Optimal Size Threshold for MRI-Detected Retropharyngeal Lymph Nodes to Predict Outcomes in Nasopharyngeal Carcinoma: A Two-Center Study.

BACKGROUND. Retropharyngeal lymph node (RLN) metastases have profound prognostic implications in patients with nasopharyngeal carcinoma (NPC). However, the AJCC staging system does not specify a size threshold for determining RLN involvement, resulting in inconsistent thresholds in practice. OBJECTIVE. The purpose of this article was to determine the optimal size threshold for determining the presence of metastatic RLNs on MRI in patients with NPC, in terms of outcome predictions. METHODS. This retrospective study included 1752 patients (median age, 46 years; 1297 men, 455 women) with NPC treated by intensity-modulated radiotherapy (RT) from January 2010 to March 2014 from two hospitals; 438 patients underwent MRI 3-4 months after treatment. Two radiologists measured the minimal axial diameter (MAD) of the largest RLN for each patient using a consensus process. A third radiologist measured MAD in 260 randomly selected patients to assess interobserver agreement. Initial ROC and restricted cubic spline (RCS) analyses were used to derive an optimal MAD threshold for predicting progression-free survival (PFS). The threshold's predictive utility was assessed in multivariable Cox regression analyses, controlling for standard clinical predictors. The threshold's utility for predicting PFS and overall survival (OS) was compared with a 5-mm threshold using Kaplan-Meier curves and log-rank tests. RESULTS. The intraclass correlation coefficient for MAD was 0.943. ROC and RCS analyses yielded an optimal threshold of 6 mm. In multivariable analyses, MAD of 6 mm and greater independently predicted PFS in all patients (HR = 1.35, p = .02), patients with N0 or N1 disease (HR = 1.80, p = .008), and patients who underwent posttreatment MRI (HR = 1.68, p = .04). In patients with N1 disease without cervical lymph node involvement, 5-year PFS was worse for MAD greater than or equal to 6 mm than for MAD that was greater than or equal to 5 mm but less than 6 mm (77.2% vs 89.7%, p = .03). OS was significantly different in patients with stage I and stage II disease defined using a 6-mm threshold (p = .04), but not using a 5-mm threshold (p = .09). The 5-year PFS rate was associated with a post-RT MAD of 6 mm and greater (HR = 1.68, p = .04) but not a post-RT MAD greater than or equal to 5 mm (HR = 1.09, p = .71). CONCLUSION. The findings support a threshold MAD of 6 mm for determining RLN involvement in patients with NPC. CLINICAL IMPACT. Future AJCC staging updates should consider incorporation of the 6-mm threshold for N-category and tumor-stage determinations.

Integrating Tetrathiafulvalene and Nickel-Bis(dithiolene) Units into Donor-Acceptor Covalent Organic Frameworks for Stable and Efficient Photothermal Conversion.

Tetrathiafulvalene (TTF) and Ni-bis(dithiolene) are typical conductive units widely studied in electronics, optics, and photochemistry. However, their applications in near-infrared (NIR) photothermal conversion are often limited by insufficient NIR absorption and low chemical/thermal stability. Herein, we integrate TTF and Ni-bis(dithiolene) into a covalent organic framework (COF) with stable and efficient NIR and solar photothermal conversion performance. Two isostructural COFs, namely Ni-TTF and TTF-TTF, are successfully isolated which are composed of TTF and Ni-bis(dithiolene) units as donor-acceptor (D-A) pairs or TTF units only. Both COFs show high BET surface areas and good chemical/thermal stability. Notably, compared with TTF-TTF, the periodic D-A arrangement in Ni-TTF significantly lowers the bandgap, leading to unprecedented NIR and solar photothermal conversion performance.

Reproductive biology of an endangered lithophytic shrub and implications for its conservation.

