Strength characteristics of different stress spaces of red sandstone under loading and unloading tests.

Red sandstone tests were conducted on the rock mechanics test system to clarify the strength and failure characteristics of red sandstone under triaxial loading and different unloading confining pressure rates. Strength change rules of the red sandstone in various stress spaces were analyzed. Results show that a large initial confining pressure indicates a long yield section and large axial strain. A small unloading confining pressure rate indicates a long yield section and large axial strain at failure under the identical initial confining pressure. The confining pressure reduction increases with the unloading confining pressure rate increasing when the red sandstone fails. The stress path of unloading confining pressure weakens the red sandstone cohesion and strengthens its internal friction angle. The general octahedral shear stress formula for judging whether the red sandstone fails under loading and different unloading rates was acquired on the basis of the octahedral shear stress characteristics of the red sandstone. In addition, a 3D empirical criterion for evaluating the red sandstone strength was constructed through the deviator plane function of Eekelen and the strength envelope curve on the meridian plane. A great initial confining pressure indicates serious internal damage of the red sandstone at failure under the identical unloading rate of confining pressure. A low unloading rate of confining pressure indicates internal serious damage of the red sandstone at failure when the initial confining pressure is the same. The analysis of macroscopic failure characteristics revealed that the stress path significantly influences the failure mechanism of the red sandstone. The results are instructive for determining the stability of underground engineering of the red sandstone.

Role of long non-coding RNA in inflammatory bowel disease.

Inflammatory bowel disease (IBD) is a group of recurrent chronic inflammatory diseases, including Crohn's disease (CD) and ulcerative colitis (UC). Although IBD has been extensively studied for decades, its cause and pathogenesis remain unclear. Existing research suggests that IBD may be the result of an interaction between genetic factors, environmental factors and the gut microbiome. IBD is closely related to non-coding RNAs (ncRNAs). NcRNAs are composed of microRNA(miRNA), long non-coding RNA(lnc RNA) and circular RNA(circ RNA). Compared with miRNA, the role of lnc RNA in IBD has been little studied. Lnc RNA is an RNA molecule that regulates gene expression and regulates a variety of molecular pathways involved in the pathbiology of IBD. Targeting IBD-associated lnc RNAs may promote personalized treatment of IBD and have therapeutic value for IBD patients. Therefore, this review summarized the effects of lnc RNA on the intestinal epithelial barrier, inflammatory response and immune homeostasis in IBD, and summarized the potential of lnc RNA as a biomarker of IBD and as a predictor of therapeutic response to IBD in the future.

Effects of biogas slurry on hydrothermal carbonization of digestate: Synergistic valorization of hydrochars and aqueous phase.

In this study, livestock manure digestate (LMD) was used as feedstock for hydrothermal carbonization (HTC) at different temperature (180-260 °C) and residence time (0-4 h). Nutrient flow and distribution during the HTC process were evaluated by comparing the effects of livestock manure biogas slurry (LBS) and ultrapure water (UW) to determine the optimal reaction conditions for the synergistic production and application of hydrochars (HC) and aqueous phases (AP). Compared with UW, the HC yields derived from LBS as solvent were increased by 27.05-38.24% under the same conditions. The C content, high heating value (HHV), and energy densification of HC obtained from LMD and UW were higher than those obtained from LMD and LBS, and the ash content was lower. While, LBS circumstance improved the porosity, N content and some trace elements e.g. Ca, Fe and Mg in HC that showed excellent fertility potential. In addition, the recovery rate of K, TOC, NH4+-N, and TN concentrations in AP were significantly higher in the LBS circumstance than in UW. The results show that the addition of UW is more favorable for fuel generation, and the HC obtained from LMD and UW at 220 °C has the potential to be used as a fuel. Whereas, the addition of LBS enhanced the potential of HC and AP for agricultural applications simultaneously. It is recommended to use HC and AP obtained from LMD and LBS at 240 °C for using as fertilizer.

Association between the Dietary Inflammatory Index and fracture risk in older adults: a systematic review and meta-analysis.

