Detection of Urinary Misfolded Proteins for Imminent Prediction of Preeclampsia in Pregnant Women With Suspected Cases: Protocol for a Prospective Noninterventional Study.

BACKGROUND: Preeclampsia (PE) is one of the most common hypertensive diseases, affecting 2%-8% of all pregnancies. The high maternal and fetal mortality rates of PE are due to a lack of early identification of affected pregnant women that would have led to closer monitoring and care. Recent data suggest that misfolded proteins might be a promising biomarker for PE prediction, which can be detected in urine samples of pregnant women according to their congophilia (aggregated) characteristic. OBJECTIVE: The main purpose of this trial is to evaluate the value of the urine congophilia-based detection of misfolded proteins for the imminent prediction of PE in women presenting with suspected PE. The secondary objectives are to demonstrate that the presence of urine misfolded proteins correlates with PE-related maternal or neonatal adverse outcomes, and to establish an accurate PE prediction model by combining misfolded proteins with multiple indicators. METHODS: At least 300 pregnant women with clinical suspicion of PE will be enrolled in this prospective cohort study. Participants should meet the following inclusion criteria in addition to a suspicion of PE: ≥18 years old, gestational week between 20+0 and 33+6, and single pregnancy. Consecutive urine samples will be collected, blinded, and tested for misfolded proteins and other PE-related biomarkers at enrollment and at 4 follow-up visits. Clinical assessments of PE status and related complications for all participants will be performed at regular intervals using strict diagnostic criteria. Investigators and participants will remain blinded to the results. Follow-up will be performed until 42 days postpartum. Data from medical records, including maternal and fetal outcomes, will be collected. The performance of urine misfolded proteins alone and combined with other biomarkers or clinical variables for the prediction of PE will be statistically analyzed. RESULTS: Enrollment started in July 2023 and was still open upon manuscript submission. As of March 2024, a total of 251 eligible women have been enrolled in the study and enrollment is expected to continue until August 2024. Results analysis is scheduled to start after all participants reach the follow-up endpoint and complete clinical data are collected. CONCLUSIONS: Upon completion of the study, we expect to derive an accurate PE prediction model, which will allow for proactive management of pregnant women with clinical suspicion of PE and possibly reduce the associated adverse pregnancy outcomes. The additional prognostic value of misfolded proteins is also expected to be confirmed. TRIAL REGISTRATION: Chinese Clinical Trials Registry ChiCTR2300074878; https://www.chictr.org.cn/showproj.html?proj=202096. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): PRR1-10.2196/54026.

A lasso and random forest model using flow cytometry data identifies primary myelofibrosis.

Thrombocythemia (ET), polycythemia vera (PV), primary myelofibrosis (PMF), prefibrotic/early (pre-PMF), and overt fibrotic PMF (overt PMF) are classical Philadelphia-Negative (Ph-negative) myeloproliferative neoplasms (MPNs). Differentiating between these types based on morphology and molecular markers is challenging. This study aims to clarify the application of flow cytometry in the diagnosis and differential diagnosis of classical MPNs. This study retrospectively analyzed the immunophenotypes, clinical characteristics, and laboratory findings of 211 Ph-negative MPN patients, including ET, PV, pre-PMF, overt PMF, and 47 controls. Compared to ET and PV, PMF differed in white blood cells, hemoglobin, blast cells in the peripheral blood, abnormal karyotype, and WT1 gene expression. PMF also differed from controls in CD34+ cells, granulocyte phenotype, monocyte phenotype, percentage of plasma cells, and dendritic cells. Notably, the PMF group had a significantly lower plasma cell percentage compared with other groups. A lasso and random forest model select five variables (CD34+CD19+cells and CD34+CD38- cells on CD34+cells, CD13dim+CD11b- cells in granulocytes, CD38str+CD19+/-plasma, and CD123+HLA-DR-basophils), which identify PMF with a sensitivity and specificity of 90%. Simultaneously, a classification and regression tree model was constructed using the percentage of CD34+CD38- on CD34+ cells and platelet counts to distinguish between ET and pre-PMF, with accuracies of 94.3% and 83.9%, respectively. Flow immunophenotyping aids in diagnosing PMF and differentiating between ET and PV. It also helps distinguish pre-PMF from ET and guides treatment decisions.

