Endoscopic treatment of pouch inlet and afferent limb strictures: stricturotomy vs. balloon dilation.

BACKGROUND: Strictures are common complications after ileal pouch surgery. The aim of this study is to evaluate the efficacy and safety of endoscopic stricturotomy vs. endoscopic balloon dilation (EBD) in the treatment of pouch inlet strictures. METHODS: All consecutive ulcerative colitis patients with the diagnosis of pouch inlet or afferent limb strictures treated in our Interventional Inflammatory Bowel Disease Unit (i-IBD) from 2008 to 2017 were extracted. The primary outcomes were surgery-free survival and post-procedural complications. RESULTS: A total of 200 eligible patients were included in this study, with 40 (20.0%) patients treated with endoscopic stricturotomy and 160 (80.0%) patients treated with EBD. Symptom improvement was recorded in 11 (42.3%) patients treated with endoscopic stricturotomy and 16 (13.2%) treated with EBD. Subsequent surgery rate was comparable between the two groups (9 [22.5%] vs. 33 [20.6%], P = 0.80) during a median follow-up of 0.6 years (interquartile range [IQR] 0.4-0.8) vs. 3.6 years (IQR 1.1-6.2) in patients receiving endoscopic stricturotomy and EBD, respectively. The overall surgery-free survival seems to be comparable as well (P = 0.12). None of the patients in the stricturotomy group developed pouch failure, while 9 patients (5.6%) had pouch failure in the balloon dilation group (P = 0.17). Procedural bleeding was seen in three occasions (4.7% per procedure) in patients receiving endoscopic stricturotomy and perforation was seen in three occasions (0.8% per procedure) in patients receiving EBD (P = 0.02). In multivariable analysis, an increased length of the stricture (hazard ratio [HR] 1.4, 95% confidence interval [CI] 1.0-1.8) and concurrent pouchitis (HR 2.5, 95% CI 1.0-5.7) were found to be risk factors for the requirement of surgery. CONCLUSION: Endoscopic stricturotomy and EBD were both effective in treating patients with pouch inlet or afferent limb strictures, EBD had a higher perforation risk while endoscopic stricturotomy had a higher bleeding risk.

circCAMSAP1 Promotes Tumor Growth in Colorectal Cancer via the miR-328-5p/E2F1 Axis.

Increasing studies indicated that circular RNAs (circRNAs) play important roles in cancer progression. However, the roles of circRNAs in colorectal cancer (CRC) remain largely unknown. In this study, we determined the circRNA expression profile by next-generation RNA sequencing from eight CRC and paired non-cancerous matched tissues. circCAMSAP1 (originating from exon 2 to exon 3 of the CAMSAP1 gene, hsa_circ_0001900) was significantly upregulated in CRC tissues. Increased circCAMSAP1 expression was significantly correlated with advanced tumor/node/metastasis (TNM) stage and shortened overall survival. An elevation of circCAMSAP1 expression was detected via droplet digital PCR in the serum of CRC patients prior to surgery. Functionally, circCAMSAP1 promoted the malignant behavior of CRC. Mechanism study of upstream biogenesis of circCAMSAP1 indicated that circCAMSAP1 cyclization in CRC was mediated by splicing factor epithelial-splicing regulatory protein 1. Moreover, circCAMSAP1 acted as a sponge for miR-328-5p and abrogated its suppression on transcription factor E2F1. Taken together, our data indicated an essential role of the circCAMSAP1/miR-328-5p/E2F1 axis in the progression of CRC, which implied that circCAMSAP1 could serve as a diagnostic and prognostic biomarker as well as a potential therapeutic target for CRC.

Anti-cryptococcal activity of preussolides A and B, phosphoethanolamine-substituted 24-membered macrolides, and leptosin C from coprophilous isolates of Preussia typharum.

