CRISPR-Cas9 Editing of the HBG1 and HBG2 Promoters to Treat Sickle Cell Disease.

BACKGROUND: Sickle cell disease is caused by a defect in the ß-globin subunit of adult hemoglobin. Sickle hemoglobin polymerizes under hypoxic conditions, producing deformed red cells that hemolyze and cause vaso-occlusion that results in progressive organ damage and early death. Elevated fetal hemoglobin levels in red cells protect against complications of sickle cell disease. OTQ923, a clustered regularly interspaced short palindromic repeats (CRISPR)-Cas9-edited CD34+ hematopoietic stem- and progenitor-cell (HSPC) product, has a targeted disruption of the HBG1 and HBG2 (γ-globin) gene promoters that increases fetal hemoglobin expression in red-cell progeny. METHODS: We performed a tiling CRISPR-Cas9 screen of the HBG1 and HBG2 promoters by electroporating CD34+ cells obtained from healthy donors with Cas9 complexed with one of 72 guide RNAs, and we assessed the fraction of fetal hemoglobin-immunostaining erythroblasts (F cells) in erythroid-differentiated progeny. The gRNA resulting in the highest level of F cells (gRNA-68) was selected for clinical development. We enrolled participants with severe sickle cell disease in a multicenter, phase 1-2 clinical study to assess the safety and adverse-effect profile of OTQ923. RESULTS: In preclinical experiments, CD34+ HSPCs (obtained from healthy donors and persons with sickle cell disease) edited with CRISPR-Cas9 and gRNA-68 had sustained on-target editing with no off-target mutations and produced high levels of fetal hemoglobin after in vitro differentiation or xenotransplantation into immunodeficient mice. In the study, three participants received autologous OTQ923 after myeloablative conditioning and were followed for 6 to 18 months. At the end of the follow-up period, all the participants had engraftment and stable induction of fetal hemoglobin (fetal hemoglobin as a percentage of total hemoglobin, 19.0 to 26.8%), with fetal hemoglobin broadly distributed in red cells (F cells as a percentage of red cells, 69.7 to 87.8%). Manifestations of sickle cell disease decreased during the follow-up period. CONCLUSIONS: CRISPR-Cas9 disruption of the HBG1 and HBG2 gene promoters was an effective strategy for induction of fetal hemoglobin. Infusion of autologous OTQ923 into three participants with severe sickle cell disease resulted in sustained induction of red-cell fetal hemoglobin and clinical improvement in disease severity. (Funded by Novartis Pharmaceuticals; ClinicalTrials.gov number, NCT04443907.).

Hybrid Ascharite/Reduced Graphene Oxide with Polysulfide Adsorption Host for Advanced Lithium-Sulfur Batteries.

Balancing the adsorption of lithium-polysulfide intermediates on polar host material surfaces and the effect of their electronic conductivity in the subsequent oxidation and reduction kinetics of electrochemical reactions is necessary and remains a challenge. Herein, we have evaluated the role of polarity and conductivity in preparing a series of ascharite/reduced graphene oxide (RGO) aerogels by dispersing strong polar ascharite nanowires of varying mass into the conductive RGO matrix. When severed as Li-S battery cathodes, the optimized S@ascharite/RGO cathode with a sulfur content of 73.8 wt % demonstrates excellent rate performance and cycle stability accompanied by a high-capacity retention for 500 cycles at 1.0 C. Interesting advantages including the enhanced adsorption ability by the formation of the Mg-S and Li bonds, the continuous and quick electron/ion transportations assembled conductive RGO framework, and the effective deposition of Li2S are combined in the ascharite/RGO aerogel hosts. The electrochemical results further demonstrate that the polarity of ascharite components for the S cathode plays a dominant role in the improvement of electrochemical performance, but the absence of a conductive substrate leads to serious capacity attenuation, especially the rate performance. The balanced design protocol provides a universal method for the synthesis of multiple S hosts for high-performance LSBs.

