Poly(3-Methylthiophene)/Graphene Composite Cathode for Rechargeable Aluminum-Ion Batteries.

To reduce the dependence on traditional fossil energy, developing efficient energy storage systems is urgent. The reserves of aluminum resources in the earth's crust are extremely rich, which makes aluminum-ion batteries a promising competitor of new energy storage devices. Here, we report a poly(3-methylthiophene)/graphene (P3TH/Graphene) composite as the cathode of an aluminum-ion battery. The adjustment of polymer chain spacing by the methyl side chain provides a channel conducive to the transport of large-size AlCl4- complexes. The addition of electron donor groups also changes the electron delocalization characteristics of polymers and improves the specific capacity of the material. At the same time, the in situ composite of graphene can enhance the Π-Π interaction to form a favorable electronic transmission channel. At a current density of 200 mA g-1, the P3TH/Graphene composite showed a specific capacity of ∼150 mA g-1. The flexible structure of the polymer also guarantees the excellent rate capability of the composite.

Discovery of novel anaplastic lymphoma kinase (ALK) and histone deacetylase (HDAC) dual inhibitors exhibiting antiproliferative activity against non-small cell lung cancer.

A series of novel benzimidazole derivatives were designed and synthesised based on the structures of reported oral available ALK inhibitor and HDAC inhibitor, pracinostat. In enzymatic assays, compound 3b, containing a 2-acyliminobenzimidazole moiety and hydroxamic acid side chain, could inhibit both ALK and HDAC6 (IC50 = 16 nM and 1.03 µM, respectively). Compound 3b also inhibited various ALK mutants known to be involved in crizotinib resistance, including mutant L1196M (IC50, 4.9 nM). Moreover, 3b inhibited the proliferation of several cancer cell lines, including ALK-addicted H2228 cells. To evaluate its potential for treating cancers in vivo, 3b was used in a human A549 xenograft model with BALB/c nude mice. At 20 mg/kg, 3b inhibited tumour growth by 85% yet had a negligible effect on mean body weight. These results suggest a attracting route for the further research and optimisation of dual ALK/HDAC inhibitors.

Methyl-Symmetrically Substituted Poly(3,4-Dimethylthiophene) as Cathode for Aluminum Ion Batteries.

The aggravation of energy problems and the scarcity of lithium resources have forced us to look for new energy storage systems. Aluminum ion batteries, as a promising energy storage system, have the advantages of environmental friendliness and abundant aluminum resources, and have the potential for application in large-scale energy storage and personal portable electronic devices. To solve the stability problem of aluminum ion batteries during cycling for large-scale energy storage needs, we report a polythiophene-based conductive polymer, poly(3,4-dimethylthiophene) (PDMT), as a high performance cathode material for aluminum ion batteries. By introducing two methyl groups on the thiophene ring, we successfully adjust the local charge density of the heterocyclic thiophene, thus changing the electron delocalization characteristics, and improving the electrochemical reaction activity of the polythiophene (PTH) material as a redox electrode material. This also maintains the symmetry and regularity of the polymer structure, giving the material better cycling stability. The discharge specific capacity reaches 110 mAh g-1 at a current density of 200 mA g-1, far exceeding conventional PTH cathodes (~70 mAh g-1), and the capacity retention rate is 92.7 % after 1000 cycles. It also shows excellent rate performance due to the flexible structure of the conductive polymer.

Programmed T cells infiltration into lung metastases with harnessing dendritic cells in cancer immunotherapies by catalytic antigen-capture sponges.

T lymphocytes served as immune surveillance to suppress metastases by physically interacting with cancer cells. Whereas tumor immune privilege and heterogeneity protect immune attack, it limits immune cell infiltration into tumors, especially in invasive metastatic clusters. Here, a catalytic antigen-capture sponge (CAS) containing the catechol-functionalized copper-based metal organic framework (MOF) and chloroquine (CQ) for programming T cells infiltration is reported. The intravenously injected CAS accumulates at the tumor via the folic acid-mediated target and margination effect. In metastases, Fenton-like reaction induced by copper ions of CAS disrupts the intracellular redox potential, i.e., chemodynamic therapy (CDT), thereby reducing glutathione (GSH) levels. Furthermore, CQ helps inhibit autophagy by inducing lysosomal deacidification during CDT. This process leads to the breakdown of self-defense mechanisms, which exacerbates cytotoxicity. The therapies promote the liberation of tumor-associated antigens, such as neoantigens and damage-associated molecular patterns (DAMPs). Subsequently, the catechol groups present on CAS perform as antigen reservoirs and transport the autologous tumor-associated antigens to dendritic cells, resulting in prolonged immune activation. The CAS, which is capable of forming in-situ, serves as an antigen reservoir in CDT-mediated lung metastasis and leads to the accumulation of immune cells in metastatic clusters, thus hindering metastatic tumors.