Cryptococcus neoformans is a serious human pathogen with limited options for treatment. We have interrogated extracts from fungal fermentations to find Cryptococcus-inhibiting natural products using assays for growth inhibition and differential thermosensitivity. Extracts from fermentations of four fungal strains from wild and domestic animal dung from Arkansas and West Virginia, USA were identified as Preussia typharum. The extracts exhibited two antifungal regions. Purification of one region yielded new 24-carbon macrolides incorporating both a phosphoethanolamine unit and a bridging tetrahydrofuran ring. The structures of these metabolites were established mainly by analysis of high-resolution mass spectrometry and 2D NMR data. Relative configurations were assigned using NOESY data, and the structure assignments were supported by NMR comparison with similar compounds. These new metabolites are designated preussolides A and B. The second active region was caused by the cytotoxin, leptosin C. Genome sequencing of the four strains revealed biosynthetic gene clusters consistent with those known to encode phosphoethanolamine-bearing polyketide macrolides and the biosynthesis of dimeric epipolythiodioxopiperazines. All three compounds showed moderate to potent and selective antifungal activity toward the pathogenic yeast C. neoformans.

Acrophiarin (antibiotic S31794/F-1) from Penicillium arenicola shares biosynthetic features with both Aspergillus- and Leotiomycete-type echinocandins.

The antifungal echinocandin lipopeptide, acrophiarin, was circumscribed in a patent in 1979. We confirmed that the producing strain NRRL 8095 is Penicillium arenicola and other strains of P. arenicola produced acrophiarin and acrophiarin analogues. Genome sequencing of NRRL 8095 identified the acrophiarin gene cluster. Penicillium arenicola and echinocandin-producing Aspergillus species belong to the family Aspergillaceae of the Eurotiomycetes, but several features of acrophiarin and its gene cluster suggest a closer relationship with echinocandins from Leotiomycete fungi. These features include hydroxy-glutamine in the peptide core instead of a serine or threonine residue, the inclusion of a non-heme iron, α-ketoglutarate-dependent oxygenase for hydroxylation of the C3 of the glutamine, and a thioesterase. In addition, P. arenicola bears similarity to Leotiomycete echinocandin-producing species because it exhibits self-resistance to exogenous echinocandins. Phylogenetic analysis of the genes of the echinocandin biosynthetic family indicated that most of the predicted proteins of acrophiarin gene cluster exhibited higher similarity to the predicted proteins of the pneumocandin gene cluster of the Leotiomycete Glarea lozoyensis than to those of the echinocandin B gene cluster from A. pachycristatus. The fellutamide gene cluster and related gene clusters are recognized as relatives of the echinocandins. Inclusion of the acrophiarin gene cluster into a comprehensive phylogenetic analysis of echinocandin gene clusters indicated the divergent evolutionary lineages of echinocandin gene clusters are descendants from a common ancestral progenitor. The minimal 10-gene cluster may have undergone multiple gene acquisitions or losses and possibly horizontal gene transfer after the ancestral separation of the two lineages.

Arenicolins: C-Glycosylated Depsides from Penicillium arenicola.

During investigation of the secondary metabolism of four strains of Penicillium arenicola, two new depsides, arenicolins A (1) and B (2), were isolated and characterized. Their structures were established mainly by analysis of NMR and HRMS data and by comparison with known compounds. These depsides incorporate intriguing structural features, including dual alkyl side chains and a C-glycosyl unit, with 1 also containing an acylated 2-hydroxymethyl-4,5,6-trihydroxycyclohexenone moiety. Although the arenicolins were produced by all strains tested, arenicolin A (1) was obtained using only one of five medium compositions employed, while arenicolin B (2) was produced in all media tested. Neither compound showed antibacterial or antifungal activity, but 1 exhibited cytotoxicity toward mammalian cell lines, including colorectal carcinoma (HCT-116), neuroblastoma (IMR-32), and ductal carcinoma (BT-474), with IC50 values of 7.3, 6.0, and 9.7 µM, respectively.

Post-index procedural gain in body mass index is associated with recurrent ileal pouch sinus after endoscopic or surgical therapy.

