Radiation enteropathy-related depression: A neglectable course of disease by gut bacterial dysbiosis.

Radiation enteropathy (RE) is common in patients treated with radiotherapy for pelvic-abdominal cancers. Accumulating data indicate that gut commensal bacteria determine intestinal radiosensitivity. Radiotherapy can result in gut bacterial dysbiosis. Gut bacterial dysbiosis contributes to the pathogenesis of RE. Mild to moderate depressive symptoms can be observed in patients with RE in clinical settings; however, the rate of these symptoms has not been reported. Studies have demonstrated that gut bacterial dysbiosis induces depression. In the state of comorbidity, RE and depression may be understood as local and abscopal manifestations of gut bacterial disorders. The ability of comorbid depression to worsen inflammatory bowel disease (IBD) has long been demonstrated and is associated with dysfunction of cholinergic neural anti-inflammatory pathways. There is a lack of direct evidence for RE comorbid with depression. It is widely accepted that RE shares similar pathophysiologic mechanisms with IBD. Therefore, we may be able to draw on the findings of the relationship between IBD and depression. This review will explore the relationship between gut bacteria, RE, and depression in light of the available evidence and indicate a method for investigating the mechanisms of RE combined with depression. We will also describe new developments in the treatment of RE with probiotics, prebiotics, and fecal microbial transplantation.

Quenching thirst with poison? Paradoxical effect of anticancer drugs.

Anticancer drugs have been developed with expectations to provide long-term or at least short-term survival benefits for patients with cancer. Unfortunately, drug therapy tends to provoke malignant biological and clinical behaviours of cancer cells relating not only to the evolution of resistance to specific drugs but also to the enhancement of their proliferation and metastasis abilities. Thus, drug therapy is suspected to impair long-term survival in treated patients under certain circumstances. The paradoxical therapeutic effects could be described as 'quenching thirst with poison', where temporary relief is sought regardless of the consequences. Understanding the underlying mechanisms by which tumours react on drug-induced stress to maintain viability is crucial to develop rational targeting approaches which may optimize survival in patients with cancer. In this review, we describe the paradoxical adverse effects of anticancer drugs, in particular how cancer cells complete resistance evolution, enhance proliferation, escape from immune surveillance and metastasize efficiently when encountered with drug therapy. We also describe an integrative therapeutic framework that may diminish such paradoxical effects, consisting of four main strategies: (1) targeting endogenous stress response pathways, (2) targeting new identities of cancer cells, (3) adaptive therapy- exploiting subclonal competition of cancer cells, and (4) targeting tumour microenvironment.

Effect of Torrefaction on the Physiochemical Characteristics and Pyrolysis of the Corn Stalk.

Torrefaction of biomass is one of the most promising pretreatment methods for deriving biofuels from biomass via thermochemical conversion processes. In this work, the changes in physicochemical properties and morphology features of the torrefied corn stalk, the changes in physicochemical properties and morphology features of the torrefied corn stalk were investigated. The results of this study showed that the elemental content and proximate analysis of the torrefied corn stalk significantly changed compared with those of the raw corn stalk. In particular, at 300 °C, the volatile content decreased to 41.79%, while the fixed carbon content and higher heating value increased to 42.22% and 21.31 MJ/kg, respectively. The H/C and O/C molar ratios of torrefied corn stalk at the 300 °C were drastically reduced to 0.99 and 0.27, respectively, which are similar to those of conventional coals in China. Numerous cracks and pores were observed in the sample surface of torrefied corn stalk at the torrefaction temperature range of 275 °C-300 °C, which could facilitate the potential application of the sample in the adsorption process and promote the release of gas products in pyrolysis. In the pyrolysis phase, the liquid products of the torrefied corn stalk decreased, but the H2/CO ratio and the lower heating value of the torrefied corn stalk increased compared with those of the raw corn stalk. This work paves a new strategy for the investigation of the effect of torrefaction on the physiochemical characteristics and pyrolysis of the corn stalk, highlighting the application potential in the conversion of biomass.

From clinical variables to multiomics analysis: a margin morphology-based gross classification system for hepatocellular carcinoma stratification.

