Can humidifier reservoir bacteria colonize the circuit during mechanical ventilation: An in vitro study.

BACKGROUND: Although the circuit condensate, an ideal bacterial reservoir during mechanical ventilation, may flow into the humidifier reservoir, no studies have investigated if humidifier reservoir colonized bacteria colonize other circuit locations with airflow. AIMS: We aimed to prove whether the humidifier reservoir colonized bacteria colonize other circuit locations with airflow and provide some advice on the disposal of condensate in the clinical setting. STUDY DESIGN: An in vitro experiment was conducted. Mechanical ventilation simulators (n = 90) were divided into sterile water group (n = 30) and broth group (n = 60). In the sterile water group, sterile water was used for humidification, either Acinetobacter baumannii or Pseudomonas aeruginosa were inoculated to humidifier water in the humidifier reservoir, each accounted for 50% of the simulators. The broth group was performed the same as the sterile water group except for the addition of broth into the humidified water. After 24, 72, and 168 h of continuous ventilation, the humidifier water and different locations of the circuits were sampled for bacterial culture. RESULTS: All bacterial culture results of the sterile water group were negative. Bacteria in the humidifier water continued to proliferate in the broth group. With prolonged ventilation, the bacteria at the humidifier reservoir outlet increased. The bacteria at the humidifier reservoir outlet were much more in the Pseudomonas aeruginosa subgroup than in the Acinetobacter baumannii subgroup and the difference was statistically significant (p < .05). During continuous ventilation, no bacterial growth occurred at 10 cm from the humidifier reservoir outlet and the Y-piece of the ventilator circuits. CONCLUSIONS: Sterile water in the humidifier reservoir was not conducive to bacterial growth. Even if bacteria grew in the humidifier reservoir and could reach the humidifier reservoir outlet, colonization of further circuit locations with the airflow was unlikely. During a certain mechanical ventilation time, the amount of bacteria reaching the outlet of the humidifier reservoir varied due to different mobility of bacteria. RELEVANCE TO CLINICAL PRACTICE: In a clinical setting, nurses should not worry about a small amount of condensate backflow into the humidifier reservoir. Draining condensate into the humidifier reservoir can be used as a low risk and convenient method in clinical practice.

SZC-6, a small-molecule activator of SIRT3, attenuates cardiac hypertrophy in mice.

Sirtuin3 (SIRT3), a class III histone deacetylase, is implicated in various cardiovascular diseases as a novel therapeutic target. SIRT3 has been proven to be cardioprotective in a model of Ang II-induced cardiac hypertrophy. However, a few small-molecule compounds targeting deacetylases could activate SIRT3. In this study, we generated a novel SIRT3 activator, 3-(2-bromo-4-hydroxyphenyl)-7-hydroxy-2H-chromen-2-one (SZC-6), through structural optimization of the first SIRT3 agonist C12. We demonstrated that SZC-6 directly bound to SIRT3 with Kd value of 15 µM, and increased SIRT3 deacetylation activity with EC50 value of 23.2 ± 3.3 µM. In neonatal rat cardiomyocytes (NRCMs), pretreatment with SZC-6 (10, 20, 40 µM) dose-dependently attenuated isoproterenol (ISO)-induced hypertrophic responses. Administration of SZC-6 (20, 40 and 60 mg·kg-1·d-1, s.c.) for 2 weeks starting from one week prior ISO treatment dose-dependently reversed ISO-induced impairment of diastolic and systolic cardiac function in wild-type mice, but not in SIRT3 knockdown mice. We showed that SZC-6 (10, 20, 40 µM) dose-dependently inhibited cardiac fibroblast proliferation and differentiation into myofibroblasts, which was abolished in SIRT3-knockdown mice. We further revealed that activation of SIRT3 by SZC-6 increased ATP production and rate of mitochondrial oxygen consumption, and reduced ROS, improving mitochondrial function in ISO-treated NRCMs. We also found that SZC-6 dose-dependently enhanced LKB1 phosphorylation, thereby promoting AMPK activation to inhibit Drp1-dependent mitochondrial fragmentation. Taken together, these results demonstrate that SZC-6 is a novel SIRT3 agonist with potential value in the treatment of cardiac hypertrophy partly through activation of the LKB1-AMPK pathway.

