CdBi2S4-Decorated Aminated Polyacrylonitrile Nanofiber for Photocatalytic Treatment of Cr(VI) and Tetracycline Wastewater.

The significant threat posed by the high toxicity of heavy metals and antibiotics in water pollutants has prompted a growing emphasis on the development of highly efficient removal methods for these pollutants. In this paper, flexible electrospinning polyacrylonitrile (PAN) nanofiber-supported CdBi2S4 was synthesized via a hydrothermal method, followed by amination treatment with diethylenetriamine (DETA). The as-prepared CdBi2S4/NH2-PAN nanofiber, enriched with sulfur vacancies, demonstrated outstanding visible-light trapping ability and a suitable band gap, leading to efficient separation and transport of photogenerated carriers, ultimately resulting in exceptional photocatalytic capability. The optimal 3-CdBi2S4/NH2-PAN nanofiber achieved impressive reduction rates of 92.26% for Cr(VI) and 96.45% for tetracycline hydrochloride (TCH) within 120 min, which were much higher than those for CdS/NH2-PAN, Bi2S3/NH2-PAN, and CdBi2S4/PAN nanofibers. After five cycles, the removal rate of the CdBi2S4/NH2-PAN nanofiber consistently remained above 90%. Their ease of separation and recovery from the application environment contributes to their practicality. Additionally, compared with conventional suspended particle catalyzers, the composite nanofiber exhibited remarkable flexibility and self-supporting properties.

Identification of a novel thermostable transaminase and its application in L-phosphinothricin biosynthesis.

Transaminase (TA) is a crucial biocatalyst for enantioselective production of the herbicide L-phosphinothricin (L-PPT). The use of enzymatic cascades has been shown to effectively overcome the unfavorable thermodynamic equilibrium of TA-catalyzed transamination reaction, also increasing demand for TA stability. In this work, a novel thermostable transaminase (PtTA) from Pseudomonas thermotolerans was mined and characterized. The PtTA showed a high specific activity (28.63 U/mg) towards 2-oxo-4-[(hydroxy)(methyl)phosphinoyl]butyric acid (PPO), with excellent thermostability and substrate tolerance. Two cascade systems driven by PtTA were developed for L-PPT biosynthesis, including asymmetric synthesis of L-PPT from PPO and deracemization of D, L-PPT. For the asymmetric synthesis of L-PPT from PPO, a three-enzyme cascade was constructed as a recombinant Escherichia coli (E. coli G), by co-expressing PtTA, glutamate dehydrogenase (GluDH) and D-glucose dehydrogenase (GDH). Complete conversion of 400 mM PPO was achieved using only 40 mM amino donor L-glutamate. Furthermore, by coupling D-amino acid aminotransferase (Ym DAAT) from Bacillus sp. YM-1 and PtTA, a two-transaminase cascade was developed for the one-pot deracemization of D, L-PPT. Under the highest reported substrate concentration (800 mM D, L-PPT), a 90.43% L-PPT yield was realized. The superior catalytic performance of the PtTA-driven cascade demonstrated that the thermodynamic limitation was overcome, highlighting its application prospect for L-PPT biosynthesis. KEY POINTS: • A novel thermostable transaminase was mined for L-phosphinothricin biosynthesis. • The asymmetric synthesis of L-phosphinothricin was achieved via a three-enzyme cascade. • Development of a two-transaminase cascade for D, L-phosphinothricin deracemization.

Cervical vertebral Hounsfield units are a better predictor of Zero-P subsidence than the T-score of DXA in patients following single-level anterior cervical discectomy and fusion with zero-profile anchored spacer.

OBJECTIVES: To determine the predictive effect of Hounsfield unit (HU) values in the cervical vertebral body measured by computed tomography (CT) and T-scores measured by dual-energy X-ray absorptiometry (DXA) on Zero-P subsidence after anterior cervical discectomy and fusion (ACDF)with Zero-P. In addition, we evaluated the most reliable measurement of cervical HU values. METHODS: We reviewed 76 patients who underwent single-level Zero-P fusion for cervical spondylosis. HU values were measured on CT images according to previous studies. Univariate analysis was used to screen the influencing factors of Zero-P subsidence, and then, logistic regression was used to determine the independent risk factors. The area under the receiver operating characteristic curve (AUC) was used to evaluate the ability to predict Zero-P subsidence. RESULTS: Twelve patients (15.8%) developed Zero-P subsidence. There were significant differences between subsidence group and non-subsidence group in terms of age, axial HU value, and HU value of midsagittal, midcoronal, and midaxial (MSCD), but there were no significant differences in lowest T-score and lowest BMD. The axial HU value (OR = 0.925) and HU value of MSCD (OR = 0.892) were independent risk factors for Zero-P subsidence, and the lowest T-score was not (OR = 1.186). The AUC of predicting Zero-P subsidence was 0.798 for axial HU value, 0.861 for HU value of MSCD, and 0.656 for T-score. CONCLUSIONS: Lower cervical HU value indicates a higher risk of subsidence in patients following Zero-P fusion for single-level cervical spondylosis. HU values were better predictors of Zero-P subsidence than DXA T-scores. In addition, the measurement of HU value in the midsagittal, midcoronal, and midaxial planes of the cervical vertebral body provides an effective method for predicting Zero-P subsidence.