OBJECTIVE: Selecting interventions for patients with solitary hepatocellular carcinoma (HCC) remains a challenge. Despite gross classification being proposed as a potential prognostic predictor, its widespread use has been restricted due to inadequate studies with sufficient patient numbers and the lack of established mechanisms. We sought to investigate the prognostic impacts on patients with HCC of different gross subtypes and assess their corresponding molecular landscapes. DESIGN: A prospective cohort of 400 patients who underwent hepatic resection for solitary HCC was reviewed and analysed and gross classification was assessed. Multiomics analyses were performed on tumours and non-tumour tissues from 49 patients to investigate the mechanisms underlying gross classification. Inverse probability of treatment weight (IPTW) was used to control for confounding factors. RESULTS: Overall 3-year survival rates varied significantly among the four gross subtypes (type I: 91%, type II: 80%, type III: 74.6%, type IV: 38.8%). Type IV was found to be independently associated with poor prognosis in both the entire cohort and the IPTW cohort. The four gross subtypes exhibited three distinct transcriptional modules. Particularly, type IV tumours exhibited increased angiogenesis and immune score as well as decreased metabolic pathways, together with highest frequency of TP53 mutations. Patients with type IV HCC may benefit from adjuvant intra-arterial therapy other than the other three subtypes. Accordingly, a modified trichotomous margin morphological gross classification was established. CONCLUSION: Different gross types of HCC showed significantly different prognosis and molecular characteristics. Gross classification may aid in development of precise individualised diagnosis and treatment strategies for HCC.

Long-term exposure to genistein inhibits the proliferation of gallbladder cancer by downregulating the MCM complex.

Soy isoflavones are natural tyrosine kinase inhibitors closely associated with decreased morbidity and mortality of various tumors. The activation of tyrosine kinases such as ERBB2 is the mechanism by which cholecystitis transforms into gallbladder cancer (GBC), therefore, it is important to investigate the relationship between long-term exposure to soy isoflavones and the occurrence and progression of GBC. This case-control study (n = 85 pairs) found that the high level of plasma soy isoflavone-genistein (GEN) was associated with a lower risk of gallbladder cancer (≥326.00 ng/mL compared to ≤19.30 ng/mL, crude odds ratio 0.15, 95% CI 0.04-0.59; P for trend = 0.016), and that the level of GEN exposure negatively correlated with Ki67 expression in GBC tissue (n = 85). Consistent with these results, the proliferation of GBC cells was inhibited in the long-term exposure models of GEN in vitro and in vivo. The long-term exposure to GEN reduced the tyrosine kinase activity of ERBB2 and impaired the function of the PTK6-AKT-GSK3ß axis, leading to downregulation of the MCM complex in GBC cells. In summary, long-term exposure to GEN associated with soy products intake might play a certain role in preventing GBC and even inhibiting the proliferation of GBC cells.

Hsa_circ_0090002 regulates miR-186-5p/HECTD1 axis to mediate brain microvascular endothelial cell dysfunction.

BACKGROUND: Ischemic injury is a common nervous disease associated with the dysfunction of human brain microvascular endothelial cells (HBMECs). Circular RNAs (circRNAs) have key roles in ischemic injury. This research aims to investigate the role and mechanism of circ_0090002 in ischemic injury. METHODS: HBMECs were stimulated by oxygen-glucose deprivation (OGD). Circ_0090002, microRNA-186-5p (miR-186-5p), and homologous to the E6-AP Carboxyl Terminus domain E3 ubiquitin ligase 1 (HECTD1) levels were detected by quantitative reverse transcription polymerase chain reaction or Western blotting. Cell viability and migration were determined using Cell Counting Kit-8 (CCK-8) assay and wound healing assay. Flow cytometry and caspase-3 activity assay were used for apoptosis analysis. The oxidative injury and cell toxicity were assessed by reactive oxygen species (ROS) and lactic dehydrogenase (LDH) release assay kits, respectively. The interaction was investigated by dual-luciferase reporter, RNA immunoprecipitation (RIP) and RNA pull-down assays. In vivo assay was performed in rats. RESULTS: Circ_0090002 expression was reduced in OGD-stimulated HBMECs. Circ_0090002 overexpression attenuated OGD-induced reduction of cell viability and migration but elevation of apoptosis, oxidative stress and cell toxicity. Circ_0090002 sponged miR-186-5p and miR-186-5p overexpression reversed the protective role of circ_0090002 against the OGD-induced cell injury. MiR-186-5p targeted HECTD1miR-186-5p knockdown mitigated cell damages in by increasing HECTD1 level in OGD-treated HBMECs. Circ_0090002 could upregulate the HECTD1 expression via regulating miR-186-5p. Circ_0090002 inhibited infarct volume of brain in rats. CONCLUSION: These results demonstrated that circ_0090002 mitigated OGD-induced cell dysfunction in HBMECs by targeting the miR-186-5p/HECTD1 axis.

Surgical treatment of a rare case of hepatocellular carcinoma with right atrial metastasis: A case report.

