The superiority of isomeric, fluorination and curtailed π-conjunction on A-D-A type acceptors for organic photovoltaics.

The performance of organic solar cell (OSC) devices has been significantly enhanced by the dramatic evolution of A-D-A type non-fullerene acceptors (NFAs). Nevertheless, the structure-property-performance relationship of NFAs in the OSC device is unclear. Here, the intrinsic design factors of isomeric, fluorination and π-conjunction curtailing on the photophysical properties of benzodi (thienopyran) (BDTP) (named NBDTP-M, NBDTTP-M, NBDTP-Fin, and NBDTP-Fout)-based NFAs are discussed. The results show that fluorination on the terminal group of NBDTP-Fout could effectively decrease the highest occupied orbital (HOMO) energy level and the lowest unoccupied orbital (LUMO) energy level. And the long π-conjugated donor unit for NBDTTP-M could increase the HOMO energy level and bring a small HOMO-LUMO energy bandgap. Meanwhile, the substitution of external oxygen atoms and the fluorine atoms in the terminal group could introduce positive changes to the electrostatic potential of the NBDTP-Fout, favouring the charge separation at the donor/acceptor interface. Moreover, the structural design of external oxygen atom substitution, fluorination on the terminal group and curtailed π-conjugated donor unit could decrease the electron vibration-coupling of exciton diffusion, exciton dissociation and electronic transfer processes. The suppression of the exciton decay and charge recombination in those high-performance NFAs indicate that the investigated molecular designs could be effective for further improvement of OSCs.

A nationwide survey on the management of neonatal respiratory distress syndrome: insights from the MUNICH survey in 394 Chinese hospitals.

BACKGROUND: At present, preterm infants with respiratory distress syndrome (RDS) in China present higher mortality and morbidity rates than those in high-income countries. The aim of this nationwide survey was to assess the clinical management of RDS in China. METHODS: A nationwide cross-sectional survey to assess adherence to RDS management recommendations was performed. One neonatologist per hospital was randomly selected. The primary outcome was the key care of RDS management. RESULTS: Among the 394 participating hospitals, 88·3% were birthing centres. The number of doctors and nurses per bed were 0·27 and 0·72, respectively. Antenatal corticosteroids (any dose) were administered to 90% of the women at risk of preterm birth at < 34 weeks of gestation (90·0% inborn vs. 50·0% outborn, p < 0·001). The median fraction of inspired oxygen (FiO2) for initial resuscitation was 0·30 for babies born at ≤ 32 weeks of gestation and 0·25 for those born at > 32 weeks. T-piece resuscitators were available in 77·8% of delivery rooms (DRs) (tertiary hospitals: 82·5% vs. secondary hospitals: 63·0%, p < 0·001). Surfactant was used in 51·6% of the DRs. Less invasive surfactant administration (LISA) was used in 49·7% of the hospitals (tertiary hospitals: 55·3% vs. secondary hospitals: 31·5%, p < 0·001). Primary non-invasive ventilation was initiated in approximately 80·0% of the patients. High-frequency oscillation ventilation was primarily reserved for rescue after conventional mechanical ventilation (MV) failure. Caffeine was routinely used during MV in 59·1% of the hospitals. Bedside lung ultrasonography was performed in 54·3% of the health facilities (tertiary hospitals: 61·6% vs. secondary hospitals: 30·4%, p < 0·001). Qualified breast milk banks and Family Integrated Care (FICare) were present in 30·2% and 63·7% of the hospitals, respectively. CONCLUSIONS: Significant disparities in resource availability and guidelines adherence were evident across hospitals. Future strategies should address DR facilities and medication access, technical training, staff allocation, and ancillary facility development for a better management of RDS patients in China.

Addition of ruxolitinib and decitabine to modified busulfan/cyclophosphamide conditioning regimen for prophylaxis relapse in high-risk acute myeloid leukemia: the phase 2 prospective study.

