Ptth regulates lifespan through innate immunity pathway in Drosophila.

The prothoracicotropic hormone (Ptth) is well-known for its important role in controlling insect developmental timing and body size by promoting the biosynthesis and release of ecdysone. However, the role of Ptth in adult physiology is largely unexplored. Here we show that Ptth null mutants (both males and females) show extended lifespan and healthspan, and exhibit increased resistance to oxidative stress. Transcriptomic analysis reveals that age-dependent upregulation of innate immunity pathway is attenuated by Ptth mutants. Intriguingly, we find that Ptth regulates the innate immunity pathway, specifically in fly oenocytes, the homology of mammalian hepatocytes. We further show that oenocyte-specific overexpression of Relish shortens the lifespan, while oenocyte-specific downregulation of ecdysone signaling extends lifespan. Consistently, knocking down torso, the receptor of Ptth in the prothoracic gland also promotes longevity of the flies. Thus, our data reveal a novel function of the insect hormone Ptth in longevity regulation and innate immunity in adult Drosophila.

Leveraging History to Predict Infrequent Abnormal Transfers in Distributed Workflows.

Scientific computing heavily relies on data shared by the community, especially in distributed data-intensive applications. This research focuses on predicting slow connections that create bottlenecks in distributed workflows. In this study, we analyze network traffic logs collected between January 2021 and August 2022 at the National Energy Research Scientific Computing Center (NERSC). Based on the observed patterns, we define a set of features primarily based on history for identifying low-performing data transfers. Typically, there are far fewer slow connections on well-maintained networks, which creates difficulty in learning to identify these abnormally slow connections from the normal ones. We devise several stratified sampling techniques to address the class-imbalance challenge and study how they affect the machine learning approaches. Our tests show that a relatively simple technique that undersamples the normal cases to balance the number of samples in two classes (normal and slow) is very effective for model training. This model predicts slow connections with an F1 score of 0.926.

Performance of Balloon-Assisted Enteroscopy for Non-ERCP Indications in Patients with Surgically Altered Gastrointestinal Anatomy.

BACKGROUND AND AIMS: Surgically altered gastrointestinal (GI) tract anatomy hinders deep enteroscopy. While enteroscopy-assisted endoscopic retrograde cholangiopancreatography (ERCP) in patients with altered GI anatomy has been heavily investigated, the role of non-ERCP balloon-assisted enteroscopy (BAE) has yet to be fully elucidated.Please check and confirm the author names and initials are correct. Also, kindly confirm the details in the metadata are correct.I have checked all you asked and have no correction.  Thank you. METHODS: A multicenter retrospective study of non-ERCP BAEs in patients with surgically altered GI tract anatomy at two tertiary academic hospitals was performed from January 2006 to December 2020. Altered GI tract anatomy was defined by surgical reconstruction affecting the length, angle, or overall trajectory of the endoscope during the intended approach. The main outcome measurements included technical success rate, diagnostic and therapeutic yields, and complication rate.Please check the edit made in the title of the article and correct if necessary.No more correction. Thank you. RESULTS: A total of 68 patients with surgically altered GI tract anatomy underwent 56 antegrade and 24 retrograde non-ERCP BAE procedures. The technical success rate was 86.2% in both, including 83.9% via antegrade approach and 91.7% via retrograde approach. Antegrade approach in Roux-en-Y anatomy was associated with the lowest success rate of 77.8%, whereas retrograde approach in patients with colon resection resulted in the highest rate of 100%. The diagnostic and therapeutic yields of non-ERCP BAE were 79.4% and 82.9%, respectively. The diagnostic yields varied according to the procedural indications. The major complication was luminal perforation in one case (1.3%). CONCLUSIONS: Non-ERCP BAE is effective and safe via both antegrade and retrograde approaches with a high technical success rate and diagnostic and therapeutic yields in patients with surgically altered GI tract anatomy.

KLHL12 can form large COPII structures in the absence of CUL3 neddylation.