RATIONALE: Hepatocellular carcinoma (HCC) with intracavitary metastasis extending to the heart, also known as inferior vena cava (IVC) tumor thrombus, is an extremely rare late-stage disease with no effective treatment. In fact, the median survival is reportedly less than 2 months; thus, there is an urgent need for better treatment. PATIENT CONCERNS: In this study, a 48-year-old patient was admitted to our hospital to seek medical treatment for advanced primary HCC with right atrial metastasis. DIAGNOSIS: The patient was diagnosed as primary HCC with a large mass in the right lobe of the liver and intracavitary metastasis to the right atrium. INTERVENTIONS: A new surgical treatment of right hemihepatectomy, complete resection of the involved IVC and the right atrium thrombus, plus reconstruction of the resected IVC using autologous pericardial tube graft were undertaken and successfully performed. OUTCOMES: The patient recovered rapidly, and 14 days after the surgical procedures, he was discharged from the hospital. Notably, serum levels of alpha-fetoprotein dropped to normal range and no clinical signs of recurrence were observed during follow-up. LESSONS: This report highlights an unusual case of right atrial metastasis from HCC. The surgical treatment appeared to be suitable and effective, together with postoperative administration of lenvatinib, a tyrosine kinase multitarget inhibitor selected by performing whole-exome sequencing. These therapies have offered favorable clinical outcomes such as prevention of recurrence and prolongation of patient survival. In addition, clinicians may benefit from our experience for their future treatment of patients with similar clinical conditions.

Colorectal Cancer Immune Infiltrates: Significance in Patient Prognosis and Immunotherapeutic Efficacy.

Colorectal cancer occurrence and progression involve multiple aspects of host immune deficiencies. In these events, immune cells vary their phenotypes and functions over time, thus enabling the immune microenvironment to be "tumor-inhibiting" as well as "tumor-promoting" as a whole. Because of the association of tumoricidal T cell infiltration with favorable survival in cancer patients, the Immunoscore system was established. Critically, the tumoral Immunoscore serves as an indicator of CRC patient prognosis independent of patient TNM stage and suggests that patients with high Immunoscores in their tumors have prolonged survival in general. Accordingly, stratifications according to tumoral Immunoscores provide new insights into CRC in terms of comparing disease severity, forecasting disease progression, and making treatment decisions. An important application of this system will be to shed light on candidate selection in immunotherapy for CRC, because the T cells responsible for determining the Immunoscore serve as responders to immune checkpoint inhibitors. However, the Immunoscore system merely provides a standard procedure for identifying the tumoral infiltration of cytotoxic and memory T cells, while information concerning the survival and function of these cells is still absent. Moreover, other infiltrates, such as dendritic cells, macrophages, and B cells, can still influence CRC prognosis, implying that those might also influence the therapeutic efficacy of immune checkpoint inhibitors. On these bases, this review is designed to introduce the Immunoscore system by presenting its clinical significance and application in CRC.

A novel label-free photoelectrochemical sensor based on N,S-GQDs and CdS co-sensitized hierarchical Zn2SnO4 cube for detection of cardiac troponin I.

A novel label-free photoelectrochemical (PEC) sensor based on graphene quantum dots doped with nitrogen and sulfur (N,S-GQDs) and CdS co-sensitized hierarchical Zn2SnO4 cube was fabricated to detect cardiac troponin I (cTnI). The unique hierarchical Zn2SnO4 cube was synthesized successfully by the solvothermal method, which has a large specific surface to load functional materials. N,S-GQDs nanoparticles were assembled to the surface of cubic Zn2SnO4 coated ITO electrode, which efficiently accelerated the electronic transition and improved photo-to-current conversion efficiency. Then, CdS nanoparticles further were modified by in-situ growth method to form Zn2SnO4/N,S-GQDs/CdS composite with prominent photocurrent, which was 30 times that of the Zn2SnO4 cube alone. In this work, the specific immune recognition between cTnI antigens and cTnI antibodies (anti-cTnI) reduced the intensity of the photoelectric signal. And the intensity decreased linearly with the logarithm of cTnI concentration range from 0.001 ng/mL to 50 ng/mL with a detection limit of 0.3 pg/mL. With high sensitivity, excellent selectivity, good stability and reproducibility, the fabricated PEC sensor showed promising applications in the sensor, clinical diagnosis of myocardial infarction and PEC analysis.

Modulation of mitogen­activated protein kinase attenuates sepsis­induced acute lung injury in acute respiratory distress syndrome rats.

