Multi-mechanism antitumor/antibacterial effects of Cu-EGCG self-assembling nanocomposite in tumor nanotherapy and drug-resistant bacterial wound infections.

Chemotherapy and surgery stand as primary cancer treatments, yet the unique traits of the tumor microenvironment hinder their effectiveness. The natural compound epigallocatechin gallate (EGCG) possesses potent anti-tumor and antibacterial traits. However, the tumor's adaptability to chemotherapy due to its acidic pH and elevated glutathione (GSH) levels, coupled with the challenges posed by drug-resistant bacterial infections post-surgery, impede treatment outcomes. To address these challenges, researchers strive to explore innovative treatment strategies, such as multimodal combination therapy. This study successfully synthesized Cu-EGCG, a metal-polyphenol network, and detailly characterized it by using synchrotron radiation and high-resolution mass spectrometry (HRMS). Through chemodynamic therapy (CDT), photothermal therapy (PTT), and photodynamic therapy (PDT), Cu-EGCG showed robust antitumor and antibacterial effects. Cu+ in Cu-EGCG actively participates in a Fenton-like reaction, generating hydroxyl radicals (·OH) upon exposure to hydrogen peroxide (H2O2) and converting to Cu2+. This Cu2+ interacts with GSH, weakening the oxidative stress response of bacteria and tumor cells. Density functional theory (DFT) calculations verified Cu-EGCG's efficient GSH consumption during its reaction with GSH. Additionally, Cu-EGCG exhibited outstanding photothermal conversion when exposed to 808 nm near-infrared (NIR) radiation and produced singlet oxygen (1O2) upon laser irradiation. In both mouse tumor and wound models, Cu-EGCG showcased remarkable antitumor and antibacterial properties.

Plasma Concentration of Posaconazole in Septic Shock Patients with Continuous Renal Replacement Therapy: A Case Report.

Objective: This study aims to evaluate the impact of continuous renal replacement therapy (CRRT) on the plasma concentrations of Posaconazole in critically ill patients. Case presentation: In this study, we reported a patient with septic shock, cardiac arrest, and Multiple Organ Dysfunction Syndrome showed improvement following anti-infective treatment with Posaconazole. The patient's condition improved after Posaconazole was administered for anti-infective treatment. The concentration of Posaconazole was measured during CRRT. The results showed that the trough concentrations of Posaconazole were 1.9mg/L and 0.8mg/L on the 7th and 11th days of CRRT, respectively. The peak concentrations of Posaconazole were 6.6 mg/L and 4.3 mg/L on the 7th and 11th days of CRRT. On the first and second day after the discontinuation of CRRT, the trough concentrations of Posaconazole were 0.7 mg/L and 0.8 mg/L, and the peak concentrations were 2.6 mg/L and 2.2 mg/L. These results indicated that the trough and peak concentrations of Posaconazole were not significantly different before and after CRRT. No adverse reactions occurred during the follow-up. Conclusion: Posaconazole plasma concentrations remained stable during and after CRRT, suggesting that dose adjustments are not necessary in these clinical settings.

Association of Lipoprotein(a) Levels With Myocardial Infarction in Patients With Low-Attenuation Plaque.

BACKGROUND: Lipoprotein(a) (Lp[a]) is associated with an increased risk of myocardial infarction (MI). However, the mechanism underlying this association has yet to be fully elucidated. OBJECTIVES: This multicenter study aimed to investigate whether association between Lp(a) and MI risk is reinforced by the presence of low-attenuation plaque (LAP) identified by coronary computed tomography angiography (CCTA). METHODS: In a derivation cohort, a total of 5,607 patients with stable chest pain suspected of coronary artery disease who underwent CCTA and Lp(a) measurement were prospectively enrolled. In validation cohort, 1,122 patients were retrospectively collected during the same period. High Lp(a) was defined as Lp(a) ≥50 mg/dL. The primary endpoint was a composite of time to fatal or nonfatal MI. Associations were estimated using multivariable Cox proportional hazard models. RESULTS: During a median follow-up of 8.2 years (Q1-Q3: 7.2-9.3 years), the elevated Lp(a) levels were associated with MI risk (adjusted HR [aHR]: 1.91; 95% CI: 1.46-2.49; P < 0.001). There was a significant interaction between Lp(a) and LAP (Pinteraction <0.001) in relation to MI risk. When stratified by the presence or absence of LAP, Lp(a) was associated with MI in patients with LAP (aHR: 3.03; 95% CI: 1.92-4.76; P < 0.001). Mediation analysis revealed that LAP mediated 73.3% (P < 0.001) for the relationship between Lp(a) and MI. The principal findings remained unchanged in the validation cohort. CONCLUSIONS: Elevated Lp(a) augmented the risk of MI during 8 years of follow-up, especially in patients with LAP identified by CCTA. The presence of LAP could reinforce the relationship between Lp(a) and future MI occurrence.

