Evaluation of renal tubular function by multiparametric functional MRI in early diabetes.

Purpose To evaluate the tubular function in an alloxan-induced type 1 diabetes mellitus (DM) rabbit model measured by renal oxygenation (R2*), oxygen extraction fraction (OEF), and renal blood flow (RBF) using blood oxygenation level dependent, asymmetric spin echo, and arterial spin labeling MRI. Methods Twenty-six rabbits were randomized into the 3-day DM group (n = 13) and the 7-day DM group (n = 13). We performed pairs of multiparametric MRIs (before and after furosemide injection) at baseline and 3/7 days post-DM, and scored pathological kidney injury. We performed statistical analyses using non-parametric, chi-square, and Spearman correlation tests. Results At baseline, medullary R2* significantly decreased by 24.97% and 16.74% in the outer and inner stripes of the outer medulla (OS and IS, p = 0.006 and 0.003, respectively) after furosemide administration. While the corresponding OEF decreased by 15.91% for OS and 16.67% for IS (both p = 0.003), and no significant change in medullary RBF was observed (p > 0.05). In the 3-day DM group, the decrease of medullary R2* and OEF post-furosemide became unremarkable, suggesting tubular dysfunction. We noticed similar changes in the 7-day DM group. Correlation analysis showed pathological tubular injury score significantly correlated with medullary ∆R2* (post-furosemide - pre-furosemide difference, r = 0.82 for OS and 0.82 for IS) and ∆OEF (r = 0.82 for OS and 0.82 for IS) (p < 0.001, respectively). Conclusion: The combination of medullary OEF and R2* in response to furosemide could detect renal tubular dysfunction in early DM.

[Analysis of influence of MR signs on Harris score in ARCO stages 2-4 femoral head necrosis].

OBJECTIVE: To analysis and determine MR signs of Harris score ARCO stages 2-4 in osteonecrosis of femoral head (ONFH). METHODS: Thirty-four patients with ONFH of ARCO stages 2 to 4 who underwent routine MR, T2 mapping, 3D-SPACE sequence examination and Harris score were retrospectively collected from January 2019 to June 2020, and 3 patients were excluded, and 31 patients were finally included, including 23 males and 8 females, aged from 18 to 62 years old with an average of(40.0±10.8) years old. Among them 21 patients with bilateral femoral head necrosis, totally 52 cases, including 17 with ARCO stage 2 patients, 24 ARCO stage 3, and 11 ARCO stage 4. MR imaging signs (femoral head collapse depth, ONFH index, bone marrow edema, hyperplasia, grade and T2 value of cartilage injury, and joint effusion) were scored and measured on the picture archiving and communication system (PACS) workstation, and the cartilage quantitative parameter T2 value was calculated and measured on Siemens postprocessing workstation. Pearson correlation analysis was used to evaluate the correlation between various MR signs and Harris score, and then multiple linear regression analysis was used to examine impact of MR signs on Harris hip score. RESULTS: Femoral head collapse depth(r=-0.563, P=0.000), grade of cartilage injury(r=-0.500, P=0.000), and joint effusion (r=-0.535, P=0.000) were negatively correlated with Harris score by Pearson correlation analysis. Multiple linear regression analysis showed that joint effusion(ß=-6.198, P=0.001) and femoral head collapse depth(ß=-4.085, P=0.014) had a significant negative impact on Harris hip score. CONCLUSION: Femoral head collapse depth and joint effusion both had significant negative relationship with Harris hip score. It is recommended to routinely evaluate femoral head collapse depth and joint effusion quantitatively and gradedly, so as to efficiently and accurately assist clinical diagnosis and treatment.

Genome-Wide Analyses of SlFWL Family Genes and Their Expression Profiles under Cold, Heat, Salt and Drought Stress in Tomato.

PLAC8 is a cysteine-rich protein that serves as a central mediator of tumor evolution in mammals. PLAC8 motif-containing proteins widely distribute in fungi, algae, higher plants and animals that have been described to be implicated in fruit size, cell number and the transport of heavy metals such as cadmium or zinc. In tomatoes, FW2.2 is a PLAC8 motif-containing gene that negatively controls fruit size by regulating cell division and expansion in the carpel ovary during fruit development. However, despite FW2.2, other FWL (FW2.2-Like) genes in tomatoes have not been investigated. In this study, we identified the 21 SlFWL genes, including FW2.2, examined their expression profiles under various abiotic adversity-related conditions. The SlFWL gene structures and motif compositions are conserved, indicating that tomato SlFWL genes may have similar roles. Cis-acting element analysis revealed that the SlFWL genes may participate in light and abiotic stress responses, and they also interacted with a variety of phytohormone-responsive proteins and plant development elements. Phylogenetic analyses were performed on five additional plant species, including Arabidopsis, pepper, soybean, rice and maize, these genes were classified into five subfamilies. Based on the results of collinearity analyses, the SlFWL genes have a tighter homologous evolutionary relationship with soybean, and these orthologous FWL gene pairs might have the common ancestor. Expression profiling of SlFWL genes show that they were all responsive to abiotic stresses, each subgroup of genes exhibited a different expression trend. Our findings provide a strong foundation for investigating the function and abiotic stress responses of the SlFWL family genes.