Sepsis is the most important predisposing cause inducing acute respiratory distress syndrome (ARDS); however, the mechanism of sepsis leading to the development of ARDS remains to be elucidated. Suppression of the mitogen­activated protein kinase (MAPK) signal by blocking the phosphorylation of Jun N­terminal kinase (JNK) and p38 in lung tissues could alleviate acute lung injury induced by sepsis. MAPK signaling may have a crucial role in development of the sepsis­induced acute lung injury. The specific inhibitors of JNK and p38 MAPK, SP600125 and SB203580, were administrated by intragastric injection 4 h before induction of ARDS after cecal ligation and puncture (CLP). Rats were sacrificed at 1, 6 or 24 h after CLP challenge. The histological evaluation, lung water content, and biochemical analysis were performed. The results revealed that the JNK and p38 MAPK inhibitor improved lung permeability, attenuated system inflammation, further alleviated the lung injury induced by sepsis. In conclusion, JNK and p38 MAPK signaling are essential for the development of ARDS following sepsis. Further studies are needed to illuminate the detailed mechanisms of JNK and p38 MAPK signaling in sepsis­induced ARDS.

Optimal three-dimensional reconstruction for lung cancer tissues.

The existing three-dimensional (3D) x-ray reconstruction methods for lung cancer tissue reconstruct the investigated objects based on a series of two-dimensional (2D) image sections and a chosen 3D reconstruction algorithm. However, because these procedures apply the same segmentation method for all 2D image sections, they may not achieve the optimal segmentation for each section. As a result, the reconstructed 3D images have limited spatial resolution. Furthermore, the existing 3D reconstruction method is time-consuming and results in a limited time resolution. This research presents an innovation of 3D reconstruction by reformulating two main components of the method. First, a validity index for fuzzy clustering is used to obtain the optimal segmentations of any 2D x-ray image. The process is realized by automatically determining the optimal number of clusters for the image. Second, unlike the existing 3D reconstruction methods, a fast-FCM algorithm is used to speed up the 2D image segmenting process, thereby raising the time resolution of the 3D reconstruction process. With the aid of commonly used VTK software, the proposed method has been used to visualize four classes of typical lung cancer tissues: adenocarcinoma, large cell carcinoma, small cell carcinoma, and squamous cell carcinoma. Experimental results validate the effectiveness and efficiency of the proposed algorithm. Thus, the method contributes a useful tool for x-ray-based 3D image reconstruction.

Elevated Preoperative Neutrophil-Lymphocyte Ratio Is Associated with Poor Prognosis in Hepatocellular Carcinoma Patients Treated with Liver Transplantation: A Meta-Analysis.

This study aims to investigate the prognostic value of neutrophil to lymphocyte ratio (NLR) in hepatocellular carcinoma (HCC) patients treated with liver transplantation (LT) through meta-analysis. Relevant articles were sought in PubMed, Embase, and Wangfang databases up to July 2015. A total of 1687 patients from 10 studies were included in this meta-analysis. Meta-analysis results showed that elevated NLR was significantly associated with poorer overall survival (OS) (HR = 2.71, 95% CI: 1.91-3.83) and poorer disease-free survival (DFS) (HR = 3.61, 95% CI: 2.23-5.84) in HCC patients treated with LT. Moreover, subgroup analysis showed the significant association between elevated preoperative NLR and poor prognosis was not altered by cutoff values of NLR or types of LT. Therefore, elevated preoperative NLR is associated with poor prognosis in HCC patients treated with LT. Preoperative NLR should be used to predict the prognosis of HCC after LT in our clinical work.

Prognostic significance of parameters from pretreatment (18)F-FDG PET in hepatocellular carcinoma: a meta-analysis.

PURPOSE: The prognostic value of (18)F-deoxyglucose positron emission tomography ((18)F-FDG PET) on hepatocellular carcinoma (HCC) remains inconclusive. This study aims to investigate the prognostic role of pretreatment (18)F-FDG PET on HCC patients by meta-analysis. METHODS: PubMed, Embase, Cochrane library, and Wanfang databases were searched until June 2015. Hazard ratios (HRs) with corresponding 95% confidence intervals (CIs) were synthesized by Stata 10.0, and the combined results were used as effective values. RESULTS: Twenty-two studies containing a total of 1721 patients were identified. According to random-effect model, meta-analysis results showed that high Tumor SUV/Liver SUV (Tsuv/Lsuv) ratio was significantly associated with poorer overall survival (OS) (HR = 2.04; 95% CI 1.50-2.79; P = 0.000) and poorer disease-free survival (HR = 7.17; 95% CI 3.58-14.36; P = 0.000); and high Tumor SUV (Tsuv) value was also correlated with poor OS (HR = 1.53; 95% CI 1.26-1.87; P = 0.000). Meanwhile, subgroup analysis results showed that the significant association above was not altered by study sample size, parameter cutoff value, analytic method, and follow-up period, but there was no significant association between Tsuv/Lsuv ratio and OS in patients who underwent resection (HR = 1.71; 95% CI 1.00-2.92; P = 0.052). CONCLUSIONS: Both high Tsuv/Lsuv ratio and high Tsuv value are associated with poor prognosis in HCC patients. Therefore, pretreatment (18)F-FDG PET is a useful tool in predicting the prognosis of HCC patients. More studies with explicit treatment modalities are required to investigate the prognostic value of pretreatment (18)F-FDG PET on HCC patients.