Bioactive α-Pyrone Analogs from the Endophytic Fungus Diaporthe sp. CB10100: α-Glucosidase Inhibitory Activity, Molecular Docking, and Molecular Dynamics Studies.

Two α-pyrone analogs were isolated from the endophytic fungus Diaporthe sp. CB10100, which is derived from the medicinal plant Sinomenium acutum. These analogs included a new compound, diaporpyrone F (3), and a known compound, diaporpyrone D (4). The structure of 3 was identified by a comprehensive examination of HRESIMS, 1D and 2D NMR spectroscopic data. Bioinformatics analysis revealed that biosynthetic gene clusters for α-pyrone analogs are common in fungi of Diaporthe species. The in vitro α-glucosidase inhibitory activity and antibacterial assay of 4 revealed that it has a 46.40% inhibitory effect on α-glucosidase at 800 µM, while no antibacterial activity against methicillin-resistant Staphylococcus aureus (MRSA), Mycolicibacterium (Mycobacterium) smegmatis or Klebsiella pneumoniae at 64 µg/mL. Molecular docking and molecular dynamics simulations of 4 with α-glucosidase further suggested that the compounds are potential α-glucosidase inhibitors. Therefore, α-pyrone analogs can be used as lead compounds for α-glucosidase inhibitors in more in-depth studies.

Development of an aminotransferase-driven biocatalytic cascade for deracemization of d,l-phosphinothricin.

2-oxo-4-[(hydroxy)(methyl)phosphinoyl]butyric acid (PPO) is the essential precursor keto acid for the asymmetric biosynthesis of herbicide l-phosphinothricin (l-PPT). Developing a biocatalytic cascade for PPO production with high efficiency and low cost is highly desired. Herein, a d-amino acid aminotransferase from Bacillus sp. YM-1 (Ym DAAT) with high activity (48.95 U/mg) and affinity (Km = 27.49 mM) toward d-PPT was evaluated. To circumvent the inhibition of by-product d-glutamate (d-Glu), an amino acceptor (α-ketoglutarate) regeneration cascade was constructed as a recombinant Escherichia coli (E. coli D), by coupling Ym d-AAT, d-aspartate oxidase from Thermomyces dupontii (TdDDO) and catalase from Geobacillus sp. CHB1. Moreover, the regulation of the ribosome binding site was employed to overcome the limiting step of expression toxic protein TdDDO in E. coli BL21(DE3). The aminotransferase-driven whole-cell biocatalytic cascade (E. coli D) showed superior catalytic efficiency for the synthesis of PPO from d,l-phosphinothricin (d,l-PPT). It revealed the production of PPO exhibited high space-time yield (2.59 g L-1 h-1 ) with complete conversion of d-PPT to PPO at high substrate concentration (600 mM d,l-PPT) in 1.5 L reaction system. This study first provides the synthesis of PPO from d,l-PPT employing an aminotransferase-driven biocatalytic cascade.

MRI-based multiregional radiomics for preoperative prediction of tumor deposit and prognosis in resectable rectal cancer: a bicenter study.

OBJECTIVE: To build T2WI-based multiregional radiomics for predicting tumor deposit (TD) and prognosis in patients with resectable rectal cancer. MATERIALS AND METHODS: A total of 208 patients with pathologically confirmed rectal cancer from two hospitals were prospectively enrolled. Intra- and peritumoral features were extracted separately from T2WI images and the least absolute shrinkage and selection operator was used to screen the most valuable radiomics features. Clinical-radiomics nomogram was developed by radiomics signatures and the most predictive clinical parameters. Prognostic model for 3-year recurrence-free survival (RFS) was constructed using univariate and multivariate Cox analysis. RESULTS: For TD, the area under the receiver operating characteristic curve (AUC) for intratumoral radiomics model was 0.956, 0.823, and 0.860 in the training cohort, test cohort, and external validation cohort, respectively. AUC for the peritumoral radiomics model was 0.929, 0.906, and 0.773 in the training cohort, test cohort, and external validation cohort, respectively. The AUC for combined intra- and peritumoral radiomics model was 0.976, 0.918, and 0.874 in the training cohort, test cohort, and external validation cohort, respectively. The AUC for clinical-radiomics nomogram was 0.989, 0.777, and 0.870 in the training cohort, test cohort, and external validation cohort, respectively. The prognostic model constructed by combining intra- and peritumoral radiomics signature score (radscore)-based TD and MRI-reported lymph nodes metastasis (LNM) indicated good performance for predicting 3-year RFS, with AUC of 0.824, 0.865, and 0.738 in the training cohort, test cohort and external validation cohort, respectively. CONCLUSION: Combined intra- and peritumoral radiomics model showed good performance for predicting TD. Combining intra- and peritumoral radscore-based TD and MRI-reported LNM indicated the recurrence risk. CLINICAL RELEVANCE STATEMENT: Combined intra- and peritumoral radiomics model could help accurately predict tumor deposits. Combining this predictive model-based tumor deposits with MRI-reported lymph node metastasis was associated with relapse risk of rectal cancer after surgery. KEY POINTS: • Combined intra- and peritumoral radiomics model provided better diagnostic performance than that of intratumoral and peritumoral radiomics model alone for predicting TD in rectal cancer. • The predictive performance of the clinical-radiomics nomogram was not improved compared with the combined intra- and peritumoral radiomics model for predicting TD. • The prognostic model constructed by combining intra- and peritumoral radscore-based TD and MRI-reported LNM showed good performance for assessing 3-year RFS.

