Efficient Initialization of Fluxonium Qubits based on Auxiliary Energy Levels.

Fast and high-fidelity qubit initialization is crucial for low-frequency qubits such as fluxonium, and in applications of many quantum algorithms and quantum error correction codes. In a circuit quantum electrodynamics system, the initialization is typically achieved by transferring the state between the qubit and a short-lived cavity through microwave driving, also known as the sideband cooling process in atomic system. Constrained by the selection rules from the parity symmetry of the wave functions, the sideband transitions are only enabled by multiphoton processes which require multitone or strong driving. Leveraging the flux tunability of fluxonium, we circumvent this limitation by breaking flux symmetry to enable an interaction between a noncomputational qubit transition and the cavity excitation. With single-tone sideband driving, we realize qubit initialization with a fidelity exceeding 99% within a duration of 300 ns, robust against the variation of control parameters. Furthermore, we show that our initialization scheme has a built-in benefit in simultaneously removing the second-excited state population of the qubit, and can be easily incorporated into a large-scale fluxonium processor.

Surface-Imprinted Polysiloxane with Recognition Ability Based on an ITO Layer for Rapid Detection of Fusarium oxysporum f. sp. cubense by the Naked Eye.

Direct observation by the naked eye of fluorescence-stained microbes adsorbed on surface imprinted polymers (SIPs) is highly challenging and limited by speed, accuracy and the semiquantitative nature of the method. In this study, we tested for the presence of spores of Fusarium oxysporum f. sp. cubense race 4 (Foc4), which cause severe banana Fusarium wilt disease and reduces the area of banana plants. This kind of spore can become dormant in soil, which means that the detection of secreted molecules (molecular imprinting) in soil may be inaccurate; detection methods such as polymerase chain reaction (PCR) and Raman spectroscopy are more accurate but time-consuming and inconvenient. Therefore, a semiquantitative and rapid SIP detection method for Foc4 was proposed. Based on the ITO conductive layer, a reusable and naked-eye-detectable Foc4-PDMS SIP film was prepared with a site density of approximately 9000 mm-2. Adsorption experiments showed that when the Foc4 spore concentration was between 104 to 107 CFU/mL, the number of Foc4 spores adsorbed and the fluorescence intensity were strongly correlated with the concentration and could be fully distinguished by the naked eye after fluorescence staining. Adsorption tests on other microbes showed that the SIP film completely recognized only the Foc series. All the results were highly consistent with the naked-eye observations after fluorescence staining, and the results of the Foc4-infected soil experiment were also close to the ideal situation. Taken together, these results showed that Foc4-PDMS SIPs have the ability to rapidly and semiquantitatively detect the concentration of Foc in soil, which can provide good support for banana cultivation. This method also has potential applications in the detection of other fungal diseases.

Non­m6A RNA modifications in haematological malignancies.

Dysregulated RNA modifications, stemming from the aberrant expression and/or malfunction of RNA modification regulators operating through various pathways, play pivotal roles in driving the progression of haematological malignancies. Among RNA modifications, N6-methyladenosine (m6A) RNA modification, the most abundant internal mRNA modification, stands out as the most extensively studied modification. This prominence underscores the crucial role of the layer of epitranscriptomic regulation in controlling haematopoietic cell fate and therefore the development of haematological malignancies. Additionally, other RNA modifications (non-m6A RNA modifications) have gained increasing attention for their essential roles in haematological malignancies. Although the roles of the m6A modification machinery in haematopoietic malignancies have been well reviewed thus far, such reviews are lacking for non-m6A RNA modifications. In this review, we mainly focus on the roles and implications of non-m6A RNA modifications, including N4-acetylcytidine, pseudouridylation, 5-methylcytosine, adenosine to inosine editing, 2'-O-methylation, N1-methyladenosine and N7-methylguanosine in haematopoietic malignancies. We summarise the regulatory enzymes and cellular functions of non-m6A RNA modifications, followed by the discussions of the recent studies on the biological roles and underlying mechanisms of non-m6A RNA modifications in haematological malignancies. We also highlight the potential of therapeutically targeting dysregulated non-m6A modifiers in blood cancer.

