Outcome of infants with acute lymphoblastic leukemia treated with the Chinese Children's Cancer Group Acute Lymphoblastic Leukemia 2015 study protocol.

Not available.

Cytoplasmic tail of transmembrane dscam controls antibacterial responses by regulating cell proliferation-related genes in hemocytes of Chinese mitten crab (Eriocheir sinensis).

In arthropods, the involvement of Dscam (Down syndrome cell adhesion molecule) in innate immunity has been extensively demonstrated. Its cytoplasmic tail contains multiple conserved functional sites, which indicates its involvement in different intracellular signaling pathways. In this study, we focused on the role of the cytoplasmic tail of Dscam in the Chinese mitten crab (Eriocheir sinensis) immune defense. In the group with cytoplasmic tail knockdown (the site was located on constant exons 37 and 38), 3885 differentially expressed genes (DEGs) were identified. The DEGs were enriched in small molecule binding, protein-containing complex binding, and immunity-related pathways. The expression of selected genes were validated using quantitative real-time reverse transcription PCR. We identified key Cell cycle, Janus kinase (JAK)-signal transducer, activator of transcription (STAT) and mitogen-activated protein kinase (MAPK) signaling pathway genes, the results indicated that the cytoplasmic tail of Dscam controls antibacterial responses by regulating cell proliferation-related genes in hemocytes.

In situ reprogramming of cardiac fibroblasts into cardiomyocytes in mouse heart with chemicals.

Cardiomyocytes are terminal differentiated cells and have limited ability to proliferate or regenerate. Condition like myocardial infarction causes massive death of cardiomyocytes and is the leading cause of death. Previous studies have demonstrated that cardiac fibroblasts can be induced to transdifferentiate into cardiomyocytes in vitro and in vivo by forced expression of cardiac transcription factors and microRNAs. Our previous study have demonstrated that full chemical cocktails could also induce fibroblast to cardiomyocyte transdifferentiation both in vitro and in vivo. With the development of tissue clearing techniques, it is possible to visualize the reprogramming at the whole-organ level. In this study, we investigated the effect of the chemical cocktail CRFVPTM in inducing in situ fibroblast to cardiomyocyte transdifferentiation with two strains of genetic tracing mice, and the reprogramming was observed at whole-heart level with CUBIC tissue clearing technique and 3D imaging. In addition, single-cell RNA sequencing (scRNA-seq) confirmed the generation of cardiomyocytes from cardiac fibroblasts which carries the tracing marker. Our study confirms the use of small molecule cocktails in inducing in situ fibroblast to cardiomyocyte reprogramming at the whole-heart level and proof-of-conceptly providing a new source of naturally incorporated cardiomyocytes to help heart regeneration.

Discovery of a novel BTK inhibitor S-016 and identification of a new strategy for the treatment of lymphomas including BTK inhibitor-resistant lymphomas.

Bruton's tyrosine kinase (BTK) has emerged as a therapeutic target for B-cell malignancies, which is substantiated by the efficacy of various irreversible or reversible BTK inhibitors. However, on-target BTK mutations facilitating evasion from BTK inhibition lead to resistance that limits the therapeutic efficacy of BTK inhibitors. In this study we employed structure-based drug design strategies based on established BTK inhibitors and yielded a series of BTK targeting compounds. Among them, compound S-016 bearing a unique tricyclic structure exhibited potent BTK kinase inhibitory activity with an IC50 value of 0.5 nM, comparable to a commercially available BTK inhibitor ibrutinib (IC50 = 0.4 nM). S-016, as a novel irreversible BTK inhibitor, displayed superior kinase selectivity compared to ibrutinib and significant therapeutic effects against B-cell lymphoma both in vitro and in vivo. Furthermore, we generated BTK inhibitor-resistant lymphoma cells harboring BTK C481F or A428D to explore strategies for overcoming resistance. Co-culture of these DLBCL cells with M0 macrophages led to the polarization of M0 macrophages toward the M2 phenotype, a process known to support tumor progression. Intriguingly, we demonstrated that SYHA1813, a compound targeting both VEGFR and CSF1R, effectively reshaped the tumor microenvironment (TME) and significantly overcame the acquired resistance to BTK inhibitors in both BTK-mutated and wild-type BTK DLBCL models by inhibiting angiogenesis and modulating macrophage polarization. Overall, this study not only promotes the development of new BTK inhibitors but also offers innovative treatment strategies for B-cell lymphomas, including those with BTK mutations.

Association between metabolic dysfunction-associated fatty liver disease and abdominal aortic aneurysm.