Modifiable risk factors for ventilator associated diaphragmatic dysfunction: a multicenter observational study.

BACKGROUND: Diaphragmatic dysfunction is known to be associated with difficulties weaning from invasive mechanical ventilation and is related to worse patient outcomes yet our understanding of how to prevent diaphragmatic dysfunction remains incomplete. We examined potentially modifiable risk factors for diaphragmatic dysfunction and attempted to estimate benefits attributable to altering these modifiable risk factors. METHODS: This prospective multicenter observational study was undertaken in the general ICUs of two tertiary care teaching hospitals. Critically ill adults expected to receive invasive mechanical ventilation for at least 48 h were enrolled. Diaphragm function was assessed by ultrasound each study day, with dysfunction defined as thickening fraction less than 20%. RESULTS: From January to December 2019, 856 patients were screened and 126 patients were enrolled. Overall, 40.5% (51/126) of patients experienced diaphragmatic dysfunction during invasive mechanical ventilation. Patients with diaphragmatic dysfunction were more likely to develop ventilator associated pneumonia (risk difference [RD] + 12.9%, 95% Confidence Interval [CI] 1.4 to 24.4%, P = 0.028), were more likely to experience extubation failure (RD + 8.5%, 95% CI 0.4 to 16.6%, P = 0.039) and required a longer duration of invasive mechanical ventilation (RD + 1.3 days, 95% CI 0.1 to 2.5 days, P = 0.035). They also required a longer hospital stay (RD + 1.2 days, 95% CI 0.04 to 2.4 days, P = 0.041) and were more likely to die before hospital discharge (RD + 18.1%, 95% CI 3.7 to 32.5%, P = 0.014). Multivariable analysis considered the impact of age, sex, pre-existing nutritional status, caloric intake, amino acid intake, acute disease severity, modes of mechanical ventilation, measures of respiratory status, sedation, pain control and baseline diaphragm thickness. Only SOFA score (P = 0.008) and early amino acid intake (P = 0.001) remained significant independent risk factors for the onset of diaphragmatic dysfunction. Causal path modeling suggested early amino acid intake may significantly reduce diaphragmatic dysfunction (RRR 29%, 95% CI 10% to 48%, P = 0.003) and may also reduce mortality (RRR 49%, 95% CI 25% to 73%, P < 0.0001). CONCLUSIONS: Amino acid intake during the first 24 h of ICU stay may represent an important, modifiable risk factor for diaphragmatic dysfunction and may have a direct causal effect on mortality. We recommend additional research on this topic.

The application of apparent diffusion coefficients derived from intratumoral and peritumoral zones for assessing pathologic prognostic factors in rectal cancer.