BACKGROUND: Plants in cliff habitats may evolve specific reproductive strategies to cope with harsh environments, and unraveling these reproductive characteristics can improve our understanding of survival strategies and lithophyte evolution. This understanding is especially important for efforts to protect rare and endemic plants. Here, we investigated the reproductive biology of Lonicera oblata, an endangered lithophytic shrub that is scattered in highly fragmented and isolated cliff habitats of the Taihang and Yan mountains in North China. RESULTS: Flowers of L. oblata are herkogamous and protandrous, characteristics that can prevent autogamy at the single-flower level, and insects are necessary for pollination. The outcrossing index, pollen/ovule ratio, and the results of hand pollination were measured and all revealed a mixed mating system for L. oblata, that combines cross-fertilization and partial self-fertilization. The floral traits of L. oblata of zygomorphic and brightly yellowish corolla, heavy fragrance, and rich nectar, suggest an entomophilous pollination system. Sweat bees were observed as the most effective pollinators but their visiting frequencies were not high. Pollen limitation may limit the reproductive success of L. oblata. CONCLUSIONS: We determined the reproductive characteristics of L. oblata, a critically endangered species endemic to cliffs in North China, providing insight into its endangerment and suggesting conservation strategies. L. oblata has highly pollinator-dependent self-fertilization as part of a mixed mating system. Floral features such as low-flowering synchrony, asynchronous anthers dehiscence, and high duration of stigma receptivity, improve pollination efficiency in the case of low pollinator service. Our work provides reference information to understand the survival strategies and conservation of L. oblata and other lithophytes.

Combination of Quantitative Computed Tomography and Blood Biochemistry for Evaluating the Relationship Between Nutrition and Bone Mineral Density in Patients on Maintenance Hemodialysis.

PURPOSE: To investigate the effect of nutritional factors on bone mineral density (BMD) using quantitative computed tomography combined with blood biochemistry in patients on maintenance hemodialysis (MHD). METHODS: Sixty patients on MHD were divided into osteopenia (n = 20) and nonosteopenia (n = 40) groups. BMD, fat, and muscle mass were measured by quantitative computed tomography. The calcification of coronary artery and hilar lymph node and computed tomography attenuation values of the liver and spleen were also analyzed. Differences between the two groups were compared, and the risk factors for osteopenia were analyzed by logistic regression analysis. RESULTS: Patients in the osteopenia group had lower albumin levels than those in the nonosteopenia group (37.84 ± 3.00 vs 42.03 ± 4.05 g/L; P < .001). Logistic regression showed that patients with lower albumin levels had a higher risk of osteopenia (odds ratio, 1.462; 95% confidence interval, 1.313-1.801; P = .003). BMD was negatively correlated with fat mass (r = -0.365, P = .004) and positively correlated with the ratio of muscle mass to fat mass (r = 0.431, P = .001). There was no significant difference in the rate of calcification of coronary artery or hilar lymph nodes between the two groups. Computed tomography values of the liver and spleen were positively correlated with the duration of dialysis (r = 0.55, P = .001; r = 0.42, P < .001, respectively). CONCLUSION: Low albumin levels are associated with an increased risk of osteopenia in patients on MHD. Abdominal fat is a risk factor for reduction in BMD in MHD patients, and the ratio of abdominal muscle mass to fat mass is a protective factor for BMD.

Rosiglitazone attenuates hypoxia-induced renal cell apoptosis by inhibiting NF-κB signaling pathway in a PPARγ-dependent manner.