BACKGROUND: Ileal pouch-anal anastomosis has become the standard surgical procedure for patients with ulcerative colitis who require colectomy. Presacral sinus is a common complication after the surgery. Pouch sinus results from chronic anastomotic or suture line leak. An excessive gain in body mass index (BMI) has been shown to be associated with poor pouch outcome. The aim of this study was to evaluate whether an increase in BMI was associated with recurrences of chronic pouch sinus after endoscopic or surgical treatment. METHODS: All consecutive ulcerative colitis patients with an ileal pouch sinus successfully treated with either endoscopic sinusotomy or redo surgery from 2006 to 2016 were identified from our IRB approved, prospectively maintained Pouch Registry. An excessive gain in BMI was defined as an increase in BMI ≥ 10% from the baseline of the initial endoscopic or surgical treatment. The primary outcome was sinus recurrence after initial complete healing. RESULTS: This study included a total of 171 patients. Sinus recurrence was seen in 48 (28.1%) patients. A higher rate of recurrence of sinus was found in patients with BMI gain (≥ 10%) (22.9% vs. 8.9%, p = 0.01). However, the recurrence-free survival in Kaplan-Meier analysis between the BMI gain and non-BMI gain groups was not statistically significant (p = 0.10). In multivariate analysis, excessive BMI gain [odds ratio (OR) 3.0, 95% confidence interval (CI) 1.0-9.0)] and Crohn's disease of the pouch (OR 2.9, 95% CI 1.0-8.1) were independently associated with sinus recurrence. The healing rate of recurrent sinus after subsequent endoscopic or surgical treatment was comparable between those who had an excessive increase in BMI and those who maintained a relatively stable weight (63.6% vs. 70.3%, p = 0.81). However, the recurrent presacral sinus-related pouch failure rate was numerically higher in patients with an excessive BMI gain (36.4% vs. 16.2%, p = 0.31). CONCLUSIONS: An excessive gain in BMI after initial successful pouch sinus treatment is associated with an increased risk for sinus recurrence. Weight control may help decrease the risk for recurrence of pouch sinus.

Apc.LaeA and Apc.VeA of the velvet complex govern secondary metabolism and morphological development in the echinocandin-producing fungus Aspergillus pachycristatus.

The impact of the global secondary metabolite regulators LaeA and VeA on echinocandin B production and morphological development was evaluated in the industrial production strain Aspergillus pachycristatus NRRL 11440. Other representative secondary metabolites were examined as well to determine if the velvet complex functions as in A. nidulans and other species of fungi. Genetic methods used for gene manipulations in A. nidulans were applied to A. pachycristatus. Separate deletions of genes Apc.laeA and Apc.veA resulted in similar yet differing phenotypes in strain NRRL 11440. Disruption of Apc.laeA and Apc.veA significantly reduced, but did not eliminate, the production of echinocandin B. Similar to what has been observed in A. nidulans, the production of sterigmatocystin was nearly eliminated in both mutants. Quantitative reverse transcription PCR analyses confirmed that selected genes of both the echinocandin B and sterigmatocystin gene clusters were down-regulated in both mutant types. The two mutants differed with respect to growth of aerial hyphae, pigmentation, development of conidiophores, conidial germination rate, and ascospore maturation. Further functional annotation of key regulatory genes in A. pachycristatus and related Aspergillus species will improve our understanding of regulation of echinocandin production and co-produced metabolites.

Identification of Secondary Metabolites from Aspergillus pachycristatus by Untargeted UPLC-ESI-HRMS/MS and Genome Mining.