OBJECTIVE: We explored correlations between the Dietary Inflammatory Index (DII) and fracture risk in older adults. METHODS: We systematically searched MEDLINE, PubMed, Science Direct, Scopus, and CNKI for all relevant epidemiological studies published through October 16, 2023. Because observational studies were included in the meta-analysis, we used a random-effects model to pool the study-specific effect sizes and 95% confidence intervals (CIs). We assessed study quality using the Newcastle-Ottawa scale. This meta-analysis was registered in PROSPERO. RESULTS: Eight studies with 462,986 participants were included, with five cohort studies, two cross-sectional studies, and one case-control study. An analysis of heterogeneity among the eight included studies resulted in I2 = 87.1%, indicating significant between-study heterogeneity; hence, the random-effects model was adopted to generate the combined effect size. We found that the DII was positively associated with fracture (relative risk: 1.188, 95% CI: 1.043-1.354). This result was further confirmed in leave-one-out sensitivity analysis. CONCLUSIONS: Our study provides evidence suggesting that diets high in pro-inflammatory components might increase the fracture risk among older people. Decreased consumption of pro-inflammatory foods and increased consumption of anti-inflammatory foods are suggested to prevent adverse fracture outcomes. More prospective studies involving both sexes are warranted to verify the results.

Evaluation of the accuracy of seven intraoral scanners for the full dentate and partially edentulous complete-arch mandibular casts: An in vitro comparison.

Statement of problem: Intraoral scanners (IOSs) are widely used in dentistry, providing high accuracy in short-range scanning. Nevertheless, when scanning the full dental arch, it remains a challenge. Furthermore, there is a lack of studies reporting the differences in scan accuracy between dental arches with large-span mucosal areas and fully dentate casts or optimal IOS selection for different dental statuses. Purpose: This study aimed to evaluate the accuracy and scanning time of different IOSs for full dentate (FD) and partially edentulous (PE) casts with missing teeth in the #34-#44 range and to determine the IOSs with the optimal clinical adaptability and scanning accuracy for different complete-arch casts. Material and methods: Reference scans of two complete-arch (FD and PE) casts were obtained using a laboratory scanner (Ceramill Map 600). Subsequently, the same casts were scanned ten times each by seven IOSs (3Shape Trios 3, CS3600, Planmeca Emerald, iTero Element 5D, Medit i500, BAMBOO B1, and Shining Aoralscan 3), and the scanning time was recorded. The test data were superimposed on the reference scans for the selected areas, and three-dimensional deviations between the reference and test casts (trueness), and between test casts (precision) were determined using reverse engineering software (Geomagic Wrap). The dataset was analyzed using a two-factor analysis of variance with post-hoc Bonferroni tests. Results: Two-factor analysis of variance revealed significant differences in accuracy and scanning time for different casts (P < 0.001) and IOSs (P < 0.001). For the FD cast, the i500 (0.35 ± 0.11 mm trueness) and CS3600 (0.23 ± 0.12 mm precision) performed worse than the remaining scanners. For the PE cast, the BAMBOO B1(0.89 ± 0.58 mm trueness; 0.88 ± 0.48 mm precision) performed worse than the remaining scanners. There were no differences in the accuracy of scanning between the Element 5D and Emerald for both cast types. However, the scanning time differed significantly between the different IOSs (P < 0.001). Regardless of the cast type, the fastest and slowest scans were performed by the Trios3 and CS3600 scanners respectively. Conclusions: The accuracy and scanning time differed between the different IOSs and types of complete-arch casts.

Coordinate-based data analysis of the accuracy of five intraoral scanners for scanning completely dentate and partially edentulous mandibular arches.

