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Background: Previous studies have demonstrated that TRIB3 plays a carcinogenic role in tumor progression. However, the exploration of TRIB3 at the pan-cancer level has not been reported.Aims: This study aimed to conduct a comprehensive pan-cancer analysis of TRIB3.Objectives: We explored the expression pattern and functional mechanism of TRIB3 on the basis of multiple databases.Methods: We first explored the expression level of TRIB3 in the TCGA database. Then, the receiver operation characteristic curve (ROC), Kaplan-Meier plotter, and Cox regression were used to estimate the diagnostic and prognostic value of TRIB3, respectively. We also explored the relationship between TRIB3 and the infiltration of tumor immune cells, as well as the expression of immune checkpoint molecules. Gene enrichment and protein interaction network analysis were carried out to identify possible carcinogenic molecular mechanisms and functional pathways. Finally, we compared the non-promoter region methylation of TRIB3 in normal and tumor tissues and explored potential systems with unique functions in TRIB3-mediated tumorigenesis.Results: The expression level of TRIB3 was elevated in multiple tumor types, and the high expression of TRIB3 was associated with poor prognosis. TRIB3 had a higher frequency of genetic changes in several tumors and showed varying trends in TRIB3 methylation levels. Additionally, high expression of TRIB3 was also associated with infiltration of cancer-related fibroblasts and different types of immune cells and was positively correlated with the expression of immune checkpoint molecules. Furthermore, gene enrichment analysis suggested that TRIB3 may play a role in the malignant progression of cancer by participating in protein post-translational modifications and activating transcription initiation factors.Conclusion: Our pan-cancer analysis provided the potential carcinogenic role of TRIB3 in tumors and verified a promising target for clinical immune treatment.

The catalytic α-deuteration of sulfides was developed under mild conditions by using alkali metal amides [KN(SiMe3)2and CsN(SiMe3)2] as the catalyst. This approach successfully achieves a selective and efficient H/D exchange reaction of sulfides with D2without using transition metal catalysts. A series of deuterium-labeled thioanisoles and alkyl methyl sulfides were obtained in good to high levels of deuterium incorporation.

The objective of this randomised controlled trial was to compare the periodontal healing at the distal of the adjacent second molar after coronectomy or surgical removal and the surgical morbidities of the 2 techniques.

Nicotinic acetylcholine receptors (nAChRs) regulate pain pathways with various outcomes depending on receptor subtypes, neuron types, and locations. But it remains unknown whether α4β2 nAChRs abundantly expressed in the substantia nigra pars reticulata (SNr) have potential to mitigate hyperalgesia in pain states. We observed that injection of nAChR antagonists into the SNr reduced pain thresholds in naïve mice, whereas injection of nAChR agonists into the SNr relieved hyperalgesia in mice, subjected to capsaicin injection into the lower hind leg, spinal nerve injury, chronic constriction injury, or chronic nicotine exposure. The analgesic effects of nAChR agonists were mimicked by optogenetic stimulation of cholinergic inputs from the pedunculopontine nucleus (PPN) to the SNr, but attenuated upon downregulation of α4 nAChRs on SNr GABAergic neurons and injection of dihydro-β-erythroidine into the SNr. Chronic nicotine-induced hyperalgesia depended on α4 nAChRs in SNr GABAergic neurons and was associated with the reduction of ACh release in the SNr. Either activation of α4 nAChRs in the SNr or optogenetic stimulation of the PPN-SNr cholinergic projection mitigated chronic nicotine-induced hyperalgesia. Interestingly, mechanical stimulation-induced ACh release was significantly attenuated in mice subjected to either capsaicin injection into the lower hind leg or SNI. These results suggest that α4 nAChRs on GABAergic neurons mediate a cholinergic analgesic circuit in the SNr, and these receptors may be effective therapeutic targets to relieve hyperalgesia in acute and chronic pain, and chronic nicotine exposure.

