Multiomics Analyses Reveal the Complexity of Interaction between Two Strains of Magnaporthe oryzae.

Plants growing in open environments are frequently coinfected by multiple strains of the same pathogen. However, few investigations have been carried out to reveal the outcomes and underlying mechanisms of such infections. This study aimed to observe the behaviors of two different strains under coinfection and cocultivation. We constructed an experimental system to study such interactions directly by labeling Magnaporthe oryzae strains with the green fluorescent proteins and mushroom cherry fluorescent protein to observe mixed strain behavior in vivo and in vitro. Moreover, multiomics analyses were conducted to explore the underlying mechanisms at the genomic, transcriptomic, and metabolomic levels. Our results revealed that coinfection with two strains can affect disease severity and that the more weakly virulent strain benefits from the coinfection system. We also found that amino acid variation might negatively influence such interactions at transcriptomic and metabolomic levels. In addition, we showed that the overexpression of a glutamine-related gene improved strain competitiveness during mixture cultivation. Collectively, our results provided experimental methods to analyze the interaction between two strains of M. oryzae and preliminarily explored the interacted mechanism of two strains under cocultivation through multiomics analyses.

Higher dietary inflammatory index is associated with increased all-cause mortality in adults with chronic kidney disease.

Background: Diet property grounded on inflammatory potential, evaluated by the dietary inflammatory index (DII), has been proven to be connected with mortality, while studies of adults with chronic kidney disease (CKD) are scarce. Objective: The purpose of this research was to evaluate the interrelationships between DII and all-cause mortality among adults with CKD. Methods: In the National Health and Nutrition Examination Survey (NHANES) 2001-2006, we identified and evaluated data of 4,554 adults with CKD. DII scores were calculated from 24 h of dietary consumption at baseline. Vital status was followed through 31 December 2015. The association of all-cause mortality with DII score was assessed using the Kaplan-Meier curve and the Cox regression analysis. Results: After an average follow-up of 132.103 months, a total of 1,246 (27.36%) deaths were recorded. The death rates in the DII tertile categories were 24.04, 26.81, and 31.23%, respectively. The Kaplan-Meier curve showed increased death risks for the high DII tertile as compared with the low DII tertile. After we adjusted for a broad range of possible confounders, the estimation between extreme tertiles of DII scores presented a positive and significant association with all-cause mortality [hazard ratio (HR): 1.21, 95% CI: 1.05-1.39]. Conclusion: Our results confirm the hypothesis that proinflammatory diets contribute to the increased all-cause mortality in adults with CKD.

Transcriptome and Quasi-Targeted Metabolome Analyze Overexpression of 4-Hydroxyphenylpyruvate Dioxygenase Alleviates Fungal Toxicity of 9-Phenanthrol in Magnaporthe oryzae.

Magnaporthe oryzae, the causal agent of rice blast disease, produces devastating damage to global rice production. It is urgent to explore novel strategies to overcome the losses caused by this disease. 9-phenanthrol is often used as a transient receptor potential melastatin 4 (TRPM4) channel inhibitor for animals, but we found its fungal toxicity to M. oryzae. Thus, we explored the antimicrobial mechanism through transcriptome and metabolome analyses. Moreover, we found that overexpression of a gene encoding 4-hydroxyphenylpyruvate dioxygenase involved in the tyrosine degradative pathway enhanced the tolerance of 9-phenanthrol in M. oryzae. Thus, our results highlight the potential fungal toxicity mechanism of 9-phenanthrol at metabolic and transcriptomic levels and identify a gene involving 9-phenanthrol alleviation. Importantly, our results demonstrate the novel mechanism of 9-phenanthrol on fungal toxicity that will provide new insights of 9-phenanthrol for application on other organisms.

Enhanced trace-amount terahertz vibrational absorption spectroscopy using surface spoof polarization in metasurface structures.

Terahertz (THz) absorption spectroscopy is a powerful tool for molecular label-free fingerprinting, but it faces a formidable hurdle in enhancing the broadband spectral signals in trace-amount analysis. In this paper, we propose a sensing method based on the geometry scanning of metal metasurfaces with spoof surface polarization sharp resonances by numerical simulation. This scheme shows a significant absorption enhancement factor of about 200 times in an ultra-wide terahertz band to enable the explicit identification of various analytes, such as a trace-amount thin lactose film samples. The proposed method provides a new, to the best of our knowledge, choice for the enhancement of wide terahertz absorption spectra, and paves the way for the detection of trace-amount chemical, organic, or biomedical materials in the terahertz regime.