Evidence for chronic headaches induced by pathological changes of myodural bridge complex.

Clinical studies have shown that there may be a certain relationship between pathological changes of the myodural bridge complex (MDBC) and chronic headaches of unknown cause. But there is still a lack of experimental evidence to explain the possible mechanism. This study aims to further confirm this relationship between MDBC and chronic headaches and explore its potential occurrence mechanism in rats. Bleomycin (BLM) or phosphate-buffered saline (PBS) was injected into the myodural bridge fibers of rats to establish the hyperplastic model of MDBC. After 4 weeks, the occurrence of headaches in rats was evaluated through behavioral scores. The immunohistochemistry staining method was applied to observe the expression levels of headache-related neurotransmitters in the brain. Masson trichrome staining results showed that the number of collagen fibers of MDBC was increased in the BLM group compared to those of the other two groups. It revealed hyperplastic changes of MDBC. The behavioral scores of the BLM group were significantly higher than those of the PBS group and the blank control group. Meanwhile, expression levels of CGRP and 5-HT in the headache-related nuclei of the brain were increased in the BLM group. The current study further confirms the view that there is a relationship between pathological changes of MDBC and chronic headaches of unknown cause. This study may provide anatomical and physiological explanations for the pathogenesis of some chronic headaches of unknown cause.

Red mud-based perovskite oxygen carrier preparation for chemical looping gasification of municipal sludge.

Chemical looping gasification (CLG) is a promising technology that utilizes lattice oxygen for partial oxidation of solid organic waste to produce high-quality syngas. The utilization of low-cost and high-performance oxygen carriers (OCs) is important for the success of this technology. The red mud from aluminum production was mixed with calcium and manganese oxides to prepare CaMn0.5Fe0.5O3-δ perovskite OCs. The comparative redox tests were carried out to analyze the reactivity using a thermogravimetric analyzer (TGA). Multiple cycle CLG experiments were conducted on a wet municipal sludge in a lab-scale fluidized bed to produce the hydrogen-rich gas. The results showed that the CaMn0.5Fe0.5O3-δ-washed demonstrated higher oxygen transfer capacity and better cycling stability with a maximum weight loss of 7.3096 %. After the 5th cycle in CLG, the syngas obtained using CaMn0.5Fe0.5O3-δ-washed maintained a H2 volume fraction exceeding 40%. However, an increase in CO2 production was also observed, which could be due to the catalytic effect of MnO in the OC on the steam-reforming reaction. The XRD curves showed that fresh CaMn0.5Fe0.5O3-δ-washed exhibited prominent diffraction peaks characteristic of perovskite. It was observed that after undergoing 5 cycles, the presence of iron calcium silicate structures containing Mn became evident due to the attachment of sludge ash, leading to the increased impurities on the surface of OCs with a decrease in the specific surface area. Additionally, some of the reacted OC particles exhibited a hollow structure, facilitating the fluidization. This preliminary study provides the basis for the improvement of the OC performance in sludge gasification.

The gut microbiota participates in the effect of linaclotide in patients with irritable bowel syndrome with constipation (IBS-C): a multicenter, prospective, pre-post study.