BACKGROUND AND AIMS: Abdominal aortic aneurysm (AAA) is the second most common aortic pathological manifestation. Metabolic dysfunction-associated fatty liver disease (MAFLD) has a wide impact on the cardiovascular system and may be a risk factor for AAA. The aim of this study was to investigate whether MAFLD is associated with the risk of AAA. METHODS AND RESULTS: We used data from the prospective UK Biobank cohort study. MAFLD is defined as hepatic steatosis plus metabolic abnormality, type 2 diabetes, or overweight/obesity. AAA is collected by ICD-10 code. Cox regression was established to analyze the association between MAFLD and AAA. A total of 370203 participants were included; the average age of the participants was 56.7 ± 8.0 years, and 134649 (36.4 %) were diagnosed with MAFLD. During the 12.5 years of follow-up, 1561 (0.4 %) participants developed AAA. After fully adjusting for confounding factors, individuals with MAFLD had a significantly increased risk of AAA (HR 1.521, 95 % CI 1.351-1.712, p < 0.001). Importantly, the risk of AAA increases with the severity of MAFLD as assessed by fibrosis scores. These associations were consistent according to sex, weight, and alcohol consumption but weaker in elderly or diabetics (P for interaction <0.05). The association between the MAFLD phenotype and AAA was independent of the polygenic risk score. Additionally, MAFLD was not associated with thoracic aortic aneurysm or aortic dissection events. CONCLUSIONS: There was a significant relationship between MAFLD and AAA. These findings strongly recommend early prevention of AAA by intervening in MAFLD.

Multi-system diseases and death trajectory of metabolic dysfunction-associated fatty liver disease: findings from the UK Biobank.

BACKGROUND: Metabolic dysfunction-associated fatty liver disease (MAFLD) is a newly defined condition encompassing hepatic steatosis and metabolic dysfunction. However, the relationship between MAFLD and multi-system diseases remains unclear, and the time-dependent sequence of these diseases requires further clarification. METHODS: After propensity score matching, 163,303 MAFLD subjects and 163,303 matched subjects were included in the community-based UK Biobank study. The International Classification of Diseases, Tenth Revision (ICD-10), was used to reclassify medical conditions into 490 and 16 specific causes of death. We conducted a disease trajectory analysis to map the key pathways linking MAFLD to various health conditions, providing an overview of their interconnections. RESULTS: Participants aged 59 (51-64) years, predominantly males (62.5%), were included in the study. During the 12.9-year follow-up period, MAFLD participants were found to have a higher risk of 113 medical conditions and eight causes of death, determined through phenome-wide association analysis using Cox regression models. Temporal disease trajectories of MAFLD were established using disease pairing, revealing intermediary diseases such as asthma, diabetes, hypertension, hypothyroid conditions, tobacco abuse, diverticulosis, chronic ischemic heart disease, obesity, benign tumors, and inflammatory arthritis. These trajectories primarily resulted in acute myocardial infarction, disorders of fluid, electrolyte, and acid-base balance, infectious gastroenteritis and colitis, and functional intestinal disorders. Regarding death trajectories of MAFLD, malignant neoplasms, cardiovascular diseases, and respiratory system deaths were the main causes, and organ failure, infective disease, and internal environment disorder were the primary end-stage conditions. Disease trajectory analysis based on the level of genetic susceptibility to MAFLD yielded consistent results. CONCLUSIONS: Individuals with MAFLD have a risk of a number of different medical conditions and causes of death. Notably, these diseases and potential causes of death constitute many pathways that may be promising targets for preventing general health decline in patients with MAFLD.

Long- and very long-chain ceramides are predictors of acute kidney injury in patients with acute coronary syndrome: the PEACP study.