Transcriptome Analysis and SNP Identification Reveal That Heterologous Overexpression of Two Uncharacterized Genes Enhances the Tolerance of Magnaporthe oryzae to Manganese Toxicity.

Manganese is a crucial trace element that constitutes the cofactors of many enzymes. However, excessive Mn2+ can be toxic for both prokaryotes and eukaryotes. The mechanism of fungal genetics and metabolism in response to Mn2+ stress remains understudied, warranting further studies. Magnaporthe oryzae is well-established as the most destructive pathogen of rice. A field strain, YN2046, more sensitive to Mn2+ toxicity than other strains, was obtained from a previous study. Herein, we explored the genetic mechanisms of Mn2+ sensitivity in YN2046 through comparative transcriptomic analyses. We found that many genes previously reported to participate in Mn2+ stress were not regulated in YN2046. These non-responsive genes might cause Mn2+ sensitivity in YN2046. Weight gene correlation network analysis (WGCNA) was performed to characterize the expression profile in YN2046. Some overexpressed genes were only found in the Mn2+ tolerant isolate YN125. Among these, many single nucleotide polymorphism (SNP) were identified between YN125 and YN2046, which might disrupt the expression levels of Mn responsive genes. We cloned two uncharacterized genes, MGG_13347 and MGG_16609, from YN125 and transformed them to YN2046 with a strong promoter. Our results showed that the heterologous overexpression of two genes in YN2046 restored its sensitivity. Transcriptomic and biochemical analyses were performed to understand Mn tolerance mechanisms mediated by the two heterologous overexpressed genes. Our results showed that heterologous overexpression of these two genes activated downstream gene expression and metabolite production to restore M. oryzae sensitivity to Mn, implying that SNPs in responsive genes account for different phenotypes of the two strains under Mn stress. IMPORTANCE Heavy metals are used for fungicides as they target phytopathogen in multiple ways. Magnaporthe oryzae is the most destructive rice pathogen and is threatening global rice production. In the eukaryotes, the regulation mechanisms of Mn homeostasis often focus on the posttranslation, there were a few results about regulation at transcript level. The comparative transcriptome analysis showed that fewer genes were regulated in the Mn-sensitive strain. WGCNA and SNP analyses found that mutations in promoter and coding sequence regions might disrupt the expression of genes involved in Mn detoxification in the sensitive strain. We transferred two unannotated genes that were cloned from the Mn-tolerant strain into a sensitive strain with strong promoters, and the transformants exhibited an enhanced tolerance to Mn2+ toxicity. Transcriptome and biochemistry results indicated that heterologous overexpression of the two genes enhanced the tolerance to Mn toxicity by reactivation of downstream genes in M. oryzae.

Cross-Wavelength Hierarchical Metamaterials Enabled for Trans-Scale Molecules Detection Simultaneously.

Metamaterials have attracted increasing attention in sensing applications. However, the critical feature sizes of meta-atom span several orders of magnitude in length scale, almost all the metamaterials are designed to operate at limited bands. It is challenging for a single type of meta-atom with ultra-broadband adaptability. Inspired by the natural hierarchical architectures, herein, the authors introduce a new constructing scheme of cross-wavelength hierarchical metamaterials with a single type of meta-atom that can realize enhancement of terahertz (THz) resonance and surface-enhanced Raman scattering (SERS) at the same time. By combining multiple subwavelength structures at different hierarchical levels into a single meta-atom, the obtained metamaterial can operate in two frequencies and realize multiple functionalities. Armed with this hierarchical metamaterial, detecting analytes as small as sub-nanoscale chemical molecules or as big as microscale biomolecules simultaneously can be realized in one single metamaterial for the first time. As a proof-of-concept example, a smart sensory packaging is developed, which allowed them to real-time monitor the kinetic growth of pathogenic bacteria and their metabolites in food without opening the packaging. They believe that their work will provide a valuable example that satisfies the unmet need for multiscale functional meta-devices.

MCRT, a multifunctional ligand of opioid and neuropeptide FF receptors, attenuates neuropathic pain in spared nerve injury model.