BACKGROUND: Interindividual variation characterizes the relief experienced by constipation-predominant irritable bowel syndrome (IBS-C) patients following linaclotide treatment. Complex bidirectional interactions occur between the gut microbiota and various clinical drugs. To date, no established evidence has elucidated the interactions between the gut microbiota and linaclotide. We aimed to explore the impact of linaclotide on the gut microbiota and identify critical bacterial genera that might participate in linaclotide efficacy. METHODS: IBS-C patients were administered a daily linaclotide dose of 290 µg over six weeks, and their symptoms were then recorded during a four-week posttreatment observational period. Pre- and posttreatment fecal samples were collected for 16S rRNA sequencing to assess alterations in the gut microbiota composition. Additionally, targeted metabolomics analysis was performed for the measurement of short-chain fatty acid (SCFA) concentrations. RESULTS: Approximately 43.3% of patients met the FDA responder endpoint after taking linaclotide for 6 weeks, and 85% of patients reported some relief from abdominal pain and constipation. Linaclotide considerably modified the gut microbiome and SCFA metabolism. Notably, the higher efficacy of linaclotide was associated with enrichment of the Blautia genus, and the abundance of Blautia after linaclotide treatment was higher than that in healthy volunteers. Intriguingly, a positive correlation was found for the Blautia abundance and SCFA concentrations with improvements in clinical symptoms among IBS-C patients. CONCLUSION: The gut microbiota, especially the genus Blautia, may serve as a significant predictive microbe for symptom relief in IBS-C patients receiving linaclotide treatment. TRIAL REGISTRATION: This trial was registered with the Chinese Clinical Trial Registry (Chictr.org.cn, ChiCTR1900027934).

Prognostic significance of the frequencies of bone marrow lymphocyte subsets in adult acute myeloid leukemia at diagnosis.

INTRODUCTION: Immune microenvironment plays an important role in the occurrence and development of acute myeloid leukemia (AML). Studies assessing the prognostic significance of bone marrow (BM) lymphocyte subsets' frequencies at diagnosis in patients with AML were limited. METHODS: Fresh BM samples collected from 97 adult AML patients at diagnosis were tested for lymphocyte, T, CD4+ T, CD8+ T, γδT, NK, and B cell frequencies using multi-parameter flow cytometry. RESULTS: Low frequencies of lymphocytes, T, CD4+ T, and CD8+ T cells were associated with significantly lower rates of one-course complete remission (CR) (all p < 0.05). Moreover, the frequency of CD4+ T cells independently predicted one-course CR achievement (p = 0.021). Low frequencies of T and CD8+ T cells were significantly associated with lower relapse-free survival (RFS) rates (p = 0.032; 0.034), respectively, and a low frequency of CD8+ T cells was associated with a significantly lower overall survival (OS) rate (p = 0.028). Combination of frequency of CD8+ T cells and ELN risk stratification showed that patients with ELN-intermediate/adverse risk + high CD8+ T cell frequency had a similar RFS rate to those with ELN-favorable risk + high CD8+ T cell frequency and those with ELN-favorable risk + low CD8+ T cell frequency (p = 0.88; 0.76), respectively. The RFS rate of patients with ELN intermediate/adverse risk + low CD8+ T cell frequency was significantly lower than that of all aforementioned patients (p = 0.021; 0.0007; 0.028), respectively. CONCLUSION: The frequencies of BM lymphocyte subsets at diagnosis predicted clinical outcomes and could help improve risk stratification in AML.

Role of exosomes in the development, diagnosis, prognosis and treatment of hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is the most common primary liver cancer. It is characterized by occult onset resulting in most patients being diagnosed at advanced stages and with poor prognosis. Exosomes are nanoscale vesicles with a lipid bilayer envelope released by various cells under physiological and pathological conditions, which play an important role in the biological information transfer between cells. There is growing evidence that HCC cell-derived exosomes may contribute to the establishment of a favorable microenvironment that supports cancer cell proliferation, invasion, and metastasis. These exosomes not only provide a versatile platform for diagnosis but also serve as a vehicle for drug delivery. In this paper, we review the role of exosomes involved in the proliferation, migration, and metastasis of HCC and describe their application in HCC diagnosis and treatment. We also discuss the prospects of exosome application in HCC and the research challenges.

The first suspected disseminated Hormographiella aspergillata infection in China, diagnosed using metagenomic next-generation sequencing: a case report and literature review.