OBJECTIVE: To investigate the diagnostic performance of the apparent diffusion coefficient (ADC) derived from intratumoral and peritumoral zones for assessing pathologic prognostic factors in rectal cancer. MATERIALS AND METHODS: One hundred forty-six patients with rectal cancer who underwent preoperative MRI were prospectively enrolled. Two radiologists independently placed free-hand regions of interest (ROIs) in the largest tumor cross section and three small ROIs on the peritumoral zone adjacent to the tumor contour. Maximum values of tumor ADC (ADCtmax), minimum values of tumor ADC (ADCtmin), mean values of tumor ADC (ADCtmean), mean values of peritumor ADC (ADCpmean), and ADCpmean/ADCtmean (ADC ratio) were obtained on ADC maps and correlated with prognostic factors using uni- and multivariate logistic regression, and receiver operating characteristic curve (ROC) analysis. RESULTS: Interobserver agreement was excellent for ADCtmax and ADCtmean (intraclass correlation coefficient [ICC], 0.915-0.958), and were good for ADCtmin, ADCpmean, and ADC ratio (ICC, 0.774-0.878). The ADC ratio was significantly higher in the poor differentiation, T3-4 stage, lymph node metastasis (LNM)-positive, extranodal extension (ENE)-positive, tumor deposit (TD)-positive, and lymphovascular invasion (LVI)-positive groups than that in the well-moderate differentiation, T1-2 stage, LNM-negative, ENE-negative, TD-negative, and LVI-negative groups (p = 0.008, < 0.001, < 0.001, 0.001, < 0.001, and < 0.001, respectively). The area under the ROC curve (AUC) of the ADC ratio was the highest for assessing poor differentiation (0.700), T3-4 stage (0.707), LNM-positive (0.776), TD-positive (0.848), and LVI-positive (0.778). Both the ADC ratio (AUC = 0.677) and ADCpmean (AUC = 0.686) showed higher diagnostic performance for assessing ENE. CONCLUSION: The ADC ratio could provide better predictive performance for assessing preoperative prognostic factors in resectable rectal cancer. KEY POINTS: • Both the peritumor/tumor ADC ratio and ADCpmean are correlated with important prognostic factors of resectable rectal cancer. • Both peritumor ADC and peritumor/tumor ADC ratio had higher diagnostic performance than tumor ADC for assessment of prognostic factors in resectable rectal cancer. • Peritumor/tumor ADC ratio showed the most capability for the assessment of prognostic factors in resectable rectal cancer.

Degradation of mirubactin to multiple siderophores with varying Fe(III) chelation properties.

Three siderophores mirubactins B-D (4-6) were identified as the degradation products of previously isolated mirubactin (1). Their structures were revealed by HR-ESI-MS/MS, NMR analyses, and density functional calculations, among which 4 contains an unusual cyclic amidine functionality. Cyclic voltammetry showed that 5 and 6 have reduced iron complexing capacity. Mirubactin (1) and Fe(III) could also form a stable complex, which may be an ingenious approach to compete for iron acquisition by the producing organisms.

Prognosis assessment model based on low serum calcium in patients with acute pulmonary thromboembolism.

BACKGROUND AND OBJECTIVE: The pulmonary embolism severity index (PESI) and simplified PESI (sPESI) are recommended to recognize patients with acute pulmonary thromboembolism (PTE) with low prognosis risk, which is of great significance for treatment. This study aims to verify the influence of hypocalcaemia on the prognosis of patients with PTE and to establish a new prognosis assessment model. METHODS: This is an observational, multicentre study enrolling patients with PTE from February 2010 to June 2020 across 12 Chinese hospitals. Variables in PESI, serum calcium levels and patient survival status as of 5 July 2020 were collected. The area under the curve of the receiver operating characteristic curve, sensitivity, specificity and Youden index were used to evaluate model performance. RESULTS: In the cohort of 4196 patients with PTE, independent associations existed between hypocalcaemia and mid- and long-term mortalities (p <0.05). By including hypocalcaemia, the new 30-day death risk prediction rule, Peking Union Medical College Hospital rule (PUMCH rule), showed significantly higher specificity (0.622 [0.582, 0.661]; p <0.001) than the PESI (0.514 [0.473, 0.554]) and sPESI (0.484 [0.444, 0.525]) and similar sensitivity (0.963 [0.810, 0.999]; p = 0.161) with PESI (0.889 [0.708, 0.976]) and sPESI (0.963 [0.810, 0.999]) in the internal validation cohort. Well-performing predictive validity was also verified on a constructed external validation cohort. CONCLUSION: Hypocalcaemia is independently associated with mid- and long-term PTE mortalities. The PUMCH rule showed significantly higher specificity than the PESI and sPESI and similar sensitivity, which may be used as a prognostic assessment tool for patients with acute PTE.

Forearm T-score as a predictor of cage subsidence in patients with degenerative lumbar spine disease following posterior single-segment lumbar interbody fusion.