The prognosis of patients with high-risk acute myeloid leukemia (AML) is dismal even after allogeneic stem cell transplantation (allo-HSCT), with relapse remaining the leading cause of treatment failure. Here, we investigated whether ruxolitinib and decitabine plus modified busulfan-cyclophosphamide (mBu/Cy) conditioning could reduce relapse in high-risk AML after allo-HSCT. This prospective, single-arm, phase II trial enrolled 37 patients who received allo-HSCT between September 2020 and March 2022 at the First Medical Center of Chinese People's Liberation Army (PLA) General Hospital. Eligible patients (10-62 years) had relapsed/refractory, positive measurable residual disease (MRD) prior to conditioning or adverse genetic abnormalities. Ruxolitinib (35 mg twice daily, days - 15 to - 10) and decitabine (20 mg/m2/day, days - 15 to - 10) were administered followed by mBu/Cy conditioning. All patients achieved engraftment. The cumulative incidences (CIs) of acute graft-versus-host disease (GVHD) grades II-IV and III-IV were 35.0% and 10.5%, respectively. The 1-year cumulative incidence of chronic GVHD was 8.1%. The 1-year CI of relapse was 29.7% among all patients, 0% in patients who achieved the first complete remission (CR1) prior to conditioning, and 0% in those with MRD-negative prior to conditioning. The 1-year non-relapse mortality was 5.4%. The 1-year probabilities of overall survival, disease-free survival, and GVHD-free relapse-free survival were 70.3%, 62.2%, and 54.1%, respectively. In conclusion, the novel conditioning showed primary efficacy in terms of a reduction in relapse in high-risk patients with AML after allo-HSCT, especially in those who achieved CR1 and MRD-negative prior to conditioning. Also, the new conditioning regimen may help reduce the incidence of chronic GVHD. ClinicalTrials.gov identifier: NCT04582604.

High-dose Furmonertinib in patients with EGFR-mutated non-small cell lung cancer and leptomeningeal metastases: A prospective real-world study.

INTRODUCTION: Leptomeningeal metastasis (LM) is one of the most severe complications of non-small cell lung cancer (NSCLC). Furmonertinib is a pan-epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) with a high rate of brain penetration and a wide therapeutic window. Here, we evaluated the efficacy and safety of high-dose furmonertinib in patients with EGFR-mutated NSCLC and LM. METHODS: This prospective real-world study included patients with EGFR-mutated NSCLC and LM treated with a high-dose furmonertinib (240 mg once daily) as a monotherapy or in combination with other treatments. The primary endpoint was overall survival (OS), and the secondary endpoints included time to treatment discontinuation (TTD) and clinical response rate. Additional efficacy evaluations included changes in brain magnetic resonance imaging (MRI) by the RANO-LM radiologic criteria. We also introduced next generation sequencing (NGS)-based assays to evaluate genomic and epigenomic features of cell-free DNA (cfDNA) in patients' cerebrospinal fluid (CSF) samples and to analyze their associations with patient outcomes. RESULTS: We enrolled 48 patients, of whom 35 (72.9%) had received third-generation EGFR-TKIs. The median OS was 8.43 months (95%CI, 5.48 to 11.39 months), while the median TTD was 8.27 months (95%CI, 5.40 to 11.14 months), and the clinical response rate was 75%. The LM objective response rate (ORR) and disease control rate (DCR) assessed with RANO-LM radiologic criteria were 50.0% and 92.1%, respectively. The adverse event profiles were consistent with previous reports of furmonertinib. Briefly, 22 (45.8%) had adverse events (AEs) possibly related to furmonertinib and three (6.3%) had a grade 3-elevated aminotransaminase or nausea or leucopenia, leading to dose reduction to 160 mg daily. Furthermore, methylation analysis of cfDNA in CSF showed that there was a significant correlation between the changes of aberrant methylated fragments (AMFs) from lung cancer cells and the response of the patients. Meanwhile, the copy number burden (CNB) scores derived from the low-pass whole genome sequencing (LP-WGS) assay may offer another objective and effective method for the diagnosis and evaluation of treatment efficacy in LM. CONCLUSION: In the real world, the high-dose furmonertinib-based treatment may potentially have clinical efficacy and tolerable safety in patients of EGFR-mutated NSCLC with LM, even in patients previously treated with other third-generation EGFR-TKIs. Methylation and CNB analysis of cfDNA in CSF may be considered objective indicators for the diagnosis of LM and evaluation of treatment response.

Ferroptosis as a molecular target of epigallocatechin gallate in diseases.