Hormographiella aspergillata is a rare and emerging cause of invasive mould infections in patients with haematological malignancies, with a mortality rate of approximately 70%. Here, we present the first reported case of suspected disseminated H. aspergillata infection in China. The patient experienced a second relapse of acute myeloid leukaemia and developed neutropenia, fever, discrepant blood pressure between limbs, and cutaneous lesions limited to the left upper extremity. Since lung tissue biopsy was not feasible, metagenomic next-generation sequencing (mNGS) and panfungal polymerase chain reaction (PCR) analysis of bronchoalveolar lavage fluid and blood samples were performed, which indicated probable H. aspergillata pulmonary infection. Histopathology of cutaneous lesions revealed numerous fungal hyphae within dermal blood vessels. mNGS of a skin biopsy sample identified H. aspergillata sequences, and the fungi was subsequently recovered from fungal culture, proving cutaneous H. aspergillata infection. Despite combined antifungal therapy, the patient died owing to disease progression. Additionally, 22 previously reported cases of invasive H. aspergillata infection were reviewed in patients with haematological malignancies. Thus, mNGS is a powerful diagnostic tool for the early and effective detection of invasive H. aspergillata infections, with the advantage of sequencing all potential pathogens, and providing results within 24 h.

Simplicillium sinense sp. nov., a novel potential pathogen of tinea faciei.

Simplicillium species are widely distributed with a broad spectrum of hosts and substrates. Generally, these species are entomopathogenic or mycoparasitic. Notably, some isolates of Simplicillium lanosoniveum and Simplicillium obclavatum were obtained from human tissues. In this study, two fungi were isolated from the annular itchy patch of infected skin of a 46-year-old man with diabetes mellitus. Based on a combination of morphological characteristics and phylogenetic analysis, a novel species, Simplicillium sinense, was introduced herein. It morphologically differs from the remaining Simplicillium in the size of phialides and conidia. Additionally, it grows slowly on YPD at 37°C. Antimicrobial susceptibility testing presented that this fungus is resistant to most azole antifungals. Therefore, the diagnosis of tinea faciei was made, and after 2 weeks of being treated with oral terbinafine (250 mg, once a day) and topical terbinafine cream for 1 month, the rash was mainly resolved and no recurrence happened after 6 months of follow-up. Herein, Simplicillium sinense was introduced as a new fungal taxon. Meanwhile, a case of superficial infection caused by S. sinense was reported. So far, it is the third Simplicillium species obtained from human tissue. Meanwhile, terbinafine is recommended as the first-line antifungal treatment against Simplicillium infection.

The Influence of the Gut Microbiota on Alzheimer's Disease: A Narrative Review.

Alzheimer's disease (AD) is a common neurodegenerative disease that tends to occur in the elderly. The main symptom is hypomnesia. More and more older people are suffering from this disease worldwide. By 2050, 152 million people worldwide are expected to have AD. It is thought that the aggregation of amyloid-beta peptides and hyper-phosphorylated tau tangles contribute to AD. The microbiota-gut-brain (MGB) axis appears as a new concept. The MGB axis is a collection of microbial molecules produced in the gastrointestinal tract that influence the physiological function of the brain. In this review, we discuss how the gut microbiota (GM) and its metabolites affect AD in different ways. Dysregulation of the GM has been shown to be involved in various mechanisms involved in memory and learning functions. We review the current literature on the role of the entero-brain axis in the pathogenesis of AD and its potential role as a future therapeutic target in the treatment and/or prevention of AD.

Oxidation of tetracycline hydrochloride with a photoenhanced MIL-101(Fe)/g-C3N4/PMS system: Synergetic effects and radical/nonradical pathways.

