Validation and comparison of 5th edition World Health Organization classification (WHO 2022) and International Consensus Classification proposals for MDS-SFB31.

The criteria of myelodysplastic syndromes (MDS) with mutated SFB31 (MDS-SFB31) proposed by the 5th edition of the WHO classification (WHO 2022) and the International Consensus Classification (ICC) need validation. We analysed 125 consecutive MDS cases with SFB31 mutation or ring sideroblasts (RS) ≥15% without excess blasts. We found that SFB31-negative MDS with RS had significantly different clinical features and worse prognosis. According to WHO 2022, the detection of ≥15% RS may substitute for SF3B1 mutation and our analyses support this proposal for similar prognosis of two groups after excluding high-risk genetic features referred by WHO 2022. Patients with variant allele frequency (VAF) <10% SFB31 tend to have briefer survival, supporting the VAF 10% threshold of ICC. Patients with multilineage dysplasia (MLD) had significantly shorter OS than those with single lineage dysplasia. MLD is still a powerful morphological marker of worse outcome in WHO 2022 and ICC-defined MDS-SF3B1.

Combination therapy with venetoclax and azacitidine for the treatment of myelodysplastic syndromes with DDX41 mutations.

Myelodysplastic syndromes (MDS) patients with DEAD-box helicase 41 (DDX41) mutations have been reported to be treated effectively with lenalidomide; however, there are no randomized studies to prove it. Venetoclax and azacitidine are safe and effective in high-risk MDS/AML. In this study, we evaluated the efficacy of venetoclax and azacitidine combination therapy in eight consecutive MDS patients with DDX41 mutations at our centre from March 2021 to November 2023. We retrospectively analyzed the genetic features and clinical characteristics of these patients. Our findings suggest that MDS patients with DDX41 mutation may benefit from the therapy, for six subjects received this regimen as initial therapy and five of the six subjects achieved complete remission.

Nano-selenium foliar intervention-induced resistance of cucumber to Botrytis cinerea by activating jasmonic acid biosynthesis and regulating phenolic acid and cucurbitacin.

PURPOSE AND METHODS: Botrytis cinerea is the primary disease affecting cucumber production. It can be managed by applying pesticides and cultivating disease-resistant cucumber strains. However, challenges, such as drug resistance in pathogenic bacteria and changes in physiological strains, are obstacles in the effective management of B. cinerea. Nano-selenium (Nano-Se) has potential in enhancing crop resistance to biological stress, but the exact mechanism for boosting disease resistance remains unclear. Here, we used metabolomics and transcriptomics to examine how Nano-Se, as an immune activator, induces plant resistance. RESULT: Compared with the control group, the application of 10.0 mg/L Nano-Se on the cucumber plant's leaf surface resulted in increased levels of chlorophyll, catalase (10.2%), glutathione (326.6%), glutathione peroxidase (52.2%), cucurbitacin (41.40%), and metabolites associated with the phenylpropane synthesis pathway, as well as the total antioxidant capacity (21.3%). Additionally, the expression levels of jasmonic acid (14.8 times) and related synthetic genes, namely LOX (264.1%), LOX4 (224.1%), and AOC2 (309.2%), were up-regulated. A transcription analysis revealed that the CsaV3_4G002860 gene was up-regulated in the KEGG enrichment pathway in response to B. cinerea infection following the 10.0 mg/L Nano-Se treatment. DISCUSSION: In conclusion, the activation of the phenylpropane biosynthesis and branched-chain fatty acid pathways by Nano-Se promotes the accumulation of jasmonic acid and cucurbitacin in cucumber plants. This enhancement enables the plants to exhibit resistance against B. cinerea infections. Additionally, this study identified a potential candidate gene for cucumber resistance to B. cinerea induced by Nano-Se, thereby laying a theoretical foundation for further research in this area. © 2023 Society of Chemical Industry.

Nano-selenium enhances melon resistance to Podosphaera xanthii by enhancing the antioxidant capacity and promoting alterations in the polyamine, phenylpropanoid and hormone signaling pathways.