Recombination, the process of DNA exchange between homologous chromosomes during meiosis, plays a major role in genomic diversity and evolutionary change. Variation in recombination rate is widespread despite recombination often being essential for progression of meiosis. One such variation is heterochiasmy, where recombination rates differ between sexes. Heterochiasmy has been observed across broad taxonomic groups, yet it remains an evolutionary enigma. We used Lep-MAP3, a pedigree-based software that is efficient in handling large datasets, to generate linkage maps for the hihi or stitchbird (Notiomystis cincta), utilising information from >36 K SNPs and 36 families. We constructed 29 linkage maps, including for the previously unscaffolded Z chromosome. The hihi is an endangered passerine endemic to Aotearoa New Zealand that is sexually dimorphic and exhibits high levels of sexual conflict, including sperm competition. Patterns in recombination in the hihi are consistent with those in other birds, including higher recombination rates in micro-chromosomes. Heterochiasmy in the hihi is male-biased, in line with predictions of the Haldane-Huxley rule, with the male linkage map being 15% longer. Micro-chromosomes exhibit heterochiasmy to a greater extent, contrary to that reported in other birds. At the intra-chromosomal level, heterochiasmy is higher nearer to chromosome ends and in gene-rich regions. Regions of extreme heterochiasmy are enriched for genes implicated in cell structure. This study adds an important contribution in assessing evolutionary theories of heterochiasmy and provides a framework for future studies investigating fine-scale heterochiasmy.

Static recrystallization (SRX) characteristics of a powder metallurgy superalloy were investigated by isothermal compression at 1080–1170 °C under strain rates of 0.01–0.1 s−1, strains of 0.1, 0.22, or 0.5, and holding time of 0–300 s. The impacts of temperature, strain rate, holding time, and strain on the SRXed grain size, volume fraction, and microtexture were explored by electron backscatter diffraction technique. It was found that temperature played a key role in these processes. As SRX progressed, the <110> fiber parallel to the axis compression direction gradually weakened and was replaced by the <001> fiber because <001> was the preferred recrystallization orientation and grain growth direction for the Ni-based superalloy. Moreover, high temperatures and low strain rates promoted the formation of the <001> fiber. Three nucleation mechanisms during SRX process were found: grain boundary bulging, primary twin assistance, and subgrain coalescence. Grain boundary bulging occurred under all process conditions; however, at low temperatures and high strain rates, the latter two mechanisms could provide additional nucleation modes. In addition, SRX size and volume fraction models were established.

The combination cancer therapy of nitric oxide (NO) with gene therapy is a promising method for tumor treatment. However, efficient co-delivery of gas and therapeutic genes to tumor cells remains a challenge. Herein, we designed a nano-sized ultraviolet (UV) light-responsive cationic lipid vector DPNO(Zn). Fluorescence spectroscopy and confocal imaging experiments revealed that DPNO(Zn)lipid nanoparticles (LNPs) could rapidly release NO under low-power UV light irradiation. Moreover, the fluorescence turn-on might take place along with the release of NO, indicating the self-reporting ability. Gene delivery experiments showed that DPNO(Zn)LNPs had good gene transfection ability, making such materials a good candidate for gas/gene combination therapy. In vitro antitumor assay demonstrated that the co-delivery system was more effective in inhibiting tumor cell proliferation than individual NO or pTrail treatment. Studies on the mechanism of tumor cell apoptosis induced by NO/pTrail co-delivery showed that NO could not only effectively increase the accumulation of p53 protein in tumor cells, thereby promoting the activation of caspase-3, but also induce mitochondrial damage. On the other hand, the Trail protein expressed by pTrail gene could enhance the degree of NO-induced caspase-3 activation, indicating the synergistic effect. These results proved that DPNO(Zn)LNP may serve as a multifunctional nanocarrier for potential tumor therapy.

Existing evidence indicates that gut fungal dysbiosis might play a key role in the pathogenesis of colorectal cancer (CRC). We sought to explore whether reversing the fungal dysbiosis by terbinafine, an approved antifungal drug, might inhibit the development of CRC. A population-based study from Sweden identified a total of 185 patients who received terbinafine after their CRC diagnosis and found that they had a decreased risk of death (hazard ratio = 0.50) and metastasis (hazard ratio = 0.44) compared with patients without terbinafine administration. In multiple mouse models of CRC, administration of terbinafine decreased the fungal load, the fungus-induced myeloid-derived suppressor cell (MDSC) expansion, and the tumor burden. Fecal microbiota transplantation from mice without terbinafine treatment reversed MDSC infiltration and partially restored tumor proliferation. Mechanistically, terbinafine directly impaired tumor cell proliferation by reducing the ratio of nicotinamide adenine dinucleotide phosphate (NADP+) to reduced form of nicotinamide adenine dinucleotide phosphate (NADPH), suppressing the activity of glucose-6-phosphate dehydrogenase (G6PD), resulting in nucleotide synthesis disruption, deoxyribonucleotide (dNTP) starvation, and cell-cycle arrest. Collectively, terbinafine can inhibit CRC by reversing fungal dysbiosis, suppressing tumor cell proliferation, inhibiting fungus-induced MDSC infiltration, and restoring antitumor immune response.