STATEMENT OF PROBLEM: Current methods for assessing the accuracy of intraoral scanners (IOSs) that reduce errors and provide comprehensive data compared with previous methods are lacking. PURPOSE: The purpose of this in vitro study was to present a coordinate-based data analysis method to compare the accuracy of 5 IOSs for scanning completely dentate and partially edentulous casts. MATERIAL AND METHODS: Reference scans of 2 complete arch casts (completely and partially dentate) were digitized using a high-precision laboratory scanner (Ceramill Map 600). Each cast was scanned 10 times each using 5 IOSs (3Shape TRIOS 3, Planmeca Emerald, iTero Element 5D, Medit i500, and Shining Aoralscan 3). The dataset of all 10 test groups was analyzed by using a reverse engineering software program (Geomagic Wrap). Each test cast was aligned with the reference cast by 3-dimensional (3D) superimposition to determine the translation and rotation along the x-, y-, and z-axes. The dataset was analyzed using the Kruskal-Wallis and post hoc Bonferroni tests (α=.05). RESULTS: Significant differences were observed in all parameters among all scanners when scanning the same cast (P<.05). Significant differences were observed in at least 1 parameter for all scanners, except Element 5D after scanning different casts using the same scanner. Deviations in the test data generally relocated toward the mesial, buccal, and apical sides, and the casts were almost always rotated clockwise around the y-axis and counterclockwise around the z-axis. For the completely dentate cast, among all IOSs, Element 5D demonstrated the highest accuracy in most of the measured parameters, specifically in the y-axis translation (0.06[0.07] mm), z-axis translation (0.08[0.05] mm), and y-axis rotation (0.21[0.16] degree) (P<.05). For the partially edentulous cast, Element 5D displayed higher accuracy in most of the measured parameters, including the x-axis translation (0.11[0.14] mm) and z-axis rotation (0.12[0.18] degree) (P<.05). Emerald also displayed higher accuracy in most of the measured parameters, including the y-axis translation (0.05[0.08] mm) and y-axis rotation (0.14[0.12] degree) (P<.05). Element 5D exhibited no difference in the scanning accuracy between the 2 types of casts (P>.05). CONCLUSIONS: Element 5D offered a high level of accuracy and was an appropriate scanner for both situations. The method presented in this study provides a good assessment of accuracy deviations in complete arch scans using 3D coordinate-based data analysis.

PIF3 is phosphorylated by MAPK to modulate plant immunity.

Surface-localized pattern recognition receptors perceive pathogen-associated molecular patterns (PAMPs) to activate pattern-triggered immunity (PTI). Activation of mitogen-activated protein kinases (MAPKs) represents a major PTI response. Here, we report that Arabidopsis thaliana PIF3 negatively regulates plant defense gene expression and resistance to Pseudomonas syringae DC3000. PAMPs trigger phosphorylation of PIF3. Further study reveals that PIF3 interacts with and is phosphorylated by MPK3/6. By mass spectrometry and site-directed mutagenesis, we identified the corresponding phosphorylation sites which fit for SP motif. We further show that a phospho-mimicking PIF3 variant (PIF36D /pifq) conferred increased susceptibility to P. syringae DC3000 and caused lower levels of defense gene expression in plants. Together, this study reveals that PIF3 is phosphorylated by MPK3/6 and phosphorylation of the SP motif residues is required for its negative regulation on plant immunity.

Identification and Genetic Characterization of Pseudomonas syringae pv. actinidiae from Kiwifruit in Sichuan, China.

Pseudomonas syringae pv. actinidiae causes kiwifruit bacterial canker and poses a major threat to the kiwifruit industry. This study aimed to investigate the genetic characteristics of the P. syringae pv. actinidiae population from kiwifruit in Sichuan, China. Sixty-seven isolates obtained from diseased plants were characterized using morphological features, multiplex-PCR, and multilocus sequence analysis (MLSA). The isolates exhibited the typical colony morphology of P. syringae pv. actinidiae. Multiplex PCR amplification identified every isolate as P. syringae pv. actinidiae biovar 3. MLSA of the three housekeeping genes gapA, gyrB, and pfk, revealed that the reference strains of the five described biovars were clearly distinguished by a combined phylogenetic tree, and all of the tested isolates clustered with the reference strains of P. syringae pv. actinidiae biovar 3. Through a phylogenetic tree constructed from a single gene, it was found that pkf gene alone could distinguish biovar 3 from the other biovars. Furthermore, all P. syringae pv. actinidiae isolates analyzed by BOX-A1R-based repetitive extragenic palindromic (BOX)-PCR and enterobacterial repetitive intergenic consensus (ERIC)-PCR clustered into four groups. The clustering results of BOX- and ERIC-PCR indicated that group III had the largest number of isolates, accounting for 56.72 and 61.19% of all 67 isolates, respectively, and the two characterization methods were similar and complementary. The results of this study revealed that the genomes of P. syringae pv. actinidiae isolates from Sichuan had rich genetic diversity but no obvious correlation was found between clustering and geographical region. This research provides novel methodologies for rapidly detecting kiwifruit bacterial canker pathogen and a molecular differentiation at genetic level of P. syringae pv. actinidiae biovar diversity in China.

Impact of Modified Thoracic Breast Approach Lumpectomy on Prognosis of Recurrence in Radical Thyroid Carcinoma Patients.