BACKGROUND: In recent years, peroxisome proliferator-activated receptor γ (PPARγ) has been found to be closely associated with hypoxia renal disease. The aim of this study was to investigate the relationship between rosiglitazone and mitochondrial apoptosis in renal tissue and its associated mechanisms. METHODS: Twenty-four male Sprague-Dawley rats were randomly divided into three groups (n = 8 in each): normal control group, hypoxia injury group (equal volume of 0.9% saline), and PPARγ agonist group (Rosiglitazone, 10 mg/kg · d, intraperitoneally). The hypoxia injury group and PPARγ agonist group were placed in a hypoxia chamber and the simulated altitude was set at 7,000 m for 7 days. Blood and kidney samples were collected after 7 days. The quantitative real-time polymerase chain reaction and Western blot methods were used to determine the expression of PPARγ, nuclear factor kappa-B (NF-κB), B-cell lymphoma-2 (Bcl-2), and Bax. RESULTS: The results showed that compared with the normal control group, the renal tissue of rats after hypoxia was severely damaged, as shown by massive renal tubular epithelial cell degeneration and detachment, and renal tubular dilation. The NF-κB protein expression significantly increased, the Bcl-2 protein and mRNA expression significantly decreased, and Bax protein and mRNA expression significantly increased (p < .05 for all). Renal injury was much less severe in the PPARγ agonist group compared to the hypoxia injury group. CONCLUSIONS: Rosiglitazone can alleviate hypoxia renal injury, with the possible mechanism involving attenuation of apoptosis by inhibiting the activation of the NF-κB signaling pathway in a PPARγ-dependent manner and increasing Bcl-2 and decreasing Bax expression.

Camrelizumab versus placebo in combination with gemcitabine and cisplatin as first-line treatment for recurrent or metastatic nasopharyngeal carcinoma (CAPTAIN-1st): a multicentre, randomised, double-blind, phase 3 trial.

BACKGROUND: The addition of camrelizumab to gemcitabine and cisplatin showed promising activity as first-line therapy in patients with recurrent or metastatic nasopharyngeal carcinoma in a phase 1 trial. We therefore compared camrelizumab plus gemcitabine and cisplatin with placebo plus gemcitabine and cisplatin in a randomised phase 3 trial. METHODS: In this randomised, double-blind, phase 3 trial done at 28 hospitals in China, patients were eligible if they were aged 18-75 years, had an Eastern Cooperative Oncology Group (ECOG) performance status of 0-1, and had previously untreated recurrent or metastatic nasopharyngeal carcinoma. Patients were randomly assigned (1:1; using an interactive web-response system with a block size of four) to receive either camrelizumab (200 mg on day 1) or matching placebo intravenously, plus gemcitabine and cisplatin (gemcitabine 1000 mg/m2 on days 1 and 8; cisplatin 80 mg/m2 on day 1) intravenously every 3 weeks for four to six cycles, followed by maintenance therapy with camrelizumab or placebo, until radiographic progression, unacceptable toxicity, start of new anticancer treatment, investigator decision, or withdrawal of consent. Stratification factors used in randomisation were liver metastases, previous radical concurrent chemoradiotherapy, and ECOG performance status. The allocation sequence was generated by an independent randomisation group. The primary endpoint was progression-free survival per independent review committee. The significance threshold for independent review committee-assessed progression-free survival was p=0·0086 (one-sided) at the interim analysis. Efficacy and safety analyses included all patients who received at least one dose of study drug. This trial is registered with ClinicalTrials.gov, NCT03707509, and is closed for enrolment but is ongoing. FINDINGS: Between Nov 13, 2018, and Nov 29, 2019, 343 patients were screened and 263 were eligible and were randomly assigned to the camrelizumab group (n=134) or placebo group (n=129). At the prespecified interim analysis (June 15, 2020), independent review committee-assessed progression-free survival was significantly longer in the camrelizumab group (median 9·7 months [95% CI 8·3-11·4]) than in the placebo group (median 6·9 months [5·9-7·3]; hazard ratio 0·54 [95% CI 0·39-0·76]; one-sided p=0·0002). As of Dec 31, 2020, the most common grade 3 or worse adverse events of any cause were decreased white blood cell count (89 [66%] of 134 patients in the camrelizumab group vs 90 [70%] of 129 patients in the placebo group), decreased neutrophil count (86 [64%] vs 85 [66%]), anaemia (53 [40%] vs 57 [44%]), and decreased platelet count (53 [40%] vs 52 [40%]). Serious adverse events were reported in 59 (44%) of 134 patients in the camrelizumab group and 48 (37%) of 129 patients in the placebo group. Treatment-related deaths occurred in five (4%) patients in the camrelizumab group (two unknown cause of death, one multiple organ dysfunction syndrome, one pharyngeal haemorrhage, and one arrhythmia) and one (<1%) patient in the placebo group (unknown cause of death). INTERPRETATION: Our findings suggest that camrelizumab plus gemcitabine and cisplatin could be a new standard of care for patients with recurrent or metastatic nasopharyngeal carcinoma in the first-line setting. Longer follow-up is needed to confirm this conclusion. FUNDING: Jiangsu Hengrui Pharmaceuticals (formerly Jiangsu Hengrui Medicine). TRANSLATION: For the Chinese translation of the abstract see Supplementary Materials section.

