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PURPOSE: Magrolimab is a first-in-class humanized monoclonal antibody against cluster of differentiation 47, an antiphagocytic signal used by cancer cells to evade phagocytosis. Azacitidine upregulates prophagocytic signals on AML cells, further increasing phagocytosis when combined with magrolimab. We report final phase Ib data for magrolimab with azacitidine in patients with untreated AML ineligible for intensive chemotherapy (ClinicalTrials.gov identifier: NCT03248479). PATIENTS AND METHODS: Patients with previously untreated AML, including TP53-mutant AML, received magrolimab intravenously as an initial dose (1 mg/kg, days 1 and 4), followed by 15 mg/kg once on day 8 and 30 mg/kg once weekly or every 2 weeks as maintenance. Azacitidine 75 mg/m2 was administered intravenously/subcutaneously once daily on days 1-7 of each 28-day cycle. Primary end points were safety/tolerability and proportion with complete remission (CR). RESULTS: Eighty-seven patients were enrolled and treated; 72 (82.8%) had TP53 mutations with a median variant allele frequency of 61% (range, 9.8-98.7). Fifty-seven (79.2%) of TP53-mutant patients had European LeukemiaNet 2017 adverse-risk cytogenetics. Patients received a median of 4 (range, 1-39) cycles of treatment. The most common treatment-emergent adverse events included constipation (49.4%), nausea (49.4%), and diarrhea (48.3%). Thirty (34.5%) experienced anemia, and the median hemoglobin change from baseline to first postdose assessment was -0.9 g/dL (range, -3.6 to 2.5 g/dL). Twenty-eight (32.2%) patients achieved CR, including 23 (31.9%) patients with TP53 mutations. The median overall survival in TP53-mutant and wild-type patients were 9.8 months and 18.9 months, respectively. CONCLUSION: Magrolimab with azacitidine was relatively well tolerated with promising efficacy in patients with AML ineligible for intensive induction chemotherapy, including those with TP53 mutations, warranting further evaluation of magrolimab with azacitidine in AML. The phase III randomized ENHANCE-2 (ClinicalTrials.gov identifier: NCT04778397) and ENHANCE-3 (ClinicalTrials.gov identifier: NCT05079230) studies are recruiting frontline patients with AML.

Rare earth elements (REEs) have gained attention as tracers of pedogenic processes over the last few decades. Clay-sized fractions (CSFs, < 2 μm) may play a crucial role in hosting REEs. To better understand the pedochemical signals of REEs in clay-sized phases, such as iron oxides and phyllosilicates, we analyzed REE speciation in CSFs of carbonate rocks (limestone), clastic rocks (sandstone and shale), and their derived saprolites. Our results quantified the REE content (41.2–144.6 mg kg−1) and speciation in CSFs of parent materials, revealing that REEs were primarily hosted in amorphous iron oxides (Feox1), followed by crystalline iron oxides (Feox2) and phyllosilicates. Compared to parent materials, saprolites derived from carbonate rocks exhibited more than a two-fold enrichment of REEs in major clay-sized phases, confirming the role of CSFs as REE sinks during carbonate rock weathering. Furthermore, the initial REE patterns of CSFs of carbonate rocks underwent alteration throughout the weathering process, likely due to water–mineral interactions. Our findings suggest that REEs in CSFs record the weathering fingerprint for soils derived from carbonate rocks, while they are indicative of provenance for soils originating from clastic rocks.

This study aims to evaluate the role of the peri-coronary Fat Attenuation Index (FAI) and High-Risk Plaque Characteristics (HRPC) in the assessment of coronary heart disease risk. By conducting coronary CT angiography and coronary angiography on 217 patients with newly developed chest pain (excluding acute myocardial infarction), their degree of vascular stenosis, FAI, and the presence and quantity of HRPC were assessed. The study results demonstrate a correlation between FAI and HRPC, and the combined use of FAI and HRPC can more accurately predict the risk of major adverse cardiovascular events (MACE). Additionally, the study found that patients with high FAI were more prone to exhibit high-risk plaque characteristics, severe stenosis, and multiple vessel disease. After adjustment, the combination of FAI and HRPC improved the ability to identify and reclassify MACE. Furthermore, the study identified high FAI as an independent predictor of MACE in patients undergoing revascularization, while HRPC served as an independent predictor of MACE in patients not undergoing revascularization. These findings suggest the potential clinical value of FAI and HRPC in the assessment of coronary heart disease risk, particularly in patients with newly developed chest pain excluding acute myocardial infarction.