Preparation of Antibacterial, Arginine-Modified Ag Nanoclusters in the Hydrogel Used for Promoting Diabetic, Infected Wound Healing.

Diabetic foot ulcers with complex healing wounds accompanied by bacterial infection are considered a significant clinical problem which are made worse by the lack of effective treatments. Traditional antibiotics and dressings have failed to address wound infection and healing, and multifunctional combination therapies are attractive for treating chronic wounds. In this study, arginine (Arg) was loaded onto the surface of silver nanoclusters and encapsulated in a hydrogel to achieve antibacterial, anti-inflammatory, angiogenic, and collagen deposition functions through the slow release of Arg combined with silver nanoclusters. In vitro studies indicated that Arg-Ag@H composites inhibited methicillin-resistant Staphylococcus aureus and Escherichia coli by 94 and 97%, respectively. The inhibition of bacterial biofilms reached 85%, and the migration ability of human venous endothelial cells (HUVECs) increased by 50%. In vitro studies showed that Arg-Ag@H composites increased the healing area of wounds by 26% and resulted in a 98% skin wound-healing rate. Safety studies confirmed the excellent biocompatibility of Arg-Ag@H. The results suggest that Arg-Ag@H offers new possibilities for treating chronic diabetic wounds.

Rhizobacterial compositions and their relationships with soil properties and medicinal bioactive ingredients in Cinnamomum migao.

Introduction: Rhizobacterial communities and their metabolites can affect plant growth, development, and stress resistance, as well as the biosynthesis and accumulation of bioactive compounds in medicinal plants. This relationship has been well-characterized in many medicinal herbs, although much less commonly in medicinal trees. Methods: Here, we analyzed the composition and structure of Cinnamomum migao rhizobacterial communities across nine growing regions in Yunnan, Guizhou and Guangxi, China, as well as differences in soil properties and fruit bioactive compounds. Results: Results showed that the C. migao rhizobacterial communities exhibited high species richness, but location-specific differences in structure. Site-specific differences in soil properties and bioactive compounds were also observed. Furthermore, rhizobacterial community compositions were correlated with both soil properties and fruit bioactive compounds, metabolism-related functions were most common in C. migao rhizobacteria. Discussion: Several bacterial genera, including Acidothermus, Acidibacter, Bryobacter, Candidatus_Solibacter, and Acidimicrobiales, potentially promote the biosynthesis and accumulation of 1,8-cineole, cypressene, limonene, and α-terpineol, Nitrospira and Alphaproteobacteria may play an inhibitory role. Finally, our results emphasized the critical role that soil pH and nitrogen levels play in driving rhizobacterial community structure, and specific functional bacteria can also counteract with soil properties, Acidibacter and Nitrospira can affect soil pH and nitrogen effectiveness. Overall, this study provides additional insight into the complex correlation of rhizosphere microorganisms with bioactive ingredients and soil properties of medicinal plants.

PD-1 and LAG-3-positive T cells are associated with clinical outcomes of relapsed/refractory multiple myeloma patients.

OBJECTIVE: To investigate the frequency of PD-1 and LAG-3-positive T cells in relapsed/refractory multiple myeloma (RRMM) patients and its clinical significance. METHODS: This prospective observational study enrolled a total of 71 RRMM patients, as well as 70 MM patients (non-refractory) and 70 healthy individuals during January 2018 to March 2021. The frequency of circulating CD4+ and CD8+ T cells expressing PD-1 and LAG-3 was analyzed using flow cytometry. Serum cytokines of IL-6, IL-17, CRP, TNF-α and TGF-ß were evaluated by enzyme linked immunosorbent assay (ELISA). RESULTS: Significant higher 1-year mortality rate was found in RRMM patients compared with the MM patients. In both CD4+ and CD8+ T cells, the frequencies of PD-1+, LAG-3+ and PD-1+/LAG-3+ T cells were markedly higher in the RRMM patients and the deceased patients, compared with the MM patients and the survival patients, respectively. All cytokines were remarkably higher in RRMM and MM patients than in the healthy control, while only serum levels of IL-6 and IL-17 were markedly higher in RRMM patients compared with the MM patients. Positive correlation was observed among the IL-6, IL-17 and the frequencies of circulating T cells in both CD4+ and CD8+ T cells in RRMM and MM patients. The frequency of CD8+PD-1+LAG-3+ T cells showed the best sensitivity 82.61% and specificity 76.06% for diagnosis of RRMM using ROC curve. Meanwhile, the frequency of CD4+PD-1+ cells showed the best sensitivity 84.00% and specificity 97.35% for prediction of patients' mortality by ROC curve. The frequencies of CD4+PD-1+, CD8+PD-1+/LAG-3+, as well as IL-6, IL-17 and TNF-α were found as risk factors for incidence of RRMM in all MM patients. CONCLUSION: The frequency of PD-1 and LAG-3-positive T cells is associated with the clinical severity and inflammation in RRMM patients, which may also serve as potential biomarkers for its diagnosis.