Clinical Efficacy and Safety Study of Loratadine Combined with Glucocorticoid Nasal Spray in the Treatment of Pediatric Bronchial Asthma with Seasonal Allergic Rhinitis.

To investigate the clinical efficacy and safety of Loratadine combined with Glucocorticoid nasal spray in the treatment of pediatric bronchial asthma with seasonal allergic rhinitis. A total of 100 pediatric patients with moderate to severe bronchial asthma and seasonal allergic rhinitis admitted to our hospital between January 2020 and January 2023 were included in this study. All patients met the complete inclusion and exclusion criteria. Based on different treatment interventions, they were divided into the control group (n = 50) and the observation group (n = 50). Patients in the control group received treatment with glucocorticoid nasal spray, while patients in the observation group received combined intervention with Loratadine in addition to the treatment received by the control group. The clinical treatment outcomes, incidence of adverse reactions, as well as the scores of nasal symptoms, asthma control, and peak expiratory flow rates at different treatment time points (baseline, T1: 30 days after treatment, T2: 60 days after treatment, T3: 90 days after treatment) were compared between the two groups.The combined treatment of Loratadine with Glucocorticoid nasal spray demonstrates significant clinical efficacy in the treatment of pediatric bronchial asthma with seasonal allergic rhinitis. It further promotes the recovery of peak expiratory flow rates, improves symptoms of rhinitis and asthma in pediatric patients. Importantly, the application of this combined treatment does not increase the risk of adverse reactions in pediatric patients, indicating its high safety profile. This treatment approach is worthy of clinical application and further promotion.

Deletion of cis-regulatory Element in FOXL2 Promoter in a Chinese Family of Type II Blepharophimosis-ptosis-epicanthus Inversus Syndrome with Polydactyly.

Blepharophimosis-ptosis-epicanthus inversus syndrome (BPES) is a relatively uncommon autosomal-dominant genetic disorder, primarily attributed to mutations in the forkhead box L2 (FOXL2) gene. Albeit the involvement of protein-coding regions of FOXL2 has been observed in the majority of BPES cases, whether deficiencies in regulatory elements lead to the pathogenesis remains poorly understood. Herein, an autosomal-dominant BPES type II family was included. Peripheral venous blood has been collected, and genomic DNA has been extracted from leukocytes. A whole exome sequencing analysis has been performed and analyzed (Deposited in NODE database: OER422653). The promoter region of FOXL2 was amplified using polymerase chain reaction (PCR). The luciferase reporter assay was performed to identify the activity of this region. In this study, we present a Chinese family diagnosed with type II BPES, characterized by the presence of small palpebral fissures, ptosis, telecanthus, and epicanthus inversus. Notably, all male individuals within the family display polydactyly. A 225-bp deletion in the 556-bp 5'-upstream to transcription start site of FOXL2 , decorated by multiple histone modifications, was identified in affected members of the family. This deletion significantly decreased FOXL2 promoter activity, as measured by the luciferase assay. Conclusively, a novel 255-bp-deletion of the FOXL2 promoter was identified in Chinese families with BPES. Our results expand the spectrum of known FOXL2 mutations and provide additional insight into the genotype-phenotype relationships of the BPES pathogenesis. In addition, this study indicates the important role of genetic screening of cis-regulatory elements in testing heritable diseases.

Enhancement of Mass Transfer Process for Photocatalytic Reduction in Cr(VI) by Electric Field Assistance.

The removal of Cr(VI), a highly-toxic heavy metal, from industrial wastewater is a critical issue in water treatment research. Photocatalysis, a promising technology to solve the Cr(VI) pollution problem, requires urgent and continuous improvement to enhance its performance. To address this need, an electric field-assisted photocatalytic system (PCS) was proposed to meet the growing demand for industrial wastewater treatment. Firstly, we selected PAF-54, a nitrogen-rich porous organic polymer, as the PCS's catalytic material. PAF-54 exhibits a large adsorption capacity (189 mg/g) for Cr(VI) oxyanions through hydrogen bonding and electrostatic interaction. It was then coated on carbon paper (CP) and used as the photocatalytic electrode. The synergy between capacitive deionization (CDI) and photocatalysis significantly promotes the photoreduction of Cr(VI). The photocatalytic performance was enhanced due to the electric field's influence on the mass transfer process, which could strengthen the enrichment of Cr(VI) oxyanions and the repulsion of Cr(III) cations on the surface of PAF-54/CP electrode. In addition, the PCS system demonstrates excellent recyclability and stability, making it a promising candidate for chromium wastewater treatment.