The expression profiles and prognostic values of HSP70s in hepatocellular carcinoma.

BACKGROUND: The HSP70 family of heat shock protein plays a critical role in protein synthesis and transport to maintain protein homeostasis. Several studies have indicated that HSP70s are related to the development and occurrence of various cancers. METHODS: The relationship between the overall survival rate of hepatocellular carcinoma patients and the expression of 14 HSP70s from multiple databases, such as TCGA, ONCOMINE, cBioPortal was investigated. Western Blot and PCR were used to evaluate HSPA4 and HSPA14 expressions in various HCC cells to identify suitable cell lines for further experiments .Wound-healing assays, Transwell assays and EdU assays were used to verify the effects of HSPA4 and HSPA14 on the function of hepatocellular carcinoma cells, and statistical analysis was performed. RESULTS: Hepatocellular carcinoma tissues significantly expressed the 14 HSP70s compared to the normal samples. Besides, the high HSPA1A, HSPA1B, HSPA4, HSPA5, HSPA8, HSPA13, and HSPA14 expressions were inversely associated with the overall survival rate of patients, tumor grade, and cancer stage. A PPI regulatory network was constructed using the 14 HSP70s proteins with HSPA5 and HSPA8 at the network center. Univariate and multivariate analyses showed that HSPA4 and HSPA14 could be independent risk factors for the prognosis of hepatocellular carcinoma patients. Cell experiments have also confirmed that reducing HSPA4 and HSPA14 expressions can inhibit the invasion, metastasis, and proliferation of hepatocellular carcinoma cells. CONCLUSIONS: Therefore, the HSP70s significantly influence the occurrence and development of hepatocellular carcinoma. For instance, HSPA4 and HSPA14 can be novel therapeutic targets and prognostic biomarkers for hepatocellular carcinoma.

Synthesis of Semiconducting 2H-Phase WTe2 Nanosheets with Large Positive Magnetoresistance.

Tungsten ditelluride (WTe2) is provoking immense interest because of its unique electronic properties, but studies about its semiconducting hexagonal (2H) phase are quite rare. Herein, we report the synthesis of semiconducting 2H WTe2 nanosheets with large positive magnetoresistance, for the first time, by a simple lithium-intercalation-assisted exfoliation strategy. Systematic characterizations including high-resolution transmission electron microscopy, X-ray diffraction, and Raman and X-ray photoelectron spectroscopies provide clear evidence to distinguish the structure of 2H WTe2 nanosheets from the orthorhombic (Td) phase bulk counterpart. The corresponding electronic phase transition from metal to semiconductor is also confirmed by density of states calculation, optical absorption, and electrical transport property measurements. Besides, the 2H WTe2 nanosheets exhibit large positive magnetoresistance with values of up to 29.5% (10 K) and 16.2% (300 K) at 9 T. Overall, these findings open up a promising avenue into the exploration of WTe2-based materials in the semiconductor field.

Application Value of Detection of High-Risk HPV Infection in Early Cervical Cancer Patients in Disease Diagnosis and Prognosis Evaluation.

