The let-7 miRNAwas one of the first miRNAs discovered in the nematode, Caenorhabditis elegans, and its biological functions show a high level of evolutionary conservation from the nematode to the ...human. Unlike in C. elegans, higher animals have multiple isoforms of let-7 miRNAs; these isoforms share a consensus sequence called the ＇seed sequence＇ and these isoforms are categorized into let-7 miRNA family. The expression of let-7 family is required for developmental timing and tumor suppressor function, but must be suppressed for the self-renewal of stem cells. Therefore, let-7 miRNA biogenesis must be carefully controlled. To generate a let-7 miRNA, a primary transcript is produced by RNA polymerase Ⅱ and then subsequently processed by Drosha/DGCR8, TUTase, and Dicer. Because dysregulation of let-7 processing is deleterious, biogenesis of let-7 is tightly regulated by cellular factors, such as the RNA binding proteins, LIN28A/B and DIS3L2. In this review, we discuss the biological functions and biogenesis of let-7 miRNAs, focusing on the molecular mechanisms of regulation of let-7 biogenesis in ver- tebrates, such as the mouse and the human.
Objective
Systemic lupus erythematosus (SLE) is a highly heritable complex disorder with heterogeneous clinical manifestations. In this study, we aimed to identify the genetic risk load using ...clinical and serological manifestations in SLE patients.
Methods
We genotyped a total of 1,655 Korean patients with SLE (n = 1,243 as a discovery set and n = 412 as a replication set) using a customized genome‐wide single‐nucleotide polymorphism (SNP) array, KoreanChip. A weighted genetic risk score (wGRS) for an individual was calculated from 112 well‐validated non‐HLA SNPs and HLA haplotypes of SLE‐risk loci. We analyzed associations between individual wGRS and clinical SLE subphenotypes and autoantibodies using multivariable linear or logistic regression adjusted by onset age, sex, and disease duration.
Results
Childhood‐onset SLE (<16 years) conferred the highest genetic risk compared with adult‐onset (16–50 years) or late‐onset (>50 years) SLE (P = 6.8 × 10−6). High wGRS significantly increased associations with SLE manifestations, regardless of onset age, sex, and disease duration. Individual wGRS significantly correlated positively with more clinical American College of Rheumatology criteria (β = 0.143, P = 1.8 × 10−6). Subphenotype analysis revealed significant associations between the highest and lowest wGRS quartile with risk of renal disorder (hazard ratio HR 1.74, P = 2.2 × 10−8) and anti–Sm antibody production (HR 1.85, P = 2.8 × 10−5). Higher wGRS markedly modulated the pathogenesis of proliferative and membranous lupus nephritis class III or IV (HR 1.98, P = 1.6 × 10−5) and class V (HR 2.79, P = 1.0 × 10−3), but especially lupus nephritis class V in anti–Sm‐positive SLE (area under the curve 0.68, P = 1.8 × 10−4).
Conclusion
Patients with SLE and high wGRS tended to have earlier age of SLE onset, higher anti–Sm antibody positivity, and more diverse clinical phenotypes. Genetic profiling may predict high risk for lupus nephritis and a diverse clinical course in SLE patients.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Micro‐solid oxide fuel cells (μ‐SOFCs) are fabricated on nanoporous anodic aluminum oxide (AAO) templates with a cell structure composed of a 600‐nm‐thick AAO free‐standing membrane embedded on a Si ...substrate, sputter‐deposited Pt electrodes (cathode and anode) and an yttria‐stabilized zirconia (YSZ) electrolyte deposited by pulsed laser deposition (PLD). Initially, the open circuit voltages (OCVs) of the AAO‐supported μ‐SOFCs are in the range of 0.05 V to 0.78 V, which is much lower than the ideal value, depending on the average pore size of the AAO template and the thickness of the YSZ electrolyte. Transmission electron microscopy (TEM) analysis reveals the formation of pinholes in the electrolyte layer that originate from the porous nature of the underlying AAO membrane. In order to clog these pinholes, a 20‐nm thick Al2O3 layer is deposited by atomic layer deposition (ALD) on top of the 300‐nm thick YSZ layer and another 600‐nm thick YSZ layer is deposited after removing the top intermittent Al2O3 layer. Fuel cell devices fabricated in this way manifest OCVs of 1.02 V, and a maximum power density of 350 mW cm−2 at 500 °C.
A novel fabrication method for high‐performance micro‐solid oxide fuel cells (μ‐SOFCs) on nanoporous anodic aluminum oxide supports is reported. Gas‐tight electrolyte layers are obtained by microstructure modification using atomic layer deposition (ALD). This type of μ‐SOFC shows a maximum power density of 350 mW cm−2 at 500 °C
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Genome-wide association studies (GWAS) in rheumatoid arthritis (RA) have discovered over 100 RA loci, explaining patient-relevant RA pathogenesis but showing a large fraction of missing heritability. ...As a continuous effort, we conducted GWAS in a large Korean RA case-control population.