BACKGROUND: Acute kidney injury (AKI) can be caused by multiple factors/events, including acute coronary syndrome (ACS). Ceramides are involved in atherosclerosis progression, cardiovascular events, and renal damage. Almost no studies have been conducted on the relationship between ceramide concentrations and AKI events. Therefore, we evaluated the association between plasma ceramide level at admission and AKI in patients with ACS undergoing percutaneous coronary intervention. METHODS: We enrolled 842 ACS patients from the Prospective Multicenter Study for Early Evaluation of Acute Chest Pain. AKI was defined using the criteria from the 2012 Kidney Disease: Improving Global Outcomes. Eleven C16-C26 ceramides were measured using the high-performance liquid chromatography interfaced to tandem mass spectrometer procedure. Logistic regression models were used to evaluate relationships between ceramides and AKI risk. The area under the receiver operating characteristic curves (AUC) was used to evaluate differences between ceramides. RESULTS: Overall, 139 (16.5%) patients developed AKI during hospitalisation. Patients who developed AKI had higher levels of Cer(d18:1/16:0), Cer(d18:1/18:0), Cer(d18:1/20:0), Cer(d18:1/21:0), Cer(d18:1/24:1), and Cer(d18:1/24:2) than patients who did not (P < 0.05). In risk-factor adjusted logistic regression models, these ceramides were independently associated with AKI risk (P < 0.05). Cer(d18:1/24:2) had the highest odds ratio of 3.503 (Q4 vs. Q1, 95% confidence interval: 1.743-7.040, P < 0.001). Ceramides had AUCs of 0.581-0.661 (P < 0.001) for AKI. Each ceramide combined with the Mehran risk score (AUC: 0.780) had AUCs of 0.802-0.808, greater than the Mehran risk score alone. CONCLUSION: Long-chain and very-long-chain ceramide levels may help determine the high AKI risk beyond traditional assessments.

"Sandwich" protocol based on modified SMILE regimen for children with newly extranodal NK/T cell lymphoma, nasal type: a single-arm, single-center clinical study.

Extranodal NK/T-cell lymphoma, nasal type (ENKTL), which is a rare form of mature T/NK cell lymphoma in children, currently lacks a standardized first-line treatment approach. However, a treatment protocol known as the "sandwich" regimen has been used in children newly diagnosed with ENKTL. This protocol combines the administration of methotrexate, ifosfamide, etoposide, pegaspargase, and dexamethasone (referred to as SMILE) with the addition of radiotherapy (RT). From September 2017 to December 2020, a total of five patients were included in the study, consisting of three males and two females. The median age of onset was 10.6 years (range, 9.8 to 14.0 years). Among the patients, four had nasal/nasopharyngeal disease at stage II, while one patient had extra nasal disease involving the skin at stage IV. The median EBV-DNA level in plasma was 1.68 × 103 copies/ml (range, 0.44 to 21.1 × 103copies/ml). All the patients had good overall response after 2 cycles of chemotherapy and radiotherapy, including 4 of the patients who had a complete response and 1 of the patients with partial remission. The patient with stage IV received allogeneic hematopoietic stem cell transplantation after the EBV-DNA level was elevated again during treatment. One patient in the low-risk group experienced grade 4 oral mucositis, while no other severe complications or treatment-related deaths were observed. The median follow-up period was 22 months (range, 5 to 57 months). All five patients successfully completed their treatment, with four patients achieving event-free survival, and one patient was lost to follow-up. The median OS time and EFS time was 33 months (range: 18-57 months) and 20 months (range: 5-47 months), respectively. The sandwich protocol has demonstrated a high response rate, good tolerance to chemotherapy, and no treatment-related fatalities. However, further confirmation is necessary through additional clinical studies involving larger sample sizes. Clinical trial registration number: Due to modified SMILE regimens with sandwiched radiotherapy yielded promising outcomes in children ENKTL, we have carried out a phase II multicenter clinical trial (ChiCTR220005954) for children ENKTL in China to further verify the efficacy and safety.

Association between malnutrition and stroke-associated pneumonia in patients with ischemic stroke.

BACKGROUND: Malnutrition is associated with a high risk of mortality in adults with ischemic stroke (IS). This study aimed to investigate the relationship between malnutrition and the risk of stroke-associated pneumonia (SAP) as only a few studies examined the relationship between malnutrition and the risk of SAP in IS. METHODS: Patients were included from emergency departments of five tertiary hospitals in the REtrospective Multicenter study for Ischemic Stroke Evaluation (REMISE) study from January 2020 to December 2020. Malnutrition was defined according to the Controlling Nutritional Status (CONUT), Geriatric Nutritional Risk Index (GNRI), and Prognostic Nutritional Index (PNI) systems. Multivariable logistic regression analysis was used to explore the association between malnutrition and risk of SAP. RESULTS: We enrolled 915 patients with IS, 193 (14.75%), 495 (54.1%), and 148 (16.2%) of whom were malnourished according to the PNI, CONUT, and GNRI scores, respectively. SAP occurred in 294 (32.1%) patients. After adjusting for confounding influencing factors in the logistic regression analysis, malnutrition (moderate and severe risk vs. absent malnutrition) was independently associated with an increased risk of SAP based on the PNI (odds ratio [OR], 5.038; 95% confidence interval [CI] 2.435-10.421, P < 0.001), CONUT (OR, 6.941; 95% CI 3.034-15.878, P < 0.001), and GNRI (OR, 2.007; 95% CI 1.186-3.119, P = 0.005) scores. Furthermore, adding malnutrition assessment indices to the A2DS2 score significantly improved the ability to predict SAP by analysis of receiver operating characteristic curves and net reclassification improvement. CONCLUSION: Malnutrition was notably prevalent in patients with IS and independently associated with an increased risk of SAP. Further studies are required to identify the effect of interventions on malnutrition to reduce the risk of SAP.