BACKGROUND: Posterior lumbar interbody fusion (PLIF) has become a classic treatment modality for lumbar degenerative diseases, with cage subsidence as a potentially fatal complication due to low bone mineral density (BMD), which can be measured by forearm T-score. Hounsfield units (HU) derived from computed tomography have been a reliable method for assessing BMD. OBJECTIVE: To determine the accuracy of forearm T-score in predicting cage subsidence after PLIF compared with lumbar spine HU values. METHODS: We retrospectively analyzed the clinical data of 71 patients who underwent PLIF and divided them into cage subsidence group and nonsubsidence group. The differences in preoperative HU value and forearm T-score were compared between groups, and the correlation between cage subsidence and clinical efficacy was analyzed. RESULTS: The subsidence rate for all 71 patients (31 men and 40 women) was 23.9%. There was no significant difference in age, sex ratio, body mass index, smoking status, follow-up time, spine BMD, and spine T-score between groups, except in the forearm T-score and lumbar spine HU values (P < 0.05). The forearm T-score (AUC, 0.840; 95% CI, 0.672-1.000) predicted cage subsidence more accurately than the mean global HU value (AUC, 0.744; 95% CI, 0.544-0.943). In logistic regression analysis, both forearm T-score and mean global HU value were found to be independent risk factors for cage subsidence (P < 0.05). CONCLUSIONS: Lower forearm T-scores and lower lumbar spine HU values were significantly associated with the occurrence of cage subsidence. Lower forearm T-scores indicated a higher risk of cage subsidence than lumbar spine HU values. Forearm T-score is more effective in predicting cage subsidence than spine T-score. Therefore, forearm dual-energy X-ray absorptiometry may be a fast, simple, and reliable method for predicting cage subsidence following PLIF. However, our results suggest that the degree of cage subsidence is not associated with clinical efficacy.

Resolvin Conjugates in Tissue Regeneration 1 Promote Alveolar Fluid Clearance by Activating Alveolar Epithelial Sodium Channels and Na, K-ATPase in Lipopolysaccharide-Induced Acute Lung Injury.

Acute respiratory distress syndrome (ARDS), a common and fatal clinical condition, is characterized by the destruction of epithelium and augmented permeability of the alveolar-capillary barrier. Resolvin conjugates in tissue regeneration 1 (RCTR1) is an endogenous lipid mediator derived from docosahexaenoic acid , exerting proresolution effects in the process of inflammation. In our research, we evaluated the role of RCTR1 in alveolar fluid clearance (AFC) in lipopolysaccharide-induced ARDS/acute lung injury (ALI) rat model. Rats were injected with RCTR1 (5 µg/kg) via caudal veins 8 hours after lipopolysaccharide (LPS) (14 mg/kg) treatment, and then AFC was estimated after 1 hour of ventilation. Primary type II alveolar epithelial cells were incubated with LPS (1 ug/ml) with or without RCTR1 (10 nM) for 8 hours. Our results showed that RCTR1 significantly enhanced the survival rate, promoted the AFC, and alleviated LPS-induced ARDS/ALI in vivo. Furthermore, RCTR1 remarkably elevated the protein expression of sodium channels and Na, K-ATPase and the activity of Na, K-ATPase in vivo and in vitro. Additionally, RCTR1 also decreased neural precursor cell expressed developmentally downregulated 4-2 (Nedd4-2) level via upregulating Ser473-phosphorylated-Akt expression. Besides this, inhibitors of receptor for lipoxin A4 (ALX), cAMP, and phosphatidylinositol 3-kinase (PI3K) (BOC-2, KH-7, and LY294002) notably inhibited the effects of RCTR1 on AFC. In summary, RCTR1 enhances the protein levels of sodium channels and Na, K-ATPase and the Na, K-ATPase activity to improve AFC in ALI through ALX/cAMP/PI3K/Nedd4-2 pathway, suggesting that RCTR1 may become a therapeutic drug for ARDS/ALI. SIGNIFICANCE STATEMENT: RCTR1, an endogenous lipid mediator, enhanced the rate of AFC to accelerate the resolution of inflammation in the LPS-induced murine lung injury model. RCTR1 upregulates the expression of epithelial sodium channels (ENaCs) and Na, K-ATPase in vivo and in vitro to accelerate the AFC. The efficacy of RCTR1 on the ENaC and Na, K-ATPase level was in an ALX/cAMP/PI3K/Nedd4-2-dependent manner.

Diffusion-weighted MR volume and apparent diffusion coefficient for discriminating lymph node metastases and good response after chemoradiation therapy in locally advanced rectal cancer.