Detection of Adulterated Naodesheng Tablet (Naodesheng Pian) via In-Depth Chemical Analysis and Subsequent Reconstruction of Its Pharmacopoeia Q-Markers.

Naodesheng Tablet (Naodesheng Pian), a traditional Chinese medicine formula for stroke treatment, is made up of five herbal medicines, i.e., Sanqi, Gegen, Honghua, Shanzha, and Chuanxiong. However, the current Pharmacopoeia quality-marker (Q-marker) system cannot detect possible adulteration. Our study tried to use a new strategy, i.e., standards-library-dependent ultra-high-performance liquid chromatography-quadrupole-Orbitrap mass spectrometry (UHPLC-Q-Orbitrap MS/MS) putative identification, to reconstruct the Q-marker system. Through the strategy, 30 isomers were successfully differentiated (such as 2'-hydroxygenistein, luteolin, and kaempferol; ginsenoside Rg2 and ginsenoside Rg3; ginsenoside Rf and ginsenoside Rg1). In particular, 11 compounds were unexpectedly found in Naodesheng, including 2'-hydroxygenistein, 7,4'-dihydroxyflavone, pectolinarigenin, 7-methoxy-4'-hydroxyisoflavone, scoparone, matrine, 3,3',4',5,6,7,8-heptamethoxyflavone, 5-hydroxyflavone, diosgenin, chloesteryl acetate, and (+)-4-cholesten-3-one. In total, 68 compounds were putatively identified and fully elucidated for their MS spectra. Subsequently, relevant compounds were further investigated using UV-vis scanning experiments, semi-quantitative analysis, and quantum chemical calculation. Finally, five adulterated Naodesheng Tablets were used for validation experiments. The experiment successfully detected five adulterated ones via a lower-version LC-MS analysis. On this basis, three new candidates (hydroxy safflor yellow A (HSYA), citric acid, and levistilide A), along with puerarin and notoginsenoside R1, are re-nominated as the Q-markers for LC-MS analysis. The LC-MS analysis of puerarin, notoginsenoside R1, HSYA, citric acid, and levistilide A can clearly detect adulteration regarding all five herbal medicines mentioned above. Therefore, the reconstructed Q-markers are described as a "perfect" quality control system to detect adulteration in Naodesheng and will offer a valuable recommendation for the Pharmacopoeia Commission.

Partially interpretable image deconvolution framework based on the Richardson-Lucy model.

Fluorescence microscopy typically suffers from aberration induced by system and sample, which could be circumvented by image deconvolution. We proposed a novel, to the best of our knowledge, Richardson-Lucy (RL) model-driven deconvolution framework to improve reconstruction performance and speed. Two kinds of neural networks within this framework were devised, which are partially interpretable compared with previous deep learning methods. We first introduce RL into deep feature space, which has superior generalizability to the convolutional neural networks (CNN). We further accelerate it with an unmatched backprojector, providing a five times faster reconstruction speed than classic RL. Our deconvolution approaches outperform both CNN and traditional methods regarding image quality for blurred images caused by out-of-focus or imaging system aberration.

A novel clinically significant prostate cancer prediction system with multiparametric MRI and PSA: P.Z.A. score.