CONTEXT: Ferroptosis is a novel form of cell death characterised by iron overload and lipid peroxidation. It is closely associated with many diseases, including cardiovascular diseases, tumours, and neurological diseases. The use of natural chemicals to modulate ferroptosis is of great concern because of the critical role ferroptosis plays in disease. The main active ingredient in green tea is epigallocatechin gallate (EGCG), which is the most abundant catechin in green tea. EGCG shows a wide range of biological and therapeutic effects in various diseases, including anti-inflammatory, antioxidant, anticancer, and cardioprotective. OBJECTIVE: The purpose of this article is to summarise the existing information on the relationship between EGCG and ferroptosis. METHODS: Articles related to EGCG and ferroptosis were searched in PubMed and Web of Science databases, and the literature was analysed. RESULTS AND CONCLUSION: EGCG could improve ferroptosis-related diseases and affect the development of ferroptosis by regulating the nuclear factor erythroid 2-related factor 2, autophagy, microRNA, signal transducer and activator of transcription 1, and protein kinase D1 signalling pathways.

Dual catalytic potential of isoeugenol synthase in Asarum sieboldii Miq. (AsIGS): Unveiling isoeugenol preference in vitro and eugenol production in vivo, with insights into hydrogen bonding influence.

Asarum sieboldii Miq. is an important medicinal plant valued for its diverse health benefits in the pharmaceutical industry. In the present study, we isolated and characterized isoeugenol synthase from A. sieboldii (AsIGS), an essential enzyme involved in the biosynthesis of volatile phenylpropenes. We hoped to elucidate the secondary metabolic network of eugenol in A. sieboldii plants, which constructed the prerequisite for quality improvement of the well-known TCM Asari Radix et Rhizoma. Bioinformatics analysis revealed high similarity between the DNA sequences of AsIGS and isoeugenol synthase genes from other plants, and that the association of the candidate protein AsIGS with the PIP reductase family. Moreover, the AsIGS protein displayed a molecular weight of about 34.96 kDa, with a theoretical isoelectric point of 6.01 and an average hydrophobicity of -0.092, indicating the protein's partial acidity, stability, and hydrophilic nature. Phylogenetic analysis showed that AsIGS had a close relationship with isoeugenol synthases and fewer eugenol synthases found in other species. Alphafold2 predicted the structure of the AsIGS protein, and CB-Dock2 predicted the binding sites of the ASIGS-NADPH-coniferyl acetate ternary complex. In vitro enzymatic assay results demonstrated that the optimal temperature of the AsIGS-involved catalysis for coniferyl acetate was 30 °C, and several kinetics parameters were Km (12.21 mM), Vmax (27.9 U/mg), kcat (76.26 s-1), and kcat/Km (6.49 s-1·mM-1). Furthermore, it was also determined that the AsIGS protein had varying performance at different pH levels. While the candidate protein converted coniferyl acetate into both isoeugenol and eugenol at pH 5.5, it just catalyzed the production of isoeugenol at pH 6.5. However, isoeugenol has never been detected in A. sieboldii. Altering AsIGS expression in transgenic plants impacted only eugenol contents. Compared with wild type, overexpression of AsIGS increased eugenol content by 23.3 %, while RNAi-induced down-regulation of AsIGS decreased it by 25.3 %. Taken together, these results confirmed that the AsIGS gene was involved in the biosynthesis of eugenol in A. sieboldii with a dual catalytic potential.

Similar Survival But Less Chronic GVHD in Antithymocyte Globulin-Based Myeloablative Haploidentical Transplant Compared With Matched Sibling Transplant for Adult T-cell Acute Lymphoblastic Leukemia/Lymphoma.