The Caprini Risk Score for Early Prediction of Mortality in Patients With Acute Coronary Syndrome.

BACKGROUND: The Caprini Risk Score (CRS) is a validated predictive instrument for venous thrombosis. Previous investigators have shown that a high CRS is associated with a higher risk of mortality from thrombotic diseases. OBJECTIVE: The aim of this study was to assess the association between the CRS and prognosis of patients with acute coronary syndrome (ACS). METHODS: Secondary analysis of data from a retrospective cohort study was conducted. Patients were classified into 3 CRS-based categories (CRS ≤ 2, CRS = 3-4, and CRS ≥ 5, indicating low, medium, and high, respectively). Kaplan-Meier curves and Cox regression models were used to assess the prognosis of patients with ACS. All-cause mortality and cardiac mortality were the end points. RESULTS: Two hundred fifty-four patients (12.8%) died during follow-up. Multivariate Cox regression models identified CRS as an independent risk factor for all-cause mortality among patients with ACS (CRS = 3-4 vs CRS ≤ 2, hazard ratio: 3.268, 95% confidence interval: 1.396-7.647, P = .006; CRS ≥ 5 vs CRS ≤ 2, hazard ratio: 4.099, 95% confidence interval: 1.708-9.841, P = .002). Pearson correlation analysis showed a positive correlation between CRS and fibrinogen level ( r = 0.486, R2 = 0.765, P < .001) as well as D-dimer level ( r = 0.480, R2 = 0.465, P < .001). CONCLUSION: The CRS is a useful prognostic assessment instrument for patients with ACS, and the risk stratification of patients with ACS can be achieved based on their CRS at admission.

Binding properties of odorant-binding protein 4 from bean bug Riptortus pedestris to soybean volatiles.

The bean bug Riptortus pedestris is a notorious insect pest that can damage various crops, especially soybean, in East Asia. In insects, the olfactory system plays a crucial role in host finding and feeding behaviour in which the odorant-binding proteins (OBPs) are believed to be involved in initial step in this system. In this study, we produced the R. pedestris adult antennae-expressed RpedOBP4 protein using a recombinant expression system in E. coli. Fluorescence competitive binding confirmed that RpedOBP4 has binding affinities to 7 of 20 soybean volatiles (ligands), and that a neutral condition is the best environment for it. The binding property of RpedOBP4 to these ligands was further revealed by integrating data from molecular docking, site-directed mutagenesis and ligand binding assays. This demonstrated that five amino acid residues (I30, L33, Y47, I57 and Y121) are involved in the binding process of RpedOBP4 to corresponding ligands. These findings will not only help us to more thoroughly explore the olfactory mechanism of R. pedestris during feeding on soybean, but also lead to the identification of key candidate targets for developing environmental and efficient behaviour inhibitors to prevent population expansion of R. pedestris in the future.

Dynamic molecular choreography of circadian rhythm disorders (DMCRD): a prospective cohort study protocol.

BACKGROUND: Circadian rhythm disorders (CRDs) are closely associated with the occurrence and development of various diseases, such as inflammatory and cardiovascular diseases, as well as tumors. The impact of a CRD on bodily health is a complex and comprehensive process, and its molecular mechanisms and signaling pathways are still unclear. We therefore aimed to investigate the molecular mechanism variation and adverse outcomes associated with CRDs in a prospective cohort of CRD cases and controls at term using multiomics data. The study has been tasked with developing a precise health promotion model for the prevention and management of CRDs. METHODS: This will be a 5-year prospective cohort study centered on the health management of individuals with CRDs. One hundred volunteers were recruited and had undergone baseline specimen collection, health examination, and health assessment. All of them will be followed up every year using the same protocol, and their biological specimens will be subjected to multiomics analysis after standardized processing. DISCUSSION: Longitudinal health examination, health assessment, and multiomics data will be analyzed to study the impact of CRDs on the volunteers' health status. The results of this study will promote the development of targeted health management programs based on precision medicine. TRIAL REGISTRATION: The clinical study registration has been completed (Trial Registration No. ChiCTR2100047242 ).