PURPOSE: This study aims to establish and validate a new diagnosis model called P.Z.A. score for clinically significant prostate cancer (csPCa). METHODS: The demographic and clinical characteristics of 956 patients were recorded. Age, prostate-specific antigen (PSA), free/total PSA (f/tPSA), PSA density (PSAD), peripheral zone volume ratio (PZ-ratio), and adjusted PSAD of PZ (aPSADPZ) were calculated and subjected to receiver operating characteristic (ROC) curve analysis. The nomogram was established, and discrimination abilities of the new nomogram were verified with a calibration curve and area under the ROC curve (AUC). The clinical benefits of P.Z.A. score were evaluated by decision curve analysis and clinical impact curves. External validation of the model using the validation set was also performed. RESULTS: The AUCs of aPSADPZ, age, PSA, f/tPSA, PSAD and PZ-ratio were 0.824, 0.672, 0.684, 0.715, 0.792 and 0.717, respectively. The optimal threshold of P.Z.A. score was 0.41. The nomogram displayed excellent net benefit and better overall calibration for predicting the occurrence of csPCa. In addition, the number of patients with csPCa predicted by P.Z.A. score was in good agreement with the actual number of patients with csPCa in the high-risk threshold. The validation set provided better validation of the model. CONCLUSION: P.Z.A. score (including PIRADS(P), aPSADPZ(Z) and age(A)) can increase the detection rate of csPCa, which may decrease the risk of misdiagnosis and reduce the number of unnecessary biopsies. P.Z.A. score contains data that is easy to obtain and is worthy of clinical replication.

Identification of hub genes and potential inhibitory compounds in the process of liver transplantation through transcriptome sequencing.

Liver transplantation (LT) is the best choice for patients with end-stage liver diseases. In order to better understand pathophysiological alterations in LT, we aimed to identify potential hub genes and inhibitory compounds involved in the LT process. Four pairs of peripheral blood mononuclear cell (PBMC) samples of the LT recipients before and after surgery were collected and taken for transcriptome sequencing. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed for the screened differentially expressed genes (DEGs) between pre- and post-operation groups. Common DEGs were obtained from GO and KEGG enriched pathways, followed by protein-protein interaction (PPI) network construction, hub gene identification, module analysis, and structure-based virtual screening process (SBVS). Compared to the pre-operation stage, 4745 genes were down-regulated and 798 up-regulated after LT. GO analysis showed that the DEGs were enriched in ribosome-related translation regulation, and KEGG analysis indicated that infection and immune-related pathways and diseases were largely enriched. A large number of down-regulated DEGs were not only associated with ribosome-related pathways but also with the alterations of epigenetic modifications, in particular ubiquitination. Moreover, through the PPI network of 29 common genes from GO and KEGG-enriched pathways, 7 hub genes were identified, including PTEN, MYC, EIF2S1, EIF4EBP1, HSP90AB1, TP53, and HSPA8, which were mainly involved in the PI3K-AKT signaling pathway. SBVS of the seed molecule PTEN (PDB code: 1D5R) predicted top hits compounds that may serve as potential inhibitors of PTEN, of which the compound ZINC4235331 had the lowest binding affinity of -10 kcal/mol. The significance of screened hub genes and potential inhibitors involved in the process of LT provides novel therapeutic strategies for improving the outcomes of LT recipients during surgery.

Prediction of Renal Function 1 Year After Transplantation Using Machine Learning Methods Based on Ultrasound Radiomics Combined With Clinical and Imaging Features.

Kidney transplantation is the most effective treatment for advanced chronic kidney disease (CKD). If the prognosis of transplantation can be predicted early after transplantation, it might improve the long-term survival of patients with transplanted kidneys. Currently, studies on the assessment and prediction of renal function by radiomics are limited. Therefore, the present study aimed to explore the value of ultrasound (US)-based imaging and radiomics features, combined with clinical features to develop and validate the models for predicting transplanted kidney function after 1 year (TKF-1Y) using different machine learning algorithms. A total of 189 patients were included and classified into the abnormal TKF-1Y group, and the normal TKF-1Y group based on their estimated glomerular filtration rate (eGFR) levels 1 year after transplantation. The radiomics features were derived from the US images of each case. Three machine learning methods were employed to establish different models for predicting TKF-1Y using selected clinical and US imaging as well as radiomics features from the training set. Two US imaging, four clinical, and six radiomics features were selected. Then, the clinical (including clinical and US image features), radiomics, and combined models were developed. The area under the curves (AUCs) of the models was 0.62 to 0.82 within the test set. Combined models showed statistically higher AUCs than the radiomics models (all p-values <.05). The prediction performance of different models was not significantly affected by the different machine learning algorithms (all p-values >.05). In conclusion, US imaging features combined with clinical features could predict TKF-1Y and yield an incremental value over radiomics features. A model integrating all available features may further improve the predictive efficacy. Different machine learning algorithms may not have a significant impact on the predictive performance of the model.