Single-cell transcriptomic analysis reveals transcript enrichment in oxidative phosphorylation, fluid sheer stress, and inflammatory pathways in obesity-related glomerulopathy.

Obesity-related glomerulopathy (ORG) is an independent risk factor for chronic kidney disease and even progression to end-stage renal disease. Efforts have been undertaken to elucidate the mechanisms underlying the development of ORG and substantial advances have been made in the treatment of ORG, but relatively little is known about cell-specific changes in gene expression. To define the transcriptomic landscape at single-cell resolution, we analyzed kidney samples from four patients with ORG and three obese control subjects without kidney disease using single-cell RNA sequencing. We report for the first time that immune cells, including T cells and B cells, are decreased in ORG patients. Further analysis indicated that SPP1 was significantly up-regulated in T cells and B cells. This gene is related to inflammation and cell proliferation. Analysis of differential gene expression in glomerular cells (endothelial cells, mesangial cells, and podocytes) showed that these cell types were mainly enriched in genes related to oxidative phosphorylation, cell adhesion, thermogenesis, and inflammatory pathways (PI3K-Akt signaling, MAPK signaling). Furthermore, we found that the podocytes of ORG patients were enriched in genes related to the fluid shear stress pathway. Moreover, an evaluation of cell-cell communications revealed that there were interactions between glomerular parietal epithelial cells and other cells in ORG patients, with major interactions between parietal epithelial cells and podocytes. Altogether, our identification of molecular events, cell types, and differentially expressed genes may facilitate the development of new preventive or therapeutic approaches for ORG.

Analysis of Factors and T-Lymphocyte Subset Changes in Pediatric Recurrent Respiratory Infections Post-Pidotimod Treatment.

Objective: This study aims to analyze factors contributing to recurrent respiratory tract infections (RRTIs) in pediatric patients and evaluate the efficacy of pidotimod (PI) treatment. Methods: This study utilized a retrospective cohort design, enrolling a total of 85 children diagnosed with RRTIs between September 2020 and September 2022, alongside 54 healthy children. Logistic regression analysis was employed to identify factors contributing to RRTI occurrence. Among the participants, 40 children underwent conventional treatment (control group), while 45 received PI treatment (research group). Comparative analyses were conducted to assess clinical efficacy and adverse effects between the two treatment groups. Results: The history of family members' smoking and parental allergy emerged as independent risk factors for RRTIs (P < .05, OR>1), whereas parental education level, outdoor activity, and micronutrient intake were identified as independent protective factors for RRTIs (P < .05, OR<1). Symptoms such as cough, fever, rhonchi, moist rales, and tonsillar enlargement resolved significantly faster in the research group compared to the control group (P < .05). Additionally, the research group exhibited reduced infection duration and fewer recurrent infections (P < .05). Following treatment, the overall treatment efficacy was superior in the research group compared to the control group (P < .05), with no significant difference in the incidence of adverse effects (P > .05). Post-treatment, levels of CD3+, CD4+, and CD4+/CD8+ were elevated in the research group compared to the control group, while CD8+ levels were lower (P < .05). Conclusions: Daily outdoor activity among children, family members' history of smoking, parental allergy history, education level, and micronutrient intake emerged as independent factors influencing pediatric RRTIs. Furthermore, PI was identified as a significant treatment option for RRTIs.

Self-Assembled Fe-Phenolic Acid Network Synergizes with Ferroptosis to Enhance Tumor Nanotherapy.