Analysis of MR Signs to Distinguish Between ARCO Stages 2 and 3A in Osteonecrosis of the Femoral Head.

BACKGROUND: MRI is the most effective diagnostic tool of osteonecrosis of the femoral head (ONFH), especially for early diagnosis, but its detection of subchondral or cortical fractures is less accurate than CT. Therefore, it is difficult to accurately stage ONFH in the peri-collapse period by MRI. PURPOSE: To improve the accuracy of MR for distinguishing between Association Research Circulation Osseous (ARCO) stages 2 and 3A in ONFH. STUDY TYPE: Retrospective. SUBJECTS: One hundred and fifty five cases of ARCO stage 2/3A of ONFH underwent MR examinations, M/F = 72/83. CT was used as reference standard for collapse, which was decided by an orthopedist and a radiologist in consultation. FIELD STRENGTH/SEQUENCE: 3 T/axial and coronal T1 -weighted Turbo Spin Echo (T1 W TSE) sequence, axial T2 -weighted fat-saturated (T2 W FS) TSE sequence, and coronal proton density-weighted imaging (PDWI)-FS-Dixon fat/water image. ASSESSMENT: Five potential MR signs (the maximum width of the necrotic-viable interface, bone marrow edema (BME), irregular articular surface of the femoral head, T2 heterogeneous high signal, and the absence of a necrotic-viable interface with the morphology of closed loop) were evaluated blindly by five radiologists independently and the total scores of different combinations of MR signs were calculated. STATISTICAL TESTS: Mann-Whitney U test and Chi-square test were used to evaluate age, gender, and MR signs differences between the two groups. ROC curve was used to access the distinguishing value of MR signs. The consistency of the five radiologists was analyzed by intraclass correlation coefficient. RESULTS: The area under the curve of the combined MR signs 2 for distinguishing between ARCO stages 2 and 3A was the greatest (0.967), sensitivity and specificity were 100.00% and 88.71% respectively, and greater than 1 was the threshold. DATA CONCLUSION: Combined MR signs 2 has great values in distinguishing between ARCO stages 2 and 3A in ONFH, thus helping clinical therapy. LEVEL OF EVIDENCE: 4 TECHNICAL EFFICACY: Stage 2.

Noninvasive Evaluation of Renal Hypoxia by Multiparametric Functional MRI in Early Diabetic Kidney Disease.

BACKGROUND: Renal hypoxia, which caused by a mismatch between oxygen delivery and oxygen demand, may be the primary pathophysiological pathway driving diabetic kidney disease (DKD). Blood oxygenation level-dependent (BOLD) magnetic resonance imaging (MRI) could detect hypoxia, but can be limited in distinguishing increased oxygen consumption or decreased blood supply. PURPOSE: To explore multiparametric functional MRI in evaluating mechanism of the hypoxia changes in early stage of DKD. STUDY TYPE: Prospective. ANIMAL MODEL: Thirty-five New Zealand White rabbits were divided into control group (n = 5) and alloxan-induced diabetes mellitus (DM) groups (DM3 group: n = 15, DM7 group: n = 15). FIELD STRENGTH/SEQUENCE: 3 T MRI/BOLD, arterial spin labeling (ASL), and asymmetric spin-echo (ASE). ASSESSMENT: The renal oxygenation level (R2*), renal blood flow (RBF), and oxygen extraction fraction (OEF) were evaluated by BOLD, ASL, and ASE MRI, respectively. The regions of interest were manually drawn including cortex, outer stripes of outer medulla (OS), and inner stripes of outer medulla (IS). STATISTICAL TESTS: Analysis of variance, independent-sample t-test, and paired-sample t-test were applied for comparisons among groups, between groups, and within the same group. P < 0.05 was considered statistically significant. RESULTS: All renal regions of DM3 group at Day 3 after DM induction showed significantly higher R2* and OEF values compared to baseline. The RBF values showed no statistically significant difference (P = 0.62, 0.76, 0.09 in cortex, OS, and IS, respectively). For DM7 group at Day 7, R2*, OEF, and RBF values showed no statistically significant difference compared to baseline (P = 0.06, 0.05, 0.06 of R2*; 0.70, 0.64, 0.68 of OEF; and 0.33, 0.58, 0.48 of RBF in cortex, OS, and IS, respectively). DATA CONCLUSION: BOLD MRI could detect renal hypoxia in early stage of DKD rabbit model, which was mainly revealed by increased oxygen consumption, but not affected by renal blood flow change. LEVEL OF EVIDENCE: 2 Technical Efficacy Stage: 1.