BACKGROUND: To analyze the relationship between HPV infection and early cervical cancer and postoperative survival outcomes. METHODS: A total of 556 women were recruited to receive TCT and HPV tests from October 2017 to October 2018. The type of disease was pathologically diagnosed. The HPV positive rate, HPV-DNA, and E6/E7 mRNA quantitative level were detected, and the diagnostic accuracy of the subjects was analyzed by the receiver operating characteristic (ROC). The cervical intraepithelial neoplasia (CIN) and early cervical cancer patients were radically cured and followed up for 12.0 months to analyze the recurrence rate. RESULTS: Seventy-two cases of chronic cervicitis, 54 cases of CIN, and 51 cases of cervical cancer patients were pathologically diagnosed (32 cases in early stage and 19 cases in middle and late stage). HPV positive rate increased gradually in chronic cervicitis, CIN, and cervical cancer group (p < 0.001) and HPV 16 + 18 subtype. The positive rate was significantly different (p = 0.009). HPV-DNA and E6/E7 mRNA quantification also showed significant differences (p < 0.001). ROC analysis indicated that the accuracy of HPV-DNA and E6/E7 mRNA quantitative diagnosis of malignant lesions (CIN+ cervical cancer) were 0.865 and 0.879, respectively. There were 4 cases (7.41%) of recurrence in CIN group and 5 cases (15.63%) in early cervical cancer group. There was no difference (p = 0.401) among all of the patients. All patients with recurrence were HPV positive. CONCLUSIONS: HPV detection is an indispensable screening method for early cervical cancer and precancerous lesions, and comprehensive HPV 16 and 18 subtypes. DNA and E6/E7 mRNA quantification assay would further improve the accuracy of screening.

TGF-ß Signaling Induces the Expression of OPN in Blood Vessel Endothelial Cells.

BACKGROUND: The mechanism of blood vessel formation and degeneration still remains unclear. Transforming growth factor-ß1 (TGF-ß1) signaling is a critical pathway in this progression and can induce multiple biological effects. Osteopontin (OPN) is involved in mineral metabolism and the inflammatory response associated with vascular calcification. METHODS: To identify the relationship between TGF-ß signaling pathway and OPN, we stimulated human vascular endothelial cells (HVECs) and human aortic endothelial cells (HAECs) using various concentration of TGF-ß1 in vitro. RESULTS: As assessed by flow cytometry and western blots, apoptosis levels were significantly increased with TGF-ß1 treatment. We also demonstrated that OPN increased in vitro with TGF-ß signaling by western blot and quantitative real time polymerase chain reaction (qRT-PCR) analyses. The inhibitory phosphorylation of endothelial nitric-oxide synthase (eNOS) (Thr495) was also up-regulated by TGF-ß signaling. Meanwhile, the anti-inflammatory factor Nrf2 and the activating phosphorylation of eNOS (Ser1177) were down-regulated. CONCLUSIONS: Taken together, our findings demonstrate that TGF-ß signaling can induce the expression of OPN, which may play an important role in the dysfunction of the vascular wall.

[Chemotactic response of ginseng endophyte to ginseng root exudates].

The ginseng endophytic bacteria F1 is a potential biocontrol agent for ginseng bacterial soft rot. In this paper,the chemotactic response of ginseng endophytic bacteria F1 on 8 kinds of sugar and amino acids was detected by capillary method to explore its biocontrol mechanism. The chemotactic response of F1 strain to 4 kinds of better chemotaxis substances such as glucose,glycine,L-rhamnoseand L-glutamic acid under parameters( concentration,time,temperature and pH) was studied. The results showed that under the same experimental conditions( incubation temperature 25 ℃,incubation time 60 min,chemotaxis concentration 1 mg·L~(-1)),ginseng endophytic bacteria F1 showed different degrees of response to the eight substances tested. The phenomenon of positive chemotaxis of the measured sugars and amino acids was obvious,and the chemotactic response to total ginsenosides was low. The degree of chemotaxis response is positively correlated with the chemotaxis index within a certain range of parameters,but as the temperature,p H,time,concentration and other factors continue to increase,the chemotaxis effect decreases,and F1 optimizes the chemotaxis of the four substances. The parameters are as follows: glucose: 25 ℃,10 mg·L~(-1),45 min,pH 7; glycine: 30 ℃,10 mg·L~(-1),75 min,pH7; L-rhamnose: 30 ℃,1 mg·L~(-1),30 min,pH 6; L-glutamic acid: 25 ℃,0. 1 mg·L~(-1),45 min,pH 8. The chemotactic response is more sensitive to low concentrations of chemotactic substances.