We newly generated genome-wide variant data in two independent Korean cohorts comprising 4068 RA cases and 36 487 controls, followed by a whole-genome imputation and a meta-analysis of the disease association results in the two cohorts. By integrating publicly available omics data with the GWAS results, a series of bioinformatic analyses were conducted to prioritise the RA-risk genes in RA loci and to dissect biological mechanisms underlying disease associations.
We identified six new RA-risk loci (
,
,
,
,
and
) with p
<5×10
and consistent disease effect sizes in the two cohorts. A total of 122 genes were prioritised from the 6 novel and 13 replicated RA loci based on physical distance, regulatory variants and chromatin interaction. Bioinformatics analyses highlighted potentially RA-relevant tissues (including immune tissues, lung and small intestine) with tissue-specific expression of RA-associated genes and suggested the immune-related gene sets (such as CD40 pathway, IL-21-mediated pathway and citrullination) and the risk-allele sharing with other diseases.
This study identified six new RA-associated loci that contributed to better understanding of the genetic aetiology and biology in RA.
Introduction
Stellaria alsine
has traditionally been used as both a famine relief food and an alternative medicine in East Asia. Modern pharmacological studies have revealed that
S. alsine
has ...various biological effects such as anticancer, anti-hepatoma, anti-inflammatory, and antioxidative effects. However, the anti-inflammatory properties of chemical constituents derived from this plant have not been studied well.
Objectives
To identify potential therapeutic candidate for treating inflammatory diseases such as inflammatory bowel disease (IBD).
Methods
The distribution of chemical compounds was investigated by Global Natural Product Social (GNPS)-based molecular networking (MN) analysis using UPLC-Orbitrap tandem mass spectrometry. The anti-inflammatory and antioxidative effects of
S. alsine
extracts and fractions were evaluated by measuring interleukin (IL)-8 and reactive oxygen species (ROS) productions.
Results
The active EA layer of
S. alsine
showed the highest percentage of major compounds by feature-based molecular networking. The top candidate structures of EA fraction were rapidly annotated as flavone
C
- or
O
-glycosides via an advanced analysis tool, Network Annotation Propagation (NAP). With the GNPS molecular networking-guided isolation strategy, a new
C
-glycosyl flavone rotamer (
1
) was isolated. The structures of the major (
1a
) and minor (
1b
) rotational isomers were determined by extensive NMR analysis and MS/MS fragmentation. Finally, the anti-inflammatory activity of
1
was predicted by molecular docking simulations with IL-8 protein.
Conclusion
These results suggested that the compound
1
is a potential therapeutic candidate for inflammatory bowel disease (IBD).
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
We demonstrate that wafer-scale, transferable, and transparent thin-film catalysts based on MoS sub(2), which consists of cheap and earth abundant elements, can provide a low onset potential of 1 mA ...cm super(-2) at 0.17 V versusa reversible hydrogen electrode and the high photocurrent density of 24.6 mA cm super(-2) at 0 V for a p-type Si photocathode. c-Domains with vertically stacked (100) planes in the transferable 2H-MoS sub(2) thin films, which are grown viaa thermolysis method, act as active sites for the hydrogen evolution reaction, and photogenerated electrons are efficiently transported through the n-MoS sub(2)/p-Si heterojunction.
(Maesil) is used in health foods and alternative medicine in Korea. In the present study, the anti-inflammatory and antioxidant effects of phenolics from
seed extracts were examined. First, the ...biological activities of various
extracts were evaluated, and the profiles of their chemical compounds were investigated by Global Natural Products Social (GNPS)-molecular networking. Among these extracts, fermented Maesil seed extract (FMSE) showed potent anti-inflammatory and antioxidant activity, and demonstrated the presence of phenolic clusters in GNPS-based studies. Thus, the chemical constituents of this extract were further investigated. Subsequently, the chemical composition of the active CH
Cl
fraction of FMSE was explored using an advanced GNPS analysis tool, MolNetEnhancer. In addition, the molecular structure of compound
from the CH
Cl
fraction was similarly predicted with Network Annotation Propagation (NAP). Finally, the anti-inflammatory and antioxidant effects of compound
were confirmed by lipopolysaccharide (LPS)-induced nitric oxide production and DPPH assay. Western blot analysis revealed that compound
downregulated the expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) proteins. The molecular docking simulation additionally confirmed significant interactions of
with iNOS and COX-2 proteins. Our findings suggested that an integrated GNPS-based approach could prioritize samples in the early fractionation process and improve the accuracy of target compound prediction.