[Expert consensus on the diagnosis and treatment of respiratory diseases exacerbated by nonsteroidal anti-inflammatory drugs （2024, Chengdu）].

Non-steroidal anti-inflammatory drugs-exacerbated respiratory disease （N-ERD） is a chronic respiratory disease characterized by eosinophilic inflammation, featuring chronic rhinosinusitis （CRS）, asthma, and intolerance to cyclooxygenase 1 （COX-1） inhibitors. The use of these medications can lead to an acute worsening of rhinitis and asthma symptoms. This condition has not yet received sufficient attention in China, with a high rate of misdiagnosis and a lack of related research. The Chinese Rhinology Research Group convened a group of leading young experts in otolaryngology from across the country, based on the latest domestic and international evidence-based medical practices to formulate this consensus.The consensus covers the epidemiology, pathogenesis, clinical manifestations, diagnostic methods, and treatment strategies for N-ERD, including pharmacotherapy, surgery, biologic treatments, and desensitization therapy. The goal is to improve recognition of N-ERD, reduce misdiagnosis, and enhance treatment outcomes.

The first report and biological characterization of Avian Orthoavulavirus 16 in wild migratory waterfowl and domestic poultry in China reveal a potential threat to birds.

AbstractThe Avulavirus within the family Paramyxoviridae includes at least 22 different species, and is known to cause different types of infections and even be fatal in multiple avian species. There is limited knowledge of the genetic and biological information of Avulavirus species -2 to 22 in domestic and wild birds and the disease significance of these viruses in birds is not fully determined, although as many as 10 new distinct species have been identified from wild birds and domestic poultry around the world in the last decade. This study aimed to use PCR, virus isolation, and sequencing to genetically and biologically characterize Avian Orthoavulavirus 16 (AOAV-16) in wild birds and domestic poultry collected from different locations in China between 2014 and 2022. Of five isolated AOAV-16 strains (Y1 to Y5), only the Y4 strain had a hemagglutination (HA)-negative result. All of these isolates were low virulent viruses for chickens, except Y3 which was detected simultaneously with avian influenza virus (AIV) of H9N2 subtype. Furthermore, at least four different types of intergenic sequences (IGS) between the HN and L genes junction, and the recombination event as well as interspecific transmission by wild migratory birds, existed within the species AOAV-16. These findings and results of other reported AOAV-16 strains recommend strict control measures to limit contact between wild migratory birds and domestic poultry and imply potential threats to commercial poultry and even public health challenges worldwide.

Exploring the potentials of Sesuvium portulacastrum L. for edibility and bioremediation of saline soils.

Sesuvium portulacastrum L. is a flowering succulent halophyte in the ice plant family Aizoaceae. There are various ecotypes distributed in sandy coastlines and salty marshlands in tropical and subtropical regions with the common name of sea purslane. These plants are tolerant to salt, drought, and flooding stresses and have been used for the stabilization of sand dunes and the restoration of coastal areas. With the increased salinization of agricultural soils and the widespread pollution of toxic metals in the environment, as well as excessive nutrients in waterbodies, S. portulacastrum has been explored for the desalination of saline soils and the phytoremediation of metals from contaminated soils and nitrogen and phosphorus from eutrophic water. In addition, sea purslane has nutraceutical and pharmaceutical value. Tissue analysis indicates that many ecotypes are rich in carbohydrates, proteins, vitamins, and mineral nutrients. Native Americans in Florida eat it raw, pickled, or cooked. In the Philippines, it is known as atchara after being pickled. S. portulacastrum contains high levels of ecdysteroids, which possess antidiabetic, anticancer, and anti-inflammatory activities in mammals. In this review article, we present the botanical information, the physiological and molecular mechanisms underlying the tolerance of sea purslane to different stresses, its nutritional and pharmaceutical value, and the methods for its propagation and production in saline soils and waterbodies. Its adaptability to a wide range of stressful environments and its role in the production of valuable bioactive compounds suggest that S. portulacastrum can be produced in saline soils as a leafy vegetable and is a valuable genetic resource that can be used for the bioremediation of soil salinity and eutrophic water.