Rhizosphere effect on the relationship between dissolved organic matter and functional genes in contaminated soil.

Arsenic contamination in a mining area is a potential threat to the local population. In the context of one-health, biological pollution in contaminated soil should be known and understandable. This study was conducted to clarify the effects of amendments on arsenic species and potential threat factors (e.g., arsenic-related genes (AMGs), antibiotic resistance genes (ARGs) and heavy-metal resistance genes (MRGs)). Ten groups (control (CK), T1, T2, T3, T4, T5, T6, T7, T8, and T9) were set up by adding different ratio of organic fertilizer, biochar, hydroxyapatite and plant ash. The maize crop was grown in each treatment. Compared with CK, the bioavailability of arsenic was reduced by 16.2%-71.8% in the rhizosphere soil treatments, and 22.4%-69.2% in the bulk soil treatments, except for T8. The component 2 (C2), component 3 (C3) and component 5 (C5) of dissolved organic matter (DOM) increased by 22.6%-72.6%, 16.8%-38.1%, 18.4%-37.1%, respectively, relative to CK in rhizosphere soil. A total of 17 AMGs, 713 AGRs and 492 MRGs were detected in remediated soil. The humidification of DOM might directly correlate with MRGs in both soils, while it was influenced directly on ARGs in bulk soil. This may be caused by the rhizosphere effect, which affects the interaction between microbial functional genes and DOM. These findings provide a theoretical basis for regulating soil ecosystem function from the perspective of arsenic contaminated soil.

Observation and Analysis of Ejector Hysteresis Phenomena in the Hydrogen Recirculation Subsystem of PEMFCs.

The optimization control and efficiency improvement of proton exchange membrane fuel cells (PEMFCs) are being paid more attention. Ejectors have been applied in PEMFC hydrogen recirculation subsystems due to the advantages of a simple structure and no power consumption. However, the hysteresis deviation of a proportional valve ejector is found in the loading and unloading processes such that the hysteresis phenomena can cause deviations in fuel cell control process and affect the power dynamic output stability of PEMFCs. This paper analyzes the causes and effects of proportional valve hysteresis phenomena through experiments and simulations. The results show that the resultant force of proportional valve armature is different in loading and unloading processes because of the hysteresis phenomena, and the maximum flow deviation is up to 0.42 g/s. The hysteresis phenomena of flow rate further cause a deviation of 68.7-89.3 kW in PEMFC power output. Finally, a control compensation model is proposed to effectively reduce the deviation. This study provides a reference for the control and optimization of PEMFC with ejector technology.

[Properties of new exotic traditional Chinese medicinal Vernonia amygdalina leaves:a literature research].

The leaves of Vernonia amygdalina Delile of the family Asteraceae(also known as "bitter leaf"), rich in biological activities, are used as both medicine and food for a long time in West tropical Africa. They have been introduced into Southeast Asia and Fujian and Guangdong provinces of China in recent years. However, little is known about the properties of the plant in traditional Chinese medicine(TCM), which limits its combination with other Chinese medicinal herbs. In this study, 473 articles on V. amygdalina leaves were selected from PubMed, Web of Science, CNKI, Wanfang Data and VIP to summarize their components, pharmacological effects and clinical research. V. amygdalina leaves presented anti-microbial, hypoglycemic, anti-hypertensive, lipid-lowering, anti-tumor, anti-inflammatory, antioxidant, and other pharmacological effects. On the basis of the theory of TCM properties, the leaves were inferred to be cold in property and bitter and sweet in flavor, acting on spleen, liver, stomach and large intestine and with the functions of clearing heat, drying dampness, purging fire, removing toxin, killing insects and preventing attack of malaria. They can be used to treat dampness-heat diarrhea, interior heat and diabetes, malaria, insect accumulation and eczema(5-10 g dry leaves by decoction per day and an appropriate amount of crushed fresh leaves applying to the affected area for external use). Due to the lack of TCM properties, V. amygdalina leaves are rarely used medicinally in China. The determination of medicinal properties of the leaves is conducive to the introduction of new exotic medicinal herbs and the development of new TCM resources, which facilitated further clinical application and research and development of Chinese medicinal herbs.