Aspergillus pachycristatus is an industrially important fungus for the production of the antifungal echinocandin B and is closely related to model organism A. nidulans. Its secondary metabolism is largely unknown except for the production of echinocandin B and sterigmatocystin. We constructed mutants for three genes that regulate secondary metabolism in A. pachycristatus NRRL 11440, and evaluated the secondary metabolites produced by wild type and mutants strains. The secondary metabolism was explored by metabolic networking of UPLC-HRMS/MS data. The genes and metabolites of A. pachycristatus were compared to those of A. nidulans FGSC A4 as a reference to identify compounds and link them to their encoding genes. Major differences in chromatographic profiles were observable among the mutants. At least 28 molecules were identified in crude extracts that corresponded to nine characterized gene clusters. Moreover, metabolic networking revealed the presence of a yet unexplored array of secondary metabolites, including several undescribed fellutamides derivatives. Comparative reference to its sister species, A. nidulans, was an efficient way to dereplicate known compounds, whereas metabolic networking provided information that allowed prioritization of unknown compounds for further metabolic exploration. The mutation of global regulator genes proved to be a useful tool for expanding the expression of metabolic diversity in A. pachycristatus.

Endoscopic sinusotomy versus redo surgery for the treatment of chronic pouch anastomotic sinus in ulcerative colitis patients.

BACKGROUND AND AIMS: Pouch sinus may be a serious adverse event in patients undergoing ileal pouch-anal anastomosis. The aim of this study was to compare endoscopic sinusotomy (ESi) and redo pouch surgery in the management of pouch sinus. METHODS: All consecutive ulcerative colitis patients with chronic pouch sinuses treated with ESi versus redo surgery from 2006 to 2016 were identified. The primary outcomes were recurrence-free and surgery-free survivals. The secondary outcome was postprocedural adverse events. RESULTS: This historical cohort study included 226 patients (ESi, n = 141; redo surgery, n = 85). Complete healing of the sinus was achieved in 75 patients (53.2%) and partial healing in 23 patients (16.3%) with ESi, and an initial complete healing (ie, no anastomotic leak before ileostomy closure) was obtained in 80 patients (94.1%) receiving redo surgery. Sinus recurrence after complete healing was seen in 17 patients (22.7%) treated with ESi and 28 patients (32.9%) treated with surgery (P = .15). Subsequent surgery was needed in 34 patients (24.1%) with ESi therapy and 18 patients (21.2%) with initial redo surgery (P = .70). Kaplan-Meier recurrence-free and surgery-free survivals after initial procedures showed no statistical difference between the 2 groups (P = .42 and P = .65, respectively). The rate of adverse events in the ESi group was significantly lower than that in the surgery group (2.5% vs 43.5%, P < .0001). CONCLUSIONS: Recurrence-free and surgery-free survivals were comparable between patients treated with ESi and redo surgery, whereas pouch redo surgery was found to be associated with a higher immediate complete healing rate yet a higher morbidity.

Endoscopic stricturotomy versus ileocolonic resection in the treatment of ileocolonic anastomotic strictures in Crohn's disease.

BACKGROUND AND AIMS: Endoscopic stricturotomy (ESt) is a novel technique in the treatment of anastomotic strictures in Crohn's disease (CD). The aim of this study was to compare the outcome of patients with ileocolonic anastomotic stricture treated with ESt versus ileocolonic resection (ICR). METHODS: This historical cohort study included consecutive CD patients with ileocolonic anastomotic stricture treated with ESt or ICR from 2010 to 2017. The primary outcomes were surgery-free survival and postprocedural adverse events. RESULTS: Thirty-five patients treated with ESt and 147 patients treated with ICR were analyzed. Median follow-up was .8 years (interquartile range [IQR], .2-1.7) and 2.2 years (IQR, 1.2-4.4) in the ESt and ICR groups, respectively (P < .001). Subsequent stricture-related surgery was needed in 4 patients (11.3%) receiving ESt and in 15 patients (10.2%) receiving ICR (P = .83). Kaplan-Meier analysis also showed no statistical difference regarding surgery-free survival between the 2 groups (P = .24). Procedure-related major adverse events were documented in 5 of 49 patients (10.2% per procedure) undergoing ESt and 47 patients (31.9%) undergoing ICR (P = .003). Risk factors for decreased surgery-free survival on multivariate analysis included preprocedural corticosteroids (hazard ratio [HR], 2.8; 95% confidence interval [CI], 1.0-8.1), multiple strictures (HR, 4.9; 95% CI, 1.7-14.2), and increased disease-related hospitalizations (HR, 4.0; 95% CI, 1.2-13.0). CONCLUSIONS: With the limitation of a shorter follow-up, ESt achieved comparable surgery-free survival with a decreased morbidity when compared with ICR.