Highlights A biochar-bacteria (2B) system was constructed based on MICP. Cd was immobilized (23.6–45.8%) in the 2B system. 2B system facilitated the formation of insoluble otavite (CdCO3). Bacteria carrying the ureC gene were boosted to lower the Cd mobility. Graphical Abstract

By 2050, the global population is projected to reach 9 [...]

Diet intake accounts for >90% of selenium (Se) exposure in humans, with rice being the main source of Se intake for >60% of the Chinese population. In this study, 48 rice grain samples labeled Se-enriched were obtained from 22 major rice producing areas in China through online sources. Their total Se contents, Se speciation, and Se bioaccessibility were evaluated to provide a holistic view of Se-enriched rice in the market. The total Se contents were 0.006–0.951 ​μg ​g−1 (average 0.249 ​μg ​g−1), which showed great regional variations, with 73% of the samples satisfying the Se-enriched standard based on GB/T22499-2008 (0.04–0.30 ​mg ​kg−1). Over 80% of Se in the rice samples was organic Se species including selenomethionine, selenocysteine and methylselenocysteine, with selenomethionine being the main Se species, accounting for 61–98%. Based on a modified physiologically-based extraction test (MPBET), the Se bioaccessibility in 33 selected samples was 8.05–49.6% (28.6%) in the gastric phase and 18.1–117% (82.5%) in the intestinal phase. Further, Se bioaccessibility was positively correlated with organic Se (r ​= ​0.89–0.93), but not with inorganic Se (selenite and selenate), suggesting that Se bioaccessibility depended on organic Se in these rice grains. The data call for re-evaluation of Se-enriched rice in the market. Further, the potential risk of long-term consumption of Se-enriched rice in the market towards human health should be studied.

In vitro strategies have widely been used to assess bioaccessibility of organic pollutants in soils. However, studies for comparing in vitro models with in vivo data are still limited. In this study, Dichlorodiphenyltrichloroethane (DDT) and its metabolites (called as DDTr) bioaccessibility in nine contaminated soils were measured using physiologically based extraction test (PBET), in vitro digestion model (IVD), and Deutsches Institut für Normung (DIN) with/without Tenax as an absorptive sink, and DDTr bioavailability was assessed using an in vivo mouse model. Whether or not Tenax was added, DDTr bioaccessibility significantly varied among three methods, suggesting that DDTr bioaccessibility depended on the in vitro method employed. Multiple linear regression analysis indicated that sink, intestinal incubation time and bile content are identified to be the dominant factors in controlling DDTr bioaccessibility. Comparison of in vitro and in vivo results demonstrated that DIN assay with Tenax (TI-DIN) provided the best prediction for DDTr bioavailability (r2 = 0.66, slope=0.78). After extending intestinal incubation time to 6 h or increasing bile content to 4.5 g/L (same to DIN assay) of the TI-PBET and TI-IVD assays, the in vivo-in vitro correlation will improved significantly, with r2 = 0.76 and slope= 1.4 for TI-PBET and r2 = 0.84 and slope= 1.9 for TI-IVD under 6 h intestinal incubation, and r2 = 0.59 and slope= 0.96 for TI-PBET and r2 = 0.51 and slope= 1.0 for TI-IVD under 4.5 g/L of bile content. The results suggest that it is essential to understand these key factors influencing bioaccessibility for the development of standardized in vitro methods, which helps to refine the risk assessment of human exposure to contaminants via soil ingestion.

Exposure of human to parabens (commonly used preservatives) is inevitable due to their extensively applied in numerous consumer products. Thus, a reliable noninvasive matrix reflecting long-term exposure to parabens is essential for human biomonitoring study. Human nails are potentially a valuable alternative for measuring intergrated exposure to parabens. In this work, we collected 100 paired nail and urine samples from university students in Nanjing, China, and measured simultaneously for six parent parabens and four metabolites. Methylparaben (MeP), ethylparaben (EtP), and propylparaben (PrP) were three predominant paraben analogue in both matrices, with the median concentrations being 12.9, 0.753, and 3.42 ng/mL in urine, and 1540, 154, and 961 ng/g in nail, respectively, while 4-hydroxybenzoic acid (4-HB) and 3,4-dihydroxybenzoic acid (3,4-DHB) were the most abundant metabolites (median values of 143 and 35.9 ng/mL, respectively) in urine. Gender-related analysis suggested that females exposed to more higher parabens than males. Significantly positive correlations were found between levels of MeP, PrP, EtP, and OH-MeP (r = 0.54–0.62, p

