Clinical characteristics of acute myeloid leukaemia patients with a large number of azurophilic granules: A single-centre retrospective study.

Large amounts of azurophilic granules are considered to be a morphological feature of acute promyelocytic leukaemia (APL). However, a small percentage of acute myeloid leukaemia (AML) patients also have a large number of azurophilic granules. A large cohort of 3210 AML patients in our hospital was screened to identify AML patients who had a large number of azurophilic granules. The clinical parameters of these patients were collected and compared with typical AML patients (control Group 1) and APL patients (control Group 2). The incidence of AML with a large number of azurophilic granules was 1.26%. The fibrinogen and D-dimer levels of patients in the study group were more similar to those of patients in control Group 2, as was the incidence of bleeding events. Additionally, patients in the study group had higher FLT3-ITD and NPM1 mutation rates than patients in control Group 1. Finally, patients in the study group had a higher 30-day mortality rate than those in control Group 2 (24.2% vs. 9.09%) and showed a higher 30-day mortality trend than those in control Group 1. Therefore, we should pay more attention to the prevention of coagulation dysfunction and bleeding events for these patients.

Plant Essential Oils: Dual Action of Toxicity and Egg-Laying Inhibition on Tetranychus urticae (Acari: Tetranychidae), Unveiling Their Potential as Botanical Pesticides.

Tetranychus urticae, a prominent pest mite in strawberry and vegetable cultivation in China, has developed escalating resistance due to extensive chemical pesticide application. Consequently, there is an urgent need to identify safe and efficacious methods to reduce resistance development. In this study, 38 commercially available plant essential oils (EOs) were screened for their acaricidal potential and ability to inhibit oviposition. The findings revealed that 13 EOs exhibited notable acaricidal activity, with lemon EO demonstrating the highest toxicity, followed by sage, patchouli, frankincense, lemongrass, palmarosa, and oregano EOs. In addition, 18 EOs displayed significant inhibitory effects on oviposition, with lemon EO exhibiting the highest inhibition rate (99.15%) and inhibition index (0.98). Subsequently, sage, frankincense, clove, lemongrass, oregano, patchouli, myrrh, black pepper, palmarosa, and geranium EOs also showed inhibition rates exceeding 50%. Despite black pepper, clove, myrrh, and oregano EOs demonstrating relatively low toxicity against T. urticae, they exhibited heightened efficacy in inhibiting oviposition and suppressing population expansion. This study conducted a comparative assessment of the acaricidal and oviposition inhibition activities of EOs and their principal constituents, thus providing a theoretical basis for the development of botanical acaricides against T. urticae.

Peripheral blood inflammatory indexes in breast cancer: A review.

Immune and inflammatory responses play an important role in tumorigenesis and metastasis. Inflammation is an important component of the tumor microenvironment, and the changes in inflammatory cells may affect the occurrence and development of tumors. Complete blood count at the time of diagnosis and treatment can reflect the inflammatory status within the tumor. Studies have shown that the number of certain inflammatory cells in peripheral blood and their ratios are important prognostic factors for many malignancies, including neutrophil, lymphocyte, monocyte, and platelet counts, as well as neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, lymphocyte-to-monocyte ratio, systemic immune-inflammation index, systemic inflammation response index and pan-immune-inflammation-value. The value of peripheral blood inflammation indexes in predicting the efficacy and prognosis of breast cancer neoadjuvant therapy is worth recognizing. This review details the application of peripheral blood inflammation indexes in the evaluation of efficacy and prediction of prognosis in neoadjuvant therapy for breast cancer, aiming to provide a more comprehensive reference for the comprehensive diagnosis and treatment of breast cancer.

The intratumor mycobiome promotes lung cancer progression via myeloid-derived suppressor cells.