Outcomes of Endoscopic Balloon Dilation vs Surgical Resection for Primary Ileocolic Strictures in Patients With Crohn's Disease.

BACKGROUND & AIMS: Few studies have compared endoscopic balloon dilation (EBD) with ileocolic resection (ICR) in the treatment of primary ileocolic strictures in patients with Crohn's disease (CD). METHODS: We performed a retrospective study to compare postprocedure morbidity and surgery-free survival among 258 patients with primary stricturing ileo(colic) CD (B2, L1, or L3) initially treated with primary EBD (n = 117) or ICR (n = 258) from 2000 through 2016. Patients with penetrating disease were excluded from the study. We performed multivariate analyses to evaluate factors associated with surgery-free survival. RESULTS: Postprocedural complications occurred in 4.7% of patients treated with EBD and salvage surgery was required in 44.4% of patients. Factors associated with reduced surgery-free survival among patients who underwent EBD included increased stricture length (hazard ratio, 2.0; 95% CI, 1.3-3.3), ileocolonic vs ileal disease (hazard ratio, 10.9; 95% CI, 2.6-45.4), and decreased interval between EBD procedures (hazard ratio, 1.2; 95% CI, 1.1-1.4). There were no significant differences in sex, age, race, or CD duration between EBD and ICR groups. Patients treated with ICR were associated with more common postoperative adverse events (32.2%; P < .0001), but a reduced need for secondary surgery (21.7%; P < .0001) and significantly longer surgery-free survival (11.1 ± 0.6 vs 5.4 ± 0.6 y; P < .001). CONCLUSIONS: In this retrospective study, we found that although EBD is initially successful with minimal adverse events, there is a high frequency of salvage surgery. Initial ICR is associated with a higher morbidity but a longer surgery-free interval. The risks and benefits should be balanced in selecting treatments for individual patients.

Enfumafungin synthase represents a novel lineage of fungal triterpene cyclases.

Enfumafungin is a glycosylated fernene-type triterpenoid produced by the fungus Hormonema carpetanum. Its potent antifungal activity, mediated by its interaction with ß-1,3-glucan synthase and the fungal cell wall, has led to its development into the semi-synthetic clinical candidate, ibrexafungerp (=SCY-078). We report on the preliminary identification of the enfumafungin biosynthetic gene cluster (BGC) based on genome sequencing, phylogenetic reconstruction, gene disruption, and cDNA sequencing studies. Enfumafungin synthase (efuA) consists of a terpene cyclase domain (TC) fused to a glycosyltransferase (GT) domain and thus represents a novel multifunctional enzyme. Moreover, the TC domain bears a phylogenetic relationship to bacterial squalene-hopene cyclases (SHC) and includes a typical DXDD motif within the active centre suggesting that efuA evolved from SHCs. Phylogenetic reconstruction of the GT domain indicated that this portion of the fusion gene originated from fungal sterol GTs. Eleven genes flanking efuA are putatively involved in the biosynthesis, regulation, transport and self-resistance of enfumafungin and include an acetyltransferase, three P450 monooxygenases, a dehydrogenase, a desaturase and a reductase. A hypothetical scheme for enfumafungin assembly is proposed in which the E-ring is oxidatively cleaved to yield the four-ring system of enfumafungin. EfuA represents the first member of a widespread lineage of fungal SHCs.

Predication of post-operative outcome of colectomy in ulcerative colitis patients using Model of End-Stage Liver Disease Score.