Powdery mildew is one of the main problematic diseases in melon production, requiring the use of chemical pesticides with disease-resistant cultivars for control. However, the often rapid acquisition of fungicidal resistance by mildew pathogens makes this practice unsustainable. The identification of crop treatments that can enhance resistance to powdery mildew resistance is therefore important to reduce melon crop attrition. This study indicates that the application of Nano-Se can reduce the powdery mildew disease index by 21-45%. The Nano-Se treatment reduced reactive oxygen species (ROS) and malondialdehyde (MDA) accumulation, with increases in glutathione (GSH), proline and 1,1-Diphenyl-2-picrylhydrazyl radical (DPPH). Increases were also observed in the activities and transcriptional levels of the antioxidant enzymes superoxide dismutase (SOD), catalase (CAT), ascorbate peroxidase (APX) and peroxidase (POD). Assays with four different cultivars of melon with differing levels of mildew resistance demonstrated that relative to the control, the Nano-Se treatment resulted in larger responses to mildew infection, including increases in the levels of putrescine (PUT; 43-112%) and spermine (SPM; 36-118%), indoleacetic acid (IAA; 43-172%) and salicylic acid (SA; 24-73%), the activities of phenylalanine ammonium lyase (PAL), trans-cinnamate 4-hydroxylase (C4H) and 4-coumarate: Co A ligase (4CL) of the phenylpropanoid pathway (22-38%, 24-126% and 19-64%, respectively). Key genes in the polyamine and phenylpropanoid pathway were also upregulated. These results indicate that the foliar application of Nano-Se improved melon defenses against powdery mildew infection, with a significant reduction in mildew disease development.

Chemical Profiling of Nitraria roborowskii Kom. by UPLC-Q-Orbitrap-MS and Their Hypolipidemic Effects in Vivo.

The Nitraria roborowskii Kom. (NRK) berries, as fruits of the genus Nitraria of the Zygophyllceae family, have been widely used as folk medicine. Modern pharmacological research has demonstrated that Nitraria berries had hypolipidemic, hypoglycemic, and immunomodulatory effects. However, more research needs to be reported on the chemical composition and biological activity of NRK. Hence, the phenolic compounds in the NRK berries were comprehensively analyzed and characterized by Ultra Performance Liquid Chromatography-Quadruple-Orbitrap MS system (UPLC-Q-Orbitrap MS) in this study. In total, 52 phenolics were identified, and all were reported for the first time. In addition, the hypolipidemic efficacy of NRK berries extract was studied in the hyperlipidemic mouse model. After treatment, the high dose group of NRK substantially reversed total cholesterol, low-density lipoprotein cholesterol, and high-density lipoprotein cholesterol levels. Through lipidomics technology, 27 potential biomarkers were characterized. And there was a significant callback at 25 of them after NRK treatment by using statistical analysis methods. Pathway analysis results demonstrated that NRK might exert therapeutic effects by regulating glycerophospholipid and glycerolipid metabolism pathways. This study could provide firsthand information on NRK berries for their phenolic compounds and potential application in preventing and treating hyperlipidemia.

Review on Pesticide Abiotic Stress over Crop Health and Intervention by Various Biostimulants.

Plants are essential for life on earth, and agricultural crops are a primary food source for humans. For the One Health future, crop health is crucial for safe, high-quality agricultural products and the development of future green commodities. However, the overuse of pesticides in modern agriculture raises concerns about their adverse effects on crop resistance and product quality. Recently, biostimulants, including microecological bacteria agents and nanoparticles, have garnered worldwide interest for their ability to sustain plant health and enhance crop resistance. This review analyzed the effects and mechanisms of pesticide stress on crop health. It also investigated the regulation of biostimulants on crop health and the multiomics mechanism, combining research on nanoselenium activating various crop health aspects conducted by the authors' research group. The paper helps readers understand the impact of pesticides on crop health and the positive influence of various biostimulants, especially nanomaterials and small molecules, on crop health.

Mitigation of Acetamiprid Residue Disruption on Pea Seed Germination by Selenium Nanoparticles and Lentinans.