Electrochemical protein biosensors for disease marker detection: progress and opportunities.

The development of artificial intelligence-enabled medical health care has created both opportunities and challenges for next-generation biosensor technology. Proteins are extensively used as biological macromolecular markers in disease diagnosis and the analysis of therapeutic effects. Electrochemical protein biosensors have achieved desirable specificity by using the specific antibody-antigen binding principle in immunology. However, the active centers of protein biomarkers are surrounded by a peptide matrix, which hinders charge transfer and results in insufficient sensor sensitivity. Therefore, electrode-modified materials and transducer devices have been designed to increase the sensitivity and improve the practical application prospects of electrochemical protein sensors. In this review, we summarize recent reports of electrochemical biosensors for protein biomarker detection. We highlight the latest research on electrochemical protein biosensors for the detection of cancer, viral infectious diseases, inflammation, and other diseases. The corresponding sensitive materials, transducer structures, and detection principles associated with such biosensors are also addressed generally. Finally, we present an outlook on the use of electrochemical protein biosensors for disease marker detection for the next few years.

The distribution and antibiotic-resistant characteristics and risk factors of pathogens associated with clinical biliary tract infection in humans.

Introduction: Biliary Infection in patients is a common and important phenomenon resulting in severe complications and high morbidity, while the distributions and drug resistance profiles of biliary bacteria and related risk factors are dynamic. This study explored the characteristics of and risk factors for biliary infection to promote the rational use of antibiotics in clinically. Methods: Bacterial identification and drug susceptibility testing were completed using the Vitek 2 Compact analysis system. The distribution and antibiotic-resistant characteristics of 3,490 strains of biliary bacteria in patients at Nankai Hospital from 2019 to 2021 were analyzed using Whonet 5.6 and SPSS 26.0 software. We then retrospectively analyzed the clinical data and risk factors associated with 2,340 strains of Gram-negative bacilli, which were divided into multidrug-resistant bacteria (1,508 cases) and non-multidrug-resistant bacteria (832 cases) by a multivariate Cox regression model. Results and discussion: A total of 3,490 pathogenic bacterial strains were isolated from bile samples, including 2,340 (67.05%) Gram-negative strains, 1,029 (29.48%) Gram-positive strains, and 109 (4.56%) fungal strains. The top five pathogenic bacteria were Escherichia coli, Klebsiella pneumoniae, Enterococcus faecium, Enterococcus faecalis, and Pseudomonas aeruginosa. The rate of Escherichia coli resistance to ciprofloxacin increased (p < 0.05), while the resistance to amikacin decreased (p < 0.05). The resistance of Klebsiella pneumoniae to cephalosporins, carbapenems, ß-lactamase inhibitors, cephalases, aminoglycosides, and quinolones increased (p < 0.05), and the resistance of Pseudomonas aeruginosa to piperacillin, piperacillin/tazobactam, ticacillin/clavulanic acid, and amicacin declined significantly (p < 0.05). The resistance of Enterococcus faecium to tetracycline increased by year (p < 0.05), and the resistance of Enterococcus faecalis to erythromycin and high-concentration gentamicin declined (p < 0.05). Multivariate logistic regression analysis suggested that the administration of third- or fourth-generation cephalosporins was an independent risk factor for biliary infection. In summary, Gram-negative bacilli were the most common pathogenic bacteria isolated from biliary infection patients, especially Escherichia coli, and the rates and patterns of drug resistance were high and in constant flux; therefore, rational antimicrobial drug use should be carried out considering risk factors.

Region-Specific CD16+ Neutrophils Promote Colorectal Cancer Progression by Inhibiting Natural Killer Cells.

