Genomics and metabolic characteristics of simultaneous heterotrophic nitrification aerobic denitrification and aerobic phosphorus removal by Acinetobacter indicus CZH-5.

This study provides for the first time a systematic understanding of Acinetobacter indicus CZH-5 performance, metabolic pathway and genomic characteristics for aerobic nitrogen (N) and phosphorus (P) removal. Acinetobacter indicus CZH-5 showed promising performance in heterotrophic nitrification aerobic denitrification and aerobic phosphorus removal. Under optimal conditions, the maximum ammonia-N, total nitrogen and orthophosphate-P removal efficiencies were 90.17%, 86.33%, and 99.89%, respectively. The wide tolerance range suggests the strong environmental adaptability of the bacteria. The complete genome of this strain was reconstructed. Whole genome annotation was used to re-construct the N and P metabolic pathways, and related intracellular substance metabolic pathways were proposed. The transcription levels of related functional genes and enzyme activities further confirmed these metabolic mechanisms. N removal was achieved via the nitrification-denitrification pathway. Furthermore, CZH-5 exhibited significant aerobic P uptake, with phosphate diesters as the main species of intracellular P.

Dual-engineered, "Trojanized" macrophages bio-modally eradicate tumors through biologically and photothermally deconstructing cancer cells in an on-demand, NIR-commanded, self-explosive manner.

To engineer tumor-tropic cells as drug delivery vehicles is a promising strategy to improve therapeutic specificity and efficacy for cancer treatment. However, conventional genetically engineered cell-based drug delivery systems are often capable of initiating single-mode therapy, and lack precise spatiotemporal control over the release of therapeutic payloads at tumor local, thus possibly causing severe systemic toxicity. Here, the macrophages are genetically engineered to encode a non-secreted form of EGFP-TNFα fusion protein and intracellularly carry near-infrared (NIR)-responsive heat-nanogenerators (HIMs). Owing to macrophages' intrinsic tumor tropism and HIMs' photo-responsiveness to NIR, these macrophages (HIMs@eMET) can actively accumulate at tumor sites and undergo controlled photothermolysis induced by NIR-induced HIMs-mediated photothermal effects (PTE). Such heat-induced cell explosion enables spatiotemporally controlled release of non-secreted TNFα from macrophages and effectively kills cancer cells. Importantly, in a preclinical tumor model, HIMs@eMET actively migrate to tumors where PTE and released EGFP-TNFα exhibit an enhanced antitumor effect, suppressing tumor growth and significantly prolonging animal survival without eliciting adverse side effects. Thus, this study demonstrates the potential of such dual-engineered macrophages in bi-modal cancer therapy.

Effects of ginger constituent 6-shogaol on gastroesophageal vagal afferent C-fibers.

BACKGROUND: Ginger has been used as an herbal medicine worldwide to relieve nausea/vomiting and gastrointestinal discomfort, but the cellular and molecular mechanisms of its neuronal action remain unclear. The present study aimed to determine the effects of ginger constituent 6-shogaol on gastroesophageal vagal nodose C-fibers. METHODS: Extracellular single-unit recording and two-photon nodose neuron imaging were performed, respectively, in ex vivo gastroesophageal-vagal preparations from wild type and Pirt-GCaMP6 transgenic mice. The action potential discharge or calcium influx evoked by mechanical distension and chemical perfusions applied to the gastroesophageal vagal afferent nerve endings were recorded, respectively, at their intact neuronal cell soma in vagal nodose ganglia. The effects of 6-shogaol on nodose C-fiber neurons were then compared and determined. KEY RESULTS: Gastroesophageal application of 6-shogaol-elicited intensive calcium influxes in nodose neurons and evoked robust action potential discharges in most studied nodose C-fibers. Such activation effects were followed by a desensitized response to the second application of 6-shogaol. However, action potential discharges evoked by esophageal mechanical distension, after 6-shogaol perfusion, did not significantly change. Pretreatment with TRPA1 selective blocker HC-030031 inhibited 6-shogaol-induced action potential discharges in gastric and esophageal nodose C-fiber neurons, suggesting that TRPA1 played a role in mediating 6-shogaol-induced activation response. CONCLUSION AND INFERENCES: This study provides evidence that ginger constituent 6-shogaol directly activates vagal afferent C-fiber peripheral gastrointestinal endings. This activation leads to desensitization to subsequent application of 6-shogaol but not subsequent esophageal mechanical distension. Further investigation is required to establish a possible contribution in its anti-emetic effects.