Steroid Receptor Coactivator-1 (SRC-1) Promoted Cell Metastasis of Gastric Cancer via VEGFC Activator by NF-κB.

The regulatory mechanism and function of steroid receptor coactivator-1 (SRC-1) was determined in vitro and the role played in gastric cancer was investigated. The study collected 64 patients with gastric cancer tissue and paracancerous tissue to investigate the clinical patterns of SRC-1 expression in gastric cancer. Quantitative polymerase chain reaction, Western blot, enzyme-linked immunosorbent assay, and immunofluorescence staining were used in this study. In patients with gastric cancer, SRC-1 serum expression levels were up-regulated. Over-expression of SRC-1 promoted cell growth and cell metastasis in vitro model of gastric cancer. However, down-regulation of SRC-1 reduced cell growth and cell metastasis in vitro model of gastric cancer. SRC-1 over-expression induced vascular endothelial growth factor C (VEGFC) protein expressions in vitro model by activation of nuclear factor-kappa B (NF-kB) expression. The inhibition of NF-κB reduced the pro-cancer effects of SRC-1 on cell growth and cell metastasis in vitro model of gastric cancer through inhibition of VEGFC expression. These results suggest that SRC-1 promoted cell metastasis of gastric cancer via VEGFC activator by NF-κB. These novel findings may shed further light on the pathogenesis of gastric cancer and on potential precursor markers.

Impact of 9-Minute Withdrawal Time on the Adenoma Detection Rate: A Multicenter Randomized Controlled Trial.

BACKGROUND & AIMS: Although current quality indicators of colonoscopy recommend 6 minutes as the minimum standard for withdrawal time (WT), the impact of a WT longer than 6 minutes on neoplasia detection is unclear. METHODS: A multicenter randomized controlled trial involving 1027 patients was conducted from January 2018 to July 2019. Participants were randomly divided into a 9-minute (n = 514) and 6-minute (n = 513) WT group, and a timer was used to adjust the withdrawal speed. The primary outcome was the adenoma detection rate (ADR). RESULTS: Intention-to-treat analysis showed a significantly higher ADR in the 9-minute versus 6-minute WT group (36.6% vs. 27.1%, P = .001). Prolonging WT from 6 to 9 minutes significantly increased ADR of the proximal colon (21.4% vs. 11.9%, P < .001) as well as of the less experienced colonoscopists (36.8% vs. 23.5%, P = .001). Improvements were also observed in the polyp detection rate (58.0% vs. 47.8%, P < .001), and mean number of polyps and adenomas detected per colonoscopy (1.1 vs. 0.9, P = .002; 0.5 vs. 0.4, P = .008, respectively). The higher ADRs in 9-minute WT were also confirmed by the per-protocol (PP) analysis and subgroup analyses, with an increased rate of sessile serrated lesion detection in the 9-minute WT by PP analysis (4.0% vs. 1.3%, P = .04). Multivariate logistic regression demonstrated that the 9-minute WT was independently associated with increased ADR (P = .005). CONCLUSIONS: Prolonging WT from 6 to 9 minutes significantly improved ADR, especially in the proximal colon and for less experienced colonoscopists. A 9-minute WT benchmark should be considered as one of the quality indicators of colonoscopy. ClinicalTrials.gov (identifier, NCT03399045).