OBJECTIVE: To determine diagnostic performance of diffusion-weighted (DW) magnetic resonance (MR) volume and apparent diffusion coefficient values (ADCs) for assessing lymph node metastases (LNM) and good response after chemoradiation therapy (CRT) in patients with locally advanced rectal cancer (LARC). MATERIALS AND METHODS: This retrospective study consisted of 61 patients with LARC who underwent pre- and post-CRT DW images. Two radiologists independently placed free-hand regions of interest in each tumor-containing section on DW images to calculate pre- and post-CRT tumor volume and tumor volume reduction rates (Δvolume). Regions of interest were drawn to include tumor on maximum cross-sectional slice to obtain ADCs. Areas under the receiver operating characteristic curves (AUCs) were calculated to evaluate diagnostic performance in identifying LNM and good response after CRT using these parameters. RESULTS: Inter-observer agreement and intra-observer agreement were excellent for pre- and post-CRT DW MR volume (intraclass correlation coefficient [ICC], 0.889-0.948) and moderate for pre- and post-CRT ADCs (ICC, 0.535-0.811). AUCs for identifying LNM were 0.508 for pre-CRT DW MR volume versus 0.705 for pre-CRT ADC, 0.855 for post-CRT DW MR volume versus 0.679 for post-CRT ADC, and 0.887 for Δvolume versus 0.533 for ΔADC. AUCs for identifying good response were 0.518 for pre-CRT volume versus 0.506 for pre-CRT ADC, 0.975 for post-CRT volume versus 0.723 for post-CRT ADC, and 0.987 for Δvolume versus 0.655 for ΔADC. CONCLUSION: DW MR Δvolume provided high diagnostic performance in discriminating LNM after CRT. DW MR Δvolume was equally as accurate as post-CRT DW MR volume for evaluating good response. KEY POINTS: • Inter-observer agreement and intra-observer agreement were excellent for pre- and post-CRT DW MR volume (intraclass correlation coefficient [ICC], 0.889-0.948) and moderate for pre- and post-CRT ADCs (ICC, 0.535-0.811). • DW MR Δvolume provided high diagnostic performance in identifying LNM after CRT (AUC, 0.887) and good response (AUC, 0.987) and was significantly more accurate than pre-CRT DW MR volume (AUC, 0.508 and 0.518, respectively) and ADCs (AUC, 0.705 and 0.506, respectively). • DW MR Δvolume (AUC, 0.987) was equally as accurate as post-CRT DW MR volume (AUC, 0.975) for evaluating good response, while pre-CRT DW MR volume and ADCs were not reliable for evaluating LNM and good response after CRT (AUC, 0.506-0.723).

Tumor size measured by multidetector CT in resectable colon cancer: correlation with regional lymph node metastasis and N stage.

BACKGROUND: Lymph node metastasis (LNM) is a risk factor for poor long-term outcomes and a prognostic factor for disease-free survival in colon cancer. Preoperative lymph node status evaluation remains a challenge. The purpose of this study is to determine whether tumor size measured by multidetector computed tomography (MDCT) could be used to predict LNM and N stage in colon cancer. MATERIAL AND METHODS: One hundred six patients with colon cancer who underwent radical surgery within 1 week of MDCT scan were enrolled. Tumor size including tumor length (Tlen), tumor maximum diameter (Tdia), tumor maximum cross-sectional area (Tare), and tumor volume (Tvol) were measured to be correlated with pathologic LNM and N stage using univariate logistic regression analysis, multivariate logistic analysis, and receiver operating characteristic (ROC) curve analysis. RESULTS: The inter- and intraobserver reproducibility of Tlen (intraclass correlation coefficient [ICC] = 0.94, 0.95, respectively), Tdia (ICC = 0.81, 0.93, respectively), Tare (ICC = 0.97, 0.91, respectively), and Tvol (ICC = 0.99, 0.99, respectively) parameters measurement are excellent. Univariate logistic regression analysis showed that there were significant differences in Tlen, Tdia, Tare, and Tvol between positive and negative LNM (p < 0.001, 0.001, < 0.001, < 0.001, respectively). Multivariate logistic regression analysis revealed that Tvol was independent risk factor for predicting LNM (odds ratio, 1.082; 95% confidence interval for odds ratio, 1.039, 1.127, p<0.001). Tlen, Tdia, Tare, and Tvol could distinguish N0 from N1 stage (p < 0.001, 0.041, < 0.001, < 0.001, respectively), N0 from N2 (all p < 0.001), N0 from N1-2 (p < 0.001, 0.001, < 0.001, < 0.001, respectively), and N0-1 from N2 (p < 0.001, 0.001, < 0.001, < 0.001, respectively). The area under the ROC curve (AUC) was higher for Tvol than that of Tlen, Tdia, and Tare in identifying LNM (AUC = 0.83, 0.82, 0.69, 0.79), and distinguishing N0 from N1 stage (AUC = 0.79, 0.78, 0.63, 0.74), N0 from N2 stage (AUC = 0.92, 0.89, 0.80, 0.89, respectively), and N0-1 from N2 stage (AUC = 0.84, 0.79, 0.76, 0.83, respectively). CONCLUSION: Tumor size was correlated with regional LNM in resectable colon cancer. In particularly, Tvol showed the most potential for noninvasive preoperative prediction of regional LNM and N stage.

Maresin Conjugates in Tissue Regeneration 1 improves alveolar fluid clearance by up-regulating alveolar ENaC, Na, K-ATPase in lipopolysaccharide-induced acute lung injury.

