Search

Abstract Perianal fistulizing Crohn’s disease (CD) is a severe gastrointestinal disorder causing extensive mucosal damage with limited treatment options. Severe manifestations of the disease appear at higher rates in non-Europeans but the genetic and cellular mechanisms driving the disease phenotypes remain poorly understood. Herein, we tested whether pathologic determinants in the epithelial stem cell compartment could be detected at the transcript level in rectal organoids derived from a diverse patient population. Rectal organoid and mucosal cells from endoscopic biopsies of each patient having perianal fistulizing CD or no disease controls were prepared for and sequenced at the single cell level. After cell type annotations based on expressed marker genes, samples were analyzed by principal components, for differential transcript expression, cell type proportions, and pathway enrichment. After QC, we produced 77,044 rectal organoid cells (n = 13 patients; 8 CD, 5 controls) with high quality sequences that identified 10 distinct epithelial subtypes, that we compared to 141,367 mucosal epithelial cells (n = 29 patients; 18 CD, 11 controls). Consistent with mucosal epithelial cells, rectal organoids prominently displayed disease signatures represented by the stem and transit amplifying regions of the rectal crypt, including alterations in transcriptional signatures of metabolic, epigenetic, and proliferating pathways. Organoids also retained their gender- and ancestral-specific gene expression signatures. However, they lacked many of the inflammatory signatures observed in epithelial cells from diseased mucosa. Perianal CD patient derived rectal organoids reflect gene expression signatures related to disease, gender, and ancestry, suggesting they harbor inherent properties amenable to further patient-specific, disease-related experimentation.

Abstract Background The prostaglandin receptor PTGER4 facilitates homeostasis in the gut. Previous reports indicate that goblet cells, marked by SPINK4 expression, might be affected by PTGER4 activity. Current evidence suggests that prostaglandin E2 (PGE2) produced by mesenchymal stromal cells (MSC) stimulates PTGER4 in epithelial cells during inflammatory conditions. Here, we investigate the subcellular mechanisms and mRNA levels downstream of PTGER4 activity in epithelial cells. Methods Mucosal cells, organoids, and MSC were obtained from patient biopsies harvested by endoscopy. Using independent and co-cultures, we manipulated the activity of PTGER4, the downstream enzymes, and mRNA levels, by using PGE2, in combination with chemical inhibitors, L-161982, H89, LB100, DAPT, LMK-235, or with butyrate. Immunofluorescence, single cell sequencing, RNAscope, ELISA, real time PCR, and Western blotting were used to examine these samples. Results SPINK4 mRNA levels were increased in organoids by co-culture with MSC or exogenous stimulation with PGE2 that could be blocked by L-161982 or LMK-235, PTGER4 or HDAC4 inhibitors, respectively. Expression of PTGER4 was co-localized with JAM-A in the basolateral surfaces in rectal epithelial cells grown as organoids. PGE2 treatment of rectal organoids decreased HDAC4, 5, and 7 phosphorylation levels that could be blocked by L-161982 treatment. Butyrate treatment, or addition of L-161982, increased the phosphorylated levels of HDAC4, 5, and 7. Conclusions These findings suggest a mechanism during mucosal injury whereby MSC production of PGE2 increases HDAC4, 5, and 7 activities in epithelial cells by upregulating PTGER4 signaling, ultimately increasing SPINK4 mRNA levels and extracellular release of SPINK4.

A large number of species in the genus Colletotrichum have been reported as causal agents of anthracnose on crops and wild plants in Korea. Many Colletotrichum isolates from the country preserved in the Korean Agricultural Culture Collection (KACC) were previously identified based on host plants and morphological characteristics, and it may lead to species misidentification. Thus, accurate fungal species identification using multi-locus sequence analyses is essential for understanding disease epidemiology and disease management strategies. In this study, combined DNA sequence analyses of internal transcribed spacer, gapdh, chs-1, his3, act, tub2, and gs were applied to re-identify 27 Colletotrichum isolates in KACC. The phylogenetic analyses showed that the isolates resulted in 11 known species, they belong to the C. dematium species complex (C. hemerocallidis, C. jinshuiense, and C. spinaciae), the C. magnum complex (C. kaifengense and C. cf. ovatense), the C. orchidearum complex (C. cattleyicola, C. plurivorum, C. reniforme, and C. sojae) and the C. orbiculare complex (C. malvarum and C. orbiculare). Of them, C. cattleyicola, C. hemerocallidis, C. kaifengense, and C. reniforme were unrecorded species in Korea. In the view of host-fungus combinations, 10 combinations are newly reported in the world and 12 are new reports in Korea, although their pathogenicity on the host was not confirmed.