The regulatory role of microRNAs in angiogenesis-related diseases.

MicroRNAs (miRNAs) are small non-coding RNAs that regulate gene expression at a post-transcriptional level via either the degradation or translational repression of a target mRNA. They play an irreplaceable role in angiogenesis by regulating the proliferation, differentiation, apoptosis, migration and tube formation of angiogenesis-related cells, which are indispensable for multitudinous physiological and pathological processes, especially for the occurrence and development of vascular diseases. Imbalance between the regulation of miRNAs and angiogenesis may cause many diseases such as cancer, cardiovascular disease, aneurysm, Kawasaki disease, aortic dissection, phlebothrombosis and diabetic microvascular complication. Therefore, it is important to explore the essential role of miRNAs in angiogenesis, which might help to uncover new and effective therapeutic strategies for vascular diseases. This review focuses on the interactions between miRNAs and angiogenesis, and miRNA-based biomarkers in the diagnosis, treatment and prognosis of angiogenesis-related diseases, providing an update on the understanding of the clinical value of miRNAs in targeting angiogenesis.

[Influence of exogenous ginsenosides on new forest soil microbial communities].

Ginsenosides are the main active ingredient and allelochemicals of Panax ginseng, and they play an important role in ginseng growth and in ecological adaptation. To study the influence of ginsenosides on soil microbial communities, the method of given exogenous total ginsenosides of different concentrations were used to study the influence of ginsenosides on new forest soil microbial community, evaluate the change of metabolic activity of microbial community and investigate the ecological effect of ginsenosides on soil microbial community. Results showed that, exogenous total ginsenosides promoted metabolic activity of microbial community in new forest soil at different concentrations compared with the control after 10 d and 40 d treatment. After 10 d,except for the Evenness index, all of the other indices indicated that the functional diversity of the soil microbial community in the new forest firstly increased then decreased with increase of the total ginsenosides concentration. The Substrate richness for 0.01 g•L⁻¹ soil treatment was significantly different from that of the control. After 20 d, 30 d and 40 d, except for the Evenness index, all of the other indices indicated that the functional diversity of the soil microbial community in the new forest increased with total ginsenosides. These results suggested that ginsenosids can change soil microbial community and microbial metabolic activity, which alter soil microbial ecology and accordingly affect the growth of ginseng with accumulation of ginsenosides in the soil.

[Research on chemotaxis response of Alternaria panax to amino acid of ginseng root exudates].

Plate assay and spore germination method were used to study the chemotaxis response of Alternaria panax to arginine, glutamic acid, aspartic acid and threonine. The result showed that the optimum temperature of A. panax chemotaxis response to four amino acids were all 25 ℃. And chemotaxis responses of A. panax were different under conditions of different concentration and pH value. The chemotaxin reached to the highest under the condition of 2 mg•L⁻¹ and pH value was 7 for arginine, glutamic acid and threonine while 20 mg•L⁻¹ and pH value was 6 for aspartic acid . The data of chemotactic migration index (CMI) were 1.24, 1.38, 1.27, 1.31 and chemotactic growth rates(CGR) were 0.451 0, 0.353 0, 0.381 3, 0.228 8 and spores germination rates(SGR) were 57.33%，63%，56.67%，58% and the dry weight of mycelial (DWM) were 372.9, 348.5, 314.4, 390.2 mg•L⁻¹ respectively. It indicated that the low and middle concentration of amino acid had significant promoting effect on chemotaxis response of A. panax. As important substances generated in ginseng root, amino acids exhibited an efficient chemotactic effect on A. panax, and some even show inhibition effect under high concentration.