The annual number of human leukocyte antigen (HLA)-haploidentical allogeneic hematopoietic stem cell transplantation (haplo-HCT) is increasing steadily. Comparative studies about haplo-HCT versus HCT with HLA-matched sibling donors (MSD-HCT) have been tried in acute myeloid leukemia and B-cell acute lymphoblastic leukemia/lymphoma (ALL). Few studies were reported in adult T-cell ALL (T-ALL). In this retrospective study, a total of 88 consecutive patients with T-ALL were enrolled who underwent MSD-HCT (n = 24) and haplo-HCT (n = 64) with antithymocyte globulin (ATG)-based graft versus host disease (GVHD) prophylaxis between 2010 and 2022. Median follow-up for survivors was similar (43.5 [range: 7-88] months for MSD-HCT versus 43.5 (range: 6-144) months in the Haplo-HCT group). The 100-day cumulative incidence of grade II to IV acute GVHD (aGVHD) was similar, 33% (95% confidence interval [CI], 16%-52%) after MSD-HCT versus 44% (95% CI, 31%-55%) after haplo-HCT, P = 0.52. The cumulative incidences of grade III-IV aGVHD were 8% (95% CI, 1%-23%) in the MSD-HCT group and 5% (95% CI, 1%-12%) in the haplo-HCT group (P = 0.50). The 2-year cumulative incidence of chronic GVHD (limited and extensive) in the haplo-HCT, 11% (95% CI, 5%-20%) was significantly lower than that in the MSD-HCT group (42% [95% CI, 21%-62%], P = 0.002). The cumulative incidence of 4-year relapse rates (44% versus 37%, P = 0.56) and non-relapse mortality (7% versus 21%, P = 0.08) did not differ between these two groups. There were also no differences in 4-year overall survival (46% versus 47%, P = 0.44) and progression-free survival (49% versus 42%, P = 0.45) between these two groups. On multivariate analysis, using busulfan/fludarabine (BU/Flu) conditioning regimen was found to be associated with worse clinical outcome. Our results suggested that ATG-based haplo-HCT platform could work as an alternative to MSD-HCT for adult patients with T-ALL. Compared with MSD-HCT, haplo-HCT might carry a low risk for cGVHD.

Acid/base responsive pseudo[3]rotaxanes from amine naphthotubes and bis-pyridinium/isoquinolinium guests.

A novel cooperative pseudo[3]rotaxane system was successfully constructed by the inclusion complexation of two identical amine naphthotubes with a bis-pyridinium/isoquinolinium guest. Single crystal structure analysis revealed that weak Csp3-H⋯O hydrogen bonds between the two hosts are responsible for the positive cooperativity during the formation of pseudo[3]rotaxanes. Moreover, intermolecular charge-transfer interactions between the electron-rich host and the electron-poor guests were observed. The pseudo[3]rotaxanes showed pH-controllable association/dissociation processes with naked-eye color changes in solution.

Accelerating acidic CO2 electroreduction: strategies beyond catalysts.

Carbon dioxide electrochemical reduction (CO2RR) into high-value-added chemicals offers an alternative pathway toward achieving carbon neutrality. However, in conventional neutral or alkaline electrolyte systems, a significant portion of CO2 is converted into (bi)carbonate due to the thermodynamically favorable acid-base neutralization reaction between CO2 and hydroxide ions. This results in the single-pass carbon efficiency (SPCE) being theoretically capped at 50%, presenting challenges for practical applications. Acidic CO2RR can completely circumvent the carbonate issue and theoretically achieve 100% SPCE, garnering substantial attention from researchers in recent years. Nevertheless, acidic CO2RR currently lags behind traditional neutral/alkaline systems in terms of product selectivity, stability, and energy efficiency, primarily because the abundance of H+ ions exacerbates the hydrogen evolution reaction (HER). Encouragingly, significant breakthroughs have been made to address these challenges, with numerous studies indicating that the regulation of the local catalytic environment may be more crucial than the catalyst itself. In this review, we will discuss the main challenges and latest strategies for acidic CO2RR, focusing on three key aspects beyond the catalyst: electrolyte regulation, local catalytic environment modification, and novel designs of gas diffusion electrodes (GDEs)/electrolyzers. We will also conclude the current advancement for acidic CO2RR and provide an outlook, with the hope that this technology will contribute to achieving carbon neutrality and advance towards practical application.

Amide naphthotube as a novel supramolecular sequestration agent for tetracaine and decamethonium.