The colon is the largest compartment of the immune system, with innate immune cells exposed to antigens in the environment. However, the mechanisms by which the innate immune system is instigated are poorly defined in colorectal cancer (CRC). Here, a population of CD16+ neutrophils that specifically accumulate in CRC tumor tissues by imaging mass cytometry (IMC), immune fluorescence, and flow cytometry, which demonstrated pro-tumor activity by disturbing natural killer (NK) cells are identified. It is found that these CD16+ neutrophils possess abnormal cholesterol accumulation due to activation of the CD16/TAK1/NF-κB axis, which upregulates scavenger receptors for cholesterol intake including CD36 and LRP1. Consequently, these region-specific CD16+ neutrophils not only competitively inhibit cholesterol intake of NK cells, which interrupts NK lipid raft formation and blocks their antitumor signaling but also release neutrophil extracellular traps (NETs) to induce the death of NK cells. Furthermore, CD16-knockout reverses the pro-tumor activity of neutrophils and restored NK cell cytotoxicity. Collectively, the findings suggest that CRC region-specific CD16+ neutrophils can be a diagnostic marker and potential therapeutic target for CRC.

Amelioration of chromium toxicity in wheat plants through exogenous application of nano silicon.

Chromium (Cr) contamination in agricultural soils poses a risk to crop productivity and quality. Emerging nano-enabled strategies show great promise in remediating soils contaminated with heavy metals and enhancing crop production. The present study was aimed to investigate the efficacy of nano silicon (nSi) in promoting wheat growth and mitigating adverse effects of Cr-induced toxicity. Wheat seedlings exposed to Cr (K2Cr2O7) at a concentration of 100 mg kg-1 showed significant reductions in plant height (29.56%), fresh weight (35.60%), and dry weight (38.92%) along with enhanced Cr accumulation in roots and shoots as compared to the control plants. However, the application of nSi at a concentration of 150 mg kg-1 showcased substantial mitigation of Cr toxicity, leading to a decrease in Cr accumulation by 27.30% in roots and 35.46% in shoots of wheat seedlings. Moreover, nSi exhibited the capability to scavenge oxidative stressors, such as hydrogen peroxide (H2O2), and malondialdehyde (MDA) and electrolyte leakage, while significantly enhancing gas exchange parameters, total chlorophyll content, and antioxidant activities (enzymatic and nonenzymatic) in plants grown in Cr-contaminated soil. This study further found that the reduced Cr uptake by nSi application was due to downregulating the expression of HMs transporter genes (TaHMA2 and TaHMA3), alongwith upregulating the expression of antioxidant-responsive genes (TaSOD and TaSOD). The findings of this investigation highlight the remarkable potential of nSi in ameliorating Cr toxicity. This enhanced efficacy could be ascribed to the distinctive size and structure of nSi, which augment its ability to counteract Cr stress. Thus, the application of nSi could serve as a viable solution for production of crops in metal contaminated soils, offering an effective alternative to time-consuming and costly remediation techniques.

Discovery of Novel Small-Molecule-Based Potential PD-L1/EGFR Dual Inhibitors with High Druggability for Glioblastoma Immunotherapy.

Based on the close relationship between programmed death protein ligand 1 (PD-L1) and epidermal growth factor receptor (EGFR) in glioblastoma (GBM), we designed and synthesized a series of small molecules as potential dual inhibitors of EGFR and PD-L1. Among them, compound EP26 exhibited the highest inhibitory activity against EGFR (IC50 = 37.5 nM) and PD-1/PD-L1 interaction (IC50 = 1.77 µM). In addition, EP26 displayed superior in vitro antiproliferative activities and in vitro immunomodulatory effects by promoting U87MG cell death in a U87MG/Jurkat cell coculture model. Furthermore, EP26 possessed favorable pharmacokinetic properties (F = 22%) and inhibited tumor growth (TGI = 92.0%) in a GBM mouse model more effectively than Gefitinib (77.2%) and NP19 (82.8%). Moreover, EP26 increased CD4+ cells and CD8+ cells in tumor microenvironment. Collectively, these results suggest that EP26 represents the first small-molecule-based PD-L1/EGFR dual inhibitor deserving further investigation as an immunomodulating agent for cancer treatment.