Although polymorphic microbiomes have emerged as hallmarks of cancer, far less is known about the role of the intratumor mycobiome as living microorganisms in cancer progression. Here, using fungi-enriched DNA extraction and deep shotgun metagenomic sequencing, we have identified enriched tumor-resident Aspergillus sydowii in patients with lung adenocarcinoma (LUAD). By three different syngeneic lung cancer mice models, we find that A. sydowii promotes lung tumor progression via IL-1ß-mediated expansion and activation of MDSCs, resulting in suppressed activity of cytotoxic T lymphocyte cells and accumulation of PD-1+ CD8+ T cells. This is mediated by IL-1ß secretion via ß-glucan/Dectin-1/CARD9 pathway. Analysis of human samples confirms that enriched A. sydowii is associated with immunosuppression and poor patient outcome. Our findings suggest that intratumor mycobiome, albeit at low biomass, promotes lung cancer progression and could be targeted at the strain level to improve patients with LUAD outcome.

Are children with sickle cell disease at particular risk from the harmful effects of air pollution? Evidence from a large, urban/peri-urban cohort.

INTRODUCTION: Pathophysiologic pathways of sickle cell disease (SCD) and air pollution involve inflammation, oxidative stress, and endothelial damage. It is therefore plausible that children with SCD are especially prone to air pollution's harmful effects. METHODS: Patient data were collected from a single-center, urban/peri-urban cohort of children with confirmed SCD. Daily ambient concentrations of particulate matter (PM2.5 ) were collected via satellite-derived remote-sensing technology, and carbon monoxide (CO), nitrogen dioxide (NO2 ), and ozone from local monitoring stations. We used multivariable regression to quantify associations of pollutant levels and daily counts of emergency department (ED) visits, accounting for weather and time trends. For comparison, we quantified the associations of pollutant levels with daily all-patient (non-SCD) ED visits to our center. RESULTS: From 2010 to 2018, there were 17,731 ED visits by 1740 children with SCD (64.8% HbSS/HbSß0 ). Vaso-occlusive events (57.8%), respiratory illness (17.1%), and fever (16.1%) were the most common visit diagnoses. Higher 3-day (lags 0-2) rolling mean PM2.5 and CO levels were associated with daily ED visits among those with SCD (PM2.5 incident rate ratio [IRR] 1.051 [95% confidence interval: 1.010-1.094] per 9.4 µg/m3 increase; CO 1.088 [1.045-1.132] per 0.5 ppm). NO2 showed positive associations in secondary analyses; ozone levels were not associated with ED visits. The comparison, all-patient ED visit analyses showed lower IRR for all pollutants. CONCLUSIONS: Our results suggest short-term air pollution levels as triggers for SCD events and that children with SCD may be more vulnerable to air pollution than those without SCD. Targeted pollution-avoidance strategies could have significant clinical benefits in this population.

AMLnet, A deep-learning pipeline for the differential diagnosis of acute myeloid leukemia from bone marrow smears.

Acute myeloid leukemia (AML) is a deadly hematological malignancy. Cellular morphology detection of bone marrow smears based on the French-American-British (FAB) classification system remains an essential criterion in the diagnosis of hematological malignancies. However, the diagnosis and discrimination of distinct FAB subtypes of AML obtained from bone marrow smear images are tedious and time-consuming. In addition, there is considerable variation within and among pathologists, particularly in rural areas, where pathologists may not have relevant expertise. Here, we established a comprehensive database encompassing 8245 bone marrow smear images from 651 patients based on a retrospective dual-center study between 2010 and 2021 for the purpose of training and testing. Furthermore, we developed AMLnet, a deep-learning pipeline based on bone marrow smear images, that can discriminate not only between AML patients and healthy individuals but also accurately identify various AML subtypes. AMLnet achieved an AUC of 0.885 at the image level and 0.921 at the patient level in distinguishing nine AML subtypes on the test dataset. Furthermore, AMLnet outperformed junior human experts and was comparable to senior experts on the test dataset at the patient level. Finally, we provided an interactive demo website to visualize the saliency maps and the results of AMLnet for aiding pathologists' diagnosis. Collectively, AMLnet has the potential to serve as a fast prescreening and decision support tool for cytomorphological pathologists, especially in areas where pathologists are overburdened by medical demands as well as in rural areas where medical resources are scarce.