Chimeric peptide MCRT (YPFPFRTic-NH2 ) was a multifunctional ligand of opioid and neuropeptide FF (NPFF) receptors and reported to be potentially antalgic in acute tail-flick test. Here, we developed spared nerve injury (SNI) model to explore its efficacy in chronic neuropathic pain. Analgesic tolerance, opioid-induced hyperalgesia and gastrointestinal transit were measured for safety evaluation. Intracerebroventricular (i.c.v.) and intraplantar (i.pl.) injections were conducted as central and peripheral routes, respectively. Results demonstrated that MCRT alleviated neuropathic pain effectively and efficiently, with the ED50 values of 4.93 nmol/kg at the central level and 3.11 nmol/kg at the peripheral level. The antagonist blocking study verified the involvement of mu-, delta-opioid and NPFF receptors in MCRT produced anti-allodynia. Moreover, the separation of analgesia from unwanted effects was preliminarily achieved and that MCRT caused neither analgesic tolerance nor hyperalgesia after chronic i.c.v. administration, nor constipation after i.pl. administration. Notably, the local efficacy of MCRT in SNI mice was about one thousandfold higher than morphine and ten thousandfold higher than pregabalin, indicating a great promise in the future treatment of neuropathic pain.

Endokinin A/B stimulates rat gastric motility through myogenic NK1 receptors located in the fundus.

Endokinin A/B (EKA/B), the common C-terminal decapeptide in endokinins A and B, is a preferred ligand of the NK1 receptor and regulates pain and itch. The study focused on the effects of EKA/B on rat gastric motility in vivo and in vitro. Gastric emptying was measured to evaluate gastric motility in vivo. Intragastric pressure and the contraction of gastric muscle strips were measured to evaluate gastric motility in vitro. Moreover, various neural blocking agents and neurokinin receptor antagonists were applied to explore the mechanisms. TAC4 and TACR1 mRNAs were expressed throughout rat stomach. EKA/B promoted gastric emptying by intraperitoneal injection in vivo. Correspondingly, EKA/B also increased intragastric pressure in vitro. Additionally, EKA/B contracted the gastric muscle strips from the fundus but not from the corpus or antrum. Further studies revealed that the contraction induced by EKA/B on muscle strips from the fundus could be significantly reduced by NK1 receptor antagonist SR140333 but not by NK2 receptor antagonist, NK3 receptor antagonist, or the neural blocking agents used. Our results suggested that EKA/B might stimulate gastric motility mainly through the direct activation of myogenic NK1 receptors located in the fundus.

Arteriovenous Graft for Hemodialysis: Effect of Cryotherapy on Postoperative Pain and Edema.

BACKGROUND: Arteriovenous grafting offers an alternative for patients whose vessels are unsuitable for arteriovenous fistula. However, as a result of subcutaneous tunnel dissection, postoperative pain and edema of the operated limb present early after surgery. As a traditional therapeutic approach, cryotherapy has the ability to suppress postoperative pain and edema. AIMS: The purpose of the study was to investigate the feasibility of cryotherapy after arteriovenous graft surgery to decrease perioperative medication usage. DESIGN: This study was a randomized controlled trial. SETTING: A large integrated health care facility in South China. PARTICIPANTS/SUBJECTS: A total of 85 hemodialysis patients who received arteriovenous graft surgery from March 2011 to February 2017 were enrolled. METHODS: The participants were divided into an intervention group and a control group according to the postoperative management. Ice packs were applied covering the operative forearm for 120 minutes after wound closure in the intervention group. General information, pain score, analgesic consumption, wound inflammation, forearm edema, and participant satisfaction were compared between the two groups. RESULTS: Cryotherapy-treated patients required less analgesia (26.19% vs. 48.84%, p < .05), reported lower pain score from 30 minutes to 48 hours postoperative (p < .05), less wound inflammation (11.90% vs. 25.58%, p < .05), and higher participant satisfaction (8.92 ± 0.57 vs. 6.52 ± 0.63, p < .05), whereas the incidence of forearm edema was equivalent (p > .05). No adverse events were reported in either group. CONCLUSIONS: Cryotherapy is a preferable intervention for patients after arteriovenous graft implantation as a result of its favorable cost, convenience, and fewer side effects.

Cryotherapy Relieves Pain and Edema After Inguinal Hernioplasty in Males With End-Stage Renal Disease: A Prospective Randomized Study.