Neferine alleviates ovariectomy-induced osteoporosis by enhancing osteogenic differentiation of bone marrow mesenchymal stem cells via regulation of the p38MAPK pathway.

OBJECTIVE: Osteoporosis, a skeletal ailment marked by bone metabolism imbalance and disruption of bone microarchitecture, Neferine, a bisbenzylisoquinoline alkaloid with diverse pharmacological activities, has received limited attention in the context of osteoporosis treatment. METHODS: We employed a bilateral ovariectomy (OVX) rat model to induce osteoporosis and subsequently administered Neferine treatment for four weeks following successful model establishment. Throughout the modeling and treatment phases, we closely monitored rat body weights. We assessed alterations in bone tissue microstructure through micro-CT, HE staining, and safranin O-fast green staining. Levels of bone formation and resorption markers in serum were evaluated using ELISA assay. Western blot analysis was employed to determine the expression levels of p38MAPK, p-p38MAPK, and bone formation-related genes in bone tissue. We isolated and cultured OVX rat BMSCs (OVX-BMSCs) and induced osteogenic differentiation while simultaneously introducing Neferine and the p38MAPK inhibitor SB203580 for intervention. RESULTS: Neferine treatment effectively curbed the rapid weight gain in OVX rats, ameliorated bone loss, and decreased serum levels of TRAP, CTX-I, PINP, and BALP. Most notably, Neferine promoted the expression of bone formation-related factors in bone tissue of OVX rats, while concurrently activating the p38MAPK signaling pathway. In in vitro experiments, Neferine facilitated the expression of bone formation-related factors in OVX-BMSCs, increased the osteogenic differentiation potential of OVX-BMSCs, and activated the p38MAPK signaling pathway. Nevertheless, SB203580 partially reversed Neferine's promotive effect. CONCLUSION: Neferine can boost the osteoblastic differentiation of BMSCs and alleviate OVX-induced osteoporosis in rats by activating the p38MAPK signaling pathway.

Crosstalk between histone/DNA modifications and RNA N6-methyladenosine modification.

N6-methyladenosine (m6A) is the most prevalent internal RNA modification in eukaryotic messenger RNAs (mRNAs), regulating gene expression at the transcription and post-transcription levels. Complex interplay between m6A and other well-studied epigenetic modifications, including histone modifications and DNA modification, has been extensively reported in recent years. The crosstalk between RNA m6A modification and histone/DNA modifications plays a critical role in establishing the chromatin state for the precise and specific fine-tuning of gene expression and undoubtedly has profound impacts on both physiological and pathological processes. In this review, we discuss the crosstalk between RNA m6A modification and histone/DNA modifications, emphasizing their sophisticated communications and the mechanisms underlying to gain a comprehensive view of the biological relevance of m6A-based epigenetic network.

Discovery of Small and Bifunctional Molecules Targeting PD-L1/CD73 for Cancer Dual Immunotherapy.

In this work, a series of bifunctional PD-L1/CD73 (cluster of differentiation 73) small-molecule inhibitors were designed and synthesized. Among them, CC-5 showed the strongest PD-L1 inhibitory effects with an IC50 of 6 nM and potent anti-CD73 activity with an IC50 of 0.773 µM. The high PD-L1/CD73 inhibitory activity of CC-5 was further confirmed by SPR assays with KD of 182 nM for human PD-L1 and 101 nM for CD73, respectively. Importantly, CC-5 significantly suppressed tumor growth in a CT26 and B16-F10 tumor model with TGI of 64.3% and 39.6%, respectively. Immunohistochemical (IHC) and flow cytometry analysis of tumor-infiltrating lymphocytes (TILs) indicated that CC-5 exerted anticancer effects via activating the tumor immune microenvironment. Collectively, CC-5 represents the first dual PD-L1/CD73 inhibitor worthy of further research as a bifunctional immunotherapeutic agent.

Elevated SCN11A concentrations associated with lower serum lipid levels in patients with major depressive disorder.