Clinical Significance of UCA1 to Predict Metastasis and Poor Prognosis of Digestive System Malignancies: A Meta-Analysis.

Purpose. Urothelial carcinoma-associated 1 (UCA1) has been reported to be overexpressed and correlated with progression in various cancers. However, the association between UCA1 expression and some clinicopathological features of digestive system malignancies, such as metastasis and survival, remains inconclusive. Therefore, a meta-analysis was performed to investigate the clinical significance of UCA1 in digestive system malignancies. Methods. Relevant literatures were searched in PubMed, Web of Science, Cochrane Library, and Embase databases updated to May 2016. Results. A total of 1089 patients from 10 studies were included in this meta-analysis. Meta-analysis results showed that digestive system malignancy patients with UCA1 overexpression were significantly more susceptible to developing lymph node metastasis (LNM) (OR = 1.85, 95% CI: 1.28-2.67) and distant metastasis (DM) (OR = 3.14, 95% CI: 1.77-5.58) and suffer from poor overall survival (OS) (HR = 2.31, 95% CI: 1.89-2.82, univariate analysis; HR = 2.24, 95% CI: 1.69-2.98, multivariate analysis) and poor disease-free survival (DFS) (HR = 2.65, 95% CI: 1.59-4.43, univariate analysis; HR = 2.50, 95% CI: 1.62-3.86, multivariate analysis). Conclusion. UCA1 overexpression was correlated with LNM, DM, poor OS, and poor DFS. UCA1 may serve as an indicator for metastasis and poor prognosis in digestive system malignancies.

Characterization of Osmads6-5, a null allele, reveals that OsMADS6 is a critical regulator for early flower development in rice (Oryza sativa L.).

AGL6-clade genes are a subfamily of MADS-box genes and preferentially expressed in floral organs. OsMADS6 and OsMADS17 are two AGL6-like genes in rice. OsMADS17 has been shown to play a minor role in floral development and appears to result from a duplication of OsMADS6. OsMADS6 was initially named as MFO1 for mosaic floral organs based on its moderate mutant phenotypes. So far, four moderate or weak mutant alleles of OsMADS6 have been described, providing valuable insights into its role in flower development. Here, we report a null allele of OsMADS6 (Osmads6-5), which exhibited a strong mutant phenotype in spikelet without affecting vegetative traits, causing all floral organs except lemma homeotically transformed into lemma-like organs (LLOs) as well as an indeterminate floral meristem, thus resulting in a mutant floret consisting of reiterating whorls of lemma and LLOs. In consistently, over-expression of OsMADS6 led to additional lodicule-, stamen- and carpel-like organs. Expression analysis showed that OsMADS6 controls the formation of the incipient primordia of lodicule, stamen and carpel via regulating the expression of class B, C and SEP-like MADS-box genes. Taken together, our results revealed that OsMADS6 acts as a critical regulator for early flower development in rice and provide novel insights into the molecular mechanism of OsMADS6.

[Genetic analysis and gene mapping of DDF1, a pleiotropic gene involving in both vegetable and reproductive growth in rice].

There are many pleiotropic genes playing key roles in regulating both vegetative growth and reproductive development in plants. A dwarf mutant of rice with deformed flowers, named as ddf1, was identified from indica rice breeding lines. Genetic analysis indicated that ddf1 was resulted from the recessive mutation of a single gene, temporarily named as DDF1. This result suggested that DDF1 is a pleiotropic gene, which controls both vegetative growth and reproductive development in rice. To map this gene, an F2 population was developed by crossing the ddf1 heterozygote with the tropical japonica rice variety DZ60. By means of bulked segregant analysis and small population-based linkage analysis using the published RM-series rice SSR markers, DDF1 was preliminarily mapped in a region between markers RM588 and RM587 on chromosome 6 with the genetic distances of 3.8 cM and 2.4 cM to the two markers, respectively. By developing new SSR markers in this interval according to the published rice genome sequence, we further mapped DDF1 in a 165 kb interval. The results will facilitate cloning of DDF1.