MIL-101(Fe)-based catalysts have been widely used for degradation of organic pollutants based on peroxymonosulfate (PMS) activation. Hence, a facile calcination and hydrothermal method was used in this study to prepare a MIL-101(Fe)/g-C3N4 composite catalyst with high activity and high stability for PMS activation to degrade tetracycline hydrochloride (TC) under visible-light irradiation. We clearly elucidated the mechanism involved in the MIL-101(Fe)/g-C3N4 photo Fenton-catalyzed PMS activation process by separating the PMS activation and pollutant oxidation processes. The synergetic effects of MIL-101(Fe) and g-C3N4 involved MIL-101(Fe) acting as an electron shuttle mediating electron transfer from the organic substrate to PMS, accompanied by redox cycling of the surface Fe(II)/Fe(III). Multiple experimental results indicated that PMS was bound to the surface of MIL-101(Fe)/g-C3N4 during visible irradiation and generation of sulfate radicals (SO4•-), hydroxyl radicals (•OH) and superoxide anion free radicals (•O2-) for the radical pathway and singlet oxygen (1O2) and holes (h+) for the nonradical pathway. The major degradation pathways for TC can be described as demethylation, deamination, deamidation and carbonylation. This work provides valuable information and advances the fundamental understanding needed for design and syntheses of metal-free conjugated polymers modified by metal-organic frameworks for heterogeneous photo-Fenton reactions.

Mesenchymal Stem Cell-Based Therapy as a New Approach for the Treatment of Systemic Sclerosis.

Systemic sclerosis (SSc) is an intractable autoimmune disease with unmet medical needs. Conventional immunosuppressive therapies have modest efficacy and obvious side effects. Targeted therapies with small molecules and antibodies remain under investigation in small pilot studies. The major breakthrough was the development of autologous haematopoietic stem cell transplantation (AHSCT) to treat refractory SSc with rapidly progressive internal organ involvement. However, AHSCT is contraindicated in patients with advanced visceral involvement. Mesenchymal stem cells (MSCs) which are characterized by immunosuppressive, antifibrotic and proangiogenic capabilities may be a promising alternative option for the treatment of SSc. Multiple preclinical and clinical studies on the use of MSCs to treat SSc are underway. However, there are several unresolved limitations and safety concerns of MSC transplantation, such as immune rejections and risks of tumour formation, respectively. Since the major therapeutic potential of MSCs has been ascribed to their paracrine signalling, the use of MSC-derived extracellular vesicles (EVs)/secretomes/exosomes as a "cell-free" therapy might be an alternative option to circumvent the limitations of MSC-based therapies. In the present review, we overview the current knowledge regarding the therapeutic efficacy of MSCs in SSc, focusing on progresses reported in preclinical and clinical studies using MSCs, as well as challenges and future directions of MSC transplantation as a treatment option for patients with SSc.

Cobalt and nitrogen co-doped monolithic carbon foam for ultrafast degradation of emerging organic pollutants via peroxymonosulfate activation.

Cobalt-based catalysts are expected as one of the most promising peroxymonosulfate (PMS) activators for the removal of organic pollutants from industrial wastewater. However, the easy agglomeration, difficult separation, and secondary pollution of cobalt ions limit their practical application. In this study, a novel, highly efficient, reusable cobalt and nitrogen co-doped monolithic carbon foam (Co-N-CMF) was utilized to activate PMS for ultrafast pollutant degradation. Co-N-CMF (0.2 g/L) showed ultrafast catalytic kinetics and higher total organic carbon (TOC) removal efficiency. Bisphenol A, ciprofloxacin, 2,4-dichlorophenoxyacetic acid, and 2,4-dichlorophenol could be completely degraded after 2, 4, 5, and 5 min, and the TOC removal efficiencies were 77.4 %, 68.9 %, 72.8 %, and 79.8 %, respectively, corresponding to the above pollution. The sulfate radical (SO4•-) was the main reactive oxygen species in Co-N-CMF/PMS based on electron paramagnetic resonance. The ecological structure-activity relationship program analysis via the quantitative structure activity relationship analysis and phytotoxicity assessment revealed that the Co-N-CMF/PMS system demonstrates good ecological safety and ecological compatibility. The Co-N-CMF catalyst has good catalytic activity and facile recycling, which provides a fine method with excellent PMS activation capacity for 2,4-dichlorophenol elimination from simulated industrial wastewater. This study provides new insights into the development of monolithic catalysts for ultrafast wastewater treatment via PMS activation.