CONTEXT: Tension-free hernioplasty under local anesthetic infiltration is a reasonable choice for end-stage renal disease patients with hernia. OBJECTIVES: The purpose of the study was to investigate the feasibility of cryotherapy after hernioplasty surgery to relieve pain and scrotal edema. METHODS: This was a prospective, randomized, and controlled trial held in a large integrated health care facility in South China. One hundred sixty-nine male patients on hemodialysis and scheduled for hernioplasty were enrolled between March 2013 and February 2017. The participants were divided into an intervention group and a control group. In the intervention group, ice packs were applied after surgery. Demographic information, vital signs, pain score, opioid consumption, wound inflammation, scrotal edema, and patient satisfaction were compared between the two groups. The primary outcome was pain score. RESULTS: Cryotherapy-treated patients required less opioid consumption (5.95 vs. 15.29 mg; P < 0.05), reported lower pain scores from 30 minutes to 48 hours after operation (P < 0.05), less wound inflammation (11.90 vs. 32.94%; P < 0.05), lower incidence of scrotal edema in the first and second days (P < 0.05), and higher patient satisfaction (8.95 vs. 6.50 cm; P < 0.05), with stable vital signs throughout the monitoring period (P > 0.05). CONCLUSION: Owing to its favorable cost, convenience, and low frequency of adverse effects, cryotherapy is useful for end-stage renal disease populations after hernioplasty to relieve pain and scrotal edema.

Trends in Oral Antibiotic, Proton Pump Inhibitor, and Histamine 2 Receptor Blocker Prescription Patterns for Children Compared With Adults: Implications for Clostridium difficile Infection in the Community.

The use of antibiotics, proton pump inhibitor (PPI), and histamine 2 receptor blocker (H2B) was compared between children and adults in the community from 2005 through 2011. Antibiotic prescription rates remained stable for children, but increased significantly for adults, P = .03. PPI prescription rates increased for children, P = .02 and for adults, P = .009. H2B prescription rates increased for children, P = .03, but not for adults. Antibiotic prescription rates were significantly higher in children than adults in all 7 years, P < .0001. In contrast, PPI prescription rates were significantly higher in adults than children in all 7 years, P < .0001. H2B prescription rates were significantly higher in adults than children 1 to 18 years old P < .0001; however, H2B prescription rates were highest in children <1 year old, P = .0001. The high use of oral antibiotics, PPI, and H2B among outpatients may be a contributing factor to the rise of Clostridium difficile infection in the community.

Genipin stimulates glucose transport in C2C12 myotubes via an IRS-1 and calcium-dependent mechanism.

Genipin, a compound derived from Gardenia jasminoides Ellis fruits, has been used over the years in traditional Chinese medicine to treat symptoms of type 2 diabetes. However, the molecular basis for its antidiabetic effect has not been fully revealed. In this study, we investigated the effects of genipin on glucose uptake and signaling pathways in C(2)C(12) myotubes. Our study demonstrates that genipin stimulated glucose uptake in a time- and dose-dependent manner. The maximal effect was achieved at 2 h with a concentration of 10 µM. In myotubes, genipin promoted glucose transporter 4 (GLUT4) translocation to the cell surface, which was observed by analyzing their distribution in subcellular membrane fraction, and increased the phosphorylation of insulin receptor substrate-1 (IRS-1), AKT, and GSK3ß. Meanwhile, genipin increased ATP levels, closed K(ATP) channels, and then increased the concentration of calcium in the cytoplasm in C(2)C(12) myotubes. Genipin-stimulated glucose uptake could be blocked by both the PI3-K inhibitor wortmannin and calcium chelator EGTA. Moreover, genipin increases the level of reactive oxygen species and ATP in C(2)C(12) myotubes. These results suggest that genipin activates IRS-1, PI3-K, and downstream signaling pathway and increases concentrations of calcium, resulting in GLUT4 translocation and glucose uptake increase in C(2)C(12) myotubes.

Naproxen-induced liver injury.