RATIONALE: Anesthetics are widely used for optimizing surgical conditions, postoperative pain management, and treating various chronic pain conditions. Tetracaine and decamethonium are representative drugs of local anesthetics and neuromuscular blocking agents, respectively. However, overdose and toxicity of the drugs always lead to serious adverse events. Thus, there is a strong demand for effective antidotes. METHODS: The binding interactions of amide naphthotubes with tetracaine and decamethonium were systematically studied using 1H NMR, ITC, and DFT calculations. The antidotal effects of amide naphthotube to tetracaine toxicity were assessed in vitro and in vivo, and the mechanism of detoxification was explored at a cellular level. Additionally, mouse models were established to evaluate the reversal activities of amide naphthotube on decamethonium-induced mortality and muscle relaxation, and the reversal mechanism was investigated through pharmacokinetic experiments. RESULTS: We have demonstrated that the anti-isomer of amide naphthotube exhibits significant binding affinities towards tetracaine (K a = 1.89×107 M-1) and decamethonium (K a = 1.01×107 M-1) in water. The host displayed good biocompatibility both in vitro and in vivo. The administration of amide naphthotube following tetracaine overdose in mouse models notably increased the overall survival rate, indicating its effective antidotal properties. The host could reverse the tetracaine-induced Na+ channels blockage at the cellular level. Moreover, the injection of amide naphthotube also reversed the mortality and paralysis induced by decamethonium in mouse models following a pharmacokinetic mechanism. CONCLUSION: An emerging artificial receptor, amide naphthotube, has strong binding affinities towards tetracaine and decamethonium. It functions as a supramolecular antidote for tetracaine poisoning and a reversal agent for decamethonium by selectively sequestering these compounds in vivo.

Voices of Parent-Carers Navigating the Care for Children With Osteogenesis Imperfecta.

Parent-carers of children with rare diseases, including osteogenesis imperfecta (OI), represent a vulnerable and largely invisible population. Despite existing research on familial OI caregiving, the unique experiences, perspectives, and feelings of parent-carers remain poorly understood, prompting this study to delve into these aspects through the subjective lens of voices. The aim of this study was to explore the voices of parent-carers in navigating the complexities of pediatric OI care. Employing a narrative design informed by social constructionism, 15 parent-carers of pediatric OI patients were purposively sampled from a tertiary hospital in Shandong Province, China, between May and August 2021. Individual face-to-face interviews were conducted, and data were analyzed using the voice-centered relational approach followed by thematic analysis. Parent-carers' narratives revealed two overarching themes. The first theme, "the all-encompassing caregiver role," highlighted the profound internal transformation parent-carers underwent, with three key aspects of experiences: "the centrality of care," "life on hold," and "guarded silence." The second theme, "navigating ambivalence," captured the complex psycho-emotional journey of parent-carers as they balanced denial and acceptance, experienced the burden and responsibility of caregiving, navigated uncertainty with hope, and sought to normalize the care recipients' experiences while acknowledging their unique needs. Our findings suggest the need for developing tailored support strategies that address not only practical challenges but also the psychosocial dimensions of caregiving, to effectively assist and empower this marginalized carer population.

Construction of Optimal Regeneration System for Chrysanthemum '11-C-2' Stem Segment with Buds.

Chrysanthemum morifolium '11-C-2' is a variety of chrysanthemums with high ornamental and tea value, experiencing significant market demand. However, as cultivation areas expand, issues such as viral infection, germplasm degradation, low proliferation coefficient, and slow proliferation rate arise, necessitating the establishment of an efficient in vitro regeneration system. This study, based on the principles of orthogonal experimental design, explored the regeneration system of Chrysanthemum cultivar '11-C-2' using sterile seedlings. The research focused on three key stages: adventitious bud differentiation, rooting culture, and acclimatization-transplantation, employing shoot-bearing stem segments and leaves as explants. The findings indicate that the optimal explant for the Chrysanthemum '11-C-2' sterile seedlings is the shoot-bearing stem segment. The best medium for adventitious bud differentiation was determined to be MS supplemented with 1.5 mg/L 6-BA and 0.5 mg/L NAA. Bud differentiation began on day 17 with a 100% differentiation rate, completing around day 48. The maximum differentiation coefficient reached 87, with an average of 26.67. The adventitious buds were then cultured for rooting in the optimal medium of 1/2 MS supplemented with 0.1 mg/L NAA. Rooting was initiated on day 4 and was completed by day 14, achieving a rooting rate of 97.62%. After a 5-day acclimatization under natural light, the rooted seedlings were transplanted into a growth substrate with a peat-to-vermiculite ratio of 1:2. The plants exhibited optimal growth, with a transplantation survival rate of 100%. The findings provide data support for the efficient large-scale propagation of '11-C-2' and lay the foundation for germplasm preservation and genetic transformation research of tea chrysanthemums.