Aberrant Expression of SIRT6 and VNN1 in Peripheral Blood Monocytes of Children with Primary Nephrotic Syndrome and Its Diagnostic and Prognostic Values.

Objective: The objective is to explore the aberrant sirtuin-6 (SIRT6) and Vanin-1 (VNN1) protein expression in peripheral blood monocytes (PBM) of children with primary nephrotic syndrome (PNS) and its diagnostic and prognostic values. Methods: 83 child patients with nephrotic syndrome (NS) and 65 healthy volunteers were enrolled in the study. The test of SIRT6 and VNN1 was performed by the Western blot. The receiver operator characteristic (ROC) curve was used to analyze the diagnostic and prognostic value of SIRT6 and VNN1 for child patients with NS. The logistic regression was used to analyze the association of SIRT6 and VNN1 with the prognosis of NS child patients. Results: SIRT6 in monocytes in the study group was inferior versus the control, while VNN1 outweighed it. The AUC of the combined detection of SIRT6 and VNN1 for the diagnosis of NS was 0.854, with a sensitivity of 80.0% and a specificity of 80.7%. The AUC of combined detection of SIRT6 and VNN1 for the prognosis of NS was 0.860, with a sensitivity of 84.6% and a specificity of 79.2%. The logistic regression analysis showed that less than 21.09 in SIRT6 was the number of risk factors for the prognosis of NS child patients (P < 0.05). Conclusion: SIRT6 and VNN1 are provided with diagnostic and prognostic values for NS.

Corresponding risk factors between cognitive impairment and type 1 diabetes mellitus: A narrative review.

Type 1 diabetes mellitus (T1DM) is a type of diabetes caused by the destruction of pancreatic ß cells and the absolute lack of insulin secretion. T1DM usually starts in adolescence or develops directly as a severe disease state of ketoacidosis. T1DM and its complications make many people suffer and have psychological problems, which make us have to pay more attention to the prevention and early control of T1DM. Cognitive impairment (CI) is one of the major complications of T1DM. It can further develop into Alzheimer's disease, which can seriously affect the quality of life of the elderly. Furthermore, the relationship between T1DM and CI is unclear. Hence, we conducted a narrative review of the existing literature through a PubMed search. We summarized some risk factors that may be associated with the cognitive changes in T1DM patients, including onset age and duration, education and gender, glycemic states, microvascular complications, glycemic control, neuropsychology and emotion, intestinal flora, dyslipidemia, sleep quality. We aimed to provide some content related to CI in T1DM, and hoped that it could play a role in early prediction and treatment to reduce the prevalence.

Bone morphogenetic protein-9 maybe an important factor which improves insulin resistance in PCOS.

BACKGROUND: Polycystic ovary syndrome (PCOS) is closely related to insulin resistance (IR). Bone morphogenetic protein-9 (BMP-9) plays an important role in maintaining glucose homeostasis, but an association between BMP-9 and PCOS has not been reported. Here, we report the changes in BMP-9 and the influence of this protein on IR in PCOS. METHODS: 57 PCOS patients were selected (among them 25 received interventional treatment with exenatide (EX) for 3 months, and 32 received no treatment). 22 normal control individuals and 30 IR patients were also recruited. We evaluated IR with the euglycaemic-hyperinsulinaemic clamp (EHC) technique. IR and the glucose metabolism rate were assessed by EHC and [3-3H]glucose tracer experiments. We determined the protein expression levels of BMP-9, p-AKT (protein kinase B) and androgen receptor in the ovaries and liver by Western blotting. RESULTS: We found that circulating BMP-9 levels were significantly decreased in PCOS with IR patients. Circulating BMP-9 levels and p-AKT levels were decreased in HFD and PCOS rats and increased after MF and EX treatment. The glucose infusion rate, glucose disappearance rate and suppression of hepatic glucose production decreased in the HFD and PCOS groups, the opposite results were found for HGP. AR protein expression levels increased in the HFD and PCOS groups and decreased in the MF and EX groups. CONCLUSIONS: Our study results suggest that BMP-9 is an independent factor that influences IR in PCOS patients. The decrease in BMP-9 levels in the liver and ovaries may be involved in IR through the PI3K/AKT signaling pathway in PCOS rats.