BACKGROUND: Nonsteroidal anti-inflammatory drugs (NSAIDs) have been reported to induce liver injury. Patterns of the injury usually range from mild elevations of liver enzymes to sometimes severe fulminant hepatic failure. Likewise, naproxen is a propionic acid derivative NSAID that was introduced in 1980 and has been available as an over-the-counter medication since 1994, but has rarely been reported to cause liver injury. METHODS: We treated a 30-year-old woman with jaundice and intractable pruritus that developed shortly after taking naproxen. We reviewed the medical history and liver histopathology of the patient as well as all previously published case reports of naproxen-associated liver toxicity in the English language literature. RESULTS: The liver biochemical profile of the patient revealed a mixed cholestasis and hepatitis pattern. Consecutive liver biopsies demonstrated focal lobular inflammation, hepatocyte drop-out, and a progressive loss of the small interlobular bile ducts (ductopenia). The biopsy performed two years after onset of the disease showed partial recovery of a small number of bile ducts; however, 10 years passed before the biochemical profile returned to near normal. CONCLUSIONS: Naproxen-associated liver toxicity remains a rare entity, but should be considered in any patient presenting with cholestasis shortly after its use. Liver injury is most commonly seen in a mixed pattern characterized by cholestasis and hepatitis. The resulting liver damage may take years to resolve.

[Washing copper (II)-contaminated soil using surfactant solutions].

The batch equilibrium washing of copper (II) in the soil matrix by anionic surfactant, sodium dodecylbenzyl sulfonate (SDBS), nonionic surfactant, octylphenoxypolyethoxyethanol (TX100), and their mixture (SDBS-TX100), was studied and compared. The influences of surfactant concentrations, washing time, pH values of solutions, ratios of soil to water and inorganic salts on washing efficiency were investigated. It was shown that the washing efficiency differed with the kinds of surfactants. Given the initial surfactant concentrations, the washing of copper (II) by single SDBS was greater than those by single TX100 and the mixed SDBS-TX100. The washing efficiency by 6 000 mg x L(-1) of SDBS was up to 46.3%, which was 5.8, 10.8, 10.8 and 19.3 times as those by SDBS-TX100 (3:1), SDBS-TX100 (1:1), SDBS-TX100 (1:3) and single TX100 respectively. When the ratio of soil to water was 1 to 10 and washing time reached 24 h, the washing efficiency achieved the maximum. pH values of solutions had obvious effect on the washing of copper (II). The washing efficiency of copper decreased sharply with the increase of pH. At the high acidity (pH = 1.50), the washing efficiency of copper (II) was up to 95%. The smaller the ratios of soil to water were, the higher the washing efficiencies would be. The existence of inorganic salts with the certain concentrations, such as Na+, Ca2+ and Mg2+, could not influence the washing capacity of surfactants, but the excessive Mg2+ (more than 500 mg x L(-1)) could resulted in the precipitation of SDBS. The results will make an implication for surfactant-enhanced remediation of soils contaminated with heavy metals.

Effects of advanced glycosylation end products and rosiglitazone on the expression and secretion of galectin-3 in human renal mesangial cells.

BACKGROUND: Galectin-3 is the most recently identified advanced glycosylation end products (AGEs) binding protein. This study aimed to investigate the effects of AGEs and rosiglitazone on the expression and secretion of galectin-3 in cultured human renal mesangial cells (HRMCs). METHODS: HRMCs were incubated with different concentrations of AGE-bovine serum albumin (BSA) (0, 50, 100, 200, and 400 mg/L) for different time (0, 24, 36, 48, and 72 hours), and exposed to AGE-BSA in the presence of different concentrations of rosiglitazone (1, 10, and 100 micromol/L). The mRNA and protein expression of galectin-3 in HRMCs were analyzed by reverse transcription polymerase chain reaction (RT-PCR) and Western blotting. The culture medium of HRMCs was collected and concentrated, and the content of galectin-3 in the medium was detected by Western blotting. RESULTS: Both RT-PCR and Western blotting revealed that AGE-BSA up-regulated the expression of galectin-3 in HRMCs in a concentration- (P < 0.05) and time-dependent (P < 0.05) manner compared with the control. Compared with the control, AGE-BSA elevated the content of galectin-3 in the culture medium of HRMCs time- and concentration-dependently (P < 0.05, respectively). Both protein and mRNA expression of galectin-3, and its content in the medium of HRMCs exposed to different concentrations of rosiglitazone in the presence of AGE-BSA were increased compared with those of cells exposed to AGE-BSA alone (P < 0.05). Rosiglitazone increased the expression and secretion of galectin-3 in a dose-dependent manner (P < 0.05). CONCLUSIONS: AGEs up-regulates the expression and secretion of galectin-3 in HRMCs. Rosiglitazone further enhances the upregulation of galectin-3 in HRMCs induced by AGEs, which suggests that rosiglitazone may play a role of reno-protection via up-regulation of galectin-3.