Glucagon receptor blockage inhibits ß-cell dedifferentiation through FoxO1.

Glucagon-secreting pancreatic α-cells play pivotal roles in the development of diabetes. Glucagon promotes insulin secretion from ß-cells. However, the long-term effect of glucagon on the function and phenotype of ß-cells had remained elusive. In this study, we found that long-term glucagon intervention or glucagon intervention with the presence of palmitic acid downregulated ß-cell-specific markers and inhibited insulin secretion in cultured ß-cells. These results suggested that glucagon induced ß-cell dedifferentiation under pathological conditions. Glucagon blockage by a glucagon receptor (GCGR) monoclonal antibody (mAb) attenuated glucagon-induced ß-cell dedifferentiation. In primary islets, GCGR mAb treatment upregulated ß-cell-specific markers and increased insulin content, suggesting that blockage of endogenous glucagon-GCGR signaling inhibited ß-cell dedifferentiation. To investigate the possible mechanism, we found that glucagon decreased FoxO1 expression. FoxO1 inhibitor mimicked the effect of glucagon, whereas FoxO1 overexpression reversed the glucagon-induced ß-cell dedifferentiation. In db/db mice and ß-cell lineage-tracing diabetic mice, GCGR mAb lowered glucose level, upregulated plasma insulin level, increased ß-cell area, and inhibited ß-cell dedifferentiation. In aged ß-cell-specific FoxO1 knockout mice (with the blood glucose level elevated as a diabetic model), the glucose-lowering effect of GCGR mAb was attenuated and the plasma insulin level, ß-cell area, and ß-cell dedifferentiation were not affected by GCGR mAb. Our results proved that glucagon induced ß-cell dedifferentiation under pathological conditions, and the effect was partially mediated by FoxO1. Our study reveals a novel cross talk between α- and ß-cells and is helpful to understand the pathophysiology of diabetes and discover new targets for diabetes treatment.NEW & NOTEWORTHY Glucagon-secreting pancreatic α-cells can interact with ß-cells. However, the long-term effect of glucagon on the function and phenotype of ß-cells has remained elusive. Our new finding shows that long-term glucagon induces ß-cell dedifferentiation in cultured ß-cells. FoxO1 inhibitor mimicks whereas glucagon signaling blockage by GCGR mAb reverses the effect of glucagon. In type 2 diabetic mice, GCGR mAb increases ß-cell area, improves ß-cell function, and inhibits ß-cell dedifferentiation, and the effect is partially mediated by FoxO1.

Cross-Disorder Analysis of Shared Genetic Components Between Cortical Structures and Major Psychiatric Disorders.

BACKGROUND AND HYPOTHESIS: Although large-scale neuroimaging studies have demonstrated similar patterns of structural brain abnormalities across major psychiatric disorders, the underlying genetic etiology behind these similar cross-disorder patterns is not well understood. STUDY DESIGN: We quantified the extent of shared genetic components between cortical structures and major psychiatric disorders (CS-MPD) by using genome-wide association study (GWAS) summary statistics of 70 cortical structures (surface area and thickness of the whole cortex and 34 cortical regions) and five major psychiatric disorders, consisting of attention deficit hyperactivity disorder (ADHD), autism spectrum disorder (ASD), bipolar disorder (BD), major depressive disorder (MDD), and schizophrenia (SCZ). Cross-disorder analyses were then conducted to estimate the degree of similarity in CS-MPD shared genetic components among these disorders. STUDY RESULTS: The CS-MPD shared genetic components have medium-to-strong positive correlations in ADHD, BD, MDD, and SCZ (r = 0.415 to r = 0.806) while ASD was significantly correlated with ADHD, BD, and SCZ (r = 0.388 to r = 0.403). These pairwise correlations of CS-MPD shared genetic components among disorders were significantly associated with corresponding cross-disorder similarities in cortical structural abnormalities (r = 0.668), accounting for 44% variance. In addition, one latent shared factor consisted primarily of BD, MDD, and SCZ, explaining 62.47% of the total variance in CS-MPD shared genetic components of all disorders. CONCLUSIONS: The current results bridge the gap between shared cross-disorder heritability and shared structural brain abnormalities in major psychiatric disorders, providing important implications for a shared genetic basis of cortical structures in these disorders.