Parenting style, resilience, and mental health of community-dwelling elderly adults in China.

BACKGROUND: Given the increasing elderly population worldwide, the identification of potential determinants of successful ageing is important. Many studies have shown that parenting style and mental resilience may influence mental health; however, little is known about the psychological mechanisms that underpin this relationship. The current study sought to explore the relationships among mental resilience, perceptions of parents' parenting style, and depression and anxiety among community-dwelling elderly adults in China. METHODS: In total, 439 community-dwelling elderly Chinese adults aged 60-91 years completed the Personal and Parents' Parenting Style Scale, Connor-Davidson Resilience Scale, Zung Self-Rating Depression Scale, and Zung Self-Rating Anxiety Scale. RESULTS: Elderly adults whose parents preferred positive and authoritative parenting styles had higher levels of mental resilience and lower levels of depression and anxiety. Elderly adults parented in the authoritarian style were found to have higher levels of depression and anxiety, with lower mental resilience. CONCLUSIONS: The findings of this study provide evidence related to successful ageing and coping with life pressures, and highlight the important effects of parenting on mental health. The results suggest that examination of the proximal determinants of successful ageing is not sufficient-distal factors may also contribute to the 'success' of ageing by modifying key psychological dispositions that promote adaptation to adversity.

[Chemotaxis response of Erwinia carotovora on sugars and amino acids of root exudates of Panax ginseng].

The chemotaxis response of Erwinia carotovora to different sugars and amino acids in four kinds of chemotactic parameters (concentration, time, temperature and pH ) was determined by capillary method. The results showed that when pH was 8, concentration was 0.025 mg•L ⁻¹, culture temperature was 25 ℃ and the duration was 60 minutes, the optimal chemotaxis rate of lysine was 2.509,when pH was 6, concentration was 0.25 mg•L ⁻¹, culture temperature was 25 ℃ and the duration was 60 minutes, the optimal chemotaxis rate of arginine was 2.218 8,when pH was 7, concentration was 0.25 mg•L ⁻¹, culture temperature was 30 ℃ and the duration was 60 minutes, the optimal chemotaxis rate of L-rhamnose was 3.091 2, when pH was 6, concentration was 0.25 mg•L ⁻¹, culture temperature was 30 ℃ and the duration was 45 minutes, the optimal chemotaxis rate of D-arabinose was 3.026 3. Sugars and amino acids had obvious chemotaxis with E. carotovora,the high concentration of carbohydrate and amino acid exited an inhibitory effect on chemotaxis response of E. carotovora, and the chemotaxis response decreased with the increase of concentration of carbohydrates and amino acids.

Autophagy inhibits endothelial progenitor cells migration via the regulation of MMP2, MMP9 and uPA under normoxia condition.

OBJECTIVE: The aim of this study was to explore the role of autophagy on the regulation of endothelial progenitor cells (EPCs) migration under normoxic condition. METHODS: After EPCs were isolated and characterized in vitro, we employed Atg5 knocking down and rapamycin to monitor the autophagy, and performed wound healing and transwell assay to assess the cell migration. On the mechanism, the expression of matrix metalloproteinases (MMPs) and urokinase type plasminogen activator (uPA) was evaluated. RESULTS: Atg5 knocking down and rapamycin could respectively inhibit and enhance autophagy, which could result in significantly increased and decreased cell migration in wound healing and transwell assay under normoxic condition. Moreover, Atg5 knocking down could significantly increase the expression of MMP2, MMP9 and uPA in EPCs while rapamycin could decrease the expression of uPA and MMP9. In addition, the mTOR-P70 S6K pathway was also involved in EPCs migration regulation. CONCLUSIONS: These results demonstrated that autophagy could regulate the EPCs migration through mTOR-P70 S6K pathway, and MMP2, MMP9 and uPA may also involve in the regulation mechanism.