Benzofuran ε-caprolactam glucosides, amides and phenylpropanoid derivatives with anti-inflammatory activity from Oxybaphus himalaicus.

(+)-(2S,3S)- and (-)-(2R,3R)-Oxybaphuslactam A glucosides are two undescribed benzofuran ε-caprolactams featuring a unique 7/6/5 fused tricyclic framework with p-glucosyl-O-phenyl unit. They were isolated from the root of Tibetan medicinal plant Oxybaphus himalaicus along with an undescribed sucrose ester, 3-O-feruloyl sucrose, an undescribed lignan glucoside, (7'R,8R,8'S)-3,3',5,5'-tetramethoxy-7',9-epoxylignan-9'-ol-7-one 4,4'-di-O-ß-D-glucopyranoside and ten known amides and phenylpropanoid derivatives. Based on the spectral analyses, X-ray crystallography and comparison of experimental and TD-DFT calculated ECD spectra, the structures of these compounds were determined. The anti-inflammatory assay showed the undescribed compounds had significant inhibitory effects on the formation of NO, TNF-α and IL-6, which were evaluated by LPS induced RAW 264.7 cell model.

Characteristics of diffusion-weighted and blood oxygen level-dependent magnetic resonance imaging in Tubulointerstitial nephritis: an initial experience.

BACKGROUND: Diffusion-weighted (DW) and blood oxygen level-dependent (BOLD) magnetic resonance imaging are classical sequences of functional MR, but the exploration in non-transplanted kidney disease is limited. OBJECTS: To analyze the characteristics of apparent diffusion coefficient (ADC) and R2* value using DW and BOLD imaging in tubulointerstitial nephritis (TIN). METHODS: Four acute TIN, thirteen chronic TIN patients, and four controls were enrolled. We used multiple gradient-echo sequences to acquire 12 T2*-weighted images to calculate the R2* map. DW imaging acquired ADC values by combining a single-shot spin-echo echo-planar imaging pulse sequence and the additional motion probing gradient pulses along the x,y, z-axes with two b values:0 and 200, as well as 0 and 800 s/mm2. ATIN patients performed DW and BOLD magnetic resonance at renal biopsy(T0) and the third month(T3). We assessed the pathological changes semiquantitatively, and conducted correlation analyses within functional MR, pathological and clinical indexes. RESULTS: In ATIN, ADCs were significantly lower(b was 0,200 s/mm2, 2.86 ± 0.19 vs. 3.39 ± 0.11, b was 0,800 s/mm2, 1.76 ± 0.12 vs. 2.16 ± 0.08, P < 0.05) than controls, showing an obvious remission at T3. Cortical and medullary R2* values (CR2*,MR2*) were decreased, significant difference was only observed in MR2*(T0 24.3 ± 2.1vs.T3 33.1 ± 4.1,P < 0.05). No relationship was found between functional MR and histopathological indexes.MR2* had a close relationship with eGFR (R = 0.682,P = 0.001) and serum creatinine(R = -0.502,P = 0.012). Patients with lower ADC when b was 0,200 s/mm2 showed more increase of ADC(R = -0.956,P = 0.044) and MR2*(R = -0.949,P = 0.05) after therapy. In CTIN group, lowered MR2* and MR2*/CR2* provided evidence of intrarenal ischemia. CTIN with advanced CKD (eGFR< 45) had significantly lower ADCb200 value. CONCLUSIONS: We observed the reduction and remission of ADC and R2* values in ATIN case series. ATIN patients had concurrently decreased ADCb800 and MR2*. The pseudo normalization of CR2* with persistently low MR2* in CTIN suggested intrarenal hypoxia.

The histone variant Sl_H2A.Z regulates carotenoid biosynthesis and gene expression during tomato fruit ripening.