Objective: This study aimed to compare the efficacy and safety of endoscopic radical thyroidectomy (ERT) via modified breast approach (MBA) with conventional open thyroidectomy in treating thyroid carcinoma (TC). Methods: One hundred patients with TC were randomized into a research group (treated with modified thoracic breast approach lumpectomy) and a control group (treated with traditional open surgery). Clinical efficacy, adverse effects, operative time, intraoperative bleeding, postoperative drainage, and length of stay (LOS) were compared between the groups. Serum calcium and parathyroid hormone levels were measured preoperatively and on postoperative days 1 and 5. Patients were followed up for 1-year prognosis, including prognostic survival, TC recurrence rate, and factors affecting their prognosis. Results: There was no difference in total treatment efficiency between the groups, but the incidence of adverse effects, intraoperative bleeding, postoperative drainage, and LOS were lower in the research group, while the operative time was higher in the control group. Serum calcium and parathyroid hormone were insufficient in both groups on postoperative day 1 compared to preoperative levels, with higher levels in the research group. On postoperative day 5, there was no difference between the groups. TC recurrence was lower in the research group, and logistic regression analysis showed that age and surgical method were independent factors affecting prognostic recurrence in TC patients. Conclusion: Modified thoracic breast approach lumpectomy for radical TC is a safe and effective technique that can improve patients' prognosis of recurrence. It is recommended for clinical practice.

Pestalotiopsis Species Associated with Blueberry Leaf Spots and Stem Cankers in Sichuan Province of China.

Blueberry leaf spots and stem cankers caused by Pestalotiopsis spp. have become a serious threat for the production of blueberry in Sichuan Province. To characterize the etiology of the diseases connected with these fungi, samples showing leaf spot and stem canker symptoms were collected from the 12 main blueberry-growing areas of Sichuan Province from 2015 to 2020 and used for pathogen isolation. In total, 91 fungal isolates were obtained with preliminary morphological identification and 48 representative strains were selected for further pathogenicity test and molecular identification. Four species, including Pestalotiopsis clavispora (Neopestalotiopsis clavispora) (57.14%), P. trachicarpicola (28.57%), P. chamaeropis (13.19%), and P. adusta (1.10%), were identified based on conidial morphology, cultural characteristics, and phylogenetic analysis of the internal transcribed spacer region, partial sequence of the ß-tubulin gene, and the translation elongation factor 1-α. Pathogenicity tests showed that four species were pathogenic to leaves and stems of blueberry. Among them, P. clavispora (N. clavispora) was the most aggressive as the predominant species to cause both leaf spot and stem canker. P. trachicarpicola and P. chamaeropis were mainly isolated from leaves but also pathogenic to stems. P. adusta was only isolated from stems but also pathogenic to leaves. To the best of our knowledge, this is the first report of P. chamaeropis and P. adusta as pathogens causing leaf spots and stem canker on blueberry. The results provide helpful information in disease diagnosis and management of blueberry.

Analysis of Human-Exoskeleton System Interaction for Ergonomic Design.

OBJECTIVE: Lower-limb exoskeleton systems are defined as gait training or walking-assisting devices for spinal cord injury or hemiplegic patients. Crutches, straps, and baffles are designed to protect subjects from falling. However, skin abrasions occur when the interaction forces are too large. In this study, the interaction forces between the human body and an exoskeleton system named the AIDER were measured to confirm whether the design was ergonomic. BACKGROUND: The AIDER system is a wearable lower-limb exoskeleton. It secures a subject by binding on the waist, thighs, shanks, and feet. METHOD: Eight healthy subjects participated in the study. The interaction forces of the waist strap, thigh baffles, shank baffles, and crutch handles were measured by pressure sensors. Ten repetitions were completed in this study. After one repetition, custom comfort questionnaires were completed by the subjects. RESULTS: Although a few of the peak values of the maximum intensities of pressure between the hands and crutch handles reached the minimum value of the pain-pressure threshold (PPT), the average pressure intensities were much smaller than the PPT value. CONCLUSIONS: The results indicated that the mechanical structure and control strategy of the AIDER must be improved to be more ergonomic in the future.

Is the six-minute walk test still reliable compared to cardiopulmonary exercise test for exercise capacity in children with congenital heart disease?