Effects of astragalus and ginseng polysaccharides on growth performance, immune function and intestinal barrier in weaned piglets challenged with lipopolysaccharide.

This experiment was conducted to evaluate the effects of astragalus polysaccharides (Aps) and ginseng polysaccharide (Gps) on growth performance, liver function, immune function, TLR4 signalling pathways and intestinal barrier in weaned piglets challenged with lipopolysaccharide (LPS). In an experiment spanning 28 days, 180 weaned piglets were randomly divided into three treatment groups: basal diet (Con), basal diet supplemented with 800 mg/kg Gps (Gps) and basal diet supplemented with 800 mg/kg Aps (Aps). At the end of the experiment, 12 piglets of each group were selected; half (n = 6) were intraperitoneally injected with LPS and half with normal saline. Dietary supplementation with Aps and Gps significantly increased (p < .05) the average daily gain and feed conversion rate. Lipopolysaccharide challenge increased (p < .05) expression of serum urea nitrogen (BUN), alanine aminotransferase (ALT), aspartate aminotransferase (AST), interleukin-1ß (IL-1ß) and tumour inflammatory factor-α (TNF-α), but decreased (p < .05) serum superoxide dismutase (SOD) level, total antioxidant capacity (T-AOC) and immunoglobulin A (IgA) expression. Lipopolysaccharide-challenged piglets fed with Aps or Gps had lower (p < .05) BUN, ALT, AST, IL-1ß and TNF-α levels and greater (p < .05) SOD, T-AOC and IgA levels. Lipopolysaccharide challenge increased (p < .05) the expression of TLR4, MyD88 and NF-κB, and LPS-challenged piglets fed diets supplemented with Aps or Gps increased TLR4 and MyD88 and decreased NF-κB expression. Lipopolysaccharide challenge reduced (p < .05) the jejunal villus height, and piglets fed with Aps or Gps had increased (p < .05) jejunal villus height. Supplementation with Aps or Gps enhanced the expression of occludin and claudin in challenged or unchallenged piglets. In conclusion, dietary supplementation with Aps or Gps enhanced piglet growth performance, alleviated liver dysfunction and reduced immunological stress caused by LPS, as well as increased the intestinal barrier function.

Effects of Clostridium butyricum and Enterococcus faecalis on growth performance, intestinal structure, and inflammation in lipopolysaccharide-challenged weaned piglets.

This study was conducted to investigate the effects of Clostridium butyricum and Enterococcus faecalis on growth performance, immune function, inflammation-related pathways, and microflora community in weaned piglets challenged with lipopolysaccharide (LPS). One hundred and eighty 28-d-old weaned piglets were randomly divided into 3 treatments groups: piglets fed with a basal diet (Con), piglets fed with a basal diet containing 6 × 109 CFU C. butyricum·kg-1 (CB), and piglets fed with a basal diet containing 2 × 1010 CFU E. faecali·kg-1 (EF). At the end of trial, 1 pig was randomly selected from for each pen (6 pigs per treatment group) and these 18 piglets were orally challenged with LPS 25 µg·kg-1 body weight. The result showed that piglets fed C. butyricum and E. faecalis had greater final BW compared with the control piglets (P < 0.05). The C. butyricum and E. faecalis fed piglets had lower levels of serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), IL-1ß, tumor inflammatory factor-α (TNF-α), and had greater level of serum interferon-γ (IFN-γ) than control piglets at 1.5 and 3 h after injection with LPS (P < 0.05). Furthermore, piglets in the C. butyricum or E. faecalis treatment groups had a greater ratio of jejunal villus height to crypt depth (V/C) compared with control piglets after challenge with LPS for 3 h (P < 0.05). Compared with the control treatment, the CB and EF treatments significantly decreased the expression of inflammation-related pathway factors (TLR4, MyD88, and NF-κB) after challenge with LPS for 3 h (P < 0.05). High-throughput sequencing revealed that C. butyricum and E. faecalis modulated bacterial diversity in the colon. The species richness and alpha diversity (Shannon) of bacterial samples in CB or EF piglets challenged with LPS were higher than those in LPS-challenged control piglets. Furthermore, the relative abundance of Bacteroidales-Rikenellanceae in the CB group was higher than that in the control group (P < 0.05), whereas EF piglets had a higher relative abundance of Lactobacillus amylovorus and Lactobacillus gasseri (P < 0.05). In conclusion, dietary supplementation with C. butyricum or E. faecalis promoted growth performance, improved immunity, relieved intestinal villus damage and inflammation, and optimized the intestinal flora in LPS-challenged weaned piglets.