The use of pesticides for pest control during the storage period of legume seeds is a common practice. This study evaluated the disruptive effects on pea seed germination and the repair effects of selenium nanoparticles (SeNPs) and lentinans (LNTs) This study examined the biomass, nutrient content, antioxidant indicators, plant hormones, phenolic compounds, and metabolites associated with the lignin biosynthesis pathway in pea sprouts. The application of acetamiprid resulted in a significant decrease in yield, amino-acid content, and phenolic compound content of pea sprouts, along with observed lignin deposition. Moreover, acetamiprid residue exerted a notable level of stress on pea sprouts, as evidenced by changes in antioxidant indicators and plant hormones. During pea seed germination, separate applications of 5 mg/L SeNPs or 20 mg/L LNTs partially alleviated the negative effects induced by acetamiprid. When used in combination, these treatments restored most of the aforementioned indicators to levels comparable to the control group. Correlation analysis suggested that the regulation of lignin content in pea sprouts may involve lignin monomer levels, reactive oxygen species (ROS) metabolism, and plant hormone signaling mediation. This study provides insight into the adverse impact of acetamiprid residues on pea sprout quality and highlights the reparative mechanism of SeNPs and LNTs, offering a quality assurance method for microgreens, particularly pea sprouts. Future studies can validate the findings of this study from the perspective of gene expression.

Case of cryptic TNIP1::PDGFRB rearrangement presenting with myelodysplastic syndrome achieved hematologic and cytogenetic remission with low-dose imatinib plus decitabine therapy.

For a long time, FIP1L1::PDGFRA fusion seems to be the only cryptic rearrangement of myeloid/lymphoid neoplasm with tyrosine kinase gene fusions. Recently, with the wide application of RNA sequencing, more cryptic rearrangements of other TK genes have been identified, especially the PDGFRB. Here we report a case of myelodysplastic syndrome with severe thrombocytopenia. Conventional karyotype analysis revealed a t (5;19) (q33; p13.2) but no PDGFRB rearrangement was detected by the PDGFRB break-apart probe. The TNIP1::PDGFRB fusion was eventually found by RNA sequencing, leading us to treat with low-dose imatinib plus decitabine, and the patient achieved hematologic improvement and cytogenetic remission.

Integrated non-targeted and targeted metabolomics analysis reveals the mechanism of inhibiting lignification and optimizing the quality of pea sprouts by combined application of nano-selenium and lentinans.

BACKGROUND: Lignification causes a detrimental impact on the quality of edible sprouts. However, the mechanism of inhibition of lignification of edible sprouts by nano-selenium and lentinans remains unclear. RESULTS: To reveal the mechanism of lignification regulation of sprouts by nano-selenium and lentinans, this study investigated the changes in antioxidant indicators, phytohormones, polyphenols, and metabolites in the lignin biosynthesis in pea sprouts following sprays of nano-selenium or/and lentinans twice. There was an overall increase in the aforementioned indices following treatment. In particular, the combined application of 5 mg L-1 nano-selenium and 20 mg L-1 lentinans was more effective than their individual applications in enhancing peroxidase, catalase, DPPH free-radical scavenging rate, luteolin, and sinapic acid, as well as inhibiting malondialdehyde generation and lignin accumulation. Combined with the results from correlation analysis, nano-selenium and lentinans may inhibit lignification by enhancing antioxidant systems, inducing phytohormone-mediated signaling, and enriching precursor metabolites (caffeyl alcohol, sinapyl alcohol, 4-coumaryl alcohol). In terms of the results of non-targeted metabolomics, the combined application of 5 mg L-1 nano-selenium and 20 mg L-1 lentinans mainly affected biosynthesis of plant secondary metabolites, biosynthesis of phenylpropanoids, phenylpropanoid biosynthesis, arginine and proline metabolism, and linoleic acid metabolism pathways, which supported and complemented results from targeted screenings. CONCLUSION: Overall, the combined sprays of nano-selenium and lentinans showed synergistic effects in delaying lignification and optimizing the quality of pea sprouts. This study provides a novel and practicable technology for delaying lignification in the cultivation of edible sprouts. © 2023 Society of Chemical Industry.

Impact of the International Consensus Classification of myelodysplastic syndromes.