Maresin Conjugates in Tissue Regeneration 1 (MCTR1) is a newly identified macrophage-derived sulfido-conjugated mediator that stimulates the resolution of inflammation. This study assessed the role of MCTR1 in alveolar fluid clearance (AFC) in a rat model of acute lung injury (ALI) induced by lipopolysaccharide (LPS). Rats were intravenously injected with MCTR1 at a dose of 200 ng/rat, 8 hours after administration of 14 mg/kg LPS. The level of AFC was then determined in live rats. Primary rat ATII (Alveolar Type II) epithelial cells were also treated with MCTR1 (100 nmol/L) in a culture medium containing LPS for 8 hours. MCTR1 treatment improved AFC (18.85 ± 2.07 vs 10.11 ± 1.08, P < .0001) and ameliorated ALI in rats. MCTR1 also significantly promoted AFC by up-regulating epithelial sodium channel (ENaC) and Na+ -K+ -adenosine triphosphatase (Na, K-ATPase) expressions in vivo. MCTR1 also activated Na, K-ATPase and elevated phosphorylated-Akt (P-Akt) by up-regulating the expression of phosphorylated Nedd4-2 (P-Nedd4-2) in vivo and in vitro. However, BOC-2 (ALX inhibitor), KH7 (cAMP inhibitor) and LY294002 (PI3K inhibitor) abrogated the improved AFC induced by MCTR1. Based on the findings of this study, MCTR1 may be a novel therapeutic approach to improve reabsorption of pulmonary oedema during ALI/acute respiratory distress syndrome (ARDS).

PCTR1 improves pulmonary edema fluid clearance through activating the sodium channel and lymphatic drainage in lipopolysaccharide-induced ARDS.

Acute respiratory distress syndrome (ARDS) is a lethal clinical syndrome characterized by damage of the epithelial barriers and accumulation of pulmonary edema fluid. Protectin conjugates in tissue regeneration 1 (PCTR1), an endogenously produced lipid mediator, are believed to exert anti-inflammatory and pro-resolution effects. PCTR1 (1 µg/kg) was injected at 8 hr after lipopolysaccharide (LPS; 14 mg/kg) administration, and the rate of pulmonary fluid clearance was measured in live rats at 1 hr after PCTR1 treatment. The primary type II alveolar epithelial cells were cultured with PCTR1 (10 nmol/ml) and LPS (1 µg/ml) for 8 hr. PCTR1 effectively improved pulmonary fluid clearance and ameliorated morphological damage and reduced inflammation of lung tissue, as well as improved the survival rate in the LPS-induced acute lung injury (ALI) model. Moreover, PCTR1 markedly increased sodium channel expression as well as Na, K-ATPase expression and activity in vivo and in vitro. In addition, PCTR1i also upregulated the expression of LYVE-1 in vivo. Besides that, BOC-2, HK7, and LY294002 blocked the promoted effect of PCTR1 on pulmonary fluid clearance. Taken together, PCTR1 upregulates sodium channels' expression via activating the ALX/cAMP/P-Akt/Nedd4-2 pathway and increases Na, K-ATPase expression and activity to promote alveolar fluid clearance. Moreover, PCTR1 also promotes the expression of LYVE-1 to recover the lymphatic drainage resulting in the increase of lung interstitial fluid clearance. In summary, these results highlight a novel systematic mechanism for PCTR1 in pulmonary edema fluid clearance after ALI/ARDS, suggesting its potential role in a therapeutic approach for ALI/ARDS.

PCTR1 ameliorates lipopolysaccharide-induced acute inflammation and multiple organ damage via regulation of linoleic acid metabolism by promoting FADS1/FASDS2/ELOV2 expression and reducing PLA2 expression.

Gram-negative bacterial infection causes an excessive inflammatory response and acute organ damage or dysfunction due to its outer membrane component, lipopolysaccharide (LPS). Protectin conjugates in tissue regeneration 1 (PCTR1), an endogenous lipid mediator, exerts fundamental anti-inflammation and pro-resolution during infection. In the present study, we examined the properties of PCTR1 on the systemic inflammatory response, organic morphological damage and dysfunction, and serum metabolic biomarkers in an LPS-induced acute inflammatory mouse model. The results show that PCTR1 reduced serum inflammatory factors and ameliorated morphological damage and dysfunction of the lung, liver, kidney, and ultimately improved the survival rate of LPS-induced acute inflammation in mice. In addition, metabolomics analysis and high performance liquid chromatography-mass spectrometry revealed that LPS-stimulated serum linoleic acid (LA), arachidonic acid (AA), and prostaglandin E2 (PGE2) levels were significantly altered by PCTR1. Moreover, PCTR1 upregulated LPS-inhibited fatty acid desaturase 1 (FADS1), fatty acid desaturase 2 (FADS2), and elongase of very long chain fatty acids 2 (ELOVL2) expression, and downregulated LPS-stimulated phospholipase A2 (PLA2) expression to increase the intrahepatic content of AA. However, these effects of PCTR1 were partially abrogated by a lipoxin A4 receptor (ALX) antagonist (BOC-2). In summary, via the activation of ALX, PCTR1 promotes the conversion of LA to AA through upregulation of FADS1, FADS2, and ELOVL2 expression, and inhibits the conversion of bound AA into free AA through downregulation of PLA2 expression to decrease the serum AA and PGE2 levels.