The pathogenesis of major depressive disorder (MDD) involves lipid metabolism. Our earlier research also revealed that MDD patients had much lower total cholesterol (TC) concentrations than healthy controls (HCs). However, it is still unclear why TC decreased in MDD. Here, based on the Ingenuity Knowledge Base's ingenuity pathway analysis, we found that sodium voltage-gated channel alpha subunit 11A (SCN11A) might serve as a link between low lipid levels and MDD. We analyzed the TC levels and used ELISA kits to measure the levels of SCN11A in the serum from 139 MDD patients, and 65 HCs to confirm this theory and explore the potential involvement of SCN11A in MDD. The findings revealed that TC levels were considerably lower and SCN11A levels were remarkably increased in MDD patients than those in HCs, while they were significantly reversed in drug-treatment MDD patients than in drug-naïve MDD patients. There was no significant difference in SCN11A levels among MDD patients who used single or multiple antidepressants, and selective serotonin reuptake inhibitors or other antidepressants. Pearson correlation analysis showed that the levels of TC and SCN11A were linked with the Hamilton Depression Rating Scales score. A substantial association was also found between TC and SCN11A. Moreover, a discriminative model made up of SCN11A was discovered, which produced an area under a curve of 0.9571 in the training set and 0.9357 in the testing set. Taken together, our findings indicated that SCN11A may serve as a link between low lipid levels and MDD, and showed promise as a candidate biomarker for MDD.

Isavuconazole Induces Neurodevelopment Defects and Motor Behaviour Impairment in Zebrafish Larvae.

Isavuconazole is a broad-spectrum antifungal drug used for the treatment of serious infections caused by invasive aspergillosis and mucormycosis in adults. With the continuous use of this drug, its safety and environmental impact have received increasing attention. However, information on the adverse effects of the drug is very limited. Fish is a particularly important model for assessing environmental risks. In this study, the aquatic vertebrate zebrafish was used as a model to study the toxic effects and mechanisms of isavuconazole. We exposed zebrafish embryos to 0.25, 0.5, and 1 mg/L of isavuconazole 6 h after fertilization. The results showed that at 72 hpf, isavuconazole exposure reduced heart rate, body length, and survival of zebrafish embryos compared to controls. Secondly, when isavuconazole reached a certain dose level (0.25 mg/L), it caused morphological changes in the Tg(elavl3:eGFP) transgenic fish line, with the head shrunk, the body bent, the fluorescence intensity becoming weaker, the abnormal motor behaviour, etc. At the same time, exposure of zebrafish embryos to isavuconazole downregulated acetylcholinesterase (AchE) and adenosine triphosphate (ATPase) activities but upregulated oxidative stress, thereby disrupting neural development and gene expression of neurotransmitter pathways. In addition, astaxanthin partially rescued the neurodevelopmental defects of zebrafish embryos by downregulating oxidative stress. Thus, our study suggests that isavuconazole exposure may induce neurodevelopment defects and behavioural disturbances in larval zebrafish.

Clinical study of enhanced recovery after surgery in laparoscopic appendectomy for acute appendicitis.

BACKGROUND: Enhanced recovery after surgery (ERAS) protocol is a comprehensive management modality that promotes patient recovery, especially in the patients undergoing digestive tumor surgeries. However, it is less commonly used in the appendectomy. AIM: To study the application value of ERAS in laparoscopic surgery for acute appendicitis. METHODS: A total of 120 patients who underwent laparoscopic appendectomy due to acute appendicitis were divided into experimental group and control group by random number table method, including 63 patients in the experimental group and 57 patients in the control group. Patients in the experimental group were managed with the ERAS protocol, and those in the control group were received the traditional treatment. The exhaust time, the hospitalization duration, the hospitalization expense and the pain score between the two groups were compared. RESULTS: There was no significant difference in age, gender, body mass index and Sunshine Appendicitis Grading System score between the experimental group and the control group (P > 0.05). Compared to the control group, the patients in the experimental group had earlier exhaust time, shorter hospitalization time, less hospitalization cost and lower degree of pain sensation. The differences were statistically significant (P < 0.01). CONCLUSION: ERAS could significantly accelerate the recovery of patients who underwent laparoscopic appendectomy for acute appendicitis, shorten the hospitalization time and reduce hospitalization costs. It is a safe and effective approach.