Hemophagocytic Lymphohistiocytosis in Langerhans Cell Histiocytosis: A Case Series and Literature Review.

Langerhans cell histiocytosis (LCH) is characterized pathologically by langerin-positive (CD207+) dendritic cell proliferation and is considered by some as a myeloid neoplastic disorder. Hemophagocytic lymphohistiocytosis (HLH) is associated with immune dysregulation characterized by the accumulation of activated macrophages and hypercytokinemia. However, these 2 histiocytosis rarely coexist. Currently, the etiology, risk factors, optimal therapy, and outcomes of LCH-HLH remain unclear. We reviewed the medical records of 7 LCH-HLH patients from our hospital and analyzed 50 LCH-HLH patients reported in scientific literature. The median age of LCH onset of these 57 LCH-HLH patients was 1 year, and 91% (52/57) of patients diagnosed as LCH were less than 2 years old. Fifty-six LCH-HLH patients belonged to the multisystem LCH category and 84% (47/56) patients had risk-organ involvement. Twenty-three LCH-HLH patients were complicated with infection and 3 patients had a primary pathogenic mutation of HLH. Overall, 90% of LCH patients developed HLH at the diagnosis or during chemotherapy. Of the 57 LCH-HLH patients, 15 died. Multisystem LCH patients with risk-organ involvement under 2 years old were most likely to develop HLH when complicated with infection at diagnosis or during chemotherapy. Identifying LCH-HLH patients during early stages and treating them with prompt chemotherapy, hematopoietic stem cell transplantation, or supportive therapies are important for better survival.

Subclinical cardiovascular disease and frailty risk: the atherosclerosis risk in communities study.

BACKGROUND: Cardiovascular disease (CVD) is associated with a greater frailty risk, but it remains unknown if pathways that contribute to CVD are associated with the frailty risk. Thus, we aimed to investigate whether elevations in high-sensitivity cardiac troponin T (hs-cTnT) and N-terminal pro-B-type natriuretic peptide (NT-proBNP) for those without known CVD at baseline are associated with a higher frailty risk. METHODS: This study used data from the Atherosclerosis Risk in Communities study. Cardiac biomarkers were measured from stored plasma samples collected at Visit 2 (1991-1993). Frailty was recorded at Visit 5 (2011-2013). Cox regression models were used to determine the association of cardiac biomarkers with frailty risk. RESULTS: Overall, 360/5199 (6.9%) participants aged 55.1 ± 5.1 years developed frailty during a median follow-up of 21.7 years. The incidence of frailty was significantly higher in participants with hs-cTnT ≥14 ng/L (vs. < 14 ng/L: 17.9% vs. 6.7%) or NT-proBNP ≥300 pg/ml (vs. < 300 pg/ml: 19.7% vs. 6.8%) (all P < 0.001). Comparing higher vs. lower cut-off levels of either hs-cTnT (14 ng/l) or NT-proBNP (300 pg/ml) demonstrated a greater than two-fold higher frailty risk, with hazard ratios (HRs) of 2.13 (95% confidence interval (CI): 1.130-4.01, P = 0.020) and 2.61 (95% CI: 1.28-5.33, P = 0.008), respectively. Individuals with both elevated hs-cTnT and NT-proBNP had a higher frailty risk than those without it (HR: 4.15; 95% CI: 1.50-11.48, P = 0.006). CONCLUSIONS: High hs-cTnT and NT-proBNP levels are strongly associated with incident frailty in the community-dwelling population without known CVD. Subclinical cardiac damage (hs-cTnT) and/or wall strain (NT-proBNP) may be the key pathway of CVD patients developing frailty. Detection of hs-cTnT and NT-proBNP may help for early screening of high-risk frailty and providing individualised intervention. TRIAL REGISTRATION: URL: https://www. CLINICALTRIALS: gov ; Unique identifier: NCT00005131 .

The Role of Sphingomyelin Metabolism in the Protection of Rat Brain Microvascular Endothelial Cells by Mild Hypothermia.