Immunophenotypic characteristics of ZNF384 rearrangement compared with BCR-ABL1, KMT2A rearrangement, and other adult B-cell precursor acute lymphoblastic leukemia.

BACKGROUND: ZNF384 rearrangement has been recently identified as a new subtype of B-cell precursor acute lymphoblastic leukemia (BCP-ALL). However, comprehensive studies clarifying immunophenotypic features and discriminating them from non-ZNF384 in adult BCP-ALL remain scarce to date. METHODS: Flow cytometric assessments were retrospectively performed in 43 patients with ZNF384 rearrangement, 45 with BCR-ABL1, 29 with KMT2A rearrangement and 44 with other BCP-ALL in the analysis cohort. RESULTS: CD33- and CD13-positive frequencies were significantly higher in patients with ZNF384 rearrangement than in those with non-ZNF384; however, no significant difference was observed in CD10- and CD123-positive frequencies. Analysis of antigen-positive cell proportion and median fluorescence intensity (MFI) further indicated that patients with ZNF384 rearrangement had significantly lower CD10 and higher CD33, CD13, and CD123 proportion and MFI. However, compared with KMT2A rearrangement, the CD10 expression in patients with ZNF384 rearrangement was higher, with the median percentage and MFI of 36.16 (3.63-94.79)% versus 4.53 (0.03-21.00)%, and 4.50 (0.86-32.26) versus 2.06 (0.87-4.04), respectively (p < 0.0001). Furthermore, compared with BCR-ABL1 and other BCP-ALL, ZNF384 rearrangement had significantly higher CD33 and CD13 proportion and MFI (p < 0.0001 and p < 0.05, respectively). In addition, higher CD123 proportion and MFI in ZNF384 rearrangement than those in the other three groups were reported for the first time (p < 0.01). A flow cytometry scoring system, including CD10%, CD33MFI, CD13%, and CD123MFI, was proposed and verified to predict ZNF384 rearrangement with high sensitivity and specificity, that is, 76.74% and 91.53% in the analysis and 87.50% and 91.30% in the validation cohort. CONCLUSIONS: The multiparameter immunophenotypic scoring system could suggest ZNF384 rearrangement.

qRT-PCR-based DNA homologous recombination-associated 4-gene score predicts pathologic complete response to platinum-based neoadjuvant chemotherapy in triple-negative breast cancer.

PURPOSE: Cumulative evidence suggests that the addition of platinum agents as neoadjuvant chemotherapy (NACT) could improve the pathologic complete response (pCR) rate in triple-negative breast cancer (TNBC). We aimed to develop a DNA homologous recombination (HR)-associated gene expression score to predict tumor sensitivity to platinum-based NACT in TNBC. METHODS: A retrospective cohort of 127 patients who were diagnosed with TNBC and received platinum-based NACT in Fudan University Shanghai Cancer Center from 2012 to 2017 was included in this study. Using quantitative reverse transcription-polymerase chain reaction (qRT-PCR), the expression levels of eight HR-associated genes were analyzed from formalin-fixed paraffin-embedded core-needle biopsy samples obtained before NACT. A random forest model was built to estimate the weight of each gene expression level and clinicopathological factors. The training set was used to modulate parameters and select the best model. The performance of the final model was evaluated in the validation set. RESULTS: A 4-gene (BRCA1, XRCC5, PARP1, and RAD51) scoring system was developed. TNBC patients with a higher score had a nearly fourfold likelihood of achieving pCR to platinum-based NACT compared with patients with a lower score [odds ratio (OR) = 3.878; P < 0.001]. At the cutoff value of - 2.644, the 4-gene scoring system showed high sensitivity in predicting pCR in the breast (93.0%) and pCR in the breast/axilla (91.8%), while at the cutoff value of - 1.969, the 4-gene score showed high specificity for pCR in the breast (85.7%) and pCR in the breast/axilla (80.8%). CONCLUSION: The qRT-PCR-based 4-gene score has the potential to predict pCR to platinum-based NACT in TNBC.