CUL3-RING ubiquitin ligases (CRL3s) are involved in various cellular processes through different Bric-a-brac, Tramtrack, and Broad-complex (BTB)-domain proteins. KLHL12, a BTB-domain protein, is suggested to play an essential role in the export of large cargo molecules such as procollagen from the endoplasmic reticulum (ER). CRL3KLHL12 monoubiquitylates SEC31, leading to an increase in COPII vesicle dimension. Enlarged COPII vesicles can accommodate procollagen molecules. Thus, CRL3KLHL12 is essential for the assembly of large COPII structures and collagen secretion. CRL3s are activated by CUL3 neddylation. Here, we evaluated the importance of CUL3 neddylation in COPII assembly and collagen secretion. Unexpectedly, the assembly of large COPII-KLHL12 structures persisted and cellular collagen levels decreased on treatment with MLN4924, a potent inhibitor of NEDD8-activating enzyme. When we introduced mutations into KLHL12 at the CUL3 interface, these KLHL12 variants did not interact with neddylated CUL3, but one of them (Mut A) still supported large COPII-KLHL12 structures. Overexpression of wild-type KLHL12, but not Mut A, lowered cellular collagen levels most likely via lysosomal degradation. Our results suggest that CUL3 neddylation is not necessary for the formation of large COPII-KLHL12 structures, but active CRL3KLHL12 contributes to the maintenance of collagen levels in the cell.

Acetyl-CoA-mediated autoacetylation of fatty acid synthase as a metabolic switch of de novo lipogenesis in Drosophila.

De novo lipogenesis is a highly regulated metabolic process, which is known to be activated through transcriptional regulation of lipogenic genes, including fatty acid synthase (FASN). Unexpectedly, we find that the expression of FASN protein remains unchanged during Drosophila larval development from the second to the third instar larval stages (L2 to L3) when lipogenesis is hyperactive. Instead, acetylation of FASN is significantly upregulated in fast-growing larvae. We further show that lysine K813 residue is highly acetylated in developing larvae, and its acetylation is required for elevated FASN activity, body fat accumulation, and normal development. Intriguingly, K813 is autoacetylated by acetyl-CoA (AcCoA) in a dosage-dependent manner independent of acetyltransferases. Mechanistically, the autoacetylation of K813 is mediated by a novel P-loop-like motif (N-xx-G-x-A). Lastly, we find that K813 is deacetylated by Sirt1, which brings FASN activity to baseline level. In summary, this work uncovers a previously unappreciated role of FASN acetylation in developmental lipogenesis and a novel mechanism for protein autoacetylation, through which Drosophila larvae control metabolic homeostasis by linking AcCoA, lysine acetylation, and de novo lipogenesis.

Reduced detection rate of artificial intelligence in images obtained from untrained endoscope models and improvement using domain adaptation algorithm.

A training dataset that is limited to a specific endoscope model can overfit artificial intelligence (AI) to its unique image characteristics. The performance of the AI may degrade in images of different endoscope model. The domain adaptation algorithm, i.e., the cycle-consistent adversarial network (cycleGAN), can transform the image characteristics into AI-friendly styles. We attempted to confirm the performance degradation of AIs in images of various endoscope models and aimed to improve them using cycleGAN transformation. Two AI models were developed from data of esophagogastroduodenoscopies collected retrospectively over 5 years: one for identifying the endoscope models, Olympus CV-260SL, CV-290 (Olympus, Tokyo, Japan), and PENTAX EPK-i (PENTAX Medical, Tokyo, Japan), and the other for recognizing the esophagogastric junction (EGJ). The AIs were trained using 45,683 standardized images from 1,498 cases and validated on 624 separate cases. Between the two endoscope manufacturers, there was a difference in image characteristics that could be distinguished without error by AI. The accuracy of the AI in recognizing gastroesophageal junction was >0.979 in the same endoscope-examined validation dataset as the training dataset. However, they deteriorated in datasets from different endoscopes. Cycle-consistent adversarial network can successfully convert image characteristics to ameliorate the AI performance. The improvements were statistically significant and greater in datasets from different endoscope manufacturers [original → AI-trained style, increased area under the receiver operating characteristic (ROC) curve, P-value: CV-260SL → CV-290, 0.0056, P = 0.0106; CV-260SL → EPK-i, 0.0182, P = 0.0158; CV-290 → CV-260SL, 0.0134, P < 0.0001; CV-290 → EPK-i, 0.0299, P = 0.0001; EPK-i → CV-260SL, 0.0215, P = 0.0024; and EPK-i → CV-290, 0.0616, P < 0.0001]. In conclusion, cycleGAN can transform the diverse image characteristics of endoscope models into an AI-trained style to improve the detection performance of AI.