[Effect of enteral nutrition as replacement of traditional bowel preparation on the intraperitoneal and intraluminal disseminated tumor cells, recurrence and metastasis in patients with colorectal cancer].

OBJECTIVE: To study the effect of enteral nutrition as replacement of mechanical bowel preparation on peritoneal and intraluminal disseminated tumor cells, recurrence and metastasis in patients with colorectal cancer. METHODS: A total of 120 colorectal cancer patients between March 2007 and December 2011 were enrolled prospectively and randomly divided into two groups. Group A (n=60) received preoperative bowel preparation with enteral nutrition fluid (30 ml·kg(-1)·d(-1)), without enema, taxative or antibiotics. Group B (n=60) underwent traditional intestinal preparation consecutively 3 days before operation, including fasting, oral antibiotic, and cleaning enema. All the patients received peritoneal lavage with 400 ml of normal saline at the time of laparotomy and 200 ml of the lavage fluid was collected. All the cases underwent distal colorectal lavage with 1000 ml of normal saline before anastomosis, and 500 ml of the lavage fluid was collected. Fluid samples were quickly sent for exfoliated cytological examination. The positive rates of exfoliated cancer cell in peritoneal cavity and intraluminal cavity, postoperative complication, recurrence and metastasis were compared between the two groups. RESULTS: In group A, exfoliated cancer cells were found in 5 of 60 cases (8.3%) in peritoneal lavage fluid and in 9 of 60 cases (15.0%) in distal colorectal lavage fluid, while in group B, cancer cells were found in 13 of 60 cases (12.5%) and 19 of 60 cases (31.7%) respectively. There were significant differences between group A and B (P=0.041, P=0.031). Fifty-five patients in group A were followed up from 16 to 46 months after surgery, as well 57 patients in group B. Rates of local recurrence and distant metastasis in Group A and B were 5.5% vs. 7.0% and 10.9% vs. 10.5% respectively. There were no significant differences (P=0.733, P=0.984). There was no significant difference in 3-year survival rate between the two groups (80% vs. 78%, P=0.312). CONCLUSIONS: Enteral nutrition instead of traditional bowel preparation can decrease the positive rate of disseminated cancer cells in peritoneal cavity or colorectal lumen, while dose not affect recurrence and metastasis rates in patients with colorectal cancer.

Laparoscopic extensive colectomy with transanal Soave pull-through for intestinal neuronal dysplasia in 17 children.

BACKGROUND: Open colectomy has been preferred for intestinal neuronal dysplasia type B (IND) due to its low morbidity rate and good functional results. The aim of this study was to investigate the feasibility and results of laparoscopic colectomy with transanal Soave pull-through for the treatment of IND in children. METHODS: Seventeen infants and children suffering from IND were treated by laparoscopic extensive colectomy with transanal Soave pull-through. The diagnosis of IND was made via anorectal manometry, X-ray contrast enema, suction biopsies, and laparoscopic full-thickness biopsies with hematoxylin-eosin staining. The technique used four or five abdominal ports. The sigmoid, transverse, and right colon up to the last ileal cove were mobilized laparoscopically in the extended form of IND. A modified Soave's anastomosis was performed. The patients' data, surgical procedures, operative data, postoperative complications and clinical outcomes were analyzed. RESULTS: Five patients underwent laparoscopic left colectomy with modified transanal Soave procedures, and the other 12 were treated by laparoscopic subtotal colectomy and required a Deloyers' maneuver for the Soave pull-through. The proximal margin of barium stagnation in patients with left colectomy was restricted to the distal end of the descending colon, sigmoid colon, and that in patients with subtotal colectomy was restricted to the proximal end of the descending colon, transverse colon, hepatic flexure, and ascending colon. Postoperative complications included anastomotic leakage, severe perianal erosions, postoperative enterocolitis, and soiling. During a mean follow-up of 4 years, bowel frequency was 4-10 times per day in 3 months postoperatively in patients with subtotal colectomy. The clinical results were good, with no stool incontinence or constipation. CONCLUSIONS: Laparoscopic procedure for left colectomy and subtotal colectomy with transanal Soave pull-through in infants and children with IND is safe, feasible, and effective. The location of barium stagnation in proximal margin may be used as a method to predict initially the proximal margin of the resected bowel segment.