Objectives: We aimed to assess the validity of the six-minute walk test (6MWT) to reflect the functional capacity of children with congenital heart disease (CHD), evaluate a possible correlation between the 6MWT distance with cardiopulmonary exercise test (CPET) variables, as well as to find a cutoff value to stratification the physical fitness in this population. Methods: We enrolled 459 children with CHD, 6-18 years old, who performed a complete CPET and 6MWT on the same day in a cross-sectional observational study. Correlations between variables of CPET and six-minute walking distance (6MWD) were analyzed and cutoff values of 6MWD were identified for the classification of the physical fitness in the population. Results: The mean distance ambulated during the 6MWT was 578 ± 65 m, 590 ± 65 m for boys, and 562 ± 62 m for girls (p < 0.001). Both VO2max and %predicted VO2max showed a correlation with the 6MWT distance (r = 0.35, p < 0.001 and r = 0.51, p < 0.001, respectively), and an inverse correlation was found between VE/VCO2 slope and the 6MWT distance (r = -0.31; p < 0.001). There appeared to be a linear association between 6MWD and VO2max up to a 6MWD of approximately 600 m. We divided the population into 4 subgroups (boys <130 cm; boys ≥130 cm; girls <130 cm; girls ≥130 cm), and get the cutoff values (554 m, 617 m, 549 m, 587 m) respectively equivalent to 80% of predicted VO2max. The 6MWT distances of another 102 patients were applied for external verification of the cutoff values. Conclusions: Our study provided evidence on when a 6MWT should be considered as a convincing complementary test in the pediatric population with CHD and explored the classification of exercise tolerance using a 6MWD value. The cut-off values for 6MWD may be qualified as an intervention target for exercise rehabilitation.

Diversity of Trichoderma species associated with soil in the Zoige alpine wetland of Southwest China.

The ecology of soil fungi is poorly understood, and recent comprehensive reports on Trichoderma are unavailable for any region, including the Zoige alpine wetland ecological region in China. One hundred soil samples were collected from different soil types and soil layers in Zoige alpine wetland ecological regions. Using the traditional suspension plating method, 80 Trichoderma strains were chosen to analyze species diversity. After a preliminary classification of morphological characteristics and the genes glyceraldehyde-3-phosphate dehydrogenase (gpd), 57 representative strains were selected and eventually identified as seven species via phylogenetic analyses of multilocus sequences based on the genes transcription elongation factor 1 alpha (tef1), encoding RNA polymerase II subunit B (rpb2) and ATP citrate lyase (acl1). Among them, T. harzianum was the dominant species isolated from five soil layers and four soil types, and had the highest isolation frequency (23%) in this zone, while T. polysporum and T. pyramidale were rare species, with isolation frequencies of less than 1%. Our detailed morphological observation and molecular phylogenetic analyses support the recognition of Trichoderma zoigense was described for the first time as a new species, while T. atrobrunneum as a new record for China was found. Our results will be used as a reference for a greater understanding of soil microbial resources, ecological rehabilitation and reconstructions in the Zoige alpine wetland.

Two plant NLR proteins confer strain-specific resistance conditioned by an effector from Pseudomonas syringae pv. actinidiae.

Pseudomonas syringae pv. actinidiae (Psa) causes bacterial canker, a devastating disease threatening the Actinidia fruit industry. In a search for non-host resistance genes against Psa, we find that the nucleotide-binding leucine-rich repeat receptor (NLR) protein ZAR1 from both Arabidopsis and Nicotiana benthamiana (Nb) recognizes HopZ5 and triggers cell death. The recognition requires ZED1 in Arabidopsis and JIM2 in Nb plants, which are members of the ZRK pseudokinases and known components of the ZAR1 resistosome. Surprisingly, Arabidopsis ZAR1 and RPM1, another NLR known to recognize HopZ5, confer disease resistance to HopZ5 in a strain-specific manner. Thus, ZAR1, but not RPM1, is solely required for resistance to P. s. maculicola ES4326 (Psm) carrying hopZ5, whereas RPM1 is primarily required for resistance to P. s. tomato DC3000 (Pst) carrying hopZ5. Furthermore, the ZAR1-mediated resistance to Psm hopZ5 in Arabidopsis is insensitive to SOBER1, which encodes a deacetylase known to suppress the RPM1-mediated resistance to Pst hopZ5. In addition, hopZ5 enhances P. syringae virulence in the absence of ZAR1 or RPM1 and that SOBER1 abolishes such virulence function. Together the study suggests that ZAR1 may be used for improving Psa resistance in Actinidia and uncovers previously unknown complexity of effector-triggered immunity and effector-triggered virulence.