Requirement of Na+/H+ Exchanger NHE1 for Vasopressin-Induced Osteogenic Signaling and Calcification in Human Aortic Smooth Muscle Cells.

BACKGROUND/AIMS: Vasopressin is a powerful stimulator of vascular calcification, augmenting osteogenic signaling in vascular smooth muscle cells (VSMCs) including upregulation of transcription factors such as core-binding factor α-1 (CBFA1), msh homeobox 2 (MSX2), and SRY-Box 9 (SOX9), as well as of tissue-nonspecific alkaline phosphatase (ALPL). Vasopressin-induced osteogenic signaling and calcification require the serum- and glucocorticoid-inducible kinase 1 (SGK1). Known effects of SGK1 include upregulation of Na+/H+ exchanger 1 (NHE1). NHE1 further participates in the regulation of reactive oxygen species (ROS). NHE1 has been shown to participate in the orchestration of bone mineralization. The present study, thus, explored whether vasopressin modifies NHE1 expression and ROS generation, as well as whether pharmacological inhibition of NHE1 disrupts vasopressin-induced osteogenic signaling and calcification in VSMCs. METHODS: Human aortic smooth muscle cells (HAoSMCs) were treated with vasopressin in the absence or presence of SGK1 silencing, SGK1 inhibitor GSK-650394, and NHE1 blocker cariporide. Transcript levels were determined by using quantitative real-time polymerase chain reaction, protein abundance by Western blotting, ROS generation with 2',7'-dichlorofluorescein diacetate fluorescence, and ALP activity and calcium content by using colorimetric assays. RESULTS: Vasopressin significantly enhanced the NHE1 transcript and protein levels in HAoSMCs, effects significantly blunted by SGK1 inhibition with GSK-650394 or SGK1 silencing. Vasopressin increased ROS accumulation, an effect significantly blocked by the NHE1 inhibitor cariporide. Vasopressin further significantly increased osteogenic markers CBFA1, MSX2, SOX9, and ALPL transcript levels, as well as ALP activity and calcium content in HAoSMCs, all effects significantly blunted by SGK1 silencing or in the presence of GSK-650394 or cariporide. CONCLUSION: Vasopressin stimulates NHE1 expression and ROS generation, an effect dependent on SGK1 and required for vasopressin-induced stimulation of osteogenic signaling and calcification of VSMCs.

Measuring green development level at a regional scale: framework, model, and application.

In this study, we propose and construct a novel model that measures regional green development level based on the "three-circle" conceptual framework for green development. Using Jiangsu Province in eastern China as a case study, the spatial-temporal characteristics and dynamics of the green development level from 2000 to 2020 were evaluated using a multi-source dataset at the grid-cell level. Our results show that (1) the analytical hierarchy process-based model proposed herein has higher reliability in terms of the development level measurement than principal component analysis and the entropy weight method. In addition, the average score of green development in the study area was approximately 0.53. Spatially, the green development level in the eastern coastal areas of the study area was found to be generally higher than in other regions, while that in southwestern regions is relatively low. In terms of sub-regions, the green development level scores of the study area have been ranked as follows: middle Jiangsu > southern Jiangsu > northern Jiangsu. (2) It was observed that the gravity center of the green development level can be divided into three stages during the study, with a whole had shifted to the north. (3) For most cities in Jiangsu, the green development level initially increased at first, then declined, and then increased again. (4) In the future, the green development level of Jiangsu Province should pay more attention to promoting regional coordinated development and relationships between society and the environment under rapid economic development.

The relationship between platelet to albumin ratio and disease activity in axial spondyloarthritis patients.