The self-assembly of mechanoluminochromic polynuclear gold(I) complexes has attracted more and more attention in the field of supramolecular gold(I) chemistry. In this work, we adopted a stepwise self-assembly strategy to precisely synthesize two polynuclear gold(I) supramolecular clusters. Through cooperative AuI···AuIand Au–N interactions, the gold(I) clusters 1+•BF4–and 24+•4BF4–with Au4and Au16cores, respectively, were successfully constructed. In these supramolecular clusters, (dppm)Au2Cl2coordination motifs and trithiocyanuric linkers were stepwise assembled via sequential thiolate–chloride/phosphine coordination substitution and Au–S/Au–N coordination bond rearrangement. Two well-defined gold(I) supramolecular clusters displayed intense emission both in the solid state and in solution. Furthermore, the ladder-shaped cluster 24+•4BF4–exhibited reversible mechanochromic luminescence behavior in the solid state as well as aggregation-caused redshifted emission in solution. Upon mechanical grinding, the emission of the cluster 24+•4BF4–changed from yellow at 582 nm to red at 612 nm. The initial emission could be fully recovered by treatment with acetonitrile.

Gefitinib has been available in the market for 20 years, but its pharmacokinetic mechanism of response is little known. In this study, we examined the pharmacokinetic and metabolomic profiles in non-small cell lung cancer (NSCLC) patients with sensitive EGFR mutations. A total of 216 advanced NSCLC patients were enrolled, and administered gefitinib at the standard dosage of 250 mg/day, which was established in heterogeneous subjects with non-sensitive mutations. We identified and quantified three main metabolites (named as M1, M2 and M3) in the plasma of patients, the correlations between the concentration of gefitinib/metabolites and efficacy were analyzed. In exploratory and validation set, gefitinib concentration was not correlated with clinical effects. Considering the result that the therapeutic effects of 250 mg/2-day was better than that of 250 mg/day in a multiple center clinical trial, the standard dose might be higher than that for maximal efficacy according to the hypothetical dose-response curve. Among the three metabolites, the IC50of M2 in HCC827 and PC9 cell lines was significantly lower, and Conc.brain/Conc.plasmaof M2 in mice was significantly higher than those of gefitinib, suggesting its higher potential to penetrate blood–brain barrier and might be more effective in the treatment of brain metastatic tumor than gefitinib. Consistently and attractively, higher M2 plasma concentration was found to be correlated with better clinical outcome in patients with brain metastases (the median PFS of CM2< 12 ng/mL and CM2≥ 12 ng/mL were 17.0 and 27.1 months, respectively, P= 0.038). The plasma concentration of M2 ≥ 12 ng/mL was a strong predictor of the PFS of NSCLC patients. In conclusion, for NSCLC patients with EGFR sensitive mutations, the standard dose is suspectable and could be decreased reasonably. M2 plays an important role in efficacy and may be more effective in the treatment of metastatic tumor than gefitinib.

The operation of a warship is commonly affected by shock loads in different directions during sailing in a rough sea, which can decrease the precision of the shipboard equipment. To improve the shock resistance performance of the shipboard equipment, an isolator is usually installed to isolate it from the vibration of the ship deck. The paper proposes a method for dynamic response and time-variant reliability analysis of an eight-rod shock isolator (ERSI). ERSI has a novel symmetrical structure, which can improve the utilization of the isolation rods compared with the classical parallel mechanism. The isolator is modeled using Denavit-Hartenberg (D-H) convention and screw theory. Then, Duhamel integral is employed to derive the dynamic response to the isolator after decoupling the governing equation using the modal analysis method. Considering impacts of uncertain factors, this paper also presents a practical method for time-variant reliability analysis of ERSI. Finally, a discussion of the practical example of this method along with a detailed analysis to evaluate the efficiency of the proposed method is presented.