TRAF6 autophagic degradation by avibirnavirus VP3 inhibits antiviral innate immunity via blocking NFKB/NF-κB activation.

Ubiquitination is an important reversible post-translational modification. Many viruses hijack the host ubiquitin system to enhance self-replication. In the present study, we found that Avibirnavirus VP3 protein was ubiquitinated during infection and supported virus replication by ubiquitination. Mass spectrometry and mutation analysis showed that VP3 was ubiquitinated at residues K73, K135, K158, K193, and K219. Virus rescue showed that ubiquitination at sites K73, K193, and K219 on VP3 could enhance the replication abilities of infectious bursal disease virus (IBDV), and that K135 was essential for virus survival. Binding of the zinc finger domain of TRAF6 (TNF receptor associated factor 6) to VP3 mediated K11- and K33-linked ubiquitination of VP3, which promoted its nuclear accumulation to facilitate virus replication. Additionally, VP3 could inhibit TRAF6-mediated NFKB/NF-κB (nuclear factor kappa B) activation and IFNB/IFN-ß (interferon beta) production to evade host innate immunity by inducing TRAF6 autophagic degradation in an SQSTM1/p62 (sequestosome 1)-dependent manner. Our findings demonstrated a macroautophagic/autophagic mechanism by which Avibirnavirus protein VP3 blocked NFKB-mediated IFNB production by targeting TRAF6 during virus infection, and provided a potential drug target for virus infection control.Abbreviations: ATG: autophagy related; BafA1: bafilomycin A1; CALCOCO2/NDP52: calcium binding and coiled-coil domain 2; Cas9: CRISPR-associated protein 9; CHX: cycloheximide; Co-IP: co-immunoprecipitation; CRISPR: clustered regularly interspaced short palindromic repeats; GAPDH: glyceraldehyde-3-phosphate dehydrogenase; GST: glutathione S-transferase; IBDV: infectious bursal disease virus; IF: indirect immunofluorescence; IFNB/IFN-ß: interferon beta; mAb: monoclonal antibody; MAP1LC3/LC3: microtubule associated protein 1 light chain 3; MOI: multiplicity of infection; MS: mass spectrometry; NFKB/NF-κB: nuclear factor kappa B; NBR1: NBR1 autophagy cargo receptor; OPTN: optineurin; pAb: polyclonal antibody; PRRs: pattern recognition receptors; RNF125: ring finger protein 125; RNF135/Riplet: ring finger protein 135; SQSTM1/p62: sequestosome 1; TAX1BP1: tax1 binding protein1; TCID50: 50% tissue culture infective dose; TRAF3: TNF receptor associated factor 3; TRAF6: TNF receptor associated factor 6; TRIM25: tripartite motif containing 25; Ub: ubiquitin; Wort: wortmannin; WT: wild type.

Roles and potential clinical implications of tissue transglutaminase in cardiovascular diseases.

Cardiovascular disease (CVD)-related mortality and morbidity are among the most critical disease burdens worldwide. CVDs encompass many diseases and involve complex pathogenesis and pathological changes. While research on these diseases has advanced significantly, treatments and their efficacy remain rather limited. New therapeutic strategies and targets must, therefore, be explored. Tissue transglutaminase (TG2) is pivotal to the pathological development of CVDs, including participating in the cross-linking of extracellular proteins, activation of fibroblasts, hypertrophy and apoptosis of cardiomyocytes, proliferation and migration of smooth muscle cells (SMCs), and inflammatory reactions. Regulating TG2 activity and expression could ensure remarkable improvements in disorders like heart failure (HF), pulmonary hypertension (PH), hypertension, and coronary atherosclerosis. In this review, we summarize recent advances in TG2: we discuss its role and mechanisms in the progression of various CVDs and its potential as a diagnostic and therapeutic target.

A fatal outcome in a patient with coeliac disease who suspended a strict gluten-free diet: a case report.

Coeliac disease (CD) is an autoimmune small bowel disease that occurs in susceptible individuals that develop an immunological reaction to gluten. A strict gluten-free diet (GFD) is the primary treatment for CD. This case report describes a patient with CD recurrence due to a discontinuation of a strict GFD by the patient. After recurrence, the patient developed fever and pancytopaenia, and quickly died of haemophagocytic lymphohistiocytosis (HLH). To the best of our knowledge, this is the first description of a case of CD associated with HLH due to discontinued GFD, which may contribute to improving the awareness of the importance of maintaining a strict GFD and having regular follow-up examinations.