The impact of the 2022 International Consensus Classification (ICC) of myelodysplastic syndromes (MDS) needs study. We analysed data from 989 MDS subjects classified using the 2016 World Health Organization (WHO) criteria to determine the impact of the new proposal. Our analyses suggested the ICC criteria of MDS-SF3B1 identifies a more homogenous disease entity than the WHO 2016 criteria of myelodysplastic syndromes with ring sideroblasts (MDS-RS). MDS, not otherwise specified with single lineage dysplasia (MDS, NOS-SLD) patients had a better prognosis than MDS, NOS with multilineage dysplasia (MDS, NOS-MLD) patients. MDS with mutated TP53 and MDS/acute myeloid leukaemia with mutated TP53 patients had the briefest survivals. These data support the ICC of MDS, which allows more accurate diagnoses and risk stratification.

IPSS-M has greater survival predictive accuracy compared with IPSS-R in persons ≥ 60 years with myelodysplastic syndromes.

There are considerable new data on mutation topography in persons with myelodysplastic syndromes (MDS). These data have been used to update conventional risk models such as the Revised International Prognostic Scoring System (IPSS-R). Whether the molecular IPSS (IPSS-M) which includes these data improves survival prediction accuracy is untested. To answer this question, we compared survival prediction accuracies of the IPSS-R and IPSS-M in 852 consecutive subjects with de novo MDS. Concordance statistics (C-statistics) of the IPSS-R and IPSS-M in the entire cohort were similar, 0.67 (95% Confidence Interval [CI] 0.64, 0.71) and 0.68 (0.64, 0.71). Average numbers of mutations and of IPSS-M related mutations were greater in persons ≥ 60 years (2.0 [Interquartile Range [IQR], 1, 3] vs. 1.6 [0, 2], P = 0.003; 1.6 [0, 2] vs. 1.3 [0, 2], P = 0.006). Subjects ≥ 60 years had a higher incidence of mutations in RUNX1, TP53, TET2, SRSF2, DNMT3A, STAG2, EZH2 and DDX41. In contrast, mutations in U2AF1 were more common in persons < 60 years. Next we tested survival prediction accuracy based on age < or ≥ 60 years. C-statistics of the IPSS-R and IPSS-M in subjects ≥ 60 years were 0.66 (0.61, 0.71) and 0.69 (0.64, 0.73) whereas in subjects < 60 years they were 0.67 (0.61, 0.72) and 0.65 (0.59, 0.71). These data indicate an advantage for the IPSS-M over the IPSS-R in subjects ≥ 60 years but not in those < 60 years probably because of a great frequency of mutations correlated with survival in those ≥ 60 years.

The Correlation Between Estimated Glucose Disposal Rate and Coagulation Indexes in Type 2 Diabetes Mellitus.

Purpose: To study the correlation between estimated glucose disposition rate (eGDR) and coagulation parameters in type 2 diabetes patients (T2DM). Materials and Methods: A total of 948 patients suffering from T2DM were enrolled for this research. Various blood coagulation parameters including prothrombin time (PT), activated partial thromboplastin time (APTT), and fibrinogen (FIB) were assessed. Body mass index (BMI), hypertension, and the levels of glycated hemoglobin (HbA1c) were used to calculate the patients' eGDRs. All patients were sorted into two groups: those with high eGDRs (eGDR≥7.5) and those with low eGDRs (eGDR<7.5). The patients were then separated into groups of men and women. The connection between eGDR and coagulation indexes was examined using Spearman correlation, Pearson correlation, and multiple linear regression analysis. Results: In comparison to the high-eGDR group, reduced PT and APTT levels with increased FIB levels were observed in the low-eGDR group (P =0.006, P <0.001, and P = 0.035, respectively). The eGDR showed a positive relation with APTT (r = 0.142, P < 0.001), a negative relation with FIB (r = -0.082, P = 0.012), and no correlation with PT (r =0.064, P =0.050) in the all patients. As well as, the eGDR demonstrated a positive relation with APTT (r = 0.173, P < 0.001), a negative relation with FIB (r = -0.093, P = 0.03), and no relation with PT (r = 0.045, P = 0.300) in the male subgroups. Additionally, this correlation persisted following the adjustment of other factors in multilinear regression analysis. However, the female subgroup demonstrated no correlation among eGDR and PT, APTT or FIB (r = 0.086, P = 0.083, r = 0.097, P = 0.05;r = -0.058, P = 0.240, respectively). Conclusion: Our study is the first to prove that eGDR demonstrates a correlation with coagulation indexes in T2DM patients. And, this correlation is gender-specific.