Eosinophilic globules in 3 cases of glomeruloid hemangioma of the head and neck: a characteristic offering more evidence for thanatosomes with or without POEMS.

Glomeruloid hemangiomas (GHs) are glomeruli-like capillary tufts lined by endothelial cells that contain periodic acid-Schiff (PAS) positive eosinophilic globules (EGs). These hemangiomas are characteristic cutaneous manifestation of POEMS syndrome (Polyneuropathy, Organomegaly, Endocrinopathy, M-protein, and Skin changes). Hemangiomas histologically identical to GHs but not associated with POEMS have recently been designated as papillary hemangiomas. In this report, we present solitary head and neck GHs in 3 patients, 2 without POEMS, with particular attention to the characteristic EGs. We performed immunostains for hemoglobin A, kappa and lambda light chains, factor VIII-related antigen, CD31 and CD34, PAS stain after diastase digestion (PASD), and electron microscopic examinations on routinely fixed tissues containing EGs. Eosinophilic globules stained uniformly positive for PASD but only peripherally positive for hemoglobin and light chains on surfaces, with interiors negative for antigens. Factor VIII-related antigen and CD31 and CD34 confirmed cells containing EGs to be endothelial. Electron microscopic examination suggested that EGs are enlarged secondary lysosomes (thanatosomes). These features fail to support red blood cells or immunoglobulins as EG constituents. Glomeruloid hemangiomas may be vascular proliferations stimulated by endothelial cells' protein phagocytosis but not by phagocytosis of either hemoglobin-containing red blood cells or immunoglobulins. The vascular lesions in POEMS syndrome appear identical to papillary hemangioma in cases without the other syndromic manifestations.

Immunohistochemical staining of palisading basal cells in Bowen's disease and basal involvement in actinic keratosis: contrasting staining patterns suggest different cells of origin.

Actinic keratosis (AK) and Bowen's disease (BD) are common patterns of in situ squamous cell carcinoma of the epidermis. In AK, atypical keratinocytes proliferate in the lower portion of the epidermis including the basal layer. In contrast, BD features atypical squamous cells in all portions of the epidermis but initially leaves basal cells in palisades along the basement membrane. To characterize immunohistochemically keratocyte proliferation in AK and Palisading Basal Cells (PBC) in BD, we stained microarray samples of 45 AK and 25 BD with Molecular Immunology Borstel (MIB-1). Subsequent immunostaining of full mounted sections examined 11 BD, 7 AK, and 4 examples of psoriasis for MIB-1 (as a proliferative marker) and p53 (as a cell cycle regulatory marker). AK stained for MIB-1 and p53 antibodies only in lower portion of epidermis and included the basal layer. BD with typical PBCs stained positive for both markers throughout the epidermis, except for the basal layer. Psoriatic biopsies stained positively for the 2 markers only in the basal and parabasal layers. Normal epidermis adjacent to the lesions in AK and BD biopsies stained sparsely in the basal layers. The correlation of different histologic patterns of epidermal involvement with different immunohistochemical patterns of stains argues for different cells of origin for BD versus AK. Lack of expression of proliferative antigens in palisading basal cells in BD provides evidence that PBCs are not the cell of origin for BD. Conversely in AK, expression of MIB-1 and p53 in basal cells argues that these cells play a role in histogenesis of AK.

Novel combinations of rate-controlling polymers for the release of leuprolide acetate in the colon.

Our objective was to investigate the controlled release and transport of leuprolide acetate polypeptide in the colon using novel combinations of rate-controlling polymers. Polymer swelling, disintegration, drug release, and transport characteristics were measured using different polymers, carbopol, chitosan and polyox, alone and in combination. Studies demonstrated Carbopol-containing combination formulations had maximum swelling and the slowest disintegration properties. A decrease in dissolution rate was observed from all combination formulations when compared with their individual counterparts. Carbopol combinations showed the slowest overall release. Drug transport studies using the everted sac technique demonstrated good correlation to the swelling, disintegration, and dissolution studies. Thus, novel polymer combinations can be used to deliver polypeptide drug to the colon effectively compared with individual polymers.