OBJECTIVES: The study aims to investigate the clinical significance of platelet to albumin ratio (PAR), neutrophil to albumin ratio (NAR), and monocyte to albumin ratio (MAR) in axial spondyloarthritis (axSpA). METHODS: Two hundred and ninety-seven axSpA patients and 71 healthy volunteers were recruited. AxSpA patients were divided into inactive group and active group. Spearman's correlation, receiver operating characteristic (ROC) curves, and binary logistic regression analysis were conducted. RESULTS: Albumin was lower in axSpA group, while neutrophil, platelet, monocyte, NAR, PAR, and MAR were higher (p < .05). Albumin was negatively correlated with BASDAI and BASFI (p < .05). Platelet, NAR, PAR, MAR, ESR, and CRP were all positively correlated with BASDAI and BASFI (p < .05). Albumin was lower in axSpA of active group, while platelet, NAR, PAR, MAR, ESR, and CRP were higher (p < .05). ROC curve indicated that the AUC of PAR for axSpA of active group was higher than that of other variables. The optimal cut-off value of PAR was 6.354, with Youden index of 0.337, specificity of 55.4%, and sensitivity of 78.4%. Logistic regression analysis result suggested that PAR was an independent indicator for axSpA disease activity. CONCLUSIONS: PAR had a high diagnostic value for axSpA of active group. PAR was a novel and reliable indicator for axSpA disease activity.

MicroRNA-99b-3p promotes angiotensin II-induced cardiac fibrosis in mice by targeting GSK-3ß.

Cardiac fibrosis is a typical pathological change in various cardiovascular diseases. Although it has been recognized as a crucial risk factor responsible for heart failure, there is still a lack of effective treatment. Recent evidence shows that microRNAs (miRNAs) play an important role in the development of cardiac fibrosis and represent novel therapeutic targets. In this study we tried to identify the cardiac fibrosis-associated miRNA and elucidate its regulatory mechanisms in mice. Cardiac fibrosis was induced by infusion of angiotensin II (Ang II, 2 mg·kg-1·d-1) for 2 weeks via osmotic pumps. We showed that Ang II infusion induced cardiac disfunction and fibrosis accompanied by markedly increased expression level of miR-99b-3p in heart tissues. Upregulation of miR-99b-3p and fibrotic responses were also observed in cultured rat cardiac fibroblasts (CFs) treated with Ang II (100 nM) in vitro. Transfection with miR-99b-3p mimic resulted in the overproduction of fibronectin, collagen I, vimentin and α-SMA, and facilitated the proliferation and migration of CFs. On the contrary, transfection with specific miR-99b-3p inhibitor attenuated Ang II-induced fibrotic responses. Similarly, intravenous injection of specific miR-99b-3p antagomir could prevent Ang II-infused mice from cardiac dysfunction and fibrosis. We identified glycogen synthase kinase-3 beta (GSK-3ß) as a direct target of miR-99b-3p. In CFs, miR-99b-3p mimic significantly reduced the expression of GSK-3ß, leading to activation of its downstream profibrotic effector Smad3, whereas miR-99b-3p inhibitor caused anti-fibrotic effects. GSK-3ß knockdown ameliorated the anti-fibrotic role of miR-99b-3p inhibitor. These results suggest that miR-99b-3p contributes to Ang II-induced cardiac fibrosis at least partially through GSK-3ß. The modulation of miR-99b-3p may provide a new approach for tackling fibrosis-related cardiomyopathy.

MicroRNA-214 contributes to Ang II-induced cardiac hypertrophy by targeting SIRT3 to provoke mitochondrial malfunction.

Reduction of expression and activity of sirtuin 3 (SIRT3) contributes to the pathogenesis of cardiomyopathy via inducing mitochondrial injury and energy metabolism disorder. However, development of effective ways and agents to modulate SIRT3 remains a big challenge. In this study we explored the upstream suppressor of SIRT3 in angiotensin II (Ang II)-induced cardiac hypertrophy in mice. We first found that SIRT3 deficiency exacerbated Ang II-induced cardiac hypertrophy, and resulted in the development of spontaneous heart failure. Since miRNAs play crucial roles in the pathogenesis of cardiac hypertrophy, we performed miRNA sequencing on myocardium tissues from Ang II-infused Sirt3-/- and wild type mice, and identified microRNA-214 (miR-214) was significantly up-regulated in Ang II-infused mice. Similar results were also obtained in Ang II-treated neonatal mouse cardiomyocytes (NMCMs). Using dual-luciferase reporter assay we demonstrated that SIRT3 was a direct target of miR-214. Overexpression of miR-214 in vitro and in vivo decreased the expression of SIRT3, which resulted in extensive mitochondrial damages, thereby facilitating the onset of hypertrophy. In contrast, knockdown of miR-214 counteracted Ang II-induced detrimental effects via restoring SIRT3, and ameliorated mitochondrial morphology and respiratory activity. Collectively, these results demonstrate that miR-214 participates in Ang II-induced cardiac hypertrophy by directly suppressing SIRT3, and subsequently leading to mitochondrial malfunction, suggesting the potential of miR-214 as a promising intervention target for antihypertrophic therapy.