The conserved histone variant H2A.Z is essential for transcriptional regulation; defense responses; and various biological processes in plants, such as growth, development, and flowering. However, little is known about how H2A.Z affects the developmental process and ripening of tomato fruits. Here, we utilized the CRISPR/Cas9 gene-editing system to generate a sl_hta9 sl_hta11 double-mutant, designated sl_h2a.z, and found that these two mutations led to a significant reduction in the fresh weight of tomato fruits. Subsequent messenger RNA (mRNA)-seq results showed that dysfunction of Sl_H2A.Z has profound effects on the reprogramming of genome-wide gene expression at different developmental stages of tomato fruits, indicating a ripening-dependent correlation between Sl_H2A.Z and gene expression regulation in tomato fruits. In addition, the expression of three genes, SlPSY1, SlPDS, and SlVDE, encoding the key enzymes in the biosynthesis pathway of carotenoids, was significantly upregulated in the later ripening stages, which was consistent with the increased contents of carotenoids in sl_h2a.z double-mutant fruits. Overall, our study reveals a role of Sl_H2A.Z in the regulation of carotenoids and provides a resource for the study of Sl_H2A.Z-dependent gene expression regulation. Hence, our results provide a link between epigenetic regulation via histone variants and fruit development, suggesting a conceptual framework to understand how histone variants regulate tomato fruit quality.

LncRNA SNHG5 promotes chondrocyte proliferation and inhibits apoptosis in osteoarthritis by regulating miR-10a-5p/H3F3B axis.

BACKGROUND: Osteoarthritis (OA) is a common degenerative joint disease in the elderly. Increasing evidence suggested that long non-coding RNAs (lncRNAs) played vital roles in OA progression. This study aimed to explore the role and mechanism of lncRNA small nucleolar RNA host gene 5 (SNHG5) in OA development. METHODS: Chondrocytes were stimulated with interleukin-1ß (IL-1ß) in vitro. The levels of SNHG5, miR-10a-5p, and H3 histone family 3B (H3F3B) were measured by quantitative real-time polymerase chain reaction (qRT-PCR) or western blot. Cell proliferation was assessed by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) assay and colony formation assay. Cell apoptosis was tested by flow cytometry. The levels of apoptosis-related and cartilage-related markers were detected by western blot. The interaction among SNHG5, miR-10a-5p, and H3F3B was confirmed by dual-luciferase reporter assay and RNA immunoprecipitation (RIP) assay. RESULTS: SNHG5 and H3F3B were downregulated, while miR-10a-5p was upregulated in OA cartilage tissues. Knockdown of SNHG5 enhanced IL-1ß-induced apoptosis in chondrocytes. Rescue experiments verified that SNHG5 hindered apoptosis in IL-1ß-stimulated chondrocytes by sponging miR-10a-5p. Moreover, H3F3B was a target of miR-10a-5p, and miR-10a-5p promoted IL-1ß-induced chondrocyte apoptosis by regulating H3F3B. In addition, SNHG5 regulated H3F3B expression via sponging miR-10a-5p in IL-1ß-treated chondrocytes. CONCLUSION: SNHG5 suppressed chondrocytes apoptosis in OA by regulating the miR-10a-5p/H3F3B axis, which provided a promising biomarker for OA treatment.

Prediction of the progression of femoral head collapse in ARCO stage 2-3A osteonecrosis based on the initial bone resorption lesion.

OBJECTIVES: To predict the progression of femoral head collapse in Association Research Circulation Osseous (ARCO) Stage 2-3A osteonecrosis based on the initial bone resorption lesion. METHODS: A retrospective analysis of the location, attenuation, and maximum area in coronal position (MAC) of the initial bone resorption lesion in ARCO Stage 2 and 3A was conducted in 85 cases of osteonecrosis of the femoral head (ONFH). The cases were divided into rapid and slow progression groups according to whether femoral head collapse at follow-up was greater than 2 mm. The characteristics of the bone resorption lesion between the two groups were compared by analysis of variance. Receiver operating characteristic curve was used to analyze the MAC, regions of A2, and C1 of bone resorption lesion in predicting collapse progression. RESULTS: The MAC of initial bone resorption lesion in rapid progression group (117.8 ± 72.1 mm2) was significantly larger than slow (53.1 ± 39.5 mm2) (p < 0.001). Regions of A2 and C1 involved were significantly higher in rapid than slow progression group. The area under the receiver operating characteristic curve of MAC, regions of A2 and C1 of bone resorption lesion to predict collapse progression were 0.81, 0.72 and 0.62 respectively. A threshold MAC of 49 mm2 had sensitivity of 86.1% and specificity of 61.9% to predict collapse progression. CONCLUSIONS: The MAC of initial bone resorption lesion in ARCO Stage 2-3A ONFH can predict the progression of femoral head collapse. If it is greater than 49 mm2 and located in regions of A2 and C1, the possibility of rapid progression is high, active monitoring and intervention should be recommended. ADVANCES IN KNOWLEDGE: This study is the first to find that the maximum area in coronal position of initial bone resorption lesion in ARCO Stage 2 or 3A can predict progression of the femoral head collapse with a threshold of 49 mm2. If the maximum area is larger than 49 mm2 and located in the anterolateral or lateral column of the femoral head, the possibility of rapid collapse progression is high, therefore, monitoring should be strengthened and active intervention should be considered.