Thymic carcinoma metastasize to the small intestine: a case report.

BACKGROUND: Thymic carcinoma is a rare mediastinal neoplasm with a high malignant potential. It often shows pleural invasion and distant metastasis. The metastasis of thymic carcinoma to the small intestine is rarely reported and difficult to distinguish from other gastrointestinal tract tumors. CASE PRESENTATION: An elderly man presented with lower abdominal pain for 2 months. Abdominal CT showed a mass communicated with the small intestinal lumen. After radical resection of the small intestinal tumor, resected specimens showed moderately differentiated squamous-cell carcinoma with lymph nodes metastases. The patient received chest CT and was found to have a mass in anterior mediastinum. Biopsies of the mass revealed thymic squamous-cell carcinoma. CONCLUSIONS: We highlighted the metastasis of thymic carcinoma to the small intestine is rare and easily misdiagnosed. In patients with a mass communicated with the small intestinal lumen, a suspicion of thymic carcinoma metastasis should not be overlooked and we should make accurate differential diagnosis from the other small intestinal tumors.

TGF-ß receptor I inhibitor enhances response to enzalutamide in a pre-clinical model of advanced prostate cancer.

BACKGROUND: Prostate cancer progression is navigated by the androgen receptor (AR) and transforming-growth factor-ß (TGF-ß) signaling. We previously demonstrated that aberrant TGF-ß signaling accelerates prostate tumor progression in a transgenic mouse model of prostate cancer via effects on epithelial-mesenchymal transition (EMT), driving castration-resistant prostate cancer (CRPC). METHODS: This study examined the antitumor effect of the combination of TGF-ß receptor I (TßRI) inhibitor, galunisertib, and FDA-approved antiandrogen enzalutamide, in our pre-clinical model. Age-matched genotypically characterized DNTGFßRII male mice were treated with either galunisertib and enzalutamide, in combination or as single agents in three "mini"-trials and the effects on tumor growth, phenotypic EMT, and actin cytoskeleton were evaluated. RESULTS: Galunisertib in combination with enzalutamide significantly suppressed prostate tumor growth, by increasing apoptosis and decreasing cell proliferation of tumor cell populations compared to the inhibitor as a monotherapy (P < 0.05). The combination treatment dramatically reduced cofilin levels, actin cytoskeleton regulator, compared to single agents. Treatment with galunisertib targeted nuclear Smad4 protein (intracellular TGF-ß effector), but had no effect on nuclear AR. Consequential to TGF-ß inhibition there was an EMT reversion to mesenchymal-epithelial transition (MET) and re-differentiation of prostate tumors. Elevated intratumoral TGF-ß1 ligand, in response to galunisertib, was blocked by enzalutamide. CONCLUSION: Our results provide novel insights into the therapeutic value of targeting TGF-ß signaling to overcome resistance to enzalutamide in prostate cancer by phenotypic reprogramming of EMT towards tumor re-differentiation and cytoskeleton remodeling. This translational work is significant in sequencing TGF-ß blockade and antiandrogens to optimize therapeutic response in CRPC.

Survival benefits of dose-dense early postoperative intraperitoneal chemotherapy in front-line therapy for advanced ovarian cancer: a randomised controlled study.

Dose-dense early postoperative intraperitoneal chemotherapy (DD-EPIC) significantly increased non-progression rate in advanced ovarian cancer (OC) patients. We report final overall survival (OS) results to further strengthen the efficacy of DD-EPIC in the front-line therapy. In this phase 2 trial, 218 patients with FIGO IIIC-IV OC were randomly allocated to receive DD-EPIC followed by intravenous (IV) chemotherapy (DD-EPIC group), or IV chemotherapy alone (IV group). The study was prespecified to detect differences in progression-free survival (PFS) and OS. At a median follow-up period of 69.1 months, the median OS was 67.5 and 46.3 months in the DD-EPIC and IV group, respectively. The probability rate of OS at 5 years was 61.0% with DD-EPIC, and 38.2% with IV (hazard ratio [HR] for death from OC, 0.70; 95% confidence interval [CI], 0.49-1.00). DD-EPIC was associated with a prolonged PFS compared with the IV group (the estimated rate of PFS at 5 years, 26.0% vs. 8.5%; HR for disease progression, 0.64; 95% CI, 0.47-0.86). DD-EPIC was associated with a longer OS than IV chemotherapy alone. It may be considered as a valuable option of the front-line therapy for advanced ovarian cancer.Trial registration: ClinicalTrials.gov, NCT01669226 (date of registration: August 20, 2012).