PURPOSE: Model of End-Stage Liver Disease (MELD) score was developed to predict mortality in patients with liver disease. The aim of this study was to investigate the relationship between preoperative MELD score and 30-day surgical outcomes using the American College of Surgeons National Surgical Quality Improvement Program. METHODS: Patients with ulcerative colitis (UC) (ICD: 556.X) who underwent colectomy were identified from NSQIP 2005 to 2013. The primary outcomes were bleeding complications, and overall morbidity and mortality. RESULTS: A total of 7534 UC patients undergoing colectomy were identified. Patients with a higher MELD score had a longer hospital stay; more bleeding; and cardiac, respiratory, renal, thromboembolic, and septic complications as well as mortality. Patients were stratified into 4 groups by MELD score: < 7, 7-11, 12-15, and > 15 and a stratified multivariate analysis was done. Patients with a MELD score 12-15 (odds ratio [OR] 1.9, 95% confidence interval [CI] 1.1-1.3) and MELD > 15 (OR 2.6, 95%CI 1.5-4.7) were at significant risk for bleeding complication. Apart from the MELD score, the presence of ascites (OR 2.5, 95%CI 1.2-5.1) or varices (OR 1.0, 95%CI 1.01-1.03) was also significantly associated with post-operative bleeding complication. MELD 12-15 and MELD > 15 were also found to be risk factors for overall morbidity (OR 5.3, 95%CI 1.8-15.7; OR 10.3, 95%CI 3.6-29.7, respectively) and mortality (OR 3.3, 95%CI 1.3-8.4; OR 5.9, 95%CI 2.4-14.6, respectively). CONCLUSION: UC patients with a higher MELD score were associated with a higher post-colectomy morbidity and mortality. MELD score > 11 was an independent indicator for post-operative bleeding, and overall complications and mortality.

Biosynthesis of pneumocandin lipopeptides and perspectives for its production and related echinocandins.

Fungal diseases are a global public health problem. Invasive fungal infections pose a serious threat to patients with compromised immune systems, such as those undergoing organ or bone marrow transplants, cancer, or HIV/AIDS. Pneumocandins are antifungal lipohexapeptides of the echinocandin family that noncompetitively inhibit of 1,3-ß-glucan synthase of fungal cell wall and provide the precursor for the semisynthesis of caspofungin, which is widely used as first-line therapy for invasive fungal infections. Recently, the biosynthetic steps leading to formation of pneumocandin B0 and echinocandin B have been elucidated, and thus, provide a framework and attractive model for further design new antifungal therapeutics around natural variations in echinocandin structural diversities via genetic and chemical tools. In this article, we analyze the biosynthetic pathway of pneumocandins and other echinocandins, provide an update on the array of pneumocandin analogues generated by genetic manipulation, and summarize advances in the enhancement of pneumocandin B0 production by random mutagenesis and fermentation optimization. We also give offer advice on the development of improved pneumocandin drug candidates and more efficient production of pneumocandin B0.

Comparison of clinical features, treatment, and outcomes of collagenous sprue, celiac disease, and collagenous colitis.

BACKGROUND: Collagenous sprue (CS) is a rare form of enteropathy that had been reported to be associated with celiac disease (CD) and collagenous colitis (CC). The aim of our study was to compare the clinical features, treatments, and outcomes of CS, CD, and CC. METHODS: All patients with histologic diagnosis of CS, CD, or CC with complete clinical data were extracted from our pathology database between 1990 and 2015. Demographic and clinical features were recorded along with treatments and outcomes. RESULTS: A total of 21 patients with CS were included. Overall CS patients were more symptomatic with 17 (81.0%) patients with diarrhea and 15 (71.4%) with unintentional weight loss. Positive celiac serology was noted in 5 (23.8%) CS patients. CS patients had higher rates for disease-related temporary total parenteral nutrition (TPN) use (38.1% vs. 1.1% vs. 1.0%, P < 0.0001) and disease-related hospitalization (52.4% vs. 3.3% vs. 8.2%, P < 0.0001) than that in CD and CC patients. Twenty CS patients received treatments, including the combination of gluten-free diet (GFD) and corticosteroids (n = 12), GFD only (n = 2), and corticosteroids only (n = 6). All CS patients showed symptomatic reliefs with treatment. Although CS patients had a higher rate for hospitalization and TPN use, disease-related death was not observed in all three groups. CONCLUSIONS: Collagenous sprue patients had more severe clinical presentation than patients with CD and CC and therefore had higher demand for temporary TPN and hospitalization. Nevertheless, a prompt use of steroids and/or GFD upon histologic diagnosis of CS may have contributed to an overall excellent prognosis.