Natural polyphenolic compound rosmarinic acid (RA) has good antitumor activity. However, the distinctive tumor microenvironment, characterized by low pH and elevated levels of glutathione (GSH), enhances the tolerance of tumors to the singular anti-tumor treatment mode using RA, resulting in unsatisfactory therapeutic efficacy. Targeting nonapoptotic programmed cell death processes may provide another impetus to inhibit tumor growth. RA possesses the capability to coordinate with metal elements. To solve the effect restriction of the above single treatment mode, it is proposed to construct a self-assembled nanocomposite, Fe-RA. Under tumor microenvironment, Fe-RA nanocomposite exerts the characteristics of POD-like enzyme activity and depletion of GSH, producing a large amount of hydroxyl radical (·OH) while disrupting the antioxidant defense system of tumor cells. Moreover, due to the enhanced permeability and retention effect (EPR), Fe-RA can transport Fe2+ to a greater extent to tumor cells and increase intracellular iron content. Causing an imbalance in iron metabolism in tumor cells and promoting cell ferroptosis. The results of the synchrotron X-ray absorption spectroscopy (XAS) and high-resolution mass spectrometry (HRMS) prove the successful complexation of Fe-RA nanocomposite. Density functional theory (DFT) explains the efficient catalytic mechanism of its peroxide-like enzyme activity and the reaction principle with GSH.

Myocardial reperfusion injury exacerbation due to ALDH2 deficiency is mediated by neutrophil extracellular traps and prevented by leukotriene C4 inhibition.

BACKGROUND AND AIMS: The Glu504Lys polymorphism in the aldehyde dehydrogenase 2 (ALDH2) gene is closely associated with myocardial ischaemia/reperfusion injury (I/RI). The effects of ALDH2 on neutrophil extracellular trap (NET) formation (i.e. NETosis) during I/RI remain unknown. This study aimed to investigate the role of ALDH2 in NETosis in the pathogenesis of myocardial I/RI. METHODS: The mouse model of myocardial I/RI was constructed on wild-type, ALDH2 knockout, peptidylarginine deiminase 4 (Pad4) knockout, and ALDH2/PAD4 double knockout mice. Overall, 308 ST-elevation myocardial infarction patients after primary percutaneous coronary intervention were enrolled in the study. RESULTS: Enhanced NETosis was observed in human neutrophils carrying the ALDH2 genetic mutation and ischaemic myocardium of ALDH2 knockout mice compared with controls. PAD4 knockout or treatment with NETosis-targeting drugs (GSK484, DNase1) substantially attenuated the extent of myocardial damage, particularly in ALDH2 knockout. Mechanistically, ALDH2 deficiency increased damage-associated molecular pattern release and susceptibility to NET-induced damage during myocardial I/RI. ALDH2 deficiency induced NOX2-dependent NETosis via upregulating the endoplasmic reticulum stress/microsomal glutathione S-transferase 2/leukotriene C4 (LTC4) pathway. The Food and Drug Administration-approved LTC4 receptor antagonist pranlukast ameliorated I/RI by inhibiting NETosis in both wild-type and ALDH2 knockout mice. Serum myeloperoxidase-DNA complex and LTC4 levels exhibited the predictive effect on adverse left ventricular remodelling at 6 months after primary percutaneous coronary intervention in ST-elevation myocardial infarction patients. CONCLUSIONS: ALDH2 deficiency exacerbates myocardial I/RI by promoting NETosis via the endoplasmic reticulum stress/microsomal glutathione S-transferase 2/LTC4/NOX2 pathway. This study hints at the role of NETosis in the pathogenesis of myocardial I/RI, and pranlukast might be a potential therapeutic option for attenuating I/RI, particularly in individuals with the ALDH2 mutation.

The risk factors for arteriovenous fistula dysfunction in maintenance hemodialysis patients: A cross-sectional study.

INTRODUCTION: Arteriovenous fistula (AVF) dysfunction is a prevalent complication among maintenance hemodialysis patients. However, the factors influencing AVF patency remain unclear. To address this, we conducted a study aimed at identifying factors contributing to AVF dysfunction in this patient population. METHODS: The study compared clinical data, vascular calcification score, and laboratory data focusing on blood cell composition and coagulation in 100 maintenance hemodialysis patients in whom an AVF had been inserted from January through September of 2022. The patients were divided into a group in which the AVF functioned without issues and a group in which the AVF was dysfunctional, defined as not able to provide a blood flow of greater than 200 mL/min. FINDINGS: Patients in the 2 groups (56 in the dysfunctional AVF group and 44 in the group with satisfactory AVF function) were similar demographically. Compared with the normally functioning AVF group, the AVF dysfunction group exhibited significantly higher Agatston calcium scores (20.5 [1.28, 298] median [Q1, Q3] vs. 1.14 [0.00, 11.6]; p = 0.01), elevated triglyceride levels (1.1 [0.6, 1.2] mmol/L vs. 0.5 [0.3, 0.8]; p < 0.01), increased prothrombin activity (113 ± 22.1% vs. 99.4 ± 23.1; p < 0.01), lower prothrombin time (10.4 [9.8, 10.8] s vs. 11.0 [10.3, 11.5]; p < 0.01), higher red blood cell (RBC) counts (3.5 ± 0.7 · 1012/L vs. 3.0 ± 0.7; p < 0.01), and elevated hemoglobin levels (98.0 ± 21.8 g/L vs. 84.9 ± 24.2; p < 0.01). Higher C-reactive protein (20.2 [3.3, 20.2] mg/L vs. 17.8 [6.2, 17.8]; p = 0.01) and procalcitonin levels (0.9 [0.4, 0.9] ng/mL vs. 0.5 [0.2, 0.7]; p < 0.01) were also noted. Logistic regression analysis indicated that platelet/lymphocyte ratio, monocyte/lymphocyte ratio, and RBC count were factors associated with AVF dysfunction. Increased monocyte/lymphocyte ratio and RBC count correlated with higher risk, while a higher platelet/lymphocyte ratio was associated with lower risk. DISCUSSION: Arteriovenous fistula dysfunction in maintenance hemodialysis patients is associated with higher proportions of specific hematological parameters, particularly elevated RBC count, and altered platelet/lymphocyte and monocyte/lymphocyte ratios.

Multifunctional Sr/Se co-doped ZIF-8 nanozyme for chemo/chemodynamic synergistic tumor therapy via apoptosis and ferroptosis.

Rationale: Cancer continues to be a significant public health issue. Traditional treatments such as surgery, radiotherapy, and chemotherapy often fall short because of intrinsic issues such as lack of specificity and poor drug delivery, leading to insufficient drug concentration at the tumor site and/or potential side effects. Consequently, improving the delivery of conventional chemotherapy drugs like doxorubicin (DOX) is crucial for their therapeutic efficacy. Successful cancer treatment is achieved when regulated cell death (RCD) of cancer cells, which includes apoptotic and non-apoptotic processes such as ferroptosis, is fundamental to successful cancer treatment. The developing field of nanozymes holds considerable promise for innovative cancer treatment approaches. Methods: A dual-metallic nanozyme system encapsulated with DOX was created, derived from metal-organic frameworks (MOFs), designed to combat tumors by depleting glutathione (GSH) and concurrently liberating DOX. The initial phase of the study examined the GSH oxidase-mimicking function of the dimetallic nanozyme (ZIF-8/SrSe) through enzyme kinetic assays and Density Functional Theory (DFT) simulations. Following this, we probed the ability of ZIF-8/SrSe@DOX to release DOX in response to the tumor microenvironment in vitro, alongside examining its anticancer capabilities and mechanisms prompting apoptosis or ferroptosis in cancer cells. Moreover, we established tumor-bearing animal models to corroborate the anti-tumor effectiveness of our nanozyme complex and to identify the involved apoptotic and ferroptotic pathways implicated. Results: Enzyme kinetic analyses demonstrated that the ZIF-8/SrSe nanozyme exhibits substantial GSH oxidase-like activity, effectively oxidizing reduced GSH to glutathione disulfide (GSSG), while also inhibiting glutathione peroxidase 4 (GPX4) and solute carrier family 7 member 11 (SLC7A11). This inhibition led to an imbalance in iron homeostasis, pronounced caspase activation, and subsequent induction of apoptosis and ferroptosis in tumor cells. Additionally, the ZIF-8/SrSe@DOX nanoparticles efficiently delivered DOX, causing DNA damage and further promoting apoptotic and ferroptotic pathways. Conclusions: This research outlines the design of a novel platform that combines chemotherapeutic agents with a Fenton reaction catalyst, offering a promising strategy for cancer therapy that leverages the synergistic effects of apoptosis and ferroptosis.

Plant Growth-Promoting Rhizobacteria Are Key to Promoting the Growth and Furanocoumarin Synthesis of Angelica dahurica var. formosana under Low-Nitrogen Conditions.

Microbiomes are the most important members involved in the regulation of soil nitrogen metabolism. Beneficial interactions between plants and microbiomes contribute to improving the nitrogen utilization efficiency. In this study, we investigated the Apiaceae medicinal plant Angelica dahurica var. formosana. We found that under a low-nitrogen treatment, the abundance of carbon metabolites in the rhizosphere secretions of A. dahurica var. formosana significantly increased, thereby promoting the ratio of C to N in rhizosphere and nonrhizosphere soils, increasing carbon sequestration, and shaping the microbial community composition, thus promoting a higher yield and furanocoumarin synthesis. Confirmation through the construction of a synthetic microbial community and feedback experiments indicated that beneficial plant growth-promoting rhizobacteria play a crucial role in improving nitrogen utilization efficiency and selectively regulating the synthesis of target furanocoumarins under low nitrogen conditions. These findings may contribute additional theoretical evidence for understanding the mechanisms of interaction between medicinal plants and rhizosphere microorganisms.

Multienzyme Active Manganese Oxide Alleviates Acute Liver Injury by Mimicking Redox Regulatory System and Inhibiting Ferroptosis.

Drug-induced liver injury (DILI) is a severe condition characterized by impaired liver function and the excessive activation of ferroptosis. Unfortunately, there are limited options currently available for preventing or treating DILI. In this study, MnO2 nanoflowers (MnO2Nfs) with remarkable capabilities of mimicking essential antioxidant enzymes, including catalase, superoxide dismutase (SOD), and glutathione peroxidase are successfully synthesized, and SOD is the dominant enzyme among them by density functional theory. Notably, MnO2Nfs demonstrate high efficiency in effectively eliminating diverse reactive oxygen species (ROS) such as hydrogen peroxide (H2O2), superoxide anion (O2 •-), and hydroxyl radical (•OH). Through in vitro experiments, it is demonstrated that MnO2Nfs significantly enhance the recovery of intracellular glutathione content, acting as a potent inhibitor of ferroptosis even in the presence of ferroptosis activators. Moreover, MnO2Nfs exhibit excellent liver accumulation properties, providing robust protection against oxidative damage. Specifically, they attenuate acetaminophen-induced ferroptosis by inhibiting ferritinophagy and activating the P62-NRF2-GPX4 antioxidation signaling pathways. These findings highlight the remarkable ROS scavenging ability of MnO2Nfs and hold great promise as an innovative and potential clinical therapy for DILI and other ROS-related liver diseases.

An analysis of differences in Carbapenem-resistant Enterobacterales in different regions: a multicenter cross-sectional study.

OBJECTIVE: This study aimed to explore the characteristics of carbapenem-resistant Enterobacterales (CRE) patients in the intensive care unit (ICU) in different regions of Henan Province to provide evidence for the targeted prevention and treatment of CRE. METHODS: This was a cross-sectional study. CRE screening was conducted in the ICUs of 78 hospitals in Henan Province, China, on March 10, 2021. The patients were divided into provincial capital hospitals and nonprovincial capital hospitals for comparative analysis. RESULTS: This study involved 1009 patients in total, of whom 241 were CRE-positive patients, 92 were in the provincial capital hospital and 149 were in the nonprovincial capital hospital. Provincial capital hospitals had a higher rate of CRE positivity, and there was a significant difference in the rate of CRE positivity between the two groups. The body temperature; immunosuppressed state; transfer from the ICU to other hospitals; and use of enemas, arterial catheters, carbapenems, or tigecycline at the provincial capital hospital were greater than those at the nonprovincial capital hospital (P < 0.05). However, there was no significant difference in the distribution of carbapenemase strains or enzymes between the two groups. CONCLUSIONS: The detection rate of CRE was significantly greater in provincial capital hospitals than in nonprovincial capital hospitals. The source of the patients, invasive procedures, and use of advanced antibiotics may account for the differences. Carbapenem-resistant Klebsiella pneumoniae (CR-KPN) was the most prevalent strain. Klebsiella pneumoniae carbapenemase (KPC) was the predominant carbapenemase enzyme. The distributions of carbapenemase strains and enzymes were similar in different regions.

Characteristics and Prognostic Factors of SARS-CoV-2 Omicron Variant Infection in Hemodialysis Patients: A Single-Center Study in China.

INTRODUCTION: This study aimed to evaluate the characteristics and prognostic factors for coronavirus disease 2019 (COVID-19) patients on maintenance hemodialysis (HD). METHODS: All admitted HD patients who were infected with SARS-CoV-2 from December 1, 2022, to January 31, 2023, were included. Patients with pneumonia were further classified into the mild, moderate, severe, and critical illness. Clinical symptoms, laboratory results, radiologic findings, treatment, and clinical outcomes were collected. Independent risk factors for progression to critical disease and in-hospital mortality were determined by the multivariate regression analysis. The receiver operating characteristic analysis with the area under the curve was used to evaluate the predictive performance of developing critical status and in-hospital mortality. RESULTS: A total of 182 COVID-19 patients with HD were included, with an average age of the 61.55 years. Out of the total, 84 (46.1%) patients did not have pneumonia and 98 (53.8%) patients had pneumonia. Among patients with pneumonia, 48 (49.0%) had moderate illness, 26 (26.5%) severe illness, and 24 (24.5%) critical illness, respectively. Elder age [HR (95% CI): 1.07 (1.01-1.13), p <0.01], increased levels of lactate dehydrogenase (LDH) [1.01 (1.003-1.01), p <0.01], and C-reactive protein (CRP) [1.01 (1.00-1.01), p = 0.04] were risk factors for developing critical illness. Elder age [1.11 (1.03-1.19), p = 0.01], increased procalcitonin (PCT) [1.07 (1.02-1.12), p = 0.01], and LDH level [1.004 (1-1.01), p = 0.03] were factors associated with increased risk of in-hospital mortality. CONCLUSION: Age, CRP, PCT, and LDH can be used to predict negative clinical outcomes for HD patients with COVID-19 pneumonia.

NaYF4 :Yb/Er@Mn3 O4 @GOX Nanocomposite for Upconversion Fluorescence Imaging and Synergistic Cascade Cancer Therapy by Apoptosis and Ferroptosis.

The cell elimination strategy based on reactive oxygen species (ROS) is a promising method for tumor therapy. However, its efficacy is significantly limited by ROS deficiency caused by H2 O2 substrate deficiency and up-regulation of cellular antioxidant defense induced by high glutathione (GSH) content in tumor cells. To overcome these obstacles, a multifunctional self-cascaded nanocomposite: glucose oxidase (GOX) loaded NaYF4 :Yb/Er@Mn3 O4 (UC@Mn3 O4 , labeled as UCMn) is constructed. Only in tumor microenvironment, it can be specifically activated through a series of cascades to boost ROS production via a strategy of open source (H2 O2 self-supplying ability). The increased ROS can enhance lipid peroxidation and induce tumor cell apoptosis by activating the protein caspase. More importantly, the nanozyme can consume GSH to inhibit glutathione peroxidase 4 (GPX4) activity, which limits tumor cell resistance to oxidative damage and triggers the tumor cell ferroptosis. Therefore, this strategy is expected to overcome the resistance of tumor to oxidative damage and achieve efficient oxidative damage of tumor. Further, degradation of the Mn3 O4 layer induced by GSH and acidic environment can promote the fluorescence recovery of UC fluorescent nuclear for tumor imaging to complete efficient integration of diagnosis and treatment for tumor.

Diagnostic performance of 3.0 T unenhanced Dixon water-fat separation coronary MR angiography in patients with low-to-intermediate risk of coronary artery disease.

PURPOSE: To evaluate the diagnostic performance of 3.0 T unenhanced compressed-sensing sensitivity encoding (CS-SENSE) Dixon water-fat separation coronary MR angiography (CMRA) in patients with low-to-intermediate risk of coronary artery disease (CAD) and its ability to grade the severity of CAD based on Coronary Artery Disease Reporting and Data System (CAD-RADS). METHODS: A total of 55 patients who was clinically evaluated as low-to-intermediate risk of CAD were finally included to undergo both 3.0 T CS-SENSE water-fat separation CMRA and coronary computed tomography angiography (CCTA), and 11 of them also underwent X-ray coronary angiography (CAG). The severity of coronary artery disease was graded in patients who had completed both CCTA and CMRA examinations by the use of CAD-RADS reports for the patients with stable chest pain, and the diagnostic consistency between the two approaches was evaluated. Diagnostic performance of CMRA was assessed using the combination of CCTA and CAG as the reference standard for excluding or confirming CAD respectively. RESULTS: The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and diagnostic accuracy of 3.0 T unenhanced water-fat separation coronary MRA were 90.0%, 95.0%, 81.8%, 97.4% and 94.0% for a patient-based analysis respectively. In comparison with CCTA, 3.0 T Dixon water-fat separation CMRA demonstrated excellent consistency in grading the severity of coronary heart disease according to CAD-RADS (0.77 for kappa value). CONCLUSION: In the group of low-to-intermediate probability for CAD, 3.0 T unenhanced CS-SENSE Dixon water-fat separation CMRA can present satisfactory diagnostic performance for the exclusion of CAD with high sensitivity and negative predictive value as well as the evaluation of grading the severity of coronary artery disease.

[Screening and promoting effect of grow-promoting fungi in rhizosphere of Angelica dahurica var. formosana].

Excessive application of chemical fertilizer has caused many problems in Angelica dahurica var. formosana planting, such as yield decline and quality degradation. In order to promote the green cultivation mode of A. dahurica var. formosana and explore rhizosphere fungus resources, the rhizosphere fungi with nitrogen fixation, phosphorus solubilization, potassium solubilization, iron-producing carrier, and IAA-producing properties were isolated and screened in the rhizosphere of A. dahurica var. formosana from the genuine and non-genuine areas, respectively. The strains were identified comprehensively in light of the morphological characteristics and ITS rDNA sequences, and the growth-promoting effect of the screened strains was verified by pot experiment. The results showed that 37 strains of growth-promoting fungi were isolated and screened from the rhizosphere of A. dahurica var. formosana, mostly belonging to Fusarium. The cultured rhizosphere growth-promoting fungi of A. dahurica var. formosana were more abundant and diverse in the genuine producing areas than in the non-genuine producing areas. Among all strains, Aspergillus niger ZJ-17 had the strongest growth promotion potential. Under the condition of no fertilization outdoors, ZJ-17 inoculation significantly promoted the growth, yield, and accumulation of effective components of A. dahurica var. formosana planted in the soil of genuine and non-genuine producing areas, with yield increases of 73.59% and 37.84%, respectively. To a certain extent, it alleviated the restriction without additional fertilization on the growth of A. dahurica var. formosana. Therefore, A. niger ZJ-17 has great application prospects in increasing yield and quality of A. dahurica var. formosana and reducing fertilizer application and can be actually applied in promoting the growth of A. dahurica var. formosana and producing biofertilizer.

A clinical strategy to improve the diagnostic performance of 3T non-contrast coronary MRA and noninvasively evaluate coronary distensibility: combination of diastole and systole imaging.

BACKGROUND: The clinical application of coronary MR angiography (MRA) combining diastole and systole imaging has never been described comprehensively in coronary artery disease (CAD) patients. We aimed to design an optimal non-contrast coronary MRA scan protocol combining diastolic and systolic imaging and to (1) evaluate its diagnostic performance for detecting significant coronary stenosis; (2) evaluate the feasibility of this protocol to noninvasively measure the coronary distensibility index (CDI). METHODS: From June 2021 to May 2022, 33 healthy volunteers and 91 suspected CAD patients scheduled for X-ray coronary angiography (CAG) were prospectively enrolled. 3T non-contrast water-fat coronary MRA was carried out twice at diastole and systole. Significant coronary stenosis was defined as a luminal diameter reduction of ≥ 50% using CAG as the reference and was evaluated as follows: (1) by coronary MRA in diastole alone; (2) by coronary MRA in systole alone; (3) by combined coronary MRA in diastole and systole. According to CAG, the patients were divided into significant CAD patients and non-significant CAD patients. The difference in CDI among participants was evaluated. RESULTS: Combined coronary MRA was completed in 31 volunteers and 76 patients. The per-patient sensitivity, specificity, and accuracy of combined coronary MRA were 97.5%, 83.3%, and 90.8%, respectively. Compared with single diastolic mode, combined coronary MRA showed equally high sensitivity but improved specificity on a per-patient basis (83.3% vs. 63.9%, adjusted P = 0.013). The CDI tested by coronary MRA decreased incrementally from healthy volunteers to non-significant and significant CAD patients. CONCLUSION: Compared with single-phase mode, 3 T non-contrast combined coronary MRA significantly improved specificity and may have potential to be a simple noninvasive method to measure CDI.

Genome-Wide Identification and Expression Analysis of bZIP Family Genes in Stevia rebaudiana.

The basic (region) leucine zippers (bZIPs) are evolutionarily conserved transcription factors widely distributed in eukaryotic organisms. In plants, they are not only involved in growth and development, defense and stress responses and regulation of physiological processes but also play a pivotal role in regulating secondary metabolism. To explore the function related to the bZIP gene family in Stevia rebaudiana Bertoni, we identified 105 SrbZIP genes at the genome-wide level and classified them into 12 subfamilies using bioinformation methods. Three main classes of cis-acting elements were found in the SrbZIP promoter regions, including development-related elements, defense and stress-responsive elements and phytohormone-responsive elements. Through protein-protein interaction network of 105 SrbZIP proteins, SrbZIP proteins were mainly classified into four major categories: ABF2/ABF4/ABI5 (SrbZIP51/SrbZIP38/SrbZIP7), involved in phytohormone signaling, GBF1/GBF3/GBF4 (SrbZIP29/SrbZIP63/SrbZIP60) involved in environmental signaling, AREB3 (SrbZIP88), PAN (SrbZIP12), TGA1 (SrbZIP69), TGA4 (SrbZIP82), TGA7 (SrbZIP31), TGA9 (SrbZIP95), TGA10 (SrbZIP79) and HY5 (SrbZIP96) involved in cryptochrome signaling, and FD (SrbZIP72) promoted flowering. The transcriptomic data showed that SrbZIP genes were differentially expressed in six S. rebaudiana cultivars ('023', '110', 'B1188', '11-14', 'GP' and 'GX'). Moreover, the expression levels of selected 15 SrbZIP genes in response to light, abiotic stress (low temperature, salt and drought), phytohormones (methyl jasmonate, gibberellic acid and salicylic acid) treatment and in different tissues were analyzed utilizing qRT-PCR. Some SrbZIP genes were further identified to be highly induced by factors affecting glycoside synthesis. Among them, three SrbZIP genes (SrbZIP54, SrbZIP63 and SrbZIP32) were predicted to be related to stress-responsive terpenoid synthesis in S. rebaudiana. The protein-protein interaction network expanded the potential functions of SrbZIP genes. This study firstly provided the comprehensive genome-wide report of the SrbZIP gene family, laying a foundation for further research on the evolution, function and regulatory role of the bZIP gene family in terpenoid synthesis in S. rebaudiana.

Analysis of the rhizosphere bacterial diversity of Angelica dahurica var. formosana from different experimental sites and varieties (strains).

Background: Rhizosphere bacteria play important roles in plant growth and secondary metabolite accumulation. Moreover, only with favorable production areas and desirable germplasm can high-yield and high-quality medicinal materials be produced. However, whether origin and germplasm indirectly affect the yield and quality of Angelica dahurica var. formosana through rhizosphere bacterial effects are not known. Methods: In this study, a high-throughput sequencing strategy was used to explore the relationship between the rhizosphere bacterial community and the cultivation of A. dahurica var. formosana from different production areas and germplasm for the first time. Results: (1) Proteobacteria was the dominant bacterial phylum in the rhizosphere soil of A. dahurica var. formosana, and these bacteria were stable and conserved to a certain extent. (2) High abundance of Proteobacteria was an important rhizospheric indicator of high yield, and high abundance of Firmicutes was an important indicator of high quality. Proteobacteria and Firmicutes might have an important relationship with the yield and quality of A. dahurica var. formosana, respectively. (3) PCoA cluster analysis demonstrated that both production area and germplasm affected the bacterial community structure in the rhizosphere of A. dahurica var. formosana to a certain extent, and production area had the greatest effect. In addition to available potassium, the rhizosphere soil nutrient levels of different production areas strongly affected the bacterial diversity and community. These findings provide a theoretical basis for the exploitation and utilization of rhizosphere microbial resources of A. dahurica var. formosana and offer a novel approach for increasing the yield and quality of this crop.