[The clinical and pathological research of complete mesocolic excision on the treatment of right colon cancer].

OBJECTIVE: To verify the clinical safety of complete mesocolic excision (CME) and manufacture pathological large slices. METHODS: A prospective analysis clinical data of 85 right colon cancer in patients by the same group of surgeons at the Department of General Surgery, Beijing Friendship Hospital, Capital Medical University from January 2012 to December 2013 which were divided into two groups: CME group (n=39) and traditional radical operation group (n=46) by surgical approach. CME group and control group were compared the differences of clinic and pathologic variables, precise tissues morphometry, lymph nodes harvest, mesocolic area and so on. By comparison to operation time, blood loss, postoperative complications, flatus restoring time, drainage removal time and length of stay, the security of CME was analyzed. Statistical methods included independent sample t-test, Wilcoxon rank sum test and χ(2) test. In order to manufacture pathological large slices, the CME operation specimens were fixed. The large slices were stained by routine HE staining to detection of circumferential resection margin. RESULTS: Mean number of total lymph nodes was increased obviously in CME group (26.8±1.9 vs. 23.2±3.4, t=4.261, P=0.000). Mean number of lymph nodes of stage Ⅰ, Ⅱ were different between two groups (25.8±3.6 vs. 18.2±4.5, 26.8±7.7 vs. 24.9±6.2, t=8.776, 2.802, P=0.000). The positive lymph nodes of CME group was higher than control group (4(7) vs. 1.5(2), P=0.032), above all with statistically significant difference. Comparing CME group with the control group, there were the larger area of mesentery ((15 555±1 263) mm(2) vs. (12 493±1 002) mm(2,) t=12.456, P=0.000), the greater distance between the tumor and the high vascular tie ((116±22) mm vs. (82±11) mm, t=9.295, P=0.000), the greater distance between the normal bowel and the high vascular tie ((92±17) mm vs. (74±10) mm, t=8.132, P=0.000) of CME, with statistically significant difference. There were no statistically significant differences from operation safety when CME group was compared with the control group. The pathological large slices of colon cancer were prepared successfully and dyed evenly than those large slices were used to observe whether the lymph tube and lymph node metastasis inside the mesocolon. Existence of direct tumor invasion could be confirmed by investigating the large slices. Cancer embolus in intravascular and micro infiltration in mesocolon also could be found. CONCLUSIONS: CME operation can get the standard excision according the mesocolic area and integrity, as well as to harvest the maximum number of lymph node. The clinical application of CME is safe and does not increase the risk of operation. Circumferential resection margins can be detected by pathological large slices.

Heparin-functionalized Pluronic nanoparticles to enhance the antitumor efficacy of sorafenib in gastric cancers.

In this study, chitosan/heparin immobilized delivery system was developed for the delivery of sorafenib in gastric cancers. The SRF NP was nanosized with spherical outfit and present in the amorphous form. The SRF NP exhibited a sustained release of drug at pH 7.4 conditions and enhanced drug released at pH 5.5 conditions. Flow cytometer analysis showed that cellular uptake of NP increased two-fold after 4h of incubation compared to 1h incubation. The SRF NP showed superior anticancer effect compared to that of free SRF in BGC-823 cancer cells. SRF NP induced a remarkable apoptosis of cancer cells consistent with the cytotoxicity assay. Approximately, ∼ 50% of cell fractions were observed in early apoptosis phase with ∼ 15% of cells in the late apoptosis stage. Consistently, SRF NP exhibited a strong band for caspase-3 and P-53 than compared to free SRF in MGC-823 cancer cells. Importantly, SRF NP showed superior anticancer effect in xenograft tumor model making it a promising delivery vehicle in the treatment of gastric cancers.