Monocyte/High-Density Lipoprotein Cholesterol Ratio Predicts Vitamin D Deficiency in Male Patients with Type 2 Diabetes Mellitus.

Purpose: This study aimed to investigate the relationship between monocyte/high-density lipoprotein cholesterol ratio (MHR) and 25-hydroxyvitamin D [25(OH) D] level in patients with type 2 diabetes mellitus (T2DM), the risk factors for vitamin D deficiency, and the clinical value of MHR as a predictor of vitamin D deficiency in this population. Patients and Methods: This was a cross-sectional study of 260 patients with T2DM from May 2021 to October 2021. Based on internationally used criteria for defining vitamin D levels, the patients were divided according to sex and levels of vitamin D into the following four groups: Group A1 (male patients with vitamin D levels <20 ng/mL), group A2 (male patients with vitamin D levels ≥20 ng/mL), group B1 (female patients with vitamin D levels <20 ng/mL), and group B2 (female patients with vitamin D levels≥20 ng/mL). The MHR was calculated as a monocyte/high-density cholesterol lipoprotein ratio. Results: The vitamin D level was independently and negatively correlated with the MHR in male patients with T2DM, but not in female patients. The MHR was an independent risk factor and predictor for the development of vitamin D deficiency in male patients, but not in female patients, with T2DM. High-density lipoprotein (HDL) was an independent protective factor for vitamin D deficiency in female patients with T2DM. Conclusion: This study suggested that the MHR was a new marker for predicting vitamin D deficiency in male patients with T2DM. Alleviating inflammation, improving lipid metabolism, and increasing HDL levels in patients with T2DM might help improve vitamin D levels, which might be important for preventing and managing T2DM. The MHR might help as a new marker to predict vitamin D deficiency in China, where primary hospitals lack the capacity for vitamin D testing on a large scale.

Correlation of Body Mass Index with Clinicopathologic Parameters in Patients with Idiopathic Membranous Nephropathy.

Objective: To investigate the association between body mass index (BMI) and clinicopathologic parameters in patients with idiopathic membranous nephropathy (IMN). Methods: This study was retrospective and included patients with biopsy-proven IMN from 2018 to 2021 in Hebei General Hospital. Patients were categorized into two groups based on BMI. Clinical and histopathologic data were analyzed at the time of renal biopsy. Pathological data included immunofluorescence staining, glomerulosclerosis (GS, 0-2), mesangial cell proliferation (MCP, 0-1), tubular atrophy (TA, 0-1), interstitial fibrosis (IF, 0-1), vascular wall thickness (VWT, 0-1) and a combination score (GMTIV) graded from 0 to 5. Results: Our study revealed that the obese group had a higher prevalence of hypertension and diabetes than the overweight/normal weight group (P=0.001, P=0.002). Systolic blood pressure (P=0.005), diastolic blood pressure (P<0.001), haemoglobin (P=0.006), triglycerides (P<0.001), serum uric acid (P=0.05), 24 h urine proteinuria concentration (UP) (P=0.012), MCP (P=0.042), IF (P=0.033), and GMITV (P=0.033) score were higher in obese group compared to the other group, while the high-density lipoprotein-cholesterol (P=0.034) and immunoglobulin A deposition score (P=0.005) were lower. Factors significantly associated with UP were the ratio of lymphocyte count to white blood cell count, serum pre-albumin, immunoglobulin G, microscopic hematuria, anti-phospholipase A2 receptor (anti-PLA2R), C3 deposit on multivariable analysis (adjusted R 2=0.343). Binary logistic regression analysis illustrated that MCP was correlated to BMI (OR=2.528, P=0.036). Ordinal logistic regression analysis demonstrated that GMTIV was associated with BMI (OR=1.114, P=0.010) and C3 deposit (OR=1.655, P=0.001). Conclusion: High BMI was associated with MCP and GMTIV score in IMN patients. Obesity may play an essential role in mesangial lesions of IMN. This study emphasized the relation between BMI and histological parameters under the universal usage of anti-PLA2R antibodies for diagnosis and prognosis in IMN.

The relationship between estimated glucose disposal rate and bone turnover markers in type 2 diabetes mellitus.