Single-Cell Genomics-Based Molecular Algorithm for Early Cancer Detection.

As one of the prime applications of liquid biopsy, the detection of tumor-derived whole cells and molecular markers is enabled in a noninvasive means before symptoms or hints from imaging procedures used for cancer screening. However, liquid biopsy is not a diagnostic test of malignant diseases per se because it fails to establish a definitive cancer diagnosis. Although single-cell genomics provides a genome-wide genetic alternation landscape, it is technologically challenging to confirm cell malignancy of a suspicious cell in body fluids due to unknown technical noise of single-cell sequencing and genomic variation among cancer cells, especially when tumor tissues are unavailable for sequencing as the reference. To address this challenge, we report a molecular algorithm, named scCancerDx, for confirming cell malignancy based on single-cell copy number alternation profiles of suspicious cells from body fluids, leading to a definitive cancer diagnosis. The scCancerDx algorithm has been trained with normal cells and cancer cell lines and validated with single tumor cells disassociated from clinical samples. The established scCancerDx algorithm then validates hexokinase 2 (HK2) as an efficient metabolic function-associated marker of identifying disseminated tumor cells in different body fluids across many cancer types. The HK2-based test, together with scCancerDx, has been investigated for the early detection of bladder cancer (BC) at a preclinical phase by detecting high glycolytic HK2high tumor cells in urine. Early BC detection improves patient prognosis and avoids radical resection for enhancing life quality.

Side-Group Effect on the Slow Relaxations of {Dy2} Single-Molecule Magnets with Confined N2O6 Donors.

Deep insights into and substantial enhancement of the effective anisotropy energy barrier for magnetization reversal (Ueff) are vitally important for the technological applications of dysprosium(III)-based single-molecule magnets (Dy-SMMs). To fully refine the ligand-field effect on spin relaxation, four centrosymmetric {Dy2} entities with formula [Dy2(CH3OH)2L2(RCOO)2] (H2L = 2-hydroxy-N'-((pyridin-2-yl)methylene)benzohydrazide) have been solvothermally prepared by varying the side groups of carboxylate coligands (RCOO-, R = CF3 for 1, H for 2, CH3 for 3, and Cp2Fe for 4). Structural analyses reveal that all of the DyIII carriers in 1-4 have the same N2O6 donor environments, and the non-coordinative R groups attached to the equatorial carboxylate bridges have not substantially changed the binding ability of the shortest Dy-Ophenolate bonds located at the axial position of the ligand field. Interestingly, the side groups have monotonically decreased the zero-field Ueff barriers of these weak antiferromagnetically coupled {Dy2} analogues from 721 K down to 379 K. Further electronic structure calculations demonstrate that the main magnetic axes of 1-4 are highly dominated by these comparable Dy-Ophenolate short bonds, and the g tensors have produced gradually increased transverse components responsible significantly for the decreased Ueff barriers. Additionally, thermally assisted relaxations occur preferably through the second (for 1) and the first (for 2-4) Kramer doublets. These interesting findings afford a new side-group effect to comprehensively understand the magnetostructural relationships and advance the rational design of high-performance Dy-SMMs.

A computational study on the adsorption of arsenic pollutants on graphene-based single-atom iron adsorbents.

Integrated gasification combined cycle (IGCC) is a promising clean technology for coal power generation; however, the high volatility and toxicity of arsenic pollutants (As2, As4, AsO and AsH3) released from an IGCC coal plant cause serious damage to human health and the ecological environment. Therefore, highly efficient adsorbents for simultaneous treatment of multiple arsenic pollutants are urgently needed. In this work, the adsorption characteristics and competitive adsorption behaviors of As2, As4, AsO, and AsH3 on four kinds of graphene-based single-atom iron adsorbents (Fe/GA) were systematically investigated through density functional theory (DFT) and ab initio molecular dynamics (AIMD) simulations. The results suggest that single-vacancy Fe/GA doped with three nitrogen atoms has the largest adsorption ability for As2, As4, AsO and AsH3. The adsorption energies of As2, AsO and As4 on Fe/GA depend on both charge transfer and orbital hybridization, while the adsorption energy of AsH3 is mainly decided by electronic transfer. The adsorption differences of As2, As4, AsO and AsH3 on four Fe/GA adsorbents can be explained through the obvious linear relationship between the adsorption energy and Fermi softness. As2, As4, AsO and AsH3 will compete for adsorption sites when they exist on the same adsorbent surface simultaneously, and the adsorption capacities of AsO and As2 are relatively stronger. After the competitive adsorption between AsO and As2, AsO occupies the adsorption site at 300-900 K. This theoretical work suggests that Fe/GA is a promising adsorbent for the simultaneous removal of multiple arsenic pollutants with high adsorption capacity and low cost.