Application of CoMn/CoFe layered double hydroxide based on metal-organic frameworks template to activate peroxymonosulfate for 2,4-dichlorophenol degradation.

Metal-organic frameworks (MOFs) have unique properties and stable structures, which have been widely used as templates/precursors to prepare well developed pore structure and high specific surface area materials. In this article, an innovative and facile method of crystal reorganization was designed by using MOFs as sacrificial templates to prepare a layered double hydroxide (LDH) nano-layer sheet structure through a pseudomorphic conversion process under alkaline conditions. The obtained CoMn-LDH and CoFe-LDH catalysts broke the ligand of MOFs and reorganized the structure on the basis of retaining a high specific surface area and a large number of pores, which had higher specific surface area and well developed pore structure compared with LDH catalysts prepared by traditional methods, and thus provide more active sites to activate peroxymonosulfate (PMS). Due to the unique framework structure of MOFs, the MOF-derived CoMn-LDH and CoFe-LDH catalysts could provide more active sites to activate PMS, and achieve a 2,4-dichlorophenol degradation of 99.3% and 99.2% within 20 minutes, respectively. In addition the two LDH catalysts displayed excellent degradation performance for bisphenol A, ciprofloxacin and 2,4-dichlorophenoxyacetic acid (2,4-D). X-ray photoelectron spectroscopy indicated that the valence state transformation of metal elements participated in PMS activation. Electron paramagnetic resonance manifested that sulfate radical (SO4•-) and singlet oxygen (1O2) were the main species for degrading pollutants. In addition, after the three-cycle experiment, the CoMn-LDH and CoFe-LDH catalysts also showed long-term stability with a slight activity decrease in the third cycle. The phytotoxicity assessment determined by the germination of mung beans proved that PMS activation by MOF-derived LDH catalysts can basically eliminate the phytotoxicity of a 2,4-D solution. This research not only developed high-activity LDH catalysts for PMS activation, but also expanded the environmental applications of MOF derivants.

Dual-readout performance of Eu3+-doped nanoceria as a phosphatase mimic for degradation and detection of organophosphate.

Eu3+-Doped nanoceria (Eu:CeO2) with self-integrated catalytic and luminescence sensing functions was synthesized by a simple and gentle one-pot method to build a dual-readout nanozyme platform for organophosphate compound (OPC) sensing in this work. The catalytic degradation of the model substrate of OPC, p-nitrophenyl phosphate (p-NPP), by as-prepared Eu:CeO2 can be completed in 2 min with little influence of temperature and pH values, highlighting the advantages of Eu:CeO2 as an artificial enzyme for dephosphorylation. Most importantly, the characteristic red emission of Eu3+ (592 nm) from Eu:CeO2 can be quenched by p-NPP, accompanied by a color change from colorless to yellow. Based on this, linear ranges of 4-50 µM with a detection limit of 3.3 µM and 1-20 µM with a detection limit of 0.6 µM for p-NPP were obtained by colorimetric and fluorescence methods, respectively. Furthermore, the fluorescence strategy was effectively applied to the determination of ethyl para-nitrophenyl (EPN), one of the most commonly used pesticides, with a detection limit of 5.86 µM. The proposed strategy was also successfully applied to the assay of p-NPP and EPN in real water samples, showing great application prospects in detecting OPC in the environment.