Interocular Asymmetry of Visual Field Loss, Intraocular Pressure, and Corneal Parameters in Primary Open-Angle Glaucoma.

OBJECTIVES: This study aimed to assess the association between the corneal biomechanical parameters and visual field (VF) loss in patients with asymmetric primary open-angle glaucoma (POAG). METHODS: A total of 89 POAG patients (50 males, 56.2%) with asymmetric VF loss, aged 65.2 ± 13.3 years, were enrolled in this study. Asymmetric VF loss was defined as an interocular difference of the global index mean deviation (MD) >2 dB. Intraocular pressure (IOP), central corneal thickness (CCT), and corneal biomechanical parameters such as maximum amplitude at the apex of highest concavity (def ampl HC) were measured. The worse eye was defined as the eye with a smaller MD. RESULTS: The worse eyes had lower MD (-11.9 ± 6.7 dB vs. -5.3 ± 5.0 dB; p < 0.001) and higher IOP (14.6 ± 3.3 vs.13.9 ± 2.6 mm Hg, p = 0.04) than the better eyes. There was no significant difference between the 2 groups for CCT. The interocular difference of MD (IDMD) was negatively correlated with the interocular difference of IOP (r = -0.22, p = 0.04), while positively correlated with the interocular difference of def ampl HC (r = 0.27, p = 0.01). In patients with moderate asymmetric VF loss (IDMD ≥6 dB), def ampl HC of the worse eyes group (1.07 ± 0.12 mm) was significantly lower than the better eyes group (1.10 ± 0.11 mm, p = 0.02). CONCLUSION: Asymmetric POAG was associated with asymmetry in IOP and corneal biomechanical parameters but not in CCT. Lower deflection amplitude and higher IOP were found in eyes with more severe VF damage in POAG patients.

Angiopoietin-2 induces angiogenesis via exosomes in human hepatocellular carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC) is the most common primary liver cancer and is a highly vascularized solid tumor. Angiopoietin-2 (ANGPT2) has been described as an attractive target for antiangiogenic therapy. Exosomes are small extracellular vesicles secreted by most cell types and contribute to cell-to-cell communication by delivering functional cargo to recipient cells. The expression of ANGPT2 in tumor-derived exosomes remains unknown. METHODS: We detected the ANGPT2 expression in HCC-derived exosomes by immunoblotting, enzyme-linked immunosorbent assay and immunogold labeling, then observed exosomal ANGPT2 internalization and recycling by confocal laser scanning microscopy, co-immunoprecipitation and immunoblotting. We used two HCC cell lines (Hep3B and MHCC97H) to overexpress ANGPT2 by lentivirus infection or knockdown ANGPT2 by the CRISPR/Cas system, then isolated exosomes to coculture with human umbilical vein endothelial cells (HUVECs) and observed the angiogenesis by Matrigel microtubule formation assay, transwell migration assay, wound healing assay, cell counting kit-8 assay, immunoblotting and in vivo tumorigenesis assay. RESULTS: We found that HCC-derived exosomes carried ANGPT2 and delivered it into HUVECs by exosome endocytosis, this delivery led to a notable increase in angiogenesis by a Tie2-independent pathway. Concomitantly, we observed that HCC cell-secreted exosomal ANGPT2 was recycled by recipient HUVECs and might be reused. In addition, the CRISPR-Cas systems to knock down ANGPT2 significantly inhibited the angiogenesis induced by HCC cell-secreted exosomal ANGPT2, and obviously suppressed the epithelial-mesenchymal transition activation in HCC. CONCLUSIONS: Taken together, these results reveal a novel pathway of tumor angiogenesis induced by HCC cell-secreted exosomal ANGPT2 that is different from the classic ANGPT2/Tie2 pathway. This way may be a potential therapeutic target for antiangiogenic therapy. Video Abstract.

sFRP1 protects H9c2 cardiac myoblasts from doxorubicin-induced apoptosis by inhibiting the Wnt/PCP-JNK pathway.