PURPOSE: To investigate the relationship between estimated glucose disposal rate (eGDR) and bone turnover markers in patients with type 2 diabetes mellitus (T2DM). MATERIALS AND METHODS: This is a cross-sectional study, which recruited 549 patients with T2DM. The eGDRs of patients were calculated based on the presence of hypertension, glycated hemoglobin, and body mass index. All patients were divided into high-eGDR group and low-eGDR group using the median of eGDR as the boundary. The patients were further divided into two subgroups: males and postmenopausal females. RESULTS: The lower the eGDR, the more severe was insulin resistance. The levels of osteocalcin (OC), type I collagen carboxyl-terminal peptide (ß-CTX), and type I procollagen amino-terminal peptide (PINP) were significantly lower in the low-eGDR group than those in the high-eGDR group. The eGDR was positively correlated with OC, ß-CTX, and PINP in all patients, and in the male subgroups. In the postmenopausal female subgroup, there was no correlation between eGDR and OC, ß-CTX, or PINP. In addition, this positive correlation remained after adjusting for other factors in multilinear regression analysis. CONCLUSION: Our study was the first to demonstrate that eGDR is positively correlated with bone turnover markers in patients with T2DM. This correlation was observed among the male patients with T2DM but not among postmenopausal female patients with T2DM.

Landscape of immunoglobulin heavy chain gene repertoire and its clinical relevance to LPL/WM.

Lymphoplasmacytic lymphoma/Waldenström macroglobulinemia (LPL/WM) is a heterogeneous disease in which the role of immunoglobulin heavy-chain genes (IGHs) remains unknown. To determine the clinical relevance of the IGH repertoire in patients with LPL/WM, we performed immunoglobulin gene rearrangement and complementarity determining region 3 (CDR3) analysis. The IGH variable gene (IGHV) repertoire was remarkably biased in LPL/WM. IGHV3-23, IGHV4-34, IGHV3-30, IGHV3-7, and IGHV3-74 accounted for one-half of the cohort's repertoire. Most cases (97.1%) were found to carry mutated IGHV genes, based on a 98% IGHV germline homology cutoff. IGHV3-30 was associated with long heavy chain CDR3, indicating there was specific antigen selection in LPL/WM. Patients with IGHV3-7 were significantly more likely to harbor the 6q deletion (P < .001) and an abnormal karyotype (P = .004). The IGHV hypermutation rate in patients with the MYD88 L265P mutation was significantly higher than that of wild-type patients (P = .050). IGHV3-23 and IGHV3-74 segments were more frequently detected in patients with MYD88-mutated LPL/WM (P = .050), whereas IGHV3-7 presented more frequently in MYD88 wild-type patients (P = .042). Patients with IGHV4, especially IGHV4-34, had higher levels of lactate dehydrogenase, and IGHV4 was a predictive marker of shorter progression-free survival. These results showed for the first time that the IGHV repertoire has clinical relevance in LPL/WM.

Myelodysplastic syndromes are multiclonal diseases derived from hematopoietic stem and progenitor cells.

Myelodysplastic syndromes (MDS) are generally considered as a group of clonal diseases derived from hematopoietic stem cells, but a number of studies have suggested that they are derived from myeloid progenitor cells. We aimed to identify the cell of origin in MDS by single-cell analyses. Targeted single-cell RNA sequencing, covering six frequently mutated genes (U2AF1, SF3B1, TET2, ASXL1, TP53, and DNMT3A) in MDS, was developed and performed on individual cells isolated from the CD34+ and six lineage populations in the bone marrow of healthy donors (HDs) and patients with MDS. The detected mutations were used as clonal markers to define clones. By dissecting the distribution of clones in six lineages, the clonal origin was determined. We identified three mutations both in HDs and patients with MDS, termed clonal hematopoiesis (CH) mutations. We also identified fifteen mutations only detected in patients with MDS, termed MDS mutations. Clonal analysis showed that CH clones marked by CH mutations and MDS clones marked by MDS mutations were derived from hematopoietic stem cells as well as various hematopoietic progenitor cells. Most patients with MDS showed the chimeric state with CH clones and MDS clones. Clone size analysis suggested that CH mutations may not contribute to clonal expansion of MDS. In conclusion, MDS comprise multiple clones derived from hematopoietic stem and progenitor cells.