Genome-Wide Identification of Circular RNAs in Response to Low-Temperature Stress in Tomato Leaves.

Abiotic stress adversely inhibits the growth and development of plants, by changing the expression of multiple genes. Circular RNAs (circRNAs), as a class of non-coding RNAs, function in transcriptional and posttranscriptional regulation. Yet, the involvement of circRNAs in abiotic stress response is rarely reported. In this study, the participation and function of circRNAs in low-temperature (LT)-induced stress response were investigated in tomato leaves. We generated genome-wide profiles of circRNAs and mRNAs in tomato leaves grown at 25°C room temperature (RT) and 12°C LT. Our results show that 1,830 circRNAs were identified in tomato leaves in both RT and LT treatments, among which 1,759 were differentially induced by the LT treatment. We find that the identified circRNAs are mainly located at exons of genes, but less distributed at introns of genes or intergenic regions. Our results suggest that there are 383 differentially expressed circRNAs predicted to function as putative sponges of 266 miRNAs to target 4,476 mRNAs in total. Moreover, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis assays indicate that multiple pathways were enriched in both differentially expressed genes induced by LT and parental genes of differentially expressed circRNAs induced by LT, revealing the key functions of circRNAs and the corresponding targeted genes in response to LT stress. Our results suggest that circRNAs may be involved in regulating metabolism (i.e., carbohydrate, amino acid, lipid, and energy), signal transduction, and environmental adaptation-related pathways and that these circRNAs were predicted to regulate the expression of transcription factors, genes in signal transduction pathways, and genes related to the Ca2+ channel through targeting the corresponding proteins, such as WRKY, NAC, cytochrome P450, and calmodulin binding protein. Taken together, our study uncovers that multiple circRNAs are isolated and differently regulated in response to LT stress and provides the resource and potential networks of circRNA-miRNA-mRNA under LT stress for further investigations in tomato leaves.

Evaluating postoperative anal fistula prognosis by diffusion-weighted MRI.

PURPOSE: The purpose of this study was to explore whether preoperative diffusion-weighted magnetic resonance imaging (DW-MRI) can be used to evaluate the prognosis of anal fistula and identify the influence factors of postoperative recurrence. METHODS: This is a retrospective study of 117 patients with anal fistula who have undergone preoperative DW-MRI and surgery. All patients were followed up by telephone or reexamination within 2 years after surgery. Of the 117 patients, 35 were excluded due to loss of follow-up and only 82 were included in this study. MRI fistula imaging-related data were analyzed, and fistula severity was scored using criteria of both local extension of fistulas and active inflammation for a total maximum score of 22. The apparent diffusion coefficient (ADC) value of the fistula in patients with anal fistula during preoperative MRI examination was measured. According to whether anal fistula patients are accompanied by perianal abscess, they are divided into two groups, namely anal fistula group and anal fistula with abscess group. Based on whether patients with anal fistula recur after surgery, they were further divided into recurrent group and non-recurrent group. RESULTS: 82 patients with anal fistula were included in this analysis, 23 of them recurred and 59 were cured. Among patients with perianal abscess, the mean ADC value of the recurrent group was (1.19 ±â€¯0.21)×10-3 mm2/s, which is significantly lower than that of the non-recurrent group (1.36 ±â€¯0.19)×10-3 mm2/s. There were significant statistical differences in ADC values between the two groups (p = 0.03). Among patients with anal fistulas without abscesses, 15 patients recurred after surgery, with a mean ADC value of (1.45 ±â€¯0.27) ×10-3 mm2/s, and 33 patients didn't occur, with a mean ADC value of (1.44 ±â€¯0.31)×10-3 mm2/s. The ADC value of preoperative fistula in patients was negative significant correlation with MRI findings score (r= -0.332, P = 0.002). Risk factors for the recurrence after anal fistula surgery include the time interval between MRI and operation, multiple fistula tracks. Fatigue, excessive intake of spicy or greasy food and diarrhea may also be external risk factors for postoperative recurrence of patients with anal fistula. CONCLUSIONS: DW-MRI has important application value for the prognosis evaluation of anal fistula. Complex type of anal fistula and improper lifestyle are the main risk factors affecting the recurrence after anal fistula surgery.