Doxorubicin (Dox) is an effective chemotherapy drug against a wide range of cancers, including both hematological and solid tumors. However, the serious cardiotoxic effect restricted its clinical application. We previously have illuminated the protective role of canonical Wnt/ß-catenin signaling in Dox-induced cardiotoxicity. Secreted frizzled-related protein 1 (sFRP1) is one of the endogenous inhibitors of both canonical and noncanonical Wnt signaling. In this study, we investigated the relationship between sFRP1 and noncanonical Wnt/PCP-JNK (Wnt/planar cell polarity-c-Jun N-terminal kinase) pathway in Dox-induced cardiotoxicity in vitro and in vivo. We showed that treatment of H9c2 cardiac myoblasts with Dox (1 µM) time-dependently suppressed cell viability accompanied by significantly decreased sFRP1 protein level and increased Wnt/PCP-JNK signaling. Pretreatment with SP600125, the Wnt/PCP-JNK signaling inhibitor, attenuated Dox-induced apoptosis of H9c2 cells. Overexpression of sFRP1 protected H9c2 cells from Dox-induced apoptosis by inhibiting the Wnt/PCP-JNK pathway. After intraperitoneal injection of a cumulative dose of 15 mg/kg Dox, rats displayed significant cardiac dysfunction; their heart showed inhibited Wnt/ß-catenin signaling and activated Wnt/PCP-JNK signaling. These results suggest that sFRP1 may be a novel target for Dox-induced cardiotoxicity.

Altered Intestinal Microbiota Composition Associated with Enteritis in Yellow Seahorses Hippocampus kuda (Bleeker, 1852).

Enteritis comprises one of the most common diseases affecting the survival of farmed yellow seahorse (Hippocampus kuda), an important economic fish species cultured worldwide. Although there are several studies describing bacteria associated with seahorse, the microbial alternations associated with enteritis in seahorse has not been extensively investigated. In the present study, high-throughput 16S rRNA gene sequencing was used to explore the changes in the intestinal microbiota of seahorse suffering from enteritis. The results showed that the diversity, structure, and function of intestinal microbiota were significantly different between healthy and diseased seahorse. Particularly, significant increase was observed in Brevinema, Mycobacterium, and Vibrio, as well as significant decrease in Psychrobacter, Bacillus, and Shewanella in diseased seahorse (P < 0.05). In addition, PICRUSt predictions revealed that the intestinal microbiota significantly changed the specific metabolic pathways (related to metabolic diseases, replication and repair, transport and catabolism, infectious diseases and immune system) in diseased seahorse (P < 0.05). Altogether, our findings point out the association between changes of the intestinal microbiota and enteritis in seahorse, which provide basic information useful for optimization of breeding regimes and improvements in the health of this endangered species in captivity.

Corrigendum to "Loss of SNHG4 Attenuated Spinal Nerve Ligation-Triggered Neuropathic Pain through Sponging miR-423-5p".

[This corrects the article DOI: 10.1155/2020/2094948.].

Loss of SNHG4 Attenuated Spinal Nerve Ligation-Triggered Neuropathic Pain through Sponging miR-423-5p.

Neuropathic pain is an intractable comorbidity of spinal cord injury. Increasing noncoding RNAs have been implicated in neuropathic pain development. lncRNAs have been recognized as significant regulators of neuropathic pain. lncRNA Small Nucleolar RNA Host Gene 4 (SNHG4) is associated with several tumors. However, the molecular mechanisms of SNHG4 in neuropathic pain remain barely documented. Here, we evaluated the function of SNHG4 in spinal nerve ligation (SNL) rat models. We observed that SNHG4 was significantly upregulated in SNL rat. Knockdown of SNHG4 was able to attenuate neuropathic pain progression via regulating behaviors of neuropathic pain including mechanical and thermal hyperalgesia. Moreover, knockdown of SNHG4 could repress the neuroinflammation via inhibiting IL-6, IL-12, and TNF-α while inducing IL-10 levels. Additionally, miR-423-5p was predicted as the target of SNHG4 by employing bioinformatics analysis. miR-423-5p has been reported to exert significantly poorer in several diseases. However, the role of miR-423-5p in the development of neuropathic pain is needed to be clarified. Here, in our investigation, RIP assay confirmed the correlation between miR-423-5p and SNHG4. Meanwhile, we found that miR-423-5p was significantly decreased in SNL rat models. SNHG4 regulated miR-423-5p expression negatively. As exhibited, the loss of miR-423-5p contributed to neuropathic pain progression, which was rescued by the silence of SNHG4. Therefore, our study indicated SNHG4 as a novel therapeutic target for neuropathic pain via sponging miR-423-5p.