Abstract Background Circular RNAs (circRNAs) are pivotal regulators of various human cancers and circ-ERBB2 is abnormally expressed in breast cancer cells. However, the role and mechanism of circ-ERBB2 in HER2-positive breast cancer are still unknown. Methods The circ-ERBB2 expressions in the tumor tissues of HER2-positive breast cancer patients were tested using quantitative real-time PCR. The circ-ERBB2 function was investigated by cell counting kit 8 assay, Transwell, flow cytometry and Western blot. Mechanistically, fluorescence in situ hybridization, RNA immunoprecipitation, RNA pull-down and dual-luciferase reporter gene assays were conducted to confirm the interaction between circ-ERBB2 and miR-136-5p or miR-198 in HER2-positive breast cancer cells. Results Circ-ERBB2 was elevated in the tumor tissues of HER2-positive breast cancer patients. Functionally, the interference with circ-ERBB2 repressed HER2-positive breast cancer cell proliferation, migration, invasion and accelerated cell apoptosis. Furthermore, the mechanistic analysis corroborated that circ-ERBB2 acted as a competing endogenous RNA for miR-136-5p or miR-198 to relieve the repressive influence of miR-136-5p or miR-198 on its target transcription factor activator protein 2C (TFAP2C). Meanwhile, in vivo assays further corroborated the oncogenic function of circ-ERBB2 in HER2-positive breast cancer. Conclusions Circ-ERBB2 accelerated HER2-positive breast cancer progression through the circ-ERBB2/miR-136-5p/TFAP2C axis or the circ-ERBB2/miR-198/TFAP2C axis.

Arsenic (As) in the aquatic environment is a considerable environmental issue, previous studies have reported the toxic effects of low concentrations (≤ 150 μg/L) of As on fish. However, limited information is available regarding the impact of low levels of As on apoptosis. To evaluate this, zebrafish embryos were exposed to different concentrations (0, 25, 50, 75, and 150 μg/L) of As (arsenite [AsIII] and arsenate [AsV]) for 120 h. Our results indicated that low concentrations of AsIII exposure significantly inhibited the survival of zebrafish larvae, and significantly increased the transcription of Caspase-9 and Caspase-3, the ratio of Bax/Bcl-2 transcription, and protein levels of Caspase-3. In contrast, AsV decreased the ratios of Bax/Bcl-2 transcription and protein levels, as well as protein levels of Caspase-3. Our data demonstrated that AsIII and AsV exert different toxic effects, AsIII induced apoptosis via the mitochondrial pathway and the extrinsic pathway, while AsV induced apoptosis only via the mitochondrial pathway.

Crop productivity and yield are adversely affected by the deficiency of P in agricultural soil. Phosphate fertilizers are used at a large scale to improve crop yields globally. With the rapid increase in human population, food demands are also increasing. To see that crop yields meet demands, farmers have continuously added phosphate fertilizers to their arable fields. As the primary source of inorganic phosphorous, rock phosphate is finite and the risk of its being jeopardized in the foreseeable future is high. Therefore, there is a dire need to improve plant-available P in soil, using feasible, environmentally friendly technologies developed on the basis of further understanding of P dynamics between soil and plants. This study systemically reviews the mechanism of P uptake and P-use efficiency by plants under starvation conditions. The recent advances in various strategies, especially imaging techniques, over the period 2012–2021 for the measurement of plant-available P are identified. The study then examines how plants fulfill P requirements from tissue-stored P during P starvation. Following this understanding, various strategies for increasing plant-available P in agricultural soil are evaluated. Finally, an update on novel carriers used to improve the P content of agricultural soil is provided.

Summary: 5hmC, 6mA, and 4mC are three common DNA modifications and are involved in various of biological processes. Accurate genome-wide identification of these sites is invaluable for better understanding their biological functions. Owing to the labor-intensive and expensive nature of experimental methods, it is urgent to develop computational methods for the genome-wide detection of these sites. Keeping this in mind, the current study was devoted to construct a computational method to identify 5hmC, 6mA, and 4mC. We initially used K-tuple nucleotide component, nucleotide chemical property and nucleotide frequency, and mono-nucleotide binary encoding scheme to formulate samples. Subsequently, random forest was utilized to identify 5hmC, 6mA, and 4mC sites. Cross-validated results showed that the proposed method could produce the excellent generalization ability in the identification of the three modification sites. Based on the proposed model, a web-server called iDNA-MS was established and is freely accessible at http://lin-group.cn/server/iDNA-MS. : Genetics; Quantitative Genetics; Bioinformatics Subject Areas: Genetics, Quantitative Genetics, Bioinformatics