Background and Aim
Endoscopic post‐papillectomy bleeding occurs in 3% to 20% of the cases, and delayed bleeding is also problematic. However, there is no consensus on how to reduce delayed ...post‐papillectomy bleeding. The aim of this study was to evaluate the efficacy of prophylactic argon plasma coagulation (APC) to minimize delayed bleeding and reduce the persistence of residual tumors after endoscopic papillectomy.
Methods
In a prospective pilot study of patients with benign ampullary tumors, the prophylactic APC group underwent APC at the resection margin following a conventional snaring papillectomy. Then, 24 h later after the papillectomy, all patients underwent a follow‐up duodenoscopy to identify post‐papillectomy bleeding and were followed up until 12 months. The main outcomes were the delayed (≥24 h) post‐papillectomy bleeding rate and the tumor persistence rate.
Results
The delayed post‐papillectomy bleeding rate was 30.8% (8/26) in the prophylactic APC group and 21.4% (6/28) in the non‐APC group (P = 0.434). The post‐procedure pancreatitis rates were 23.1% (6/26) and 35.7% (10/28), respectively (P = 0.310). The rate of tumor persistence did not differ between the two groups at 1 month (12.5% vs 7.4%, P = 0.656), 3 months (4.2% vs 3.7%, P = 1.00), 6 months (8.3% vs 3.7%, P = 0.595), and 12 months (0% vs 3.7%, P = 1.00). There were no procedure‐related mortalities or serious complications.
Conclusion
Prophylactic APC may not be effective in reducing delayed post‐papillectomy bleeding or remnant tumor ablation immediately after conventional papillectomy (Clinical trial registration—cris.nih.go.kr; KCT0001955).
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Successful biliary cannulation is a prerequisite and important component of endoscopic retrograde cholangiopancreatography, but conventional cannulation methods (CCMs) have a postendoscopic ...retrograde cholangiopancreatography pancreatitis (PEP) rate of 14.1% in patients at high risk for PEP. The aim of this study was to evaluate the effectiveness and safety of needle-knife fistulotomy (NKF), compared with a CCM, when used for primary biliary access in patients at high risk for developing PEP.
A total of 207 patients with one or more risk factors for PEP were prospectively enrolled. The patients were randomly allocated to one of 2 groups according to the primary biliary cannulation technique (NKF or CCM). We compared biliary cannulation success rates, cannulation and procedure times, and the incidence of adverse events, including PEP, between the groups.
The mean number of PEP risk factors was similar between the groups (NKF, 2.2 ± 1.0; CCM, 2.2 ± 0.9). PEP occurred in 8 patients in the CCM group and in no patients in the NKF group (9.2% vs 0%, P < 0.001). The rates of other adverse events did not differ between the groups. The biliary cannulation success rate was high in the NKF group, but relatively low in the CCM group, possibly because of the stringent failure criteria aimed at reducing PEP. However, the mean cannulation and total procedural times were longer in the NKF group than in the CCM group.
NKF is an effective and safe procedure to gain primary biliary access in patients at high risk for developing PEP. ClinicalTrials.gov, NCT02916199.
This study was conducted to evaluate the clinical feasibility of nab-paclitaxel plus gemcitabine-cisplatin triplet chemotherapy in patients with locally advanced cholangiocarcinoma in real-world ...practice.
We retrospectively reviewed patients with locally advanced cholangiocarcinoma who were treated with nab-paclitaxel plus gemcitabine-cisplatin between October 2019 and August 2021 at a single institution. The initial diagnosis of cholangiocarcinoma was histologically confirmed.
One hundred twenty-nine patients were included in this study. Among the patients with a measurable lesion (57.4%), the objective response rate and disease control were 60.8% and 91.9%, respectively. Seventy-seven patients (59.7%) were determined as resectable after triplet chemotherapy, but 73 (56.6%) underwent subsequent curative surgery. The major postoperative complication rate was 15.1%, and there were 2 postoperative mortalities (2.7%). There were 6 complete remission cases (8.2%) in the final pathology. The R0 resection was achieved in 67 patients (91.8%). Despite the initial locally advanced cholangiocarcinoma, a pathologic T stage of less than T2 was reported in 67 patients (91.8%). Fifty-two patients (71.2%) had no lymph node metastasis. Patients who underwent surgery after triplet chemotherapy had significantly higher 12-month overall survival (95.9% vs 76.8%; P < .001) than those treated with chemotherapy alone.
Nab-paclitaxel plus gemcitabine-cisplatin chemotherapy demonstrated a down-staging effect through a high response rate, indicating that this triplet chemotherapy is feasible as induction therapy in patients with locally advanced cholangiocarcinoma.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
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