Case Report: Parvovirus B19 infection complicated by hemophagocytic lymphohistiocytosis in a heart-lung transplant patient.

Immunosuppressed patients can contract parvovirus B19, and some may experience hemophagocytic lymphohistiocytosis (HLH). Herein, we describe the first report of hemophagocytic lymphohistiocytosis in a heart-lung transplant patient with concomitant parvovirus B19 infection. The patient was treated with intravenous immune globulin (IVIG) and the features of HLH were remission. This instance emphasizes the significance of parvovirus B19 monitoring in transplant patients with anemia; if HLH complicates the situation, IVIG may be an adequate remedy. Finally, a summary of the development in diagnosing and managing parvovirus B19 infection complicated by HLH is provided.

Case Report: Hemophagocytic Lymphocytosis in a Patient With Glutaric Aciduria Type IIC.

Hemophagocytic lymphocytosis (HLH) is a rare disease caused by inborn errors of immunity (IEI), secondary to infection, lymphoma or autoimmune disorders, but we often overlook the fact that HLH can be secondary to inborn errors of metabolism (IEM). Here, we describe a patient who was diagnosed with glutaric aciduria type IIC complicated by features suggestive of possible HLH. The diagnosis of glutaric aciduria type IIC, a IEM, was confirmed by whole exome sequencing. The patient was treated with coenzyme Q10 and riboflavin which effectively improved her liver function. During treatment, the patient developed severe anemia and thrombocytopenia. Persistent fever, splenomegaly, cytopenias, increased ferritin, hypertriglyceridemia, hypofibrinogenemia, and hemophagocytosis in the bone marrow pointed to the diagnosis of HLH; however, the patient eventually died of gastrointestinal bleeding. After other potential causes were ruled out, the patient was diagnosed with glutaric aciduria type IIC complicated by features suggestive of possible HLH. When cytopenias occurs in IEM patients, HLH is a possible complication that cannot be ignored. This case suggests a possible relationship between IEM and risk for immune dysregulation.

Novel strategy for membrane biofouling control in MBR with CdS/MIL-101 modified PVDF membrane by in situ visible light irradiation.

Novel control strategies for membrane biofouling with eco-friendly photocatalytic technology are critically needed in practical operation of membrane bioreactors (MBRs). In this study, a metal-organic frameworks (MOF) based photocatalytic membrane was firstly applied in an anammox MBR for a long-term biofouling control, where bacteria were inactivated and foulants were degraded simultaneously, with environmentally friendly and renewable visible light energy. By physicochemical characterization, the synthesized photocatalyst of CdS/MIL-101 showed superior visible-light photocatalytic ability, and the 1 wt% CdS/MIL-101 modified membrane C2 showed enhanced hydrophilicity and water permeability compared with the pristine membrane C0. In the long-term operation of anammox MBRs under waterproof lights irradiation, the filtration cycles of C2 (25-26 d) were obviously extended compared with C0 (10-14 d), while their average total nitrogen removal efficiencies were comparable up to 84%, indicating an excellent biofouling alleviation effect by using C2 with a satisfactory nitrogen removal performance maintained. By analysis of the biofilm on the fouled membranes, the organic foulants (especially extracellular polymeric substances) were degraded, and the live bacteria were inactivated effectively by the photocatalytic reactions of CdS/MIL-101 on C2. In the antimicrobial tests against model bacteria, C2 exhibited remarkable antimicrobial effect against both Gram-negative and Gram-positive bacteria with visible light irradiation by destruction of cell integrity with the inhibition rate of 92% for Escherichia coli and 95% for Staphylococcus aureus, respectively. In the model foulants (bovine serum albumin, sodium alginate, and humic acid) filtration tests, C2 showed higher antifouling capabilities, lower flux declining rates, and higher foulants rejection rates under visible light irradiation compared with C0. The reactive species of ·OH, e- and h+ generated on C2 were verified to play the predominant role in the anti-biofouling processes by simultaneous bacteria inactivation and foulants degradation. The findings offer a novel insight into the biofouling controlling in MBRs by simultaneous bacteria inactivation and foulants degradation with an eco-friendly method.