Histological Diagnostic Yield and Clinical Significance of the First Biopsy in Device-Assisted Enteroscopy in Patients with Small Bowel Diseases: A KASID Multicenter Study.

Device-assisted enteroscopy (DAE) enables the direct visualization of small bowel lesions with histological diagnosis; however, few studies have described the diagnostic performance of enteroscopic biopsy. We investigated the diagnostic performance of enteroscopic biopsy. We used a nationwide multicenter enteroscopy database to identify patients who underwent DAE with biopsy for small bowel diseases. The patients were classified into the tumor and non-tumor groups according to the final diagnosis. They were also divided into diagnostic and non-diagnostic groups based on the enteroscopic biopsy results. The clinical significance of the first biopsy and histological diagnostic yield of DAE were analyzed. Among the 112 procedures investigated, 32 (28.9%) were diagnosed with tumors, and 80 (71.7%) were diagnosed with non-tumor diseases. The overall histological diagnostic yield of DAE was 43.7%. The histological diagnostic yield was significantly higher in the tumor than in the non-tumor group (81.2% vs. 28.8%, p < 0.001). The mean number of biopsies was significantly higher in the diagnostic than in the non-diagnostic group (5.6 ± 3.3 vs. 3.7 ± 2.1, p = 0.001). In the diagnostic group, 87.7% of the cases were histologically confirmed at the first biopsy. Therefore, the first biopsy should be performed carefully.

Peroxisomal Stress Response and Inter-Organelle Communication in Cellular Homeostasis and Aging.

Peroxisomes are key regulators of cellular and metabolic homeostasis. These organelles play important roles in redox metabolism, the oxidation of very-long-chain fatty acids (VLCFAs), and the biosynthesis of ether phospholipids. Given the essential role of peroxisomes in cellular homeostasis, peroxisomal dysfunction has been linked to various pathological conditions, tissue functional decline, and aging. In the past few decades, a variety of cellular signaling and metabolic changes have been reported to be associated with defective peroxisomes, suggesting that many cellular processes and functions depend on peroxisomes. Peroxisomes communicate with other subcellular organelles, such as the nucleus, mitochondria, endoplasmic reticulum (ER), and lysosomes. These inter-organelle communications are highly linked to the key mechanisms by which cells surveil defective peroxisomes and mount adaptive responses to protect them from damages. In this review, we highlight the major cellular changes that accompany peroxisomal dysfunction and peroxisomal inter-organelle communication through membrane contact sites, metabolic signaling, and retrograde signaling. We also discuss the age-related decline of peroxisomal protein import and its role in animal aging and age-related diseases. Unlike other organelle stress response pathways, such as the unfolded protein response (UPR) in the ER and mitochondria, the cellular signaling pathways that mediate stress responses to malfunctioning peroxisomes have not been systematically studied and investigated. Here, we coin these signaling pathways as "peroxisomal stress response pathways". Understanding peroxisomal stress response pathways and how peroxisomes communicate with other organelles are important and emerging areas of peroxisome research.

Large-Area Synthesis of Ultrathin, Flexible, and Transparent Conductive Metal-Organic Framework Thin Films via a Microfluidic-Based Solution Shearing Process.

Iminosemiquinone-linker-based conductive metal-organic frameworks (c-MOFs) have attracted much attention as next-generation electronic materials due to their high electrical conductivity combined with high porosity. However, the utility of such c-MOFs in high-performance devices has been limited to date by the lack of high-quality MOF thin-film processing. Herein, a technique known as the microfluidic-assisted solution shearing combined with post-synthetic rapid crystallization (MASS-PRC) process is introduced to generate a high-quality, flexible, and transparent thin-film of Ni3 (hexaiminotriphenylene)2 (Ni3 (HITP)2 ) uniformly over a large-area in a high-throughput manner with thickness controllability down to tens of nanometers. The MASS-PRC process utilizes: 1) a micromixer-embedded blade to simultaneously mix and continuously supply the metal-ligand solution toward the drying front during solution shearing to generate an amorphous thin-film, followed by: 2) immersion in amine solution for rapid directional crystal growth. The as-synthesized c-MOF film has transparency of up to 88.8% and conductivity as high as 37.1 S cm-1 . The high uniformity in conductivity is confirmed over a 3500 mm2 area with an arithmetic mean roughness (Ra ) of 4.78 nm. The flexible thin-film demonstrates the highest level of transparency for Ni3 (HITP)2 and the highest hydrogen sulfide (H2 S) sensing performance (2,085% at 5 ppm) among c-MOFs-based H2 S sensors, enabling wearable gas-sensing applications.

