attention to the underlying mechanisms of how social support affects patients' self-care ability during breast cancer rehabilitation. Integrated intervention programmes targeted at enhancing social support, building resilience and alleviating depression might be beneficial to the improvement of self-care ability. PATIENT OR PUBLIC CONTRIBUTION: No patient or public contribution. REPORTING METHOD: The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) checklist for cross-sectional studies was applied to report the results.

Extraction Optimization of Phenolic Compounds from Triadica sebifera Leaves: Identification, Characterization and Antioxidant Activity.

Triadica sebifera (T. sebifera) has attracted much attention because of the high oil content in its seeds, but there are few systematic studies on the phenolic compounds of T. sebifera leaves (TSP). In this study, the extraction process of TSP was optimized by response surface methodology. The phenolic components of these extracts were analyzed by high-performance liquid chromatography (HPLC). Moreover, the effects of hot air drying (HD), vacuum drying (VD) and freeze drying (FD) on the antioxidant activity and characterization of T. sebifera leaf extract (TSLE) were evaluated. Under the conditions of ethanol concentration 39.8%, liquid-solid ratio (LSR) 52.1, extraction time 20.2 min and extraction temperature 50.6 °C, the maximum TSP yield was 111.46 mg GAE/g dw. The quantitative analysis and correlation analysis of eight compounds in TSP showed that the type and content of phenolic compounds had significant correlations with antioxidant activity, indicating that tannic acid, isoquercitrin and ellagic acid were the main components of antioxidant activities. In addition, through DPPH and ABTS determination, VD-TSLE and FD-TSLE showed strong scavenging ability, with IC50 values of 138.2 µg/mL and 135.5 µg/mL and 73.5 µg/mL and 74.3 µg/mL, respectively. Fourier transform infrared spectroscopy (FTIR) and scanning electron microscopy (SEM) infrared spectroscopy revealed small differences in the extracts of the three drying methods. This study lays a foundation for the effective extraction process and drying methods of phenolic antioxidants from T. sebifera leaves, and is of great significance for the utilization of T. sebifera leaves.

Spanish-Speaking Caregiver Preferences for Social Determinants of Health Screening.

Equitable social determinants of health (SDOH) screening has been recommended by the Centers for Medicare & Medicaid Services and the Joint Commission; however, little is known about Spanish-speaking caregiver preferences on how they would like to be screened. We conducted a cross-sectional study at 3 pediatric clinics (October-December 2019). Caregivers completed (in English or Spanish) an SDOH screening preferences survey. Three hundred eighty-two of 443 caregivers approached (response rate = 86.2%) completed the survey. Most were female, preferred Spanish, and completed only high school. Spanish-speaking caregivers had greater odds of preferring verbal SDOH screening (odds ratio: 4.1; 95% confidence interval, 1.8-9.2) than English-speaking caregivers. Verbal SDOH screening should be a consideration in families who speak Spanish. Future studies should utilize qualitative methods to further explore Spanish-speaking caregiver preferences for SDOH screening.

Synthesis of Alkene Atropisomers with Multiple Stereogenic Elements via Catalytic Asymmetric Rearrangement of 3-Indolylmethanols.

Catalytic enantioselective preparation of alkene atropisomers with multiple stereogenic elements and discovery of their applications have become significant but challenging issues in the scientific community due to the unique structures of this class of atropisomers. We herein report the first catalytic atroposelective preparation of cyclopentenyl[b]indoles, a new kind of alkene atropisomers, with stereogenic point and axial chirality via an unusual rearrangement reaction of 3-indolylmethanols under asymmetric organocatalysis. Notably, this novel type of alkene atropisomers have promising applications in developing chiral ligands or organocatalysts, discovering antitumor drug candidates and fluorescence imaging materials. Moreover, the theoretical calculations have elucidated the possible reaction mechanism and the non-covalent interactions to control the enantioselectivity. This approach offers a new synthetic strategy for alkene atropisomers with multiple stereogenic elements, and represents the first catalytic enantioselective rearrangement reaction of 3-indolylmethanols, which will advance the chemistry of atropisomers and chiral indole chemistry.

Effects of greater erythroid Cl-/HCO3- transporter (band 3) expression on ventilation and gas exchange during exhaustive exercise.

Band 3 protein is a Cl-/[Formula: see text] transporter on the red blood cell (RBC) surface with an important role in CO2 excretion. Greater band 3 expression by roughly 20% is found in people with the GP.Mur blood type. Intriguingly, a disproportional percentage of those with GP.Mur excel in field-and-track sports. Could higher band 3 activity benefit an individual's physical performance? This study explored the impact of GP.Mur/higher band 3 expression on ventilation and gas exchange during exhaustive exercise. We recruited 36 nonsmoking, elite male athletes (36.1% GP.Mur) from top sports universities to perform incremental exhaustive treadmill cardiopulmonary exercise testing (CPET). We analyzed CPET data with respect to absolute running time and to individual's %running time and %maximal O2 uptake. We found persistently higher respiratory frequencies and slightly lower tidal volume in GP.Mur athletes, resulting in a slightly larger increase of ventilation as the workload intensified. The expiratory duty cycle (Te/Ttot) was persistently longer and inspiratory duty cycle (Ti/Ttot) was persistently shorter for GP.Mur subjects throughout the run. Consequently, end-tidal pressure of carbon dioxide ([Formula: see text], a surrogate marker for alveolar and arterial CO2 tension-[Formula: see text] and [Formula: see text]) was lower in the GP.Mur athletes during the early stages of exercise. In conclusion, athletes with GP.Mur and higher band 3 expression hyperventilate more during exercise in a pattern that uses a greater fraction of time for expiration than inspiration to increase the rate of CO2 excretion than increased tidal volume. This greater ventilation response reduced Pco2 and may help to extend exercise capacity in high-level sports.NEW & NOTEWORTHY Higher expression of the Cl-/[Formula: see text] transporter band 3 anion exchanger-1 (AE1) on the red blood cell membrane, as in people with the GP.Mur blood type, increases the rate of CO2 excretion during exercise.