On-site calibration method for a binocular vision sensor based on the phase-shift algorithm.

When a binocular vision sensor (BVS) is installed in a narrow space, traditional calibration methods are limited as all targets should be placed in more than three different positions. To solve this problem, an on-site calibration method based on the phase-shift algorithm is proposed in our paper. Intrinsic parameters of these two cameras should be first calibrated offline. Series of phase-shift patterns are projected onto any one target with known three-dimensional information to determine the relationship between two cameras. The target utilized in our proposed method can be selected arbitrarily, which is suitable to achieve the on-site calibration of BVS, especially in industrial vibration environments. Experiments are conducted to validate the effectiveness and robustness of our proposed method.

[The auxiliary diagnostic value of ECP and MPO expression in nasal secretions in different types of rhinitis].

Objective:To evaluate the expression of eosinophil cationic protein and myeloperoxidase in nasal secretions in different types of rhinitis, and to explore their values in the differential diagnosis of different types of rhinitis. Methods:Six hundred and eighty-four subjects were selected, including 62 subjects in the acute rhinitis group, 378 subjects in the allergic rhinitis group, 94 subjects in the vasomotor rhinitis group, 70 subjects in the eosinophilic non-allergic rhinitis group, and 80 subjects in the control group. Nasal secretion samples were collected from the five groups, and the percentages of inflammatory cells were counted by Rachel's staining, and the expression of ECP/MPO was detected by colloidal gold assay. The correlation between the clinical diagnosis, the inflammatory cells in the nasal secretions and the expression of ECP/MPO was analyzed. Results:Nasal cytological smears showed that compared with the control group, the percentage of eosinophils in the AR and NARES groups were significantly higher （P<0.05）, while the percentage of neutrophils was not different （P>0.05）; the percentage of neutrophils was significantly higher in the acute rhinitis group compared with the control group （P<0.05）, while the percentage of eosinophils was not statistically different （P>0.05）; in vasomotor rhinitis group, the eosinophils and neutrophils were not statistically different compared with the control group（P> 0.05）. The colloidal gold results showed that there were differences in the expression of ECP/MPO in different types of rhinitis, among which 49 cases （79.0%） in the acute rhinitis group expressed ECP+/MPO+; 267 cases （70.6%） in the AR group and 56 cases （75.7%） in the NARES group expressed ECP+/MPO-; 80 cases （85.1%） in the vasomotor rhinitis group and 69 cases （86.3%） in the control group expressed ECP-/MPO-. Conclusion:The differences in ECP and MPO expression between different types of rhinitis have certain reference value for the differential diagnosis of different types of rhinitis and the selection of treatment programs.

RIPK3 deficiency blocks R-2-hydroxyglutarate-induced necroptosis in IDH-mutated AML cells.

Mutant isocitrate dehydrogenases (IDHs) produce R-2-hydroxyglutarate (R-2HG), which inhibits the growth of most acute myeloid leukemia (AML) cells. Here, we showed that necroptosis, a form of programmed cell death, contributed to the antileukemia activity of R-2HG. Mechanistically, R-2HG competitively inhibited the activity of lysine demethylase 2B (KDM2B), an α-ketoglutarate-dependent dioxygenase. KDM2B inhibition increased histone 3 lysine 4 trimethylation levels and promoted the expression of receptor-interacting protein kinase 1 (RIPK1), which consequently caused necroptosis in AML cells. The expression of RIPK3 was silenced because of DNA methylation in IDH-mutant (mIDH) AML cells, resulting in R-2HG resistance. Decitabine up-regulated RIPK3 expression and repaired endogenous R-2HG-induced necroptosis pathway in mIDH AML cells. Together, R-2HG induced RIPK1-dependent necroptosis via KDM2B inhibition in AML cells. The loss of RIPK3 protected mIDH AML cells from necroptosis. Restoring RIPK3 expression to exert R-2HG's intrinsic antileukemia effect will be a potential therapeutic strategy in patients with AML.