Collagen has a unique SEC24 preference for efficient export from the endoplasmic reticulum.

SEC24 is mainly involved in cargo sorting during COPII vesicle assembly. There are four SEC24 paralogs (A-D) in vertebrates, which are classified into two subgroups (SEC24A/B and SEC24C/D). Pathological mutations in SEC24D cause osteogenesis imperfecta with craniofacial dysplasia in humans. sec24d mutant fish also recapitulate the phenotypes. Consistent with the skeletal phenotypes, the secretion of collagen was severely defective in mutant fish, emphasizing the importance of SEC24D in collagen secretion. However, SEC24D patient-derived fibroblasts show only a mild secretion phenotype, suggesting tissue-specificity in the secretion process. Using Sec24d KO mice and cultured cells, we show that SEC24A and SEC24B also contribute to endoplasmic reticulum (ER) export of procollagen. In contrast, fibronectin 1 requires either SEC24C or SEC24D for ER export. On the basis of our results, we propose that procollagen interacts with multiple SEC24 paralogs for efficient export from the ER, and that this is the basis for tissue-specific phenotypes resulting from SEC24 paralog deficiency.

Predictive Factors for Differentiating Gastrointestinal Stromal Tumors from Leiomyomas Based on Endoscopic Ultrasonography Findings in Patients with Gastric Subepithelial Tumors: A Multicenter Retrospective Study.

BACKGROUND/AIMS: The utility of endoscopic ultrasonography (EUS) for differentiating gastrointestinal stromal tumors (GISTs) and leiomyomas of the stomach is not well known. We aimed to evaluate the ability of EUS for differentiating gastric GISTs and leiomyomas. METHODS: We retrospectively reviewed the medical records of patients with histopathologically proven GISTs (n=274) and leiomyomas (n=87). In two consensus meetings, the inter-observer variability in the EUS image analysis was reduced. Using logistic regression analyses, we selected predictive factors and constructed a predictive model and nomogram for differentiating GISTs from leiomyomas. A receiver operating characteristic (ROC) curve analysis was performed to measure the discrimination performance in the development and internal validation sets. RESULTS: Multivariate analysis identified heterogeneity (odds ratio [OR], 9.48), non-cardia (OR, 19.11), and older age (OR, 1.06) as independent predictors of GISTs. The areas under the ROC curve of the predictive model using age, sex, and four EUS factors (homogeneity, location, anechoic spaces, and dimpling or ulcer) were 0.916 (sensitivity, 0.908; specificity, 0.793) and 0.904 (sensitivity, 0.908; specificity, 0.782) in the development and internal validation sets, respectively. CONCLUSION: The predictive model and nomogram using age, sex and homogeneity, tumor location, presence of anechoic spaces, and presence of dimpling or ulcer on EUS may facilitate differentiation between GISTs and leiomyomas.

Endoscopy within 7 days after detecting high calprotectin levels can be useful for therapeutic decision-making in ulcerative colitis.

ABSTRACT: The aim of this study was to assess the appropriate time interval to identify the association between the fecal calprotectin (FC) test and endoscopic activity, and to evaluate whether the time interval affects the therapeutic plan adjustment in patients with ulcerative colitis (UC).This study included 103 patients who underwent FC tests and endoscopic examinations within the past three months. The FC test results classified cases into three groups as follows: moderate to severe (>200, >250, or >300 µg/g), mild (100-200, 100-250, or 100-300 µg/g), and inactive (<100 µg/g) activity. The Mayo endoscopic subscore was used to determine endoscopic activity. Therapeutic plan adjustment included the addition or increased dosage of anti-inflammatory drugs, steroids, immunomodulators, and biologics.Using the cutoff value for FC of 200 µg/g, the appropriate time interval for dividing the association and non-association between Mayo endoscopic subscore and FC was 7 days (sensitivity, 74.4%; specificity, 50.0%; area under the curve [AUC], 0.6032). When using FC 250 or 300 µg/g, the appropriate time interval was 5.5 days, with a sensitivity of 71.7% and specificity of 49.1 (AUC 0.5862) in FC 250 µg/g, a sensitivity of 69.6%, and a specificity of 47.4 (AUC 0.5549) for FC 300 µg/g. Therapeutic plans changed in 29.1% of patients. In patients with shorter intervals (≤7 days) between the FC test and endoscopy, significant therapeutic plan adjustments were observed in patients with UC (36.5% vs. 17.5%, P = .047).Although the need for endoscopy within 7 days after detecting high FC (≥ 200 µg/g) was not statistically supported, endoscopy within a shorter interval (≤7 days) in UC patients with high FC can help determine the therapeutic plan.