Tumor-Derived Immunoglobulin-Like Transcript 4 Promotes Postoperative Relapse via Inducing Vasculogenic Mimicry through MAPK/ERK Signaling in Hepatocellular Carcinoma.

Conventional anti-angiogenesis drugs are usually unsatisfactory in hepatocellular carcinoma (HCC) treatment. Therefore, it is urgent to find new precise therapeutic targets and to further develop more effective drugs for the treatment of HCC. Vasculogenic mimicry (VM) is different from classic endothelium-dependent angiogenesis and is associated with a poor prognosis in patients with malignant tumor. However, the mechanism underlying VM is complex and not fully defined. Ig-like transcript (ILT)-4, as a negative regulator of immune response, was recently found to be expressed in many solid tumors. However, whether and how ILT4 regulates VM remains unclear. This study found VM enriched in HCC tissues, especially in tissues from patients with relapse within 5 years after surgery. Similarly, ILT4 expression level was also higher in HCC tissues from patients with relapse within 5 years after surgery. Linear regression analysis revealed a positive correlation between the expression of ILT4 and VM density. Furthermore, Overexpression/knockdown of ILT4 expression upregulated/down-regulated VM-related marker, three-dimensional tube formation, and migration and invasion in HCC cell lines in vitro. In mechanistic studies, ILT4 promoted VM formation via MAPK/ERK signaling. This study provides a rationale and mechanism for ILT4-mediated postoperative relapse via inducing VM in HCC. The related molecular pathways can be used as novel therapeutic targets for the inhibition of HCC angiogenesis and postoperative relapse.

Toward Integrated Multifunctional Laser-Induced Graphene-Based Skin-Like Flexible Sensor Systems.

The burgeoning demands for health care and human-machine interfaces call for the next generation of multifunctional integrated sensor systems with facile fabrication processes and reliable performances. Laser-induced graphene (LIG) with highly tunable physical and chemical characteristics plays vital roles in developing versatile skin-like flexible or stretchable sensor systems. This Progress Report presents an in-depth overview of the latest advances in LIG-based techniques in the applications of flexible sensors. First, the merits of the LIG technique are highlighted especially as the building blocks for flexible sensors, followed by the description of various fabrication methods of LIG and its variants. Then, the focus is moved to diverse LIG-based flexible sensors, including physical sensors, chemical sensors, and electrophysiological sensors. Mechanisms and advantages of LIG in these scenarios are described in detail. Furthermore, various representative paradigms of integrated LIG-based sensor systems are presented to show the capabilities of LIG technique for multipurpose applications. The signal cross-talk issues are discussed with possible strategies. The LIG technology with versatile functionalities coupled with other fabrication strategies will enable high-performance integrated sensor systems for next-generation skin electronics.

Vanadium (V) reduction and the performance of electroactive biofilms in microbial fuel cells with Shewanella putrefaciens.

The electron transfer ability of biofilms significantly influences the electrochemical activity of microbial fuel cells (MFCs). However, there is limited understanding of pentavalent vanadium (V(V)) bioreduction and microbial response characteristics in MFCs. In this study, the effect of gradient concentrations of V(V) on the performance of EABs with Shewanella putrefaciens in MFCs was investigated. The results showed that as V(V) concentration increased (0-100 mg/L), the voltage output, power densities, polarization, and electrode potential decreased. V(V) was found to act as an electron acceptor and was reduced during MFCs operation, with a yield of 83.16% being observed at 25 mg/L V(V). Cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS) indicated declining electrochemical performance of the MFCs with escalating V(V) concentration. The content of protein and polysaccharide from extracellular polymeric substances (EPS) in anodic biofilms increased to 66.75 and 49.15 mg/L at 75 mg/L V(V), respectively. Three-dimensional fluorescence spectroscopy confirmed increased humic substances in EPS extraction with V(V) exposure. The functional genes narG, nirK, and gor involved in V(V) reduction were upregulated with rising V(V) concentration through quantitative polymerase chain reaction (qPCR) analysis. Additionally, riboflavin, cytochrome c, nicotinamide adenine dinucleotide (NADH), and electron transport system activity (ETSA), key indicators for assessing electron transfer behavior, exhibited a negative correlation with various V(V) concentrations, decreasing by 31.81%, 57.14%, 67.39%, and 51.41%, respectively, at a concentration of 100 mg/L V(V) compared to the blank control. These findings contribute valuable insights into the response of EABs to V(V) exposure, presenting potential strategies for enhancing their effectiveness in the treatment of vanadium-contaminated wastewater.