Comprehensive quality evaluation of Lignum Caraganae and rapid discrimination of Caragana jubata and Caragana changduensis based on characteristic compound fingerprints by HPLC-UV and HPLC-MS/MS coupled with chemometrics analysis.

INTRODUCTION: Caragana jubata Poir (CJ) and Caragana changduensis Liou f. (CC) are the two main original plants of Lignum Caraganae (LIC, a clinically effective Tibetan materia medica) and the red heartwoods of CJ and CC have been used for the treatment of polycythemia, hypertension and menstrual disorders. OBJECTIVE: To establish a comprehensive method for rapid quality assessment of LIC based on revealing the characteristic components of LIC and to discriminate the plant sources and LIC from its adulterations. METHODOLOGY: A multi-index and synthetically balanced orthogonal design L9 (34 ) experiment was performed to obtain an efficient ultrasonic extraction condition of LIC sample. High-performance liquid chromatography coupled with an ultraviolet detector (HPLC-UV) techniques were developed for fingerprinting and quantitative analysis of 14 major compounds in LIC, and the main components were identified by HPLC tandem mass spectrometry (HPLC-MS/MS). HPLC fingerprint and chemometrics analysis were employed to visualise the distinction and relationship of LIC obtained from CJ and CC and to determine their potential characteristic markers. RESULTS: Fourteen compounds including a new compound were identified and quantified in LIC. The potential characteristic markers in LIC were identified based on qualitative and fingerprint analysis. The hierarchical cluster analysis (HCA) and principle component analysis (PCA) showed obvious discrimination between LIC obtained from CJ and CC. Five batches of LIC samples were authenticated, and its adulterations were successfully found. CONCLUSION: A facile HPLC combined with fingerprint and chemometrics methods could rapidly evaluate the quality of LIC and discriminate LIC obtained from CJ and CC.

Disentangling the effects of driving forces on soil bacterial and fungal communities under shrub encroachment on the Guizhou Plateau of China.

Global shrub encroachment (SE) affects the structure and function of grassland ecosystem. The effects of SE on plant and soil abiotic properties have been well studied; however, little is known about the extent to which driving forces structure soil microbes under SE, especially in subalpine regions of the Guizhou Plateau of China, which is undergoing progressive SE. We investigated the plant factors (viz, plant diversity and relative shrub cover), soil physicochemical properties, enzymatic activities, and microbial communities, quantified microbial element limitations under three encroachment stages, and disentangled the effects sizes of the factors that structure the diversity and composition of soil microbial communities. Redundancy analysis showed that soil factors made a greater contribution than plant factors to shaping the diversity and composition of the soil bacterial community, soil chemical factors made a greater contribution than physical factors both to structuring the diversity and composition of the soil bacterial community and to structuring the composition of the soil fungal community; and soil nutrient stoichiometry made a greater contribution than soil nutrient content to shaping soil bacterial community's diversity and fungal community's composition. In contrast, soil nutrient content made a greater contribution than soil nutrient stoichiometry to shaping the soil bacterial community's composition. The decrease in bacterial community's diversity observed under SE was attributable to increases in the carbon and nitrogen limitations consequent to SE, and the nitrogen limitation had a greater contribution to the soil bacterial community's diversity and composition than did the carbon limitation. These findings provide updated knowledge of the driving forces shaping the diversity and composition of soil microbial communities, which could be crucial for improving microbial prediction models and revealing the element cycling that occurs in SE biomes.

Effect and Mechanism of the Bruton Tyrosine Kinase (Btk) Inhibitor Ibrutinib on Rat Model of Diabetic Foot Ulcers.