Large-area synthesis of nanoscopic catalyst-decorated conductive MOF film using microfluidic-based solution shearing.

Conductive metal-organic framework (C-MOF) thin-films have a wide variety of potential applications in the field of electronics, sensors, and energy devices. The immobilization of various functional species within the pores of C-MOFs can further improve the performance and extend the potential applications of C-MOFs thin films. However, developing facile and scalable synthesis of high quality ultra-thin C-MOFs while simultaneously immobilizing functional species within the MOF pores remains challenging. Here, we develop microfluidic channel-embedded solution-shearing (MiCS) for ultra-fast (≤5 mm/s) and large-area synthesis of high quality nanocatalyst-embedded C-MOF thin films with thickness controllability down to tens of nanometers. The MiCS method synthesizes nanoscopic catalyst-embedded C-MOF particles within the microfluidic channels, and simultaneously grows catalyst-embedded C-MOF thin-film uniformly over a large area using solution shearing. The thin film displays high nitrogen dioxide (NO2) sensing properties at room temperature in air amongst two-dimensional materials, owing to the high surface area and porosity of the ultra-thin C-MOFs, and the catalytic activity of the nanoscopic catalysts embedded in the C-MOFs. Therefore, our method, i.e. MiCS, can provide an efficient way to fabricate highly active and conductive porous materials for various applications.

Craniofacial Diseases Caused by Defects in Intracellular Trafficking.

Cells use membrane-bound carriers to transport cargo molecules like membrane proteins and soluble proteins, to their destinations. Many signaling receptors and ligands are synthesized in the endoplasmic reticulum and are transported to their destinations through intracellular trafficking pathways. Some of the signaling molecules play a critical role in craniofacial morphogenesis. Not surprisingly, variants in the genes encoding intracellular trafficking machinery can cause craniofacial diseases. Despite the fundamental importance of the trafficking pathways in craniofacial morphogenesis, relatively less emphasis is placed on this topic, thus far. Here, we describe craniofacial diseases caused by lesions in the intracellular trafficking machinery and possible treatment strategies for such diseases.

Clinical Outcomes between P1 and P0 Lesions for Obscure Gastrointestinal Bleeding with Negative Computed Tomography and Capsule Endoscopy.

BACKGROUND: A simple classification for the relevance of lesions (P0, P1, and P2; no bleeding potential, less likely to bleed, and more likely to bleed, respectively) based on capsule endoscopy (CE) findings has been used. This study aimed at investigating rebleeding rates and predictive factors of P0 and P1 lesions after obtaining negative findings in both, CE and computed tomography (CT), for patients with obscure gastrointestinal bleeding (OGIB). METHODS: Among 193 patients resulted in negative CE findings defined as P0 or P1 lesions, 84 patients with negative results on CT images were enrolled in this study. The rebleeding rates and predictive factors were assessed in the P0 and P1 groups. RESULTS: Overall rebleeding rate in patients with negative CT and CE was 17.9%; 18.4% in the P0 group; 17.4% in the P1 group within a median follow-up duration of 18.5 months. In the P0 and P1 groups, the cumulative rebleeding rates were 9.2%, 25.4%, and 25.4%, and 6.9%, 11.8%, and 18.6% at 12, 24, and 60 months, respectively (p = 0.97). There were no independent rebleeding associated factors in the P0 group, whereas Charlson comorbidity index (CCI) (hazard ratio (HR) = 2.019, 95% confidence interval (CI): 1.158-3.519, p = 0.013), and initial low hemoglobin (Hb) level (<8 g/dL) (HR = 15.085, 95% CI: 1.182-192.514, p = 0.037) were independent predictive factors responsible for rebleeding in the P1 group. CONCLUSIONS: Despite having negative findings on CT and CE, patients with OGIB have a significant potential rebleeding risk. Although there was no significant difference in rebleeding rates between the P0 and P1 groups on CE, the P1 group, with CCI or low initial Hb level, should be cautiously observed after the first bleeding episode.