Aberrant FBXW7-mediated ubiquitination and degradation of ZMYND8 enhances tumor progression and stemness in bladder cancer.

ZMYND8, an epigenetic regulator, was identified as a common oncogene across various tumors. However, little was reported about the association between ZMYND8 and bladder cancer. Besides, aberrant mechanisms that contribute to abnormal ZMYND8 expressions still remain unclear. In the current study, we first found that ZMYND8 protein levels were significantly elevated in Bca samples versus normal tissues, but not the mRNA levels. We then utilized the Cell Counting Kit-8 (CCK-8) assay, clone formation assay and transwell analysis to confirm that ZMYND8 could remarkably promote the tumor progression in vitro, including growth capacity and migration. Bioinformatic predictive analysis revealed that E3 ubiquitin ligase FBXW7 interacts directly with ZMYND8 and degrades ZMYND8 in a polyubiquitination manner. Low FBXW7 was a hazard factor for promoting and depending on accumulated ZMYND8 proteins to promote Bca progression. Gene set enrichment analysis (GSEA) further indicated that ZMYND8 was notably associated with stemness process, which was well functionally validated. Lastly, ZMYND8 deficiency was observed to inhibit tumor growth of Bca in vivo, revealing a promising translational significance in Bca treatment. In conclusion, our study for the first time provided evidence for a novel mechanism of FBXW7/ZMYND8 axis in Bca, providing therapeutic vulnerability for individualized cancer treatment.

Characterization of Volatile Organic Compounds Produced by Bacillus siamensis YJ15 and Their Antifungal Activity Against Botrytis cinerea.

To develop an effective and environmentally safe strategy to control postharvest gray mold caused by Botrytis cinerea, Bacillus siamensis strain YJ15 isolated from blueberry was used to test the biocontrol potential. It is interesting to find that the volatile organic compounds (VOCs) emitted from strain YJ15 exhibited significant antifungal activity against Botrytis cinerea as well as 11 other plant-pathogenic fungi, with a percentage of mycelial growth inhibition from 74.96 to 92.81%. Additionally, VOCs from strain YJ15 could reduce significantly the disease incidence and lesion diameter with the increasing of fermentation time, indicating great biocontrol potential for controlling blueberry postharvest gray mold. Furthermore, the VOCs were collected by using headspace solid-phase microextraction fiber, and the composition of VOCs was further revealed by using gas chromatography coupled with quadruple mass spectrometry. In total, 24 kinds of VOCs, including 5 alkanes, 2 aldehydes, 3 ketones, 5 alcohols, 1 alkene, 5 acids and esters, 2 aromatic compounds, and 1 sulfur compound, were emitted at 1, 3, 5, and 7 days after inoculation. Among these VOCs, eight antifungal VOCs could inhibit mycelial growth of B. cinerea. It is important to highlight that, although 1-butanol and 3-methyl-1-butanol were the most abundant compounds, 2-ethylhexanol, 1-heptanol, and 1,3-xylene have proved to be more toxic to B. cinerea than 3-methyl-1-butanol, propanethioic acid, 2,2-dimethyl-, ethyl 2-methylbutyrate, 2-heptanone, and 1-butanol, which provide new, promising biofumigants for the control of postharvest gray mold caused by B. cinerea.