The nigrostriatal dopaminergic (DA) system, which includes DA neurons in the ventral and dorsal tiers of the substantia nigra pars compacta (vSNc, dSNc) and DA terminals in the dorsal striatum, is critically implicated in motor control. Accumulating studies demonstrate that both the nigrostriatal DA system and motor function are impaired in aged subjects. However, it is unknown whether dSNc and vSNc DA neurons and striatal DA terminals age in similar patterns, and whether these changes parallel motor deficits. To address this, we performed ex vivo patch-clamp recordings in dSNc and vSNc DA neurons, measured striatal dopamine release, and analyzed motor behaviors in rodents. Spontaneous firing in dSNc and vSNc DA neurons and depolarization-evoked firing in dSNc DA neurons showed inverse V-shaped changes with age. But depolarization-evoked firing in vSNc DA neurons increased with age. In the dorsal striatum, dopamine release declined with age. In locomotor tests, 12-month-old rodents showed hyperactive exploration, relative to 6- and 24-month-old rodents. Additionally, aged rodents showed significant deficits in coordination. Elevating dopamine levels with a dopamine transporter inhibitor improved both locomotion and coordination. Therefore, key components in the nigrostriatal DA system exhibit distinct aging patterns and may contribute to age-related alterations in locomotion and coordination.

Vacuolar protein sorting 33B (VPS33B) is important for intracellular vesicular trafficking process and protein interactions, which is closely associated with the arthrogryposis, renal dysfunction, and cholestasis syndrome. Our previous study has shown a crucial role of Vps33bin regulating metabolisms of bile acids and lipids in hepatic Vps33bdeficiency mice with normal chow, but it remains unknown whether VPS33B could contribute to cholestatic liver injury. In this study we investigated the effects of hepatic Vps33bdeficiency on bile acid metabolism and liver function in intrahepatic cholestatic mice. Cholestasis was induced in Vps33bhepatic knockout and wild-type male mice by feeding 1% CA chow diet for 5 consecutive days. We showed that compared with the wild-type mice, hepatic Vps33bdeficiency greatly exacerbated CA-induced cholestatic liver injury as shown in markedly increased serum ALT, AST, and ALP activities, serum levels of total bilirubin, and total bile acid, as well as severe hepatocytes necrosis and inflammatory infiltration. Target metabolomics analysis revealed that hepatic Vps33bdeficiency caused abnormal profiles of bile acids in cholestasis mice, evidenced by the upregulation of conjugated bile acids in serum, liver, and bile. We further demonstrated that the metabolomics alternation was accompanied by gene expression changes in bile acid metabolizing enzymes and transporters including Cyp3a11, Ugt1a1, Ntcp, Oatp1b1, Bsep, and Mrp2. Overall, these results suggest a crucial role of hepatic Vps33bdeficiency in exacerbating cholestasis and liver injury, which is associated with the altered metabolism of bile acids.

Pancreatic ductal adenocarcinoma (PDAC), cancer with a high mortality rate and the highest rate of KRASmutation, reportedly internalizes proteins via macropinocytosis to adapt to low amino acid levels in the tumor microenvironment. Here, we aimed to identify a key regulator of macropinocytosis for the survival of tumor cells in a low amino acid environment in PDAC. FYVE, RhoGEF, and PH domain-containing protein 6 (FGD6) were identified as key regulators of macropinocytosis. FGD6 promoted PDAC cell proliferation, macropinocytosis, and tumor growth both in vitro and in vivo. The macropinocytosis level was decreased with FGD6 knockdown in PDAC cell lines. Moreover, FGD6 promoted macropinocytosis by participating in the trans-Golgi network and enhancing the membrane localization of growth factor receptors, especially the TGF-beta receptor. TGF-beta enhanced macropinocytosis in PDAC cells. Additionally, YAP nuclear translocation induced by a low amino acid tumor environment initiated FGD6 expression by coactivation with YY1. Clinical data analysis based on TCGA and GEO datasets showed that FGD6 expression was upregulated in PDAC tissue, and high FGD6 expression was correlated with poor prognosis in patients with PDAC. In tumor tissue from KrasG12D/+/Trp53R172H/−/Pdx1-Cre (KPC) mice, FGD6 expression escalated during PDAC development. Our results uncover a previously unappreciated mechanism of macropinocytosis in PDAC. Strategies to target FGD6 and growth factors membrane localization might be developed for the treatment of PDAC.