BACKGROUND: Sphingomyelin, composed of ceramide (CER), sphingosine (Sph), and sphingosine-1-phosphate (S1P), is an essential structural component of cellular membranes and plays an important role in the signal transduction regulating cell proliferation, differentiation, and apoptosis. CER is mainly metabolized to Sph, and under the action of sphingosine kinases (SphKs), Sph produces S1P, which can be converted back to Sph by S1P phosphatase. It is suggested that the fate of cells is controlled partly by the interconversion of CER and intracellular S1P. SphK2 is considered the main kinase of S1P synthesis in the central nervous system. The objective of this study was to explore the hypothesis that SphK2 and sphingomyelin metabolism participated in the process of cell apoptosis and the protection of mild hypothermia. METHODS: Rat brain microvascular endothelial cells were divided into groups for intervention of SphK2 inhibitor, SphK2 small interfering RNA (SiRNA) transfection, ischemia-reperfusion, and mild hypothermia. After interventions, cell apoptosis was detected by 4,6-diamino-2-phenyl indole (DAPI) and flow cytometry, the expression of apoptosis-related protein was detected by Western Blot, and SphK2 enzyme activity and the content of sphingomyelin were determined. RESULTS: ABC294640 and transfection of SphK2 SiRNA could increase apoptosis, accompanied by the increase of the expression of proapoptotic genes Caspase3 and Bax and the decrease of the expression of BCL-2. This effect could be partially reversed with mild hypothermia. Ischemia-reperfusion injury, transfection of SphK2 SiRNA, and the addition of ABC294640 could significantly inhibit the activity of SphK2, accompanied by the increase of CERs and the decrease of S1P. Mild hypothermia could reverse the changes of sphingolipids but have no significant effect on the activity of sphk2. CONCLUSIONS: Mild hypothermia can inhibit the occurrence of apoptosis and reverse the changes of apoptosis-related genes and sphingomyelin content induced by ischemia-reperfusion injury, but the effect on sphk2 enzyme activity was not significant.

Root Rot Disease of Torreya grandis Caused by Fusarium fujikuroi in China.

Torreya grandis is an evergreen plant endemic of China and widely grown in Southern China. Its fruit is a precious nut in China, rich in vitamins and minerals, can be directly eaten, can also be used as medicinal plants with functions of lowering blood lipids and softening blood vessels (Wang 2022). From 2018 to 2020, typical root rot symptoms of Torreya grandis was found in plantations in Huangshan and surrounding areas of Huangshan, Anhui province, China. About 15 to 32% of root rot disease incidence was recorded at the plantation. Diseased plants were observed with symptoms such as yellow to brownish leaves without lesions and later drying, and rotten roots looked dark brown while the roots of heathy plants showed white, and eventually leading to the death of the diseased plant. The root rot symptomatic plants were collected in June of 2020. Tissues were cut to the length of 0.3 to 0.5 cm, then surface sterilized by 2% sodium hypochlorite for 2 min and 75% alcohol for 1 min, rinsed three times in sterile distilled water, and placed on potato dextrose agar (PDA) and incubated at 25℃ for 5 to 9 days. Eight isolates with similar morphology were isolated from single spores. On PDA, the isolates produced abundant aerial white mycelia with septation and turned violet to dark pink on the reverse side of the culture. Morphological characteristic was determined using a pure culture grown on synthetic low nutrient agar (SNA). Two types of conidia, microconidia and macroconidia, were observed on SNA. Macroconidia were long and slender, usually 3 to 5 septate, measuring 2.7 to 4.3 × 22.3 to 49.6 µm (n=30), and narrowed at the both ends. Microconidia were abundant, oval, clavate or ovate, zero to one septate and measured 1.6 to 3.9 × 4.4 to 13.0 µm (n=50). According to the culture and conidial characteristics, the isolates were tentatively identified as Fusarium species (Leslie and Summerell 2006). Four isolates were random selected for molecular identification. The general primers ITS1/ITS4 for internal transcribed spacer (ITS) (White et al. 1990), EF1/EF2 for translation elongation factor (TEF1) (O'Donnell et al. 1998), 5F2/7cR for the second largest subunit of RNA polymerase Ⅱ(RPB2) (O'Donnell et al., 2007), H3-1a/H3-1b for Histone H3 (Jacobs et al., 2010), F5/R8 for subunits 1 of DNA-directed RNA polymerase Ⅱ (RPB1) (O'Donnell et al. 2010) and MS3F/MS3R for mitochondrial small subunit (mtSSU) (Stenglein et al. 2010) were amplified, respectively. The products were sequenced and deposited in GenBank with accession numbers of MW350689, MW029444, ON077156, ON077158, ON077157, ON054432, respectively. Blast analysis showed 99.40 to 100% sequence homology with known F. fujikuroi isolates. A phylogenetic analysis based on the concatenated sequences clustered from the combined datasets (TEF1, RPB2, Histone H3, RPB1 and mtSSU) revealed the isolate most closely related to the F. fujikuroi (100% bootstrap). Fifteen 2-year-old healthy plants of Torreya grandis were selected for the pathogenicity test. A conidial suspension (1×106 conidia/ml) was prepared by collecting spores from 10-day-old cultures on PDA. The root of each plants inoculated with 200 ml of a 106 conidia/ml suspension, and the five control plants inoculated with sterilized water. The plants were incubated in green house with 25℃ (14 h light)/22℃ (10 h dark) at 85% humidity. Two weeks later, 100% of artificially inoculated plants showed the same symptoms similar to those observed in the plantation, like yellow leaves, dark brown and rotten roots, meanwhile, the roots of control plants displayed healthy. From symptomatic roots, the pathogen was reisolated which satisfying Koch's postulates. F. fujikuroi causes root rot of soybean and Reineckia carnea (Detranaltes et al. 2021, Sun et al. 2018).To the best of our knowledge, this is the first report of F. fujikuroi causing root rot of Torreya grandis in China.