[Effects of compound malt pills on expressions of ERα and ERß in ovaries of rats with letrozole-induced polycystic ovarian syndrome].

OBJECTIVE: To explore the effect of compound malt pills (CMP) on polycystic ovarian syndrome (PCOS) rat model induced by letrozole and the underlying mechanisms.
 METHODS: To establish a PCOS rat model, 48 female SD rats aged 6 weeks were randomly divided into 6 groups (n=8): A normal group, a model control group, a positive control group, a low-dose CMP group, a middle-dose CMP group, and a high-dose CMP group. Rats were treated for 21 days after the PCOS model was successfully established. Ovarian morphology changes were observed, and the expressions of ERα and ERß was examined by immunohistochemistry, Western blot and RT-PCR, respectively.
 RESULTS: Compared with the normal group, the number of follicular cystic dilatation in the model control group was increased and the granulosa cells were decreased. After the treatment, the number of follicular cystic dilatation was reduced compared with the model control group, but the primordial follicles, corpus luteum and granulosa cells were increased. The expressions of ERα and ERß in the model control group were significantly decreased (P<0.01), which were increased in the intervention groups (P<0.05 or P<0.01).
 CONCLUSION: CMP may play a role in the treatment of PCOS by regulating the expressions of ERα and ERß.

Coordinated and distinct functions of velvet proteins in Fusarium verticillioides.

Velvet-domain-containing proteins are broadly distributed within the fungal kingdom. In the corn pathogen Fusarium verticillioides, previous studies showed that the velvet protein F. verticillioides VE1 (FvVE1) is critical for morphological development, colony hydrophobicity, toxin production, and pathogenicity. In this study, tandem affinity purification of FvVE1 revealed that FvVE1 can form a complex with the velvet proteins F. verticillioides VelB (FvVelB) and FvVelC. Phenotypic characterization of gene knockout mutants showed that, as in the case of FvVE1, FvVelB regulated conidial size, hyphal hydrophobicity, fumonisin production, and oxidant resistance, while FvVelC was dispensable for these biological processes. Comparative transcriptional analysis of eight genes involved in the ROS (reactive oxygen species) removal system revealed that both FvVE1 and FvVelB positively regulated the transcription of a catalase-encoding gene, F. verticillioides CAT2 (FvCAT2). Deletion of FvCAT2 resulted in reduced oxidant resistance, providing further explanation of the regulation of oxidant resistance by velvet proteins in the fungal kingdom.

Efficacy and Safety of Upadacitinib in the Treatment of Chronic Pouchitis, Cuffitis, and Crohn's Disease of the Pouch.

Upadacitinib has shown efficacy in the treatment of moderate-to-severe ulcerative colitis and Crohn's disease (CD). The use of upadacitinib in the treatment of chronic antibiotics-refractory pouchitis (CARP), as well as CD of the pouch, has not been previously reported. We treated a series of 6 patients with CARP or CD of the pouch with a minimal 6 weeks of upadacitinib. The patients showed minimal or no significant improvement in clinical and endoscopic presentations. Our findings warrant further study to validate the efficacy and safety of upadacitinib in the treatment of CARP or CD of the pouch.