Characteristics of symptomatic belching in patients with belching disorder and patients who exhibit gastroesophageal reflux disease with belching.

BACKGROUND/AIMS: Belching disorder (BD) is clinically distinct from gastroesophageal reflux disease (GERD) with belching. Supragastric belching (SGB) is closely associated with reflux episodes. This study investigates belch characteristics in association with reflux, compared between patients with BD and those who had GERD with belching. METHODS: Impedance pH monitoring data from 10 patients with BD and 10 patients with GERD who exhibited belching were retrospectively analyzed. Belches were considered "isolated" or "reflux-related" and acidic/non-acidic. Belch characteristics were compared between patients with BD and those with GERD. RESULTS: Symptomatic belches were more frequent in patients with BD than in patients with GERD (median, 160.5 vs 56.0, P < 0.05). SGB was the most common type in both groups; common subtypes comprised "isolated" in patients with BD and "isolated during the reflux period" in patients with GERD. Reflux-related SGB was more common in patients with GERD than in BD (78.3% vs 45.2%, P < 0.005). Both "preceding belching" including the reflux period and acidic SGB were more common in patients with GERD than in BD (31.8% vs 8.6% and 38.1% vs 8.9%, both P < 0.05). Supragastric belch number positively correlated with all reflux episodes in patients with GERD (adjusted R2 = 0.572, P = 0.007). CONCLUSIONS: BD is characterized by more belching, compared to GERD. SGB is more frequently associated with reflux in GERD than in BD; acidity may be related to GERD. In BD, SGB is typically non-acidic and unrelated to reflux. Distinct SGB characteristics may reflect different pathogenic mechanisms of reflux and associated symptoms.

Enteroscopy in Crohn's Disease: Are There Any Changes in Role or Outcomes Over Time? A KASID Multicenter Study.

Background/Aims: Although balloon-assisted enteroscopy (BAE) enables endoscopic visualization of small bowel (SB) involvement in Crohn's disease (CD), there is no data on the changes in outcomes over time. We therefore investigated the changes in BAE use on CD patients over different time periods in terms of its role and clinical outcomes. Methods: We used a multicenter enteroscopy database to identify CD patients with SB involvement who underwent BAE (131 procedures, 116 patients). We compared BAE-related factors and outcomes between the first period (70 procedures, 60 patients) and the second period (61 procedures, 56 patients). The specific cutoff point for dividing the two periods was 2007, when BAE guidelines were introduced. Results: Initial diagnosis of SB involvement in CD was the most common indication for BAE during each period (50.0% vs 31.1%, p=0.034). The largest change was in the number of BAE uses for stricture evaluation and/or treatment, which increased significantly in the latter period (2.9% vs 21.3%, p=0.002). The diagnostic yield in patients with suspected CD was 90.7% in the first period and 95.0% in the second (p=0.695). More endoscopic interventions were performed in the second period than in the first (5.1% vs 17.6%, p=0.041). Enteroscopic success rates were high throughout (100% in the first period vs 80.0% in the second period, p>0.999). In the first and second periods, therapeutic plans were adjusted in 62.7% and 61.4% of patients, respectively. Conclusions: The overall clinical indications, outcomes, and effectiveness of BAE were constant over time in CD patients with SB involvement, with the exception that the frequency of enteroscopic intervention increased remarkably.

The role of platelet to lymphocyte ratio and neutrophil to lymphocyte ratio in ulcerative colitis.