With the rapid development of various portable electronic devices, lithium ion battery electrode materials with high energy and power density, long cycle life and low cost were pursued. Vanadium-based oxides/sulfides were considered as the ideal next-generation electrode materials due to their high capacity, abundant reserves and low cost. However, the inherent low conductivity and ion diffusion coefficient limit their practical applications in lithium ion batteries. In recent years, vanadium-based electrode materials have been designed into various nanostructures through a variety of nanofabrication processes to overcome the electrochemical performance bottleneck caused by the above disadvantages due to the new properties of nanomaterials that cannot be achieved at the solid level. However, how to obtain high-performance vanadium-based electrode nanomaterials with controllable morphology and structure through low-cost and environmentally friendly processes is still a huge challenge. In this paper, the basic structure, modified morphologies and synthesis methods of vanadium-based electrode materials for lithium ion batteries were reviewed. In addition, the disadvantages, new challenges and future development direction of vanadium electrode materials were also discussed.

The deprotonative functionalization of toluenes, for their weak acidity, generally needs strong bases, thus leading to the requirement of harsh conditions and the generation of by-products. Direct nucleophilic acyl substitution reaction of amides with organometallic reagents could provide an ideal solution for ketone synthesis. However, the inert amides and highly reactive organometallic reagents bring great challenges for an efficient and selective synthetic approach. Herein, we reported an lithium diisopropylamide (LDA)-promoted benzylic aroylation of toluenes with unactivated tertiary benzamides, providing a direct and efficient synthesis of various aryl benzyl ketones. This process features a kinetic deprotonative functionalization of toluenes with a readily available base LDA. Mechanism studies revealed that the directed ortho-lithiation of the tertiary benzamide with LDA promoted the benzylic kinetic deprotonation of toluene and triggered the nucleophilic acyl substitution reaction with the amide.

Laser surface modification technology is one of the most advanced technologies, which uses laser to modify the characteristics of the surface to offer superior performance for various industrial applications. In this study, laser surface hardening behavior of GM246 case iron was investigated. Result shows that excellent laser surface hardening of GM246 cast iron need low power density and scanning speed. With power of 2500 W, scanning speed of 300 mm/min and power density of 2500 W/cm2, the laser surface hardening of GM246 cast iron achieved the hardness of 790HV, which was 2-3 times higher than the hardness of base metal. Also, the depth of laser surface hardening case achieved 0.9 mm and the hardening case demonstrated three subzones.

Metastasis is a major cause of cancer-related deaths. Tumor-intrinsic properties can determine whether tumor metastasis occurs or not. Here, by comparing the gene expression patterns in primary colorectal cancer (CRC) patients with or without metastasis, we found that Collagen Triple Helix Repeat Containing 1 (CTHRC1) in primary CRC served as a metastasis-associated gene. Animal experiments verified that CTHRC1 secreted by CRC cells promoted hepatic metastasis, which was closely correlated with macrophage infiltration. Depletion of macrophages by liposomal clodronate largely abolished the promoting effect of CTHRC1 on CRC liver metastasis. Furthermore, we demonstrated that CTHRC1 modulated macrophage polarization to M2 phenotypes through TGF-β signaling. A mechanistic study revealed that CTHRC1 bound directly to TGF-β receptor II and TGF-β receptor III, stabilized the TGF-β receptor complex, and activated TGF-β signaling. The combination treatment of CTHRC1 monoclonal antibody and anti-PD-1 blocking antibody effectively suppressed CRC hepatic metastasis. Taken together, our data demonstrated that CTHRC1 is an intrinsic marker of CRC metastasis and further revealed that CTHRC1 promoted CRC liver metastasis by reshaping infiltrated macrophages through TGF-β signaling, suggesting that CTHRC1 could be a potential biomarker for the early prediction of and a therapeutic target of CRC hepatic metastasis.