[Effect of paidu baoshen pill in retarding the progression of chronic renal failure].

OBJECTIVE: To assess the impact of Paidu Baoshen Pill (PBP, modified Dahuang Zhechong Pill), in retarding the procession of chronic renal failure (CRF) of stage II-III. METHODS: The 283 patients of CRF stage II-III were randomly assigned to two groups, 151 patients in the treatment group treated with oral administration of PBP 3 g twice a day, and 132 patients in the control group with oxidative amylase aldehyde enveloped capsule 5-10 capsules thrice a day after meal. The course for both groups was 2 months, and the changes after 1 or 2 courses treatment in scoring of quality of life (QOL) and clinical symptoms, also in laboratory indexes including serum levels of creatinine (Cr), urea nitrogen (UN), and intrinsic creatinine clearance rate were observed. RESULTS: The total effective rate was 70. 86% (107/151 cases) in the treatment group and 44.70% (59/132 cases) in the control group, showing significant difference between them (X2 = 18.69, P < 0.01). Significant differences between groups were also shown in comparisons of scores of QOL and clinical symptoms after treatment. Inter-group comparison showed no difference in all the three indexes detected before treatment, but they did show statistical significance respectively after 1 and 2 courses of treatment (P < 0.05 and P < 0.01). CONCLUSION: PBP could effectively retard the progression of chronic renal failure and significantly improve the QOL of patients.

[Experimental study on effects of electro-acupuncture in improving synaptic plasticity in focal cerebral ischemia rats].

OBJECTIVE: To explore the mechanisms of electro-acupuncture (EA) in improving synaptic plasticity after cerebral ischemic injury. METHODS: Focal cerebral ischemia (FCI) model was established by middle cerebral artery occlusion (MCAO) with heat-coagulation method. The changing rules of synaptic ultrastructure, synaptophysin (P38), growth-associated protein-43 (GAP-43), brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF) in the ischemic cortex 2 and 5 weeks after FCI and the effects of EA on them were observed. RESULTS: Expression of numerical density (Nv), surface density (Sv), volume density (Vv), post synaptic density (PSD) and P38 in the ischemic cortex significantly decreased after MCAO (P<0.01). Among them, Nv and Sv were raised at the 5th week in FCI rats either treated or untreated with EA (P<0.01), but the increment of Sv was higher in those of the treated rats (P<0.01); PSD in the EA treated rats also showed a significant increase at the 5th week, which was significant higher than that in those untreated; EA showed insignificant influence on Vv and synaptic interfacial curvature; P38 lowered continuously after 2 weeks, but at the 5th week, it was higher in EA treated rats than that in untreated rats (P<0.01), while at the 2nd week, the levels in treated and untreated rats were equal. GAP-43 rose in the 2nd week after modeling, with no difference between EA treated and untreated animals, at the 5th week, it was lowered in untreated rats to near that in sham-operated rats, but maintained at higher level in EA treated rats; NGF and BDNF positive cells significantly increased after modeling (P<0.01), and showed a descending trend with the time going (P<0.01) both in rats treated or untreated with EA. CONCLUSION: EA can protect synaptic ultrastructure, promote the expression of P38, GAP-43, NGF and BDNF in the ischemic cerebral cortex, and thus improve synaptic plasticity in cerebral ischemic rats.