Pathophysiological role of prostaglandin E synthases in liver diseases.

Prostaglandin E synthases (PGESs) convert cyclooxygenase (COX)-derived prostaglandin H2 (PGH2) into prostaglandin E2 (PGE2) and comprise at least three types of structurally and biologically distinct enzymes. Two of these, namely microsomal prostaglandin E synthase-1 (mPGES-1) and mPGES-2, are membrane-bound enzymes. mPGES-1 is an inflammation-inducible enzyme that converts PGH2 into PGE2. mPGES-2 is a bifunctional enzyme that generally forms a complex with haem in the presence of glutathione. This enzyme can metabolise PGH2 into malondialdehyde and can produce PGE2 after its separation from haem. In this review, we discuss the role of PGESs, particularly mPGES-1 and mPGES-2, in the pathogenesis of liver diseases. A better understanding of the roles of PGESs in liver disease may aid in the development of treatments for patients with liver diseases.

Nutritional Risk Screening 2002 was associated with acute kidney injury and mortality in patients with acute coronary syndrome: Insight from the REACP study.

BACKGROUND AND AIMS: Acute kidney injury (AKI) is a common complication of acute coronary syndrome (ACS), and is associated with increased risk of morbidity and mortality. We aimed to evaluate the impact of malnutrition risk at admission assessed using Nutritional Risk Screening 2002 (NRS-2002) on AKI and mortality in patients with ACS. METHODS AND RESULTS: We enrolled 3185 ACS patients from the retrospective multi-centre study. AKI was defined as criteria of the 2012 Kidney Disease Improving Global Outcomes. Risk of malnutrition was defined as NRS-2002 score ≥3. The end points were AKI and all-cause mortality. There were 926 (29.1%) patients with risk of malnutrition and 481 (15.1%) patients complicated with AKI during hospitalisation, and 378 (12.0%) patients died during the 13.1 (8.5-20.4) months of follow-up. Patients with NRS-2002 score ≥3 had a higher incidence of AKI and all-cause mortality (P < 0.001). Multivariate logistic and Cox regression analysis showed that the adjusted odd ratios and hazard ratios of categorised NRS-2002 (<3 vs. ≥3) for AKI and mortality were 1.643 (95% confidence interval: 1.242-2.172, P < 0.001) and 2.026 (95% confidence interval: 1.491-2.753, P < 0.001), respectively. In structural equation modelling, the indirect effects of NRS-2002 on mortality via AKI were 54.1% (P < 0.001). CONCLUSION: The risk of malnutrition assessed using NRS-2002 was useful in identifying high-risk patients with AKI and mortality, and patients with ACS may benefit from further nutritional intervention and prevention of AKI. REGISTRATION NUMBER: ChiCTR1900024657.

Prognostic Value of the Nutritional Risk Screening 2002 Scale in Patients With Acute Myocardial Infarction: Insights From the Retrospective Multicenter Study for Early Evaluation of Acute Chest Pain.