Introduction: Klippel-Trenaunay syndrome (KTS) is a rare congenital vascular disorder characterized by a triad of cutaneous port wine capillary malformations, varicose veins, and hemihypertrophy of bone and soft tissues. Aims: To report on a rare case of KTS in an adult man manifested by painless urethral bleeding during penile erection briefly review the clinical presentation and management of the genitourinary forms of this syndrome. Methods: On presentation, the clinical features of this patient, including medical history, signs and symptoms, and imaging examinations, were recorded. After diagnosis and initial treatment, a literature review of the urethral features of KTS was performed and is discussed in this report. Results: A 35-year-old man with KTS presented with painless urethral bleeding during penile erection that was associated with posterior urethral vascular malformations. The coagulation method was used to treat the malformation, and no urethral bleeding or gross hematuria occurred during a postoperative follow-up period of 6 months. Conclusion: This case demonstrates that coagulation therapy and careful follow-up can be adequate treatment approaches for urethral features of KTS. However, the long-term efficacy of coagulation for this disorder should be investigated further.Lei H, Guan X, Han H, et al. Painless Urethral Bleeding During Penile Erection in an Adult Man With Klippel-Trenaunay Syndrome: A Case Report. Sex Med 2018;6:180–183. Key Words: Urethral Bleeding, Klippel-Trenaunay Syndrome, Vascular Malformation, Posterior Urethra, Genitourinary Manifestation

[Display omitted] Palladium-based nanocatalysts play an important role in catalyzing the cathode oxygen reduction reaction (ORR) for fuel cells working under alkaline conditions, but the performance still needs to be improved to meet the requirements for large-scale applications. Herein, Au@Pd core–shell nanowires have been developed by coating Pd atomic layers on ultrafine gold nanowires and display outstanding electrocatalytic performance towards alkaline ORR. It is found that Pd overlayers with atomic thickness can be coated on 3 nm Au nanowires under CO atmosphere and completely cover the surfaces. The obtained ultrafine Au@Pd nanowires exhibit an electrochemical active area (ECSA) of 68.5 m2/g and a mass activity of 0.91 A/mg (at 0.9 V vs. RHE), which is around 3.1 and 15.2 times higher than that of commercial Pd/C. The activity loss of the ultrafine Au@Pd nanowire after 10,000 cycles of accelerated degradation tests is only ∼20 %, demonstrating its much better stability compared to commercial Pd/C. Further characterizations combined with density functional theory (DFT) calculations demonstrate that the electronic interactions between Pd atomic layers and underlying Au can increase the electronic density of Pd and promote the efficient activation of oxygen, thus leading to the improved ORR performance. [ABSTRACT FROM AUTHOR]

OBJECTIVE: A micro-molecule peptide TP1623 of 99mTc-human epithelial growth factor receptor 2 (HER2) was prepared and the feasibility of using it as a HER2-positive molecular imaging agent for breast cancer was evaluated. METHODS: TP1623 was chemically synthesized and labeled with 99mTc. The labeling ratio and stability were detected. HER2 expression levels of breast cancer cells (SKBR3 and MDA-MB-231) and cell binding activity were measured. Biodistribution of 99mTC-TP1623 in normal mice was detected. SKBR3/MDA-MB-231-bearing nude mice models with high/low expressions of HER2 were established. Tumor tissues were stained with hematoxylin–eosin (HE) and measured by immunohistochemistry to confirm the formation of tumors and HER2 expression. SPECT imaging was conducted for HER2-overexpressing SKBR3-bearing nude mice. The T/NT ratio was calculated and compared with that of MDA-MB-231-bearing nude mice with low HER2 expression. The competitive inhibition image was used to discuss the specific binding of 99mTc- TP1623 and the tumor. RESULTS: The labeling ratio of 99mTc-TP1623, specific activity, and radiochemical purity (RCP) after 6 h at room temperature were (97.39 ± 0.23)%, (24.61 ± 0.06) TBq/mmol, and (93.25 ± 0.06)%, respectively. HER2 of SKBR3 and MDA-MB-231 cells showed high and low expression levels by immunohistochemistry, respectively. The in vitro receptor assays indicated that specific binding of TP1623 and HER2 was retained. Radioactivity in the brain was always at the lowest level, while the clearance rate of blood and the excretion rate of the kidneys were fast. HE staining showed that tumor cells were observed in SKBR3- and MDA-MB-231-bearing nude mice, with significant heteromorphism and increased mitotic count. The imaging of mice showed that targeted images could be made of 99mTc-TP1623 in high HER2-expressing tumors, while no obvious development was shown in tumors in low HER2-expressing nude mice. No development was visible in tumors in competitive inhibition of imaging, which indicates the combination of 99mTc-TP1623 and tumor was mediated by HER2. CONCLUSION: High labeling ratio and specific activity of 99mTc-TP1623 is successfully prepared; it is a molecular imaging agent for HER2-positive tumors that has potential applicative value.