Synchronous collision neuroendocrine tumor and rectal adenocarcinoma: a case report.

Collision tumors are thought to arise from the accidental meeting of two independent tumors. Adenocarcinoma is the most common malignant rectal tumor, while neuroendocrine tumor (NET) is relatively rare. Due to the endoscopy and reporting, the overall incidence of NETs was increasing recently but still less than 1 per 100,000. This means that a combination of an adenocarcinoma and NET is a very rare finding and an actual collision of these tumors even more so. We report here a highly unusual case of a 64-year-old woman who had collision tumors composed of a primary rectal adenocarcinoma and NET showing a "side by side" pattern. Resection margins are free of both the tumors. The postoperative course was uneventful. The patient underwent a protocol CT scan at 3 months after surgery, which did not show any recurrence. Both the malignant adenocarcinoma and the NET would make a great influence in the rest lifetime and a follow up will be continued, although the CT did not show any recurrence until now. To the best of our knowledge, this is the first reported case of such an occurrence.

Transthoracic versus abdominal-transhiatal resection for treating Siewert type II/III adenocarcinoma of the esophagogastric junction: a meta-analysis.

Our study aimed to explore the differences in short and long-term outcomes about the transthoracic (TH) and abdominal-transhiatal (TH) approaches for treating esophagogastric junction (AEG). A systematic review of PubMed, EMbase, Cochrane Library, China National Knowledge Infrastructure and CBMdisc was performed. All original articles comparing TH with TA were included in the study. Meta-analysis was conducted using odd ratios (OR) and weighted mean differences (WMDs).Thirteen studies including 2489 patients with adenocarcinoma of the esophagogastric junction, with 1050 patients underwent TA and 1437 patients underwent TH were pooled for this study. There were no significant difference between two approaches concerning duration of operation, blood loss, anastomotic leakage and positive of proximal incisal margin. Lymph node excised also showed no significant differences between two procedures in RCTs while in TA group of Non-RCTs, the number of lymph node dissection is higher. TH approach was associated with a longer length of hospital stay and had higher incidence of respiratory and cardiovascular complications and early postoperative mortality. Overall analysis of 1, 3, 5-year survival showed no significant difference between two approaches. Based on the study, TA approach had a positive impact than TH for AEG with respect to respiratory and cardiovascular complications, hospital stay and early mortality rates. There were no significant differences between the two approaches for long-term survival. Therefore, two surgical approaches are acceptable, and the elders with poor cardiopulmonary function, we recommended TA approach for treating it.

Inorganic pyrophosphatase (PPA1) is a negative prognostic marker for human gastric cancer.

Inorganic pyrophosphatase (PPA1) is an enzyme which has been found to be upregulated in various tumors, yet its profile in gastrointestinal cancers has not systemically investigated. In present study, gastrointestinal tissue microarrays were used to evaluate PPA1 expression and the association of PPA1 expression with clinical outcomes was determined for patients with gastric cancer by immunohistochemistry. Overexpression of PPA1 was observed in cancers of the esophagus, stomach, and pancreaticobiliary system. PPA1 was overexpressed in 143 cases (51.3%) of the 279 primary gastric tumors and was associated with larger size (> 3 cm), nodal metastasis and advanced clinical staging (P < 0.05). Moreover, survival analysis demonstrated that PPA1 expression was significantly correlated reduced overall of patients with gastric cancer. Therefore, PPA1 may serve as a potential biomarker of poor prognosis in patients with gastric cancer.

Current diagnosis and management of malignant gastrocolic fistulas: a single surgical unit's experience.