BACKGROUND/AIMS: Neutrophil to lymphocyte ratio (NLR) and platelet to lymphocyte ratio (PLR) can serve as biomarkers for diagnosing and assessing disease activity in ulcerative colitis (UC). We investigated their clinical significance in UC. METHODS: We analyzed 48 patients with UC who underwent measurement of fecal calprotectin (FC) and endoscopy and 96 age- and sex-matched healthy controls. NLR and PLR were compared between the patients and healthy controls. The endoscopic activity was divided into 2 groups: group 1 (mild to moderate inflammation) and group 2 (severe inflammation) according to the Mayo endoscopic subscore in UC. RESULTS: To diagnose UC, the optimal cutoff of NLR and PLR was 2.26 (sensitivity 54.2%; specificity 90.6%; positive likelihood ratio 5.778, 95% confidence interval [CI] 2.944-11.339; area under the curve [AUC] 0.774, 95% CI, 0.690-0.859) and 179.8 (sensitivity 35.4%; specificity 90.6%; positive likelihood ratio 3.778, 95% CI 1.821-7.838; AUC 0.654, 95% CI 0.556-0.753), respectively. The optimal cutoff to differentiate group 1 and group 2 was 3.44, 175.9, and 453 µg/g for NLR, PLR, and FC, respectively (sensitivity, 63.6% vs. 90.9% vs. 81.8%; specificity, 81.1% vs. 78.4% vs. 73.0%; positive likelihood ratio, 3.364 vs. 4.205 vs. 3.027; AUC, 0.714 vs. 0.897 vs. 0.813). PLR had the highest AUC and positive likelihood ratio. CONCLUSIONS: NLR and PLR help differentiate patients with UC from healthy controls. NLR, PLR, and FC indicate endoscopic activity and may reflect intestinal mucosal conditions.

Impaired peroxisomal import in Drosophila oenocytes causes cardiac dysfunction by inducing upd3 as a peroxikine.

Aging is characterized by a chronic, low-grade inflammation, which is a major risk factor for cardiovascular diseases. It remains poorly understood whether pro-inflammatory factors released from non-cardiac tissues contribute to the non-autonomous regulation of age-related cardiac dysfunction. Here, we report that age-dependent induction of cytokine unpaired 3 (upd3) in Drosophila oenocytes (hepatocyte-like cells) is the primary non-autonomous mechanism for cardiac aging. We show that upd3 is significantly up-regulated in aged oenocytes. Oenocyte-specific knockdown of upd3 is sufficient to block aging-induced cardiac arrhythmia. We further show that the age-dependent induction of upd3 is triggered by impaired peroxisomal import and elevated JNK signaling in aged oenocytes. We term hormonal factors induced by peroxisome dysfunction as peroxikines. Intriguingly, oenocyte-specific overexpression of Pex5, the key peroxisomal import receptor, blocks age-related upd3 induction and alleviates cardiac arrhythmicity. Thus, our studies identify an important role of hepatocyte-specific peroxisomal import in mediating non-autonomous regulation of cardiac aging.

Spontaneous Internal Anal Sphincter Relaxation During High-resolution Anorectal Manometry Is Associated With Peripheral Neuropathy and Higher Charlson Comorbidity Scores in Patients With Defecatory Disorders.

Background/Aims: We aimed to evaluate associations between comorbidities, peripheral neuropathy, and spontaneous internal anal sphincter relaxation (SAR) in patients with defecatory disorders. Methods: A patient was considered to exhibit SAR during high-resolution anorectal manometry (HR-ARM) when the nadir pressure is < 15 mmHg and the time from onset to relaxation was ≥ 15 seconds in the resting pressure frame. A case-control study was performed using HR-ARM data collected from 880 patients from January 2010 to May 2015. We identified 23 cases with SAR (median age 75 years; 15 females; 12 fecal incontinence and 11 constipation). We compared HR-ARM values, Charlson index comorbidity scores, neuropathy, and the prevalence of diseases that potentially cause neuropathy between controls and SAR patients. Each SAR case was compared to 3 controls. Controls were selected to match the age, gender, and examination year of each SAR case. Results: Compared to controls (26.1%), SAR patients (52.2%) exhibited a significantly higher frequency of fecal incontinence. SAR patients also had higher Charlson index scores (5 vs 4, P = 0.028). Nine of 23 SAR patients (39.1%) exhibited peripheral neuropathy- this frequency was higher than that for the control group (11.6%; P = 0.003). Diseases that potentially cause neuropathy were observed in 17 of 23 SAR cases and 32 of 69 controls (P = 0.022). Conclusions: SAR develops in patients with constipation and fecal incontinence but is more common in patients with fecal incontinence. Our controlled observational study implies that SAR is associated with peripheral neuropathy and more severe comorbidities.