BACKGROUND: The Nutritional Risk Screening 2002 (NRS-2002) scale is a rapid and effective screening instrument that assesses nutritional risk among hospitalized patients. OBJECTIVE: The present study aimed to explore the prognostic value of the NRS-2002 scale in acute myocardial infarction (AMI) considering its uncertain role in this particular condition. METHODS: Patients with AMI included in the Retrospective Multicenter Study for Early Evaluation of Acute Chest Pain were investigated. Kaplan-Meier survival analysis and Cox proportional hazards models were used to analyze the association between NRS-2002 and mortality in patients with AMI. The primary and secondary endpoints were all-cause and cardiac mortality during the follow-up period. RESULTS: A total of 2307 patients were enrolled, among whom 246 (10.7%) died within a median follow-up duration of 10.67 (8.04-14.33) months. Kaplan-Meier analysis revealed that patients with an NRS-2002 score of 3 or higher had poorer cumulative survival than those with an NRS-2002 score lower than 3 (P < .001). In the multivariate Cox regression analysis, patients with an NRS-2002 score of 3 or higher had more than double the risk for all-cause mortality (hazard ratio, 2.25; 95% confidence interval, 1.50-3.40; P < .001) and twice the risk for cardiac-related mortality (hazard ratio, 2.01; 95% confidence interval, 1.29-3.13; P = .002) than did patients with lower scores. CONCLUSIONS: Our results showed that the NRS-2002 screening instrument was an independent prognostic predictor for both all-cause and cardiac mortality in patients with AMI. Nutritional risk assessment based on the NRS-2002 scale may provide useful prognostic information of early nutritional risk stratification in patients with AMI.

First Report of Colletotrichum brevisporum Causing Anthracnose of Dalbergia odorifera in China.

Dalbergia odorifera T. Chen (family Fabaceae) is one of four prized species of mahogany plant in China. In June 2017, an investigation of the condition of anthracnose was carried out on apporximately 333 hectares of D. odorifera plantations in Haikou City, Hainan Province (110.19°E, 20.03°N). Approximately 40% of D. odorifera plants had disease symptoms. Lesions on leaves were brown to grayish-white containing black dots and dark-brown borders, occasionally surrounded by a yellowish-green halo. Leaf spots generally occurred along the edge of the leaf. Severely infected leaves became withered and died. Hyphal growth was recovered from symptomatic leaf tissue, surface-sterilized with a 75% ethanol solution for 30s, rinsed with sterile distilled water, plated on potato dextrose agar (PDA), and incubated at 26°C in the dark. The representative isolate JXHTC19 was recovered by transferring a hyphal tip to a fresh PDA plate to obtain a pure culture. Fungal colonies had white aerial mycelium initially, turning pale gray after 3 days. At 7 days, colonies had a cottony appearance ranging from white to dark gray with orange masses of conidia. The colony surface was slimy and aerial mycelium was sparse. Isolates displayed single-celled, cylindrical, hyaline conidia that were rounded at both ends, and were 9.7 - 16.4 µm long (avg. 13.5 µm) × 3.6 - 6.2 µm wide (vg. 4.8 µm) (n = 100). To further identify the fungus, genomic DNA was extracted from single conidial cultures of JXHTC19. The rDNA internal transcribed spacer (ITS) region, glutamine synthetase (GS) gene, partial sequence of glyceraldeyde-3-phosphate dehydrogenase-like (GAPDH) gene, actin (ACT) gene, and beta-tubulin (TUB2) gene were amplified using the primer pairs ITS4/ITS5, GS-F/GS-R, GDF1/GDR1, ACT-512F/ACT-783R, and TUB2-T1/Bt-2b (Weir et al 2012), respectively. The results showed that the ITS, GS, GAPDH, ACT and TUB2 genes of the target strain (JXHTC19) have 100%, 95%, 100%, 97% and 98% sequence homology with C. brevisporum, respectively. The sequences obtained were deposited in GenBank (MF993572, MN737615, MN737614, MG515612, and MG515615[LJ1]). All five sequences were analyzed together with representative sequences from type or ex-type specimens of the Colletotrichum genus (Yang et al. 2011, Weir et al. 2012) and a phylogenetic tree was generated via the neighbor-joining method using MEGA6. The tree placed the isolate in the same group as C. brevisporum. Thus, both morphological and molecular characteristics identified the pathogen as C. brevisporum. To verify Koch's postulates, two-year-old leaves of healthy potted D. odorifera plants (n = 6) were inoculated with a spore suspensions of JXHTC19 that contained 105 conidia/ml. Plants were sprayed with water to serve as mock-inoculated controls [LJ2](Garibaldi et al, 2020). Six plants per treatment were used in each test. The test was repeated once.Plants were incubated in moist chambers at 26°C and monitored daily for symptom development. After five days, eleven of twelve isolates [LJ3]caused lesions on all inoculated plants, whereas no symptoms developed on the mock-inoculated controls. Koch's postulates were fulfilled by reisolating the same fungus and verifying its colony and morphological characters as C. brevisporum. To our knowledge, this is the first report of this species causing anthracnose of D. odorifera in China. Corresponding measures must be adopted to manage this disease such as reducing the planting density of D. odorifera and increasing the species diversity of undergrowth vegetation. These results could help develop better monitoring and management practices for this disease.