PARP1 interacts with HMGB1 and promotes its nuclear export in pathological myocardial hypertrophy.

High-mobility group box 1 (HMGB1) exhibits various functions according to its subcellular location, which is finely conditioned by diverse post-translational modifications, such as acetylation. The nuclear HMGB1 may prevent from cardiac hypertrophy, whereas its exogenous protein is proven to induce hypertrophic response. This present study sought to investigate the regulatory relationships between poly(ADP-ribose) polymerase 1 (PARP1) and HMGB1 in the process of pathological myocardial hypertrophy. Primary-cultured neonatal rat cardiomyocytes (NRCMs) were respectively incubated with three cardiac hypertrophic stimulants, including angiotensin II (Ang II), phenylephrine (PE), and isoproterenol (ISO), and cell surface area and the mRNA expression of hypertrophic biomarkers were measured. the catalytic activity of PARP1 was remarkably enhanced, meanwhile HMGB1 excluded from the nucleus. PARP1 overexpression by infecting with adenovirus PARP1 (Ad-PARP1) promoted the nuclear export of HMGB1, facilitated its secretion outside the cell, aggravated cardiomyocyte hypertrophy, which could be alleviated by HMGB1 overexpression. PE treatment led to the similar results, while that effect was widely depressed by PARP1 silencing or its specific inhibitor AG14361. Moreover, SD rats were intraperitoneally injected with 3-aminobenzamide (3AB, 20 mg/kg every day, a well-established PARP1 inhibitor) 7 days after abdominal aortic constriction (AAC) surgery for 6 weeks, echocardiography and morphometry of the hearts were measured. Pre-treatment of 3AB relieved AAC-caused the translocation of nuclear HMGB1 protein, cardiac hypertrophy, and heart dysfunction. Our research offers a novel evidence that PARP1 combines with HMGB1 and accelerates its translocation from nucleus to cytoplasm, and the course finally causes cardiac hypertrophy.

AtPID: a genome-scale resource for genotype-phenotype associations in Arabidopsis.

AtPID (Arabidopsis thaliana Protein Interactome Database, available at http://www.megabionet.org/atpid) is an integrated database resource for protein interaction network and functional annotation. In the past few years, we collected 5564 mutants with significant morphological alterations and manually curated them to 167 plant ontology (PO) morphology categories. These single/multiple-gene mutants were indexed and linked to 3919 genes. After integrated these genotype-phenotype associations with the comprehensive protein interaction network in AtPID, we developed a Naïve Bayes method and predicted 4457 novel high confidence gene-PO pairs with 1369 genes as the complement. Along with the accumulated novel data for protein interaction and functional annotation, and the updated visualization toolkits, we present a genome-scale resource for genotype-phenotype associations for Arabidopsis in AtPID 5.0. In our updated website, all the new genotype-phenotype associations from mutants, protein network, and the protein annotation information can be vividly displayed in a comprehensive network view, which will greatly enhance plant protein function and genotype-phenotype association studies in a systematical way.

Role of intravoxel incoherent motion MRI in early assessment of the response of esophageal squamous cell carcinoma to chemoradiotherapy: A pilot study.