Human Y-chromosome haplogroup C2b-F1067 is one of the dominant paternal lineages of populations in Eastern Eurasia. In order to explore the origin, diversification, and expansion of this haplogroup, we generated 206 new Y-chromosome sequences from C2b-F1067 males and coanalyzed 220 Y-chromosome sequences of this haplogroup. BEAST software was used to reconstruct a revised phylogenetic tree of haplogroup C2b-F1067 with age estimates. The revised phylogeny of C2b-F1067 included 155 sublineages, 1986 non-private variants, and >6000 private variants. The age estimation suggested that the initial splitting of C2b-F1067 happened at about 32.8 thousand years ago (kya) and the major sublineages of this haplgroup experienced continuous expansion in the most recent 10,000 years. We identified numerous sublineages that were nearly specific for Korean, Mongolian, Chinese, and other ethnic minorities in China. In particular, we evaluated the candidate-specific lineage for the Dayan Khan family and the Confucius family, the descendants of the ruling family of the Chinese Shang dynasty. These findings suggest that ancient populations with varied C2b-F1067 sublineages played an important role during the formation of most modern populations in Eastern Eurasia, and thus eventually became the founding paternal lineages of these populations.

Interatomic potential plays an important role in molecular dynamics simulation, which determines both the efficiency and accuracy of the simulations. Lattice inversion is a method which can be used to develop interatomic potential from first principle results directly. In present work, a robust potential model based on lattice inversion is proposed. Then the potential model is applied to develop interatomic potentials for eight common FCC metals. The cohesive energy curves calculated using first principle calculations can be well reproduced, which verifies the reliability of the developed potential. Additional physical properties, including equilibrium lattice constant and cohesive energy, elastic constants, are predicted and found reasonable agreement with corresponding first principle results.

Objective: To observe the effects of electroacupuncture (EA) of different frequencies on transmission function, electromyography, nitric oxide synthase (NOS) content and interstitial cells of Cajal (ICC) expression of colon in rat models with slow transit constipation (STC). Methods: Of the 50 healthy male Wistar rats, 10 were randomly selected as a normal group and fed with ordinary diet, and the remaining 40 rats were fed with the diet added with the compound diphenoxylate at a dose of 8 mg/(kg·bw) each day for continuous 120 d. The 40 successfully established STC rat models were randomly divided into a model group, a low-frequency EA group (2 Hz), a high-frequency EA group (100 Hz), and a variable-frequency EA group (2 Hz/100 Hz), with 10 rats in each group. Rats in the normal and the model groups were not given any treatment; the low-frequency EA and the high-frequency EA groups were given EA at Tianshu (ST 25), Zusanli (ST 36) and Zhigou (TE 6) with continuous wave at the designated frequency, and the variable-frequency EA group received sparse-dense wave (2 Hz/100 Hz) EA at the same acupoints, once a day for a total of 15 d. After treatment, the colonic transmission function, electromyography, NOS content and ICC expression (calculated by the difference in the area of the C-kit positive cells) of the rats in each group were measured. Results: For the colonic transmission function, compared with the normal group, the first black stool excretion durations of rats in the other groups were significantly prolonged (all P&lt;0.05); compared with the model group, the first black stool excretion durations of rats in the three EA groups were significantly shortened (all P&lt;0.05), which was significantly shorter in the variable-frequency EA group than in the low-frequency EA and high-frequency EA groups (both P&lt;0.05). For the colonic electromyography, compared with the normal group, the amplitude was significantly increased and the frequency was accelerated in rats of the other groups (all P&lt;0.05); compared with the model group, the amplitude was significantly reduced and the frequency was slowed down in the three EA groups (both P&lt;0.05); compared with the low-frequency EA and the high-frequency EA groups, the amplitude was reduced and the frequency was significantly reduced in rats of the variable-frequency EA group (both P&lt;0.05). Compared with the normal group, the colonic NOS contents were significantly increased in the other groups (all P&lt;0.05); compared with the model group, the NOS contents were significantly reduced in the three EA groups (all P&lt;0.05); compared with the low-frequency EA and the high-frequency EA groups, the content was significantly reduced in the variable-frequency EA group (all P&lt;0.05). For the area of rat colonic C-kit-positive cells, compared with the normal group, the areas were significantly reduced in rats of other groups (all P&lt;0.05); compared with the model group, the areas were increased significantly in the three EA groups (all P&lt;0.05); compared with the low-frequency EA group, the area was increased significantly in the variable-frequency EA group (P&lt;0.05). Conclusion: EA, especially EA at the 2 Hz/100 Hz variable-frequency, has a positive treatment effect on the STC model rats. It may improve rats’ colonic function by regulating the electromyography, NOS content and ICC expression of colon.