Decitabine-Mediated Epigenetic Reprograming Enhances Anti-leukemia Efficacy of CD123-Targeted Chimeric Antigen Receptor T-Cells.

Chimeric antigen receptor (CAR) T cells represent a potentially curative therapy for patients with advanced hematological cancers; however, uncertainties surround the cell-intrinsic fitness as well as the exhaustion that restrict the capacity of CAR-T. Decitabine (DAC), a DNA demethylating agent, has been demonstrated to reverse exhaustion-associated DNA-methylation programs and to improve T cell responses against tumors. Here we show that DAC significantly enhances antileukemia functions of CD123 CAR-T cells in vitro and in vivo. Additionally, it inhibits the expression of DMNT3a and DNMT1. Using the Illumina Methylation EPIC BeadChip (850 K), we identified differentially methylated regions, most of which undergo hypomethylated changes. Transcriptomic profiling revealed that CD123 CAR-T cells treated with DAC were enriched in genes associated with naive, early memory T cells, as well as non-exhausted T cells. DAC treatment also results in upregulation of immune synapse-related genes. Finally, our data further suggest that DAC works through the regulation of cellular differentiation characterized by naive and memory phenotypes. Taken together, these findings demonstrate that DAC improves the anti-leukemia properties of CD123-directed CAR-T cells, and provides a basis for rational combinatorial CAR-T-based immunotherapy for patients with acute myeloid leukemia (AML).

[The design of muti-target antitumor drugs affecting on FTase and Raf-1 kinase].

Ras/Raf/MEK/ERK singal transduction plays an important role in cell proliferation, differentiation, apoptosis, metastasis and metabolism. This investigation focused on this signal pathway and chose farnesyl transferase (FTase) as the main target and Raf-1 kinase as the second target. A lot of compounds were selected to construct the pharmacophore models of farnesyl transferase inhibitors (FTIs) and Raf-1 kinase inhibitors by using computer-aided drug design (CADD). The pharmacophore of FTIs is constituted by a hydrogen bonding acceptor, an aromatic ring, a positive ionizable and two hydrophobic regions; the pharmacophore of Raf-1 kinase is constituted by a hydrogen donor, a hydrogen acceptor, a hydrophobic regions and an aromatic ring. There are some similarities between the two pharmacophores. After analysis of the constructions of these two pharmacophores, some new aminomethylbenzoic acid derivatives with good forecasting activity against both of FTase and Raf-1 kinase were designed with these new pharmacophore models.

[Progress in the study of antitumor drug targeting on the Ras signaling pathway].

Ras signaling pathway is closely related to the formation and growth of tumor. Currently, targeting on this signaling pathway is a hot research point for the design and development of anticancer drugs. In this paper, Ras protein as well as its related targets and inhibitors in signaling pathway were reviewed. It is expected to give research-related reference materials for the design of new anticancer drugs.

Design, synthesis, and cytoprotective effect of 2-aminothiazole analogues as potent poly(ADP-ribose) polymerase-1 inhibitors.

A series of novel poly(ADP-ribose) polymerase-1 (PARP-1) inhibitors were designed within 2-aminothiazole analogues (4-10) based on a constructed three-dimensional pharmacophore model. After synthesis, the inhibitory effect on PARP-1 activity and the cytoprotective action of these compounds were tested and evaluated. Among them, compounds 4-6 and 10 appeared to be potent PARP-1 inhibitors with IC(50) values less than 1 microM, which had been perfectly predicted by pharmacophore model. These compounds proved to be highly potent against cell injury induced by H(2)O(2) and oxygen-glucose deprivation (OGD) in PC12 cells. These novel 2-aminothiazole analogues are potentially applicable as neuroprotective agents for the treatment of neurological diseases.