EZH2 mutation is associated with the development of visceral metastasis by enhancing proliferation and invasion and inhibiting apoptosis in breast cancer cells.

BACKGROUND: The prognosis of breast cancer patients with visceral metastasis (VM) is significantly worse than that of patients without VM. We aimed to evaluate EZH2 (enhancer of zeste homolog 2) mutation as a biomarker associated with VM. METHODS: Data from forty-nine patients with metastatic breast cancer (MBC) pathologically confirmed at our hospital between March 2016 and September 2018 were collected. Metastatic tissue samples were obtained via ultrasound-guided needle biopsy, and paired peripheral blood samples were also collected. Tissue and blood samples were subjected to targeted next-generation sequencing via a 247-gene panel. Stably transfected MDA-MB-231 cells expressing wild-type EZH2 (EZH2WT) or a mutant form of EZH2 (EZH2K515R) were generated. Cell proliferation, colony formation ability, migration and invasion abilities and apoptosis were assessed using CCK-8 assays, plate colony formation assays, Transwell chamber assays and flow cytometry. RESULTS: The incidence of EZH2 mutations in the VM subgroup was greater than that in the non-VM subgroup in the entire cohort (n = 49, 42.3% vs. 13.0%, p = 0.024) and in the triple-negative breast cancer (TNBC) subgroup (n = 20, 50.0% vs. 10.0%, p = 0.05). Patients carrying EZH2 mutations had a significantly greater risk of developing VM than did those in the non-EZH2 mutation group in the entire cohort (HR 2.9) and in the TNBC subgroup (HR 6.45). Multivariate analysis revealed that EZH2 mutation was an independent prognostic factor for VM (HR 2.99, p = 0.009) in the entire cohort and in the TNBC subgroup (HR 10.1, p = 0.006). Data from cBioPortal also showed that patients with EZH2 mutations had a significantly greater risk of developing VM (HR 3.1), and the time to develop VM was significantly earlier in the EZH2 mutation group (31.5 months vs. 109.7 months, p = 0.008). Multivariate analysis revealed that EZH2 mutation (HR 2.73, p = 0.026) was an independent factor for VM after breast cancer surgery. There was no correlation between EZH2 mutations and BRCA1/2 mutations. Most of the patients (81.8%) in our cohort who developed VM carried the "c.1544A > G (p.K515R)" mutation. Compared with EZH2WT MDA-MB-231 cells, EZH2K515R MDA-MB-231 cells had greater colony formation rates (p < 0.01), greater migration and invasion rates (p < 0.001), and lower apoptosis rates (p < 0.01). The proportion of S + G2/M phase cells in the EZH2K515R group was significantly greater than that in the EZH2WT group. CONCLUSIONS: EZH2 mutation is associated with VM development in breast cancer patients. The EZH2K515R mutation leads to VM and a poor prognosis by enhancing proliferation and invasion and inhibiting apoptosis in breast cancer cells.

Clinical features and risk factors for recurrence of idiopathic pulmonary hemosiderosis in children.