BACKGROUND: Since definitive concurrent chemoradiotherapy (CRT) is standard therapy for inoperable esophageal squamous cell carcinoma (ESCC), early evaluation of treatment response is crucial for patients and would be useful in assessing response, especially in patients with severe side effects. PURPOSE: To explore the feasibility of intravoxel incoherent motion (IVIM) MRI in the early assessment of treatment response to CRT. STUDY TYPE: Prospective. POPULATION: Twenty-three inoperable ESCC patients. SEQUENCE: IVIM 3T MRI of nine b values (0, 25, 50, 75, 100, 150, 200, 500 and 800 s/mm2 ) was performed at four timepoints: pre-CRT (within 5 days before CRT), mid-CRT (2-3 weeks after the start of CRT), end-CRT (within 5 days after the end of CRT), and post-CRT (1 month after the end of CRT). ASSESSMENT: IVIM-based parameters and ADC were analyzed independently by two radiologists and treatment response was assessed by the Response Evaluation Criteria in Solid Tumors (RECIST). STATISTICAL TESTS: Analyses of variance for repeated measurements were conducted to observe dynamic changes of IVIM-based parameters (D, f, and D*) and ADC during CRT. The parameters and their change percentages (Δ%) were compared between complete response (CR) and partial response (PR) by Mann-Whitney U-test. Diagnostic performance of parameters in predicting response was tested with receiver-operating characteristic curve analysis. RESULTS: ADC, D, and f increased significantly during CRT (P < 0.001, < 0.001, and 0.001, respectively). ADC, f, Δ%ADC, and Δ%D at mid-CRT in CR group were significantly higher than those in the PR group (P = 0.002, 0.013, 0.005, and 0.011, respectively). D combined with f and ADC had highest area under curve (0.917) in identifying CR from PR. DATA CONCLUSION: IVIM parameters proved useful in assessing response to definitive concurrent CRT for inoperable ESCC and combined with ADC at an early stage of treatment was a good predictor of response. LEVEL OF EVIDENCE: 2 Technical Efficacy: Stage 4 J. MAGN. RESON. IMAGING 2018;48:349-358.

Early evaluation of radiation-induced parotid damage with diffusion kurtosis imaging: a preliminary study.

Background Radiation-induced parotid gland damage is a common complication of radiotherapy (RT) in patients with nasopharyngeal carcinoma (NPC), which always causes xerostomia, dysphagia, dental caries, and even sleep disorders. Early evaluation of radiation-induced parotid damage is required to facilitate early interventions. Purpose To early-evaluate radiation-induced parotid damage using diffusion kurtosis imaging (DKI) in patients with NPC undergoing RT. Material and Methods Thirty-two patients with NPC underwent DKI for parotid glands pre-RT (two weeks before RT), mid-RT (five weeks after RT began), and post-RT (four weeks after RT). Parotid volume, apparent diffusion coefficient (ADC), corrected diffusion coefficient (D), excess diffusion kurtosis coefficient (K) values, mean radiation dose, and xerostomia degrees were recorded and analyzed. Results During RT, parotid ADC (change rates = 41.3 ± 25.2% at mid-RT, 70.8 ± 34.3% at post-RT) and D (change rates = 41.9 ± 25.2% at mid-RT, 63.2 ± 30.2% at post-RT) increased, while parotid volume (atrophy rates = 31.5 ± 7.9% at mid-RT, 30.6 ± 10.3% at post-RT) and K (change rates = -17.8 ± 11.0% at mid-RT, -29.8 ± 9.0% at post-RT) decreased significantly (all P < 0.001). At post-RT, the change rate of parotid D values was significantly positively correlated with the mean radiation dose ( r = 0.455, P < 0.001). Parotid ADC, D, and K values showed excellent intra- and inter-observer agreement (intraclass correlation coefficient = 0.946-0.985). Conclusion Radiation-induced parotid damage in patients with NPC undergoing RT could be effectively evaluated by DKI in the early stage.

A new point mutation in ß2-tubulin confers resistance to carbendazim in Fusarium asiaticum.

Resistance to benzimidazole fungicides in many phytopathogenic fungi is caused by specific point mutations in the ß-tubulin gene (ß-tubulin). However, the mutated locus and genotype of ß-tubulin differ among phytopathogenic fungi. To validate the point mutation in Fusarium asiaticum ß2-tubulin that confers resistance to carbendazim and to analyze the molecular interaction between carbendazim and F. asiaticum ß2-tubulin. In this study, a new point mutation (GAG→GCG, E198A) at codon 198 of ß2-tubulin in a wild-type F. asiaticum strain was constructed by site-directed mutagenesis followed by a split marker strategy. The site-directed mutants were verified and exhibited a high level of resistance to carbendazim. In the absence of fungicide treatment, the biological characteristics did not differ between the site-directed mutants and the wild-type strain. Molecular docking between carbendazim and ß2-tubulin was carried out using the Surflex-Dock program in Sybyl X-2.0 version and the results indicated that the E198A mutation altered the configuration of ß2-tubulin, resulting in the change of the bonding sites and docking scores. We concluded that the point mutation of F. asiaticum ß2-tubulin conferring carbendazim resistance may not always be the bonding site for carbendazim.