The potential signaling pathway between peroxisome proliferator-activated receptor gamma and retinoic acid receptor alpha in renal interstitial fibrosis disease.

Peroxisome proliferator-activated receptorγ (PPARγ) can regulate the process of cell apoptosis and is related to the progression of renal disorders. Retinoic acid receptor alpha (RARα) is one of the nuclear receptors involved in a variety of kidney diseases. Renal interstitial fibrosis (RIF) is a common denominator of chronic kidney disease (CKD). This study investigated whether a potential signaling pathway existed between PPARγ and RARα in RIF rats with unilateral ureteral obstruction (UUO). The rats were randomly divided into four groups: a model group subjected to UUO (GU), and three other groups treated with rosiglitazone sodium (GRS), GW9662 and dimethyl sulfoxide (DMSO), n = 40, respectively. Renal tissues were collected two and four weeks after post-surgery. The relevant indicators were detected. In comparison with the GU group, the expressions of PPARγ and RARα (protein and mRNA) were increased in the GRS group, and decreased in the GW9662 group (all p < 0.01). The RIF index, mRNA and protein expression of transforming growth factor-ß1 (TGF-ß1), and the protein expressions of collagen-IV (Col-IV) and fibronectin (FN) in the GRS group were more markedly reduced than those in the GU group; their levels in the GW9662 group were elevated (all p < 0.01). PPARγ or RARα was negatively correlated to the RIF index, TGF-ß1, Col-IV and FN. PPARγ was positively correlated with RARα (all p < 0.01). In conclusion, PPARγ agonist can elevate the expression of PPARγ or RARα in RIF rats. There might be a potential signaling pathway between PPARγ and RARα in RIF disease.

Characterization and Insights Into the Nano Liposomal Magnetic Gene Vector Used for Cell Co-Transfection.

The development of magnetofection technology has brought a promising method for gene delivery. Here, we develop a novel liposomal magnetofection system, consisted of magnetic nanoparticle and liposome through molecular assembly, was applied to introduce double genes into porcin somatic cells with high co-transfection efficiency. The performace of liposomal magnetic gene nanovectors has been evaluated by involving the micro morphology, diameters distribution, zeta potentials and the capacity of loading DNA molecules. The assembly way among magnetic gene nanovectors and DNA molecules was investigated by atomic force microscopy. Liposomal nano magnetic gene vectors complexes displayed nanoscale assembly and formed compact "fishing-net structure" after combining with plasmid DNA, which is favorable to enhance the loading capacity of DNA molecules.

In vivo metabolism study of xiamenmycin A in mouse plasma by UPLC-QTOF-MS and LC-MS/MS.

Xiamenmycin A is an antifibrotic leading compound with a benzopyran skeleton that is isolated from mangrove-derived Streptomyces xiamenensis. As a promising small molecule for fibrotic diseases, less information is known about its metabolic characteristics in vivo. In this study, the time-course of xiamenmycin A in mouse plasma was investigated by relative quantification. After two types of administration of xiamenmycin A at a single dose of 10 mg/kg, the plasma concentrations were measured quantitatively by LC-MS/MS. The dynamic changes in the xiamenmycin A concentration showed rapid absorption and quick elimination in plasma post-administration. Four metabolites (M1-M4) were identified in blood by UPLC-QTOF-MS, and xiamenmycin B (M3) is the principal metabolite in vivo, as verified by comparison of the authentic standard sample. The structures of other metabolites were identified based on the characteristics of their MS and MS/MS data. The newly identified metabolites are useful for understanding the metabolism of xiamenmycin A in vivo, aiming at the development of an anti-fibrotic drug candidate for the therapeutic treatment of excessive fibrotic diseases.