Gastrocolic fistula (GCF) is associated with a variety of diseases, but in recent years it has most frequently been observed with gastric or colonic malignancy. The management of primary tumor lesions and optimal surgical treatment strategies remain controversial. In this study, we explore the clinical diagnosis and treatment of GCF by retrospectively analyzing the records of GCF patients treated between August 2008 and February 2014. Three female patients and one male patient with an average age of 61 years were diagnosed with GCF caused by malignancy during this period. The predominant symptoms were diarrhea, vomiting, weight loss, and abdominal pain. Gastrointestinal contrast series combined with fiber endoscopy was the most accurate method of diagnosing the GCF, while CT and MRI were helpful in identifying the extent of tumor invasion and evaluating the possibility of en-bloc resection. Pathological and immunohistochemical tests, including staining for CK-20, CK-7, and CDX-2, suggested that three cases originated in the colon and one case in the stomach. All four cases underwent single-stage en-bloc fistula resection; two severely malnourished patients received concurrent colostomies. One patient died of postoperative anastomotic leakage and cardiopulmonary failure, but the remaining three patients were discharged in improved condition. En-bloc resection followed by adjuvant chemotherapy can result in long term survival. Gastrointestinal contrast series combined with fiber endoscopy showed high sensitivity in the diagnosis of GCF. Immunohistochemical staining can be conducted for tumors with an unclear source. Single-stage radical en-bloc fistula resection is the recommended surgical treatment, and concurrent colostomy should be considered in severely malnourished patients.

Efficacy and safety of neoadjuvant chemotherapy with modified FOLFOX7 regimen on the treatment of advanced gastric cancer.

BACKGROUND: Gastric cancer is one of the most common types of malignant tumors in China and East Asia and has the highest mortality rate of the malignant gastrointestinal tumors. Neoadjuvant chemotherapy is a systemic or local chemotherapy that is given prior to the local treatment of malignant tumors. Neoadjuvant therapy is currently showing some positive prospects; however, its clinical effects remain controversial. In this study, we used the modified FOLFOX7 (mFOLFOX7) regimen as a neoadjuvant chemotherapy regimen. Perioperative clinical and pathological efficacy, toxicity, effects of surgery, postoperative observation, and prognosis were studied to investigate its clinical efficacy and safety. METHODS: Eighty patients with advanced gastric cancer were treated in our surgery department from 2005 to 2009; 38 of these patients received mFOLFOX7 neoadjuvant chemotherapy, the other 42 patients assigned to the control group. The perioperative effects of mFOLFOX7 chemotherapy, including clinical effects and toxicity, were observed in each patient. RESULTS: After mFOLFOX7 chemotherapy, clinical and pathologic stages decreased in 21.1% and 36.8% of the patients, respectively, but the results were not statistically significant (P = 0.129). The clinical response rate was 50% (19/38). Toxicity was mild; most adverse events were grade I or II and involved no severe infections or deaths. Compared with the control group, the radical resection rate increased (92.1% vs. 85.7%; P = 0.437); surgical effects were completed without an increased incidence of perioperative complications. The 1-, 2-, and 3-year survival rates were 78.70%, 57.40%, and 51.66%, respectively, in the neoadjuvant chemotherapy group and 78.57%, 56.87%, and 43.16%, respectively, in the control group. CONCLUSIONS: The mFOLFOX7 regimen was very effective and well-tolerated as a neoadjuvant chemotherapy for advanced gastric cancer. However, the 1-, 2-, and 3-year survival rates in the mFOLFOX7 group were not significantly different from the control group.

Gangliocytic paraganglioma of the duodenum: a case report.

Gangliocytic paraganglioma of the duodenum is an extremely rare disease. Few cases have been reported in the literature from 1957 to 2010. We reported a 67-year-old man with gangliocytic paraganglioma of the duodenum.

Transumbilical single-incision laparoscopic resection of ileocecal junction for benign disease: first report of two cases.

BACKGROUND: Transumbilical single-incision laparoscopic surgery (TUSILS) has emerged as an advanced technique for minimally invasive surgery. Recently, the authors performed TUSIL resection of the ileocecal junction for benign lesions. METHODS: The authors report the surgical technique and clinical effect of TUSIL resection of the ileocecal junction in 2 patients. RESULTS: The 2 operations were completely successful with satisfactory and scarless recovery. No postoperative complications occurred. CONCLUSIONS: TUSIL resection of the ileocecal junction was feasible and safe in the 2 patients and might lead to an expansion of the indications for TUSILS.