Application of CT texture analysis in predicting histopathological characteristics of gastric cancers.

OBJECTIVES: To explore the application of computed tomography (CT) texture analysis in predicting histopathological features of gastric cancers. METHODS: Preoperative contrast-enhanced CT images and postoperative histopathological features of 107 patients (82 men, 25 women) with gastric cancers were retrospectively reviewed. CT texture analysis generated: (1) mean attenuation, (2) standard deviation, (3) max frequency, (4) mode, (5) minimum attenuation, (6) maximum attenuation, (7) the fifth, 10th, 25th, 50th, 75th and 90th percentiles, and (8) entropy. Correlations between CT texture parameters and histopathological features were analysed. RESULTS: Mean attenuation, maximum attenuation, all percentiles and mode derived from portal venous CT images correlated significantly with differentiation degree and Lauren classification of gastric cancers (r, -0.231 ~ -0.324, 0.228 ~ 0.321, respectively). Standard deviation and entropy derived from arterial CT images also correlated significantly with Lauren classification of gastric cancers (r = -0.265, -0.222, respectively). In arterial phase analysis, standard deviation and entropy were significantly lower in gastric cancers with than those without vascular invasion; however, minimum attenuation was significantly higher in gastric cancers with than those without vascular invasion. CONCLUSION: CT texture analysis held great potential in predicting differentiation degree, Lauren classification and vascular invasion status of gastric cancers. KEY POINTS: • CT texture analysis is noninvasive and effective for gastric cancer. • Portal venous CT images correlated significantly with differentiation degree and Lauren classification. • Standard deviation, entropy and minimum attenuation in arterial phase reflect vascular invasion.

Synthesis of the novel PARP-1 inhibitor AG-690/11026014 and its protective effects on angiotensin II-induced mouse cardiac remodeling.

We previously identified AG-690/11026014 (6014) as a novel poly(ADP-ribose) polymerase-1 (PARP-1) inhibitor that effectively prevented angiotensin II (Ang II)-induced cardiomyocyte hypertrophy. In the present study, we reported a new synthesis route for 6014, and investigated its protective effects on Ang II-induced cardiac remodeling and cardiac dysfunction and the underlying mechanisms in mice. We designed a new synthesis route to obtain a sufficient quantity of 6014 for this in vivo study. C57BL/6J mice were infused with Ang II and treated with 6014 (10, 30, 90 mg·kg-1·d-1, ig) for 4 weeks. Then two-dimensional echocardiography was performed to assess the cardiac function and structure. Histological changes of the hearts were examined with HE staining and Masson's trichrome staining. The protein expression was evaluated by Western blot, immunohistochemistry and immunofluorescence assays. The activities of sirtuin-1 (SIRT-1) and the content of NAD+ were detected with the corresponding test kits. Treatment with 6014 dose-dependently improved cardiac function, including LVEF, CO and SV and reversed the changes of cardiac structure in Ang II-infused mice: it significantly ameliorated Ang II-induced cardiac hypertrophy evidenced by attenuating the enlargement of cardiomyocytes, decreased HW/BW and LVW/BW, and decreased expression of hypertrophic markers ANF, BNP and ß-MHC; it also prevented Ang II-induced cardiac fibrosis, as implied by the decrease in excess accumulation of extracellular matrix (ECM) components collagen I, collagen III and FN. Further studies revealed that treatment with 6014 did not affect the expression levels of PARP-1, but dose-dependently inhibited the activity of PARP-1 and subsequently restored the activity of SIRT-1 in heart tissues due to the decreased consumption of NAD+ and attenuated Poly-ADP-ribosylation (PARylation) of SIRT-1. In conclusion, the novel PARP-1 inhibitor 6014 effectively protects mice against AngII-induced cardiac remodeling and improves cardiac function. Thus, 6014 might be a potential therapeutic agent for heart diseases..