BACKGROUND Diabetes causes damage to the soft tissue and bone structure of the foot, referred to as "diabetic foot". Ibrutinib is a Bruton tyrosine kinase (Btk) inhibitor, and the role and mechanism of ibrutinib on the diabetic foot have not been elucidated. MATERIAL AND METHODS Male Wister rats were randomly divided into 3 groups: control group, model group, and ibrutinib group. After 14 days, the ulcer wound size of each group was measured, and the ulcer healing rate was calculated. The level of inflammatory factors interleukin (IL)-1ß, tumor necrosis factor (TNF)-alpha, and IL-6 was detected by enzyme-linked immunosorbent assay (ELISA). Real-time polymerase chain reaction (PCR) was used to analyze the changes of Toll-like receptor 2 (TLR2) and TLR4. The expression of vascular endothelial growth factor (VEGF) and the RAGE (receptor for advanced glycation end product/NF-kappaB (nuclear factor-kappa B) pathway was detected by western blot. RESULTS Blood glucose, blood lipids, serum creatinine, and urea nitrogen (BUN) levels were increased in the model group, together with increased levels of IL-1ß, TNF-alpha, IL-6, as well as TLR2 and TLR4 expression, and there were significant differences compared with the control group (P<0.05). Meanwhile, the model group showed decreased VEGF expression and increased expression of RAGE and NF-kappaB. However, ibrutinib reduced blood sugar, blood lipids, creatinine, and urea nitrogen levels, inhibited the secretion of inflammatory factors, promoted ulcer healing, improved ulcer healing rate, decreased the expression of TLR2, TLR4, RAGE, and NF-kappaB, and increased VEGF expression; there were significant differences in the ibrutinib group compared with the model group (P<0.05). CONCLUSIONS The Btk inhibitor ibrutinib can upregulate VEGF expression, inhibit the expression of TLRs, inhibit the secretion of inflammatory factors, and promote the healing of diabetic foot ulcer possibly by regulating the RAGE/NF-kappaB pathway.

Anti-inflammatory Chalcone-Isoflavone Dimers and Chalcone Dimers from Caragana jubata.

Two new chalcone-isoflavone dimers, caraganins A (1) and B (2), two new chalcone dimers, caraganins C (3) and D (4), and eight known compounds (5-12) were obtained from the red heartwood of the rhizomes of Caragana jubata. The structures of caraganins A-D were established by 1D and 2D NMR spectroscopy, HRMS and ECD analysis, and comparison with previously known compounds. The anti-inflammatory activities of the new compounds were evaluated by measuring the production of NO, IL-6, and TNF-α in mouse RAW 264.7 macrophages induced by lipopolysaccharide. Among these, compounds 2 and 4 showed the most potent inhibitory activities (IC50: 4.1 and 5.2 µM, respectively) on nitric oxide formation, and compounds 1 and 4 displayed the most potent inhibitory activities on the secretion of inflammatory factor TNF-α, with IC50 values of 11.4 and 14.7 µM. The possible biosynthetic pathways of the chalcone-isoflavone dimers and the chalcone dimers are proposed.

The Effects of Fatiguing Aerobic Exercise on the Cerebral Blood Flow and Oxygen Extraction in the Brain: A Piloting Neuroimaging Study.

The fatigue in aerobic exercise affects the task performance. In addition to the fatigue in the muscular system, the diminished performance may arise from the altered cerebral blood supply and oxygen extraction. However, the effects of the fatiguing aerobic exercise on the ability of brain to regulate the cerebral blood flow (CBF) and to extract the oxygen are not fully understood. In this pilot study, we aim to quantify such effects via advanced functional MRI techniques. Twenty healthy younger elite athletes were recruited. In the screening visit, one circle ergometer test was used to screen the maximal relative oxygen consumption (VO2max). Eleven eligible participants then completed the next MRI visit after 7 days. These participants completed a 2-min pulsed arterial spin labeling (ASL) using the PICORE/QUIPSS II and 5-min asymmetric spin echo (ASE) scan at baseline and immediately after the aerobic circle ergometer test. The CBF was then measured using the ASL images and the oxygen consumption of the brain was quantified using oxygen extraction fractions (OEF) derived from the ASE images. The test time, VO2max, and anaerobic threshold were also recorded. As compared to baseline, participants had significant reduction of global CBF (p = 0.003). Specifically, the CBF in bilateral striatum, left middle temporal gyrus (MTG) and right inferior frontal gyrus (IFG) decreased significantly (p < 0.005, K > 20). No significant changes of the OEFs were observed. Participants with greater OEF within the right striatum at baseline had longer test time, greater anaerobic threshold and relative VO2max (r 2 > 0.51, p < 0.007). Those with longer test time had less reduction of CBF within the right IFG (r 2 = 0.55, p = 0.006) and of OEF within the left striatum (r 2 = 0.52, p = 0.008). Additionally, greater anaerobic threshold was associated with less reduction of OEF within the left MTG (r 2 = 0.49, p = 0.009). This pilot study provided first-of-its-kind evidence suggesting that the fatiguing aerobic exercise alters the cerebral blood supply in the brain, but has no significant effects on the ability of brain to extract oxygenation. Future studies are warranted to further establish the CBF and OEF as novel markers for physical and physiological function to help the assessment in the sports science and clinics.