BACKGROUND: This study aims to review the clinical characteristics, therapeutic response and outcome of idiopathic pulmonary hemosiderosis (IPH), and discover the risk factors for recurrence in children with IPH, which will be helpful for the early diagnosis and reasonable treatment of this disease. METHODS: Children with a diagnosis of IPH were enrolled in the study. Clinical data of the children were collected and analysed. RESULTS: A total of 32 patients with regular follow-up after diagnosis were included in this study. Anaemia, cough and haemoptysis constituted the most common initial symptoms of the disease, and the incidences were 90.6%, 75% and 56.2%, respectively. The mean gap between the onset of symptoms and diagnosis was 5 (0.25-36) months. Most of the children experienced remission (complete and partial remission) over the course of 6 months of treatment, but 19 of the children experienced relapse. The causes of disease recurrence included respiratory tract infection (37.5%), corticosteroid (CS) reduction (18.8%), and irregular medication (6.3%). Interestingly, we found that children with history of allergy (HR 4.255, 1.107-16.356) tended to experience disease recurrence (p = 0.01). CONCLUSIONS: Cough and anaemia are the most common symptoms in children with IPH. The recurrence rate of this disease is high, and respiratory tract infection is the most common cause of its recurrence. High-dose CS impluse therapy cannot reduce the recurrence rate of the disease. Allergic history was an import factor associated with disease recurrence. TRIAL REGISTRATION: This study is a retrospective and observational study, which does not involve human specimens or clinical intervention. Therefore, clinical trial registration is not required, and there is no clinical trial number. However, the study was approved by the Institutional Review Board/Ethics Committee affiliated with West China Second University Hospital, Sichuan University (Ethics review number 2022074).

Antagonism of rhizosphere Trichoderma brevicompactum DTN19 against the pathogenic fungi causing corm rot in saffron (Crocus sativus L.) in vitro.

Introduction: Corm rot in saffron (Crocus sativus L.) significantly impacts yield and quality. Non-toxic fungi, particularly Trichoderma species, are valuable for biological control due to their production of diverse and biologically active secondary metabolites. Methods: This study aimed to isolate an effective antagonistic fungus against the pathogenic fungi causing corm rot in saffron. Four pathogenic fungi (Fusarium oxysporum, Fusarium solani, Penicillium citreosulfuratum, and Penicillium citrinum) were isolated from diseased saffron bulbs in Chongming. Initial screening through dual culture with these pathogens re-screening from rhizosphere soil samples of C. sativus based on its inhibitory effects through volatile, nonvolatile, and fermentation broth metabolites. The inhibitory effect of biocontrol fungi on pathogenic fungi in vitro was evaluated by morphological observation and molecular biology methods. Results: Antagonistic fungi were identified as Trichoderma brevicompactum DTN19. F. oxysporum was identified as the most severe pathogen. SEM (scanning electron microscope) and TEM (transmission electron microscope) observations revealed that T. brevicompactum DTN19 significantly inhibited the growth and development of F. oxysporum mycelium, disrupting its physiological structure and spore formation. Additionally, T. brevicompactum DTN19 demonstrated nitrogen fixation and production of cellulase, IAA (Indole acetic acid), and siderophores. Whole-genome sequencing of strain DTN19 revealed genes encoding protease, cellulase, chitinase, ß-glucosidase, siderophore, nitrogen cycle, and sulfate transporter-related proteins. Discussion: T. brevicompactum DTN19 may inhibit the propagation of pathogenic fungi by destroying their cell walls or producing antibiotics. It can also produce IAA and iron carriers, which have the potential to promote plant growth. Overall, T. brevicompactum DTN19 showed the development prospect of biological agents.

Ratiometric fluorescence sensing and discrimination of tetracycline analogs by using coumarin-embedded Eu-MOF nanosensor.

As widely used antibiotics, tetracycline residues exist in food and environmental media, which pose certain hidden dangers and negative effects on public health. Therefore, the sensing and discrimination of tetracycline analogs (TCs) have great significance for improving food safety and preventing environmental pollution. Herein, a 7-hydroxycoumarin-3-carboxylic acid-embedded Eu-MOF (HC@Eu-MOF) material was constructed and then developed for the detection of TCs. Upon addition of TCs, the synthesized sensor displays opposite fluorescence changes at two different wavelengths due to the simultaneous presence of the inner filter effect (IFE) and the antenna effect (AE), and achieves a stable ratio signal response within 90 s. In addition, six important tetracycline analogs, including chlortetracycline (CTC), oxytetracycline (OTC), tetracycline (TC), metacycline (MC), doxycycline (DC) and demeclocycline (DMC) can be discriminated with 100 % accuracy through the principal component analysis even in extremely complicated mixtures. Further, a smartphone-assisted portable device was applied for visual sensing of TCs. The as-developed platform possessed the characteristics of simple synthesis, fast response, high sensitivity, and high stability, which further lays a further foundation for the on-site visual detection and discrimination of TCs in real samples.