DeSUMOylation of Apoptosis Inhibitor 5 by Avibirnavirus VP3 Supports Virus Replication.

SUMOylation is a reversible posttranslational modification involved in the regulation of diverse biological processes. Growing evidence suggests that virus infection can interfere with the SUMOylation system. In the present study, we discovered that apoptosis inhibitor 5 (API5) is a SUMOylated protein. Amino acid substitution further identified that Lys404 of API5 was the critical residue for SUMO3 conjugation. Moreover, we found that Avibirnavirus infectious bursal disease virus (IBDV) infection significantly decreased SUMOylation of API5. In addition, our results further revealed that viral protein VP3 inhibited the SUMOylation of API5 by targeting API5 and promoting UBC9 proteasome-dependent degradation through binding to the ubiquitin E3 ligase TRAF3. Furthermore, we revealed that wild-type but not K404R mutant API5 inhibited IBDV replication by enhancing MDA5-dependent IFN-ß production. Taken together, our data demonstrate that API5 is a UBC9-dependent SUMOylated protein and deSUMOylation of API5 by viral protein VP3 aids in viral replication. IMPORTANCE Apoptosis inhibitor 5 (API5) is a nuclear protein initially identified for its antiapoptotic function. However, so far, posttranslational modification of API5 is unclear. In this study, we first identified that API5 K404 can be conjugated by SUMO3, and Avibirnavirus infectious bursal disease virus (IBDV) infection significantly decreased SUMOylation of API5. Mechanically, viral protein VP3 directly interacts with API5 and inhibits SUMOylation of API5. Additionally, the cellular E3 ligase TNF receptor-associated factor 3 (TRAF3) is employed by VP3 to facilitate UBC9 proteasome-dependent degradation, leading to the reduction of API5 SUMOylation. Moreover, our data reveal that SUMOylation of API5 K404 promotes MDA5-dependent beta interferon (IFN-ß) induction, and its deSUMOylation contributes to IBDV replication. This work highlights a critical role of conversion between SUMOylation and deSUMOylation of API5 in regulating viral replication.

Pathological features of persistent adnexal masses in pregnancy.

BACKGROUND: The composition of pelvic masses during pregnancy is complex, and over >70% of masses are physiology. Determining the source and nature of tumor tissue is incredibly important in clinical practice, as the proportion of metastatic and low-grade tumors in adnexal masses increase during pregnancy. This study sought to analyze the pathological features of persistent adnexal masses in pregnancy. METHODS: A retrospective case analysis method was adopted to summarize the pathologic features of persistent adnexal masses in pregnancy in 228 patients at the Beijing Chao-Yang Hospital, Capital Medical University. RESULTS: Mature teratoma was the most common histopathological type of persistent adnexal masses in pregnancy (66/228, 28.95%), followed by the corpus luteum of pregnancy (38/228, 16.67%). Borderline/malignant tumors accounted for 5.70% (13/228) of tumors. Malignant adnexal tumor tissues were derived from multiple types of tissues. a single-factor analysis showed that borderline/malignant tumors had a significant relationship with the morphological features of mass in the ultrasound (P=0.000), and had a significant relationship with initial mass size (P=0.018). A multivariate binary logistic regression analysis indicated no certain independent risk factor. A significant difference in tumor pathology distribution was noted between those who underwent emergency surgery during pregnancy, elective surgery during pregnancy, and simultaneous tumor removal during cesarean section (χ2=24.22, P=0.000). CONCLUSIONS: A special particularity exists in the pathology distribution of persistent adnexal masses in pregnancy. Additionally, extensive histological sources and the need to rule out borderline/malignancy for solid cystic tumors were noted.

Inhibition of Antiviral Innate Immunity by Avibirnavirus VP3 via Blocking TBK1-TRAF3 Complex Formation and IRF3 Activation.

The host innate immune system develops various strategies to antagonize virus infection, and the pathogen subverts or evades host innate immunity for self-replication. In the present study, we discovered that Avibirnavirus infectious bursal disease virus (IBDV) VP3 protein significantly inhibits MDA5-induced beta interferon (IFN-ß) expression by blocking IRF3 activation. Binding domain mapping showed that the CC1 domain of VP3 and the residue lysine-155 of tumor necrosis factor receptor-associated factor 3 (TRAF3) are essential for the interaction. Furthermore, we found that the CC1 domