Nontarget site-based resistance to nicosulfuron and identification of candidate genes in Cucumis melo L. var. agrestis Naud. via RNA-Seq transcriptome analysis.

Herbicide resistance is a worldwide concern for weed control. Cucumis melo L. var. agrestis Naud. (C. melo) is an annual trailing vine weed that is commonly controlled by nicosulfuron, acetolactate synthase (ALS)-inhibiting herbicides. However, long-term use of this herbicide has led to the emergence of resistance and several nicosulfuron resistant populations of C. melo have been found. Here we identified a resistant (R) C. melo population exhibiting 7.31-fold resistance to nicosulfuron compared with a reference sensitive (S) population. ALS gene sequencing of the target site revealed no amino acid substitution in R plants, and no difference in enzyme activity, as shown by ALS activity assays in vitro. ALS gene expression was not significantly different before and after the application of nicosulfuron. Pretreatment with the cytochrome P450 monooxygenase (P450) inhibitor malathion reduced nicosulfuron resistance in the R population. RNA-Seq transcriptome analysis was used to identify candidate genes that may confer metabolic resistance to nicosulfuron. We selected genes with annotations related to detoxification functions. A total of 20 candidate genes (7 P450 genes, 1 glutathione S-transferase (GST) gene, 2 ATP-binding cassette (ABC) transporters, and 10 glycosyltransferase (GT)) were identified; 12 of them (7 P450s, 1 GST, 2 ABC transporters, and 2 GTs) were demonstrated significantly differential expression between R and S by quantitative real-time RT-PCR (qRT-PCR). Our findings revealed that the resistance mechanism in C. melo was nontarget-site based. Our results also provide a valuable resource for studying the molecular mechanisms of weed resistance.

One-Pot Cu/SAPO-34 for Continuous Methane Selective Oxidation to Methanol.

Cu/SAPO-34 synthesized via a one-pot method with relatively low silicon content and copper loading at around 2 wt.% facilitated continuous oxidation of methane to methanol with a methanol space time yield of 504 µmolCH3OH/gcat/h. Remarkably, the methanol yield exceeded 1800 mmolCH3OH/molCu/h at 623 K. Typically, the presence of trace oxygen in the system was the key to maintaining the high selectivity to methanol. Characterization results from a series of techniques, including XRD, SEM, TEM, H2-TPR, NH3-TPD, UV-vis, and FTIR, indicated that Cu2+ existed in the position where it moves from hexagonal rings to elliptical cages as the active center.

MicroRNA-122-5p promotes renal fibrosis and injury in spontaneously hypertensive rats by targeting FOXO3.

Hypertensive renal injury is accompanied by tubular interstitial fibrosis leading to increased risk for renal failure. This study aimed to explore the influences of miR-122-5p in hypertension-mediated renal fibrosis and damage. 14-week-old male SHR and WKY rats were randomly assigned to treat with rAAV-miR-122-5p or rAAV-GFP for 8 weeks. There were marked increases in miR-122-5p and Kim-1 levels and decreases in FOXO3 and SIRT6 levels in hypertensive rats. Transfection with rAAV-miR-122-5p triggered exacerbation of renal fibrosis, apoptosis and inflammatory injury in SHR, associated with downregulated levels of FOXO3, SIRT6, ATG5 and BNIP3 as well as upregulated expression of Kim-1, NOX4, CTGF, and TGF-ß1. In cultured primary mouse renal tubular interstitial fibroblasts, exposure to angiotensin II resulted in obvious downregulation of FOXO3, SIRT6, ATG5, BNIP3 and nitric oxide levels as well as augmented cellular migration, oxidative stress, and inflammation, which were exacerbated by miR-122-5p mimic while rescued by miR-122-5p inhibitor and rhFOXO3, respectively. Notably, knockdown of FOXO3 strikingly blunted cellular protective effects of miR-122-5p inhibitor. In summary, miR-122-5p augments renal fibrosis, inflammatory and oxidant injury in hypertensive rats by suppressing the expression of FOXO3. Pharmacological inhibition of miR-122-5p has potential therapeutic significance for hypertensive renal injury and fibrosis-related kidney diseases.

Transcriptomic analysis of maize uncovers putative genes involved in metabolic detoxification under four safeners treatment.

Isoxadifen-ethyl (IDF) and cyprosulfamide (CSA) can effectively protect maize from nicosulfuron (NIC) injury, while mefenpyr-diethyl (MPR) and fenchlorazole-ethyl (FCO) did not. Their chemical diversity and requirement to use them in combination with the corresponding herbicides suggest that their elicitation of gene expression are complex and whether it is associated with the safening activity remains elusive. In this study, our first objective was to determine whether or not the ability of four safeners to enhance the metabolic rate of nicosulfuron. It was found that nicosulfuron degradation in maize was accelerated by IDF and CSA, but not by FCO and MPR. Transcriptomic analysis showed that the number of genes induced by IDF and CSA were larger than that induced by FCO and MPR. Overall, 34 genes associated with detoxification were identified, including glutathione S-transferase (GST), cytochrome P450 (CYP450), UDP-glucosyltransferase (UGT), transporter and serine. Moreover, 14 detoxification genes were screened for further verification by real-time PCR in two maize inbred lines. Two maize inbred lines exhibited high expression levels of four genes (GST31, GST39, AGXT2 and ADH) after IDF treatment. GST6, GST19, MATE, SCPL18 and UF3GT were specifically up-regulated in telerant maize inbred line under IDF and IDF + NIC treatments. Seven genes, namely GST31, GST6, GST19, UF3GT, MATE, ADH and SCPL18, are induced by IDF and CSA to play a vital role in regulating the detoxification process of NIC. Accordingly, the GST activity in maize was accelerated by IDF and CSA, but not by FCO and MPR. This result is consistent with transcriptome and metabolic data.These results indicate that the mitigation of NIC damage is associated with enhanced herbicide metabolism. IDF and CSA were more effective in protecting maize from NIC injury due to their ability to enhance the detoxification of specific types of herbicides, compared to FCO and MPR. The chemical specificity of four safeners is attributed to the up-regulated genes related to the detoxification pathway.

Comparison of fibrosing mediastinitis patients with vs. without markedly increased systolic pulmonary arterial pressure: a single-center retrospective study.

INTRODUCTION: Fibrosing mediastinitis (FM) complicated with pulmonary hypertension (PH) has been considered as an important cause of morbidity and mortality. This study was designed to observe the possible effects of abnormal hemodynamics on patients by conducting a between-group comparison according to the presence of markedly increased systolic pulmonary arterial pressure (SPAP), so as to provide more information for clinical management. MATERIALS AND METHODS: Fifty-one patients with clinically diagnosed FM were divided in two groups (SPAP < 50 mmHg group; SPAP ≥ 50 mmHg group) and retrospectively included in the study. Data mainly including demographic factors, echocardiographic data, results of right heart catheter and computed tomography (CT) examination were retrieved from the medical database. Echocardiographic parameters pre- and post- balloon pulmonary angioplasty (BPA) treatment were also collected in 8 patients. RESULTS: Significant changes in cardiac structure, hemodynamics and cardiac function were detected in patients complicated with markedly increased SPAP. Patients in the SPAP ≥ 50 mmHg group had increased right heart diameter, right heart ratio and velocity of tricuspid regurgitation (VTR) (p < 0.05). Deteriorated right heart function was also observed. There was no significant difference in CT findings between the two groups, except that more patients in the SPAP ≥ 50 mmHg group had pleural effusion (p < 0.05). After primary BPA in 8 patients, improvement in the right atrium proportion was observed. CONCLUSIONS: Changes due to significantly increased SPAP in patients with FM include adverse structure and function of the right heart, but differences in CT findings were not significant. Echocardiography has advantages as a noninvasive tool for the evaluation of cardiac structure, function and hemodynamics in patients with FM.

Left atrial strain for predicting recurrence in patients with non-valvular atrial fibrillation after catheter ablation: a single-center two-dimensional speckle tracking retrospective study.

BACKGROUND: Although catheter ablation (CA) is an effective treatment for non-valvular atrial fibrillation (AF), a good many of patients still have a recurrence following post-operation. Prediction of AF recurrence by evaluating left atrial (LA) phase function with speckle tracking echocardiography (STE) may be helpful for risk stratification and clinical management for AF patients. Therefore, the current study aimed to assess the prognostic value of LA strains in non-valvular AF patients after CA. METHODS: A total of 95 non-valvular AF patients (70.5% paroxysmal AF, 56.8% males, mean age 63.2 ± 9.7 years) were included in this retrospective study between October 2019 and August 2020. Transthoracic echocardiography was performed in all the subjects and STE was used to analyze the LA reservoir strain (LASr), LA conduit strain (LAScd) and LA contractile strain (LASct) during different phases before CA. Patients were followed up with until January 2022. The endpoint was AF recurrence. RESULTS: Over a median follow-up period of 26.0 months (interquartile range, 24.7-26.7 months), 26 patients experienced recurrence and 69 stayed in sinus rhythm. Compared with no-recurrence group, maximum volume of LA (LAVmax), minimum volume of LA (LAVmin) and LA volume index (LAVI) were increased in the recurrence group, while LAEF, LASr and LASct were worsened (P < 0.05). Multivariable logistic regression analysis revealed that LASct was an independent predictor of AF recurrence (odds ratio, 0.89; 95% confidence interval (CI), 0.82-0.97; P = 0.007) and receiver operating characteristic (ROC) curve analysis showed an area under the curve of LASct<8% was 0.70 (95% CI, 0.59-0.79; P = 0.0008). CONCLUSIONS: LASct was of independent predictive value of AF recurrence. LA function assessed by STE may contribute to the risk stratification for AF patients and selection of suitable patients for CA.

Transcriptome analysis and the identification of genes involved in the metabolic pathways of fenoxaprop-P-ethyl in rice treated with isoxadifen-ethyl hydrolysate.

Fenoxaprop-P-ethyl (FE) is a highly effective weed control agent for rice fields, but it causes phytotoxicity in crops. A whole-plant bioassay has revealed that isoxadifen-ethyl hydrolysate (IH) can significantly improve the tolerance of rice to FE, but the molecular mechanisms underlying this phenomenon are still unclear. In this study, we performed RNA-Seq analysis using rice seedlings treated with FE and IH to determine the IH-regulated candidate genes involved in metabolic resistance to FE. We also analyzed spatiotemporal expression using quantitative reverse transcription polymerase chain reaction to reveal the expression patterns of these genes under different treatments. The results showed that genes encoding metabolic enzymes, such as cytochrome P450 monooxygenases, glutathione-s-transferases, UDP-glycosyltransferase, carboxylesterase, and ATP-binding cassette transporter, were influenced by the application of IH. Most of these genes were upregulated, and their products were involved in various stages of FE metabolism. Tolerance to FE was primarily mediated by CarE15, CYP86A1, GSTU6, GST4, UGT13248, UGT79, and ABCC4, all of which played a vital role in regulating the detoxification process of FE. Our findings elucidated the protective mechanisms of IH, which can help alleviate the phytotoxic effects of FE and expand its potential for application in agriculture.

Reduced mechanical function of the left atrial predicts adverse outcome in pregnant women with clustering of metabolic risk factors.

INTRODUCTION: The left atrial (LA) strain and strain rate are sensitive indicators of LA function. However, they are not widely used for the evaluation of pregnant women with metabolic diseases. The aim of this study was to assess the LA strain and strain rate of pregnant women with clustering of metabolic risk factors and to explore its prognostic effect on adverse pregnancy outcomes. MATERIALS AND METHODS: Sixty-three pregnant women with a clustering of metabolic risk factors (CMR group), fifty-seven women with pregnancy-induced hypertension (PIH group), fifty-seven women with gestational diabetes mellitus (GDM group), and fifty matched healthy pregnant women (control group) were retrospectively evaluated. LA function was evaluated with two-dimensional speckle-tracking imaging. Iatrogenic preterm delivery caused by severe preeclampsia, placental abruption, and fetal distress was regarded as the primary adverse outcome. RESULTS: The CMR group showed the lowest LA strain during reservoir phase (LASr), strain during contraction phase (LASct) and peak strain rate during conduit phase (pLASRcd) among the three groups (P < 0.05). LA strain during conduit phase (LAScd) and peak strain rate during reservoir phase (pLASRr) in the CMR group were lower than those in the control and GDM groups (P < 0.05). Multivariable Cox regression analysis demonstrated systolic blood pressure (HR = 1.03, 95% CI 1.01-1.05, p = 0.001) and LASr (HR = 0.86, 95% CI 0.80-0.92, p < 0.0001) to be independent predictors of iatrogenic preterm delivery. An LASr cutoff value ≤ 38.35% predicted the occurrence of iatrogenic preterm delivery. CONCLUSIONS: LA mechanical function in pregnant women with metabolic aggregation is deteriorated. An LASr value of 38.35% or less may indicate the occurrence of adverse pregnancy outcomes.

Efficacy of peripheral arterial access for peripheral blood stem cells collection.

BACKGROUND: Transplantation of peripheral blood stem cells (PBSCs) mobilized by cytokines is increasingly applied to treat patients with hematologic diseases, such as lymphoma, multiple myeloma, leukemia, etc. Successful hematopoietic stem cell transplantation (HSCT) increasingly depends on the collection of hematopoietic stem cells (HSCs) from peripheral blood. Peripheral vein (PV) is the most common type of blood access. When the blood vessels are not well filled and the blood flow is insufficient, the machine will appear repeated low pressure alarm or pipeline coagulation, which seriously affects the collection efficiency. A peripheral artery (PA) is utilized for drawing blood, while a peripheral vein is used for blood return, that is a way to perform apheresis. The advantages of PA are that it ensures adequate extracorporeal circulation blood flow, stable blood flow rate, simple operation, and relatively low price. However, there are very few studies on the efficacy of peripheral arterial access for HSCs collection. Therefore, this retrospective study was conducted to assess the effectiveness of PA and PV access for PBSCs collection. METHODS: We performed a retrospective analysis of 150 apheresis procedures on 26 patients and 95 healthy donors collected by PV or PA access from March 1, 2020 to March 1, 2021. We compared the CD34+ cell count, collection efficiency (CE), duration of processing a single blood volume, number of low-pressure alarms, average blood flow rate and number of punctures between the two groups. Also, we analyzed adverse events. RESULTS: There was no significant difference in the quality of apheresis blood components between the PA group and the PV group. The CD34+ cells collected was 274.16 ± 216.31 × 106 in the PV group and 246.63 ± 127.94 × 106 in the PA group. The CE in the PA group was 49.50 ± 9.88%, higher than 42.39 ± 14.62% in the PV group. The duration of processing a single blood volume was 90.67 ± 15.35 min in the PV group and 79.68 ± 10.28 min in the PA group. The number of low-pressure alarms in the PA group was 0.38 ± 0.98, <2.42 ± 1.76 in the PV group, and the average blood flow rate in the PA group was 59.27 ± 2.18, higher than 54.21 ± 3.41 in the PV group. The difference was statistically significant (P < .05). The Number of punctures was 1.35 ± 0.75 in the PA group and 1.41 ± 1.01 in the PV group. There was no statistically significant difference. CONCLUSION: Peripheral artery is a safe, reliable, economical, convenient, and fast vascular access, which opens a new way to the establishment of vascular access for PBSCs collection.

Risk assessment in interstitial lung disease: the incremental prognostic value of cardiopulmonary ultrasound.

BACKGROUND: The mortality risk of chronic interstitial lung disease (ILD) is currently assessed using the ILD-GAP score. The present study evaluates whether the addition of cardiopulmonary ultrasound parameters to the ILD-GAP score can further improve the predictive value of ILD-GAP. METHODS: Medical records from 91 patients with ILD hospitalized from June 2015 to March 2016 were retrospectively examined. The Lung ultrasound (LUS) score, right ventricular (RV) function, and mechanics were obtained from the cardiopulmonary ultrasound. The ILD-GAP score was calculated from demographic characteristics and pulmonary function parameters. Patients were followed up with until May 2020. The primary endpoint was all-cause death. RESULTS: After exclusions, 74 patients with ILD were included in the analysis. During the follow-up period, 36 patients with ILD survived (ILDs), and 38 patients died (ILDd). Compared to ILDs, the ILDd cases exhibited a higher number of B-lines, LUS score, and RV end-diastolic base dimension (RVD), but lower RV function. In multivariate analysis, the ILD-GAP score (hazard ratio, 2.88; 95% CI 1.38-5.99, P = 0.005), LUS score (hazard ratio 1.13; 95% CI 1.04-1.24, P = 0.006), and RVD (hazard ratio 1.09, 95% CI 1.03-1.16, P = 0.004) were significantly related to the risk of death. Adding the LUS score and RVD to the ILD-GAP score significantly improved the predictive value compared to the ILD-GAP score alone (C statistics 0.90 vs 0.76, P = 0.018). CONCLUSION: We investigated the utility of a new prognostic model for ILD that includes both cardiopulmonary ultrasound parameters (LUS score and RVD) and the ILD-GAP score. This model better reflects the severity of pulmonary fibrosis and cardiac involvement, and has incremental predictive value over the ILD-GAP score alone.

Circulating Connective Tissue Growth Factor Is Associated with Diastolic Dysfunction in Patients with Diastolic Heart Failure.

BACKGROUND: Connective tissue growth factor (CTGF) and transforming growth factor ß1 (TGF-ß1) are emerging biomarkers for tissue fibrosis. The aim of this study was to investigate the association between circulating CTGF, TGF-ß1 levels and cardiac diastolic dysfunction in patients with diastolic heart failure (DHF). METHODS: Admitted subjects were screened for heart failure and those with left ventricular (LV) ejection fraction <45% were excluded. Diastolic dysfunction was defined as functional abnormalities that exist during LV relaxation and filling by echocardiographic criteria. Totally 114 patients with DHF and 72 controls were enrolled. Plasma levels of CTGF, TGF-ß1, and B-type natriuretic peptide (BNP) were determined. RESULTS: The plasma CTGF and TGF-ß1 levels increased significantly in patients with DHF. Circulating CTGF and TGF-ß1 levels were correlated with echocardiographic parameter E/e' and diastolic dysfunction grading in DHF patients. In multivariate logistic analysis, CTGF was significantly associated with diastolic dysfunction (odds ratio: 1.027, p < 0.001). Plasma CTGF (AUC: 0.770 ± 0.036, p < 0.001) and CTGF/BNP (AUC: 0.839 ± 0.036, p < 0.001) showed good predictive power to the diagnosis of DHF. CONCLUSIONS: This finding suggested CTGF could be involved in the pathophysiology of diastolic heart failure and CTGF/BNP might have auxiliary diagnostic value on diastolic heart failure.

Quinone-thioether metabolites of hydroquinone play a dual role in promoting a vicious cycle of ROS generation: in vitro and in silico insights.

Humans are exposed to hydroquinone (HQ) via diet, smoking, occupation, and even via inhalation of polluted air. Given its preferential distribution in kidney and liver, the impact of biotransformation on the nephrotoxicity and hepatotoxicity of HQ was evaluated. Indeed, HQ and its metabolites, benzoquinone, and quinone-thioethers (50, 100, 200, and 400 µM) all induced ROS-dependent cell death in both HK-2, a human kidney proximal epithelial cell line, and THLE-2, a human liver epithelial cell line, in a concentration-dependent manner. For a deeper insight into the biological mechanism of ROS stimulation, the bioinformatics database was reviewed. Intriguingly, 163 proteins were currently reported to form co-crystal complex with benzoquinone analogs, a large proportion of which are closely related to ROS generation. After a thorough assessment of the interaction affinity and binding energy, three key mitochondrial proteins that are particularly involved in electric transport, namely, cytochrome BC1, succinate dehydrogenase, and sulfide:quinone oxidoreductase, were highlighted for further verification. Their binding affinity and the action pattern were explored and validated by molecular docking and molecular dynamics simulations. Remarkably, quinone-thioether metabolites of HQ afforded high affinity to the above proteins that purportedly cause a surge in the generation of ROS. Therefore, HQ can be further converted into quinone-thioethers, which on one hand can function as substrates for redox cycling, and on the other hand may afford high affinity with key proteins evolved in mitochondrial electron transport system, leading to a vicious cycle of ROS generation. The combined data provide a prospective insight into the mechanisms of ROS motivation, expanding HQ-mediated toxicology profiles.

Influence of impaired right ventricular contractile reserve on exercise capacity in patients with precapillary pulmonary hypertension: A study with exercise stress echocardiography.

OBJECTIVES: Right ventricular (RV) contractile reserve reflects the ability of RV to accommodate the increased afterload and may play an essential role in the evaluation of precapillary pulmonary hypertension (PH). This study aimed to assess RV contractile reserve based on exercise stress echocardiography (ESE) and to determine the echocardiographic determinants of exercise capacity in patients with precapillary PH. METHODS: A total of 31 patients with precapillary PH and 15 age- and sex-matched healthy control subjects were prospectively recruited. All subjects underwent ESE to assess RV function at rest and under peak exercise. Changes in these parameters during exercise were calculated to quantify the RV contractile reserve. Patients with precapillary PH also underwent cardiopulmonary exercise test (CPET), and data pertaining to peak oxygen uptake (peak VO2 ) and minute ventilation/carbon dioxide production (VE/VCO2 ) were collected. RESULTS: Right ventricular contractile reserve including change in tricuspid annular plane systolic excursion (∆TAPSE), change in RV fractional area change (∆RVFAC), and change in Doppler-derived tricuspid lateral annular peak systolic velocity (∆S') was significantly depressed in precapillary PH patients compared with control subjects (P < 0.05). Parameters of RV function and RV contractile reserve were markedly associated with maximal exercise capacity (P < 0.05). ∆RVFAC was an independent predictor of peak VO2 (r2  = 0.601, P < 0.05). CONCLUSIONS: Assessment of RV contractile reserve facilitates identification of subclinical dysfunction and evaluation of clinical status and severity of precapillary PH. ESE as a noninvasive method may provide a comprehensive clinical assessment and facilitate therapeutic decision-making for these patients.

Impaired left ventricular mechanics and functional reserve are associated with reduced exercise capacity in patients with hypertrophic cardiomyopathy.

BACKGROUND: Reduced metabolic equivalents (METs) are an indicator of exercise intolerance, which predicts poor prognosis in hypertrophic cardiomyopathy (HCM) patients. We sought to evaluate the changes in left ventricular (LV) mechanics and functional reserves, as well as their association with functional capacity in HCM patients. METHODS: Seventy HCM patients and thirty controls were included in this study. LV mechanics were evaluated at rest and during exercise by echocardiography and two-dimensional speckle-tracking imaging to obtain parameters of functional reserve, LV global longitudinal strain (LVGLS), strain rate (SR), and circumferential strain. RESULTS: Hypertrophic cardiomyopathy (HCM) patients had lower LVGLS, systolic SR, early and late diastolic SR at rest and during exercise, and reduced absolute and relative systolic and diastolic reserve compared to controls. LV circumferential strain was significantly higher at rest but lower during exercise in HCM patients. Exercise capacity was markedly reduced in HCM patients, and peak exercise LVGLS (LVGLS-exe) significantly correlated with exercise capacity. Multivariate regression analyses showed that LVGLS-exe, LV filling pressure during exercise (E/e'-exe), and LV mass index (LVMI) were independent predictors of exercise capacity. Moreover, LVGLS-exe displayed incremental predictive value over E/e'-exe and LVMI for exercise intolerance. Receiver operating characteristic curve analysis showed LVGLS-exe had optimal accuracy for predicting exercise intolerance in HCM patients. CONCLUSIONS: Hypertrophic cardiomyopathy (HCM) patients have reduced LV mechanics at rest and during exercise and impaired mechanical reserve. LVGLS-exe is associated with exercise capacity and is an optimal predictive value for reduced exercise capacity in HCM patients.

Incidental finding of an asymptomatic pulmonary valve papillary fibroelastoma: A case report.

Primary cardiac tumors are rare, but papillary fibroelastoma (PFE) is reportedly the most common form, which usually occurs on the left-side valves of the heart. However, PFE involving the tricuspid and pulmonary valves has also been documented. Although PFE is benign and seldom associated with valvular dysfunction, the associated embolic complications may lead to serious consequences. Most patients with PFE lack specific clinical symptoms and the diagnosis is incidental. Surgical resection is the mainstay treatment for PFE in order to prevent the occurrence of embolic complications. In this report, we present a case of a rare asymptomatic PFE of the pulmonary valve, which was incidentally noted during a routine examination with transthoracic echocardiography (TEE). There was neither valvular dysfunction nor hemodynamic change. The PFE was surgically removed, and the diagnosis was further confirmed with histopathology.

(5R)-5-hydroxytriptolide ameliorates anti-glomerular basement membrane glomerulonephritis in NZW mice by regulating Fcγ receptor signaling.

(5R)-5-hydroxytriptolide (LLDT-8) is a novel triptolide analog that has been identified as a promising candidate for treating autoimmune diseases and has been shown to be effective in treating murine collagen-induced arthritis and lupus nephritis. In the present study, we investigated the therapeutic effect and possible mechanism of action of LLDT-8 in a murine anti-glomerular basement membrane (GBM) glomerulonephritis model. NZW mice were injected with rabbit anti-GBM serum (500 µL, ip). The mice were orally treated with LLDT-8 (0.125 mg/kg, every other day) or a positive control prednisolone (2 mg/kg every day) for 14 d. Blood and urine samples as well as spleen and kidney tissues were collected for analyses. LLDT-8 treatment did not affect the generation of mouse anti-rabbit antibodies. LLDT-8 significantly reversed established proteinuria, improved renal histopathology and attenuated renal dysfunction in glomerulonephritis mice. Furthermore, LLDT-8 inhibited inflammation in the kidney evidenced by significantly decreasing C3 and IgG deposition, reducing the levels of the pathogenic cytokines TNF-α, IL-6, IL-17, and IFN-γ, and reducing related chemokine expression and leukocyte infiltration in kidneys. Moreover, LLDT-8 treatment significantly increased the expression of FcγRIIB in the kidney and spleen. In addition, the treatment restored the reduced expression of FcγRIIB on the surface of kidney effector cells, CD11b+ cells, and interfered with FcγR-dependent signaling, especially FcγRIIB-mediated downstream kinases, such as BTK. These results demonstrate that LLDT-8 ameliorates anti-GBM glomerulonephritis by regulating the Fcγ receptor signaling.

High-Resolution Transthoracic Ultrasonography for Assessment of Pleural Lines in Patients With Dyspnea With CT Comparison: An Observational Study.

OBJECTIVES: Detection of B-line in dyspneic patients is often accompanied by abnormal changes of pleural line on transthoracic ultrasonography (TUS). The aim of the study was to evaluate the relevance and diagnostic performance of pleural line abnormalities and B-lines detected on high-resolution TUS against the computed tomography (CT) findings. METHODS: Transthoracic ultrasonography was performed in patients admitted to the emergency department with dyspnea. The pleural line and accompanying B-line were assessed using a linear transducer. The TUS findings were assessed against the corresponding high-resolution CT findings in the same location, which were considered to be the gold standard. RESULTS: Out of a total of 116 patients, 68.1% had changes of the pleural line on TUS. The characteristic changes of the pleural line were classified into four types: slightly rough pleural line with confluent B-lines on TUS corresponded with CT findings of ground-glass opacity; irregular and interrupted pleural line with confluent B-lines corresponded with parenchymal infiltration; fringed pleural line with confluent B-lines corresponded with superimposed ground-glass and irregular reticular opacities; and fringed pleural line with scattered B-lines corresponded with irregularly thickened interlobular septa. Wavy pleural line indicated subpleural emphysema. The coexistence of more than one abnormal pleural line was also found in 31 cases (26.7%). CONCLUSIONS: High-resolution TUS may help in the initial assessment of lung pathology by its ability to identify pleural line abnormalities and B-lines that are shown to be associated with CT, which could add diagnostic value in the emergency evaluation of dyspneic patients.

Single-molecule electronics: from chemical design to functional devices.

The use of single molecules in electronics represents the next limit of miniaturisation of electronic devices, which would enable us to continue the trend of aggressive downscaling of silicon-based electronic devices. More significantly, the fabrication, understanding and control of fully functional circuits at the single-molecule level could also open up the possibility of using molecules as devices with novel, not-foreseen functionalities beyond complementary metal-oxide semiconductor technology (CMOS). This review aims at highlighting the chemical design and synthesis of single molecule devices as well as their electrical and structural characterization, including a historical overview and the developments during the last 5 years. We discuss experimental techniques for fabrication of single-molecule junctions, the potential application of single-molecule junctions as molecular switches, and general physical phenomena in single-molecule electronic devices.

Improved ultraviolet upconversion emissions of Ho3+ in hexagonal NaYF4 microcrystals under 980 nm excitation.

Under 980 nm excitation, enhanced ultraviolet (UV) upconversion (UC) emissions at 242.4 nm, 276.1 nm, 289.7 nm, 296.4 nm, 303.6 nm, 357.7 nm and 387.8 nm of Ho3+ ions were observed in beta-NaYF4:20%Yb3+, 1.5%Ho3+ microcrystals (MC) which were synthesized through a hydrothermal method. The results indicated that these UV emissions came from five- and four-photon UC processes. Dynamical analysis on Ho3+ excited states suggests that, for excited Ho3+ ions, the higher the energy level is, the shorter the lifetime is.

Protective mechanisms of neral as a plant-derived safener against fenoxaprop-p-ethyl injury in rice.

BACKGROUND: The use of herbicide safeners effectively minimises crop damage while maintaining the full efficacy of herbicides. The present study aimed to assess the potential protective effects of neral (NR) as a safener, in order to mitigate injury caused by fenoxaprop-p-ethyl (FE) on rice. RESULTS: The alleviating effect of NR was similar to that of the safener isoxadifen-ethyl (IE). The root elongation of rice was significantly promoted under the FE + NR and FE + IE treatments, as compared to the FE treatment. The transcriptome analysis further suggested that the effects of NR treatment on plant metabolic pathways differed from those of IE treatment. In total, 895 and 47 up-differentially expressed genes induced by NR (NR-inducible genes) and IE (IE-inducible genes) were identified. NR-inducible genes were mainly enriched in phytohormone synthesis and signalling response, including 'response to brassinosteroid', 'response to jasmonic acid', 'response to ethylene', 'brassinosteroid metabolic process', 'brassinosteroid biosynthesis' and 'plant hormone signal transduction'. In contrast, IE-inducible genes were predominantly enriched in glutathione metabolism. The activity of glutathione S-transferase was found to be increased after IE treatment, whereas no significant increase was observed following NR treatment. Moreover, several transcription factor genes, such as those encoding AP2/ERF-ERF and (basic helix-loop-helix) bHLH were found to be significantly induced by NR treatment. CONCLUSION: This is the first report of the utilisation of NR as an herbicide safener. The results of this study suggest the toxicity of FE to rice is mitigated by NR through a distinct mechanism compared to IE. © 2023 Society of Chemical Industry.