Abstract Background End-stage renal disease (ESRD) poses a significant burden globally and in India. However, access to treatment remains limited due to resource and cost constraints. This study aimed to evaluate the health-related quality of life (HRQoL) and economic burden among haemodialysis patients. Methods A descriptive cross-sectional study using European Quality of life, EQ-5D-5L, to measure health-related quality of life across 5 domains, i.e. mobility, self-care, usual activities, pain/discomfort and anxiety/depression, was administered, across three settings—government dialysis centre, private dialysis centre and charity based dialysis centre. The health utility values were also calculated. Also, the costs incurred in dialysis were done. Results The mean (± SD) age of the participants was 55 (± 11) years, the majority of the participants were male (n = 61), 80% (n = 64) of the participants were employed before and 40% of them had lost a job, due to the morbidity of the disease. Upon analyzing the EQ-5D-5L data, it is inferred that all five domains were the same across all three setups. The direct cost incurred on the haemodialysis ranged from INR.600 to INR.3500 per month, and the indirect cost ranged fromINR.50 to INR. 3000, which is borne by the participants, in about 70% of the cases. Chief Minister Health Insurance Scheme was found to be extremely useful, wherein only 30% (n = 25) of the study participants (n=81) were insured beneficiaries. Conclusion HRQoL was moderately impaired, and treatment posed substantial financial hardship among hemodialysis patients. Expanding access to decentralized and community-based care models could help address the challenges of regular treatment and lost productivity.

The section Aspergillus includes xerophilic fungi that are economically significant and broadly distributed in natural settings as well as human habitats and are recognized for their sustenance on substrates with low water activity. Accurate identification of fungal species is essential for any reliable advances in mycological research. In this study, 108 strains from the section Aspergillus, originating from Korea and conserved at the Korean Agricultural Culture Collection, were subjected to re-identification using a combined dataset that included partial sequences of β-tubulin (BenA), Calmodulin (CaM), and RNA polymerase II second largest subunit (RPB2) genes, along with their morphological characteristics. We confirmed the presence of 12 species among the 108 strains originally isolated from Korea. Of them, nine species have been formerly reported in Korea (Aspergillus chevalieri, Aspergillus cibarius, Aspergillus cumulatus, Aspergillus glaucus, Aspergillus montevidensis, Aspergillus proliferans, Aspergillus pseudoglaucus, Aspergillus ruber, and Aspergillus tonophilus), and 3 species (Aspergillus aurantiacoflavus, Aspergillus intermedius, and Aspergillus niveoglaucus) were found to be previously unreported to be isolated from Korea. Here, the detailed characteristic features of these three unexplored species are presented, including specific morphological traits, genetic variations, and ecological niches in Korea.

Underwater Wireless Sensor Networks (UWSNs) have recently established themselves as an extremely interesting area of research thanks to the mysterious qualities of the ocean. The UWSN consists of sensor nodes and vehicles working to collect data and complete tasks. The battery capacity of sensor nodes is quite limited, which means that the UWSN network needs to be as efficient as it can possibly be. It is difficult to connect with or update a communication that is taking place underwater due to the high latency in propagation, the dynamic nature of the network, and the likelihood of introducing errors. This makes it difficult to communicate with or update a communication. Cluster-based underwater wireless sensor networks (CB-UWSNs) are proposed in this article. These networks would be deployed via Superframe and Telnet applications. In addition, routing protocols, such as Ad hoc On-demand Distance Vector (AODV), Fisheye State Routing (FSR), Location-Aided Routing 1 (LAR1), Optimized Link State Routing Protocol (OLSR), and Source Tree Adaptive Routing-Least Overhead Routing Approach (STAR-LORA), were evaluated based on the criteria of their energy consumption in a range of various modes of operation with QualNet Simulator using Telnet and Superframe applications. STAR-LORA surpasses the AODV, LAR1, OLSR, and FSR routing protocols in the evaluation reports simulations, with a Receive Energy of 0.1 mWh in a Telnet deployment and 0.021 mWh in a Superframe deployment. The Telnet and Superframe deployments consume 0.05 mWh transmit power, but the Superframe deployment only needs 0.009 mWh. As a result, the simulation results show that the STAR-LORA routing protocol outperforms the alternatives.

The Nilgiri large burrowing spider, Haploclastus nilgirinus Pocock, 1899, an endemic tarantula in the Nilgiris Region of India, is critical for conservation yet poorly understood in terms of its ecology and habitat. This study addresses this gap by examining the nesting habits, tree-hole dynamics, and prey diversity of the species in Coonoor, The Nilgiris, specifically within tea plantations and fruit orchards. Observations focused on seven pear trees serving as nesting sites, with detailed measurements of nesting holes, including outer and inner circumference, depth, trunk base, ground-based height (gbh), and height from the ground. Data were collected over four consecutive months, both morning and evening. Insect diversity in the orchard was also assessed through counts and diversity indices, revealing variability among trees. The seventh tree had the highest spider population, with 13 spiders in 10 nests. Insect orders such as Blattodea, Orthoptera, Diptera, Hemiptera, and Lepidoptera were most prevalent around the seventh tree’s nests. Across all trees, a total of 25 spiders in 21 nests were documented, with variations in hole size and other tree measurements. This research provides crucial insights into the nesting habits, tree-hole dynamics, and prey diversity of this species, informing conservation efforts for this vulnerable species. As H. nilgirinus faces threats from habitat destruction, climate change, and illegal trade, understanding its ecological needs is vital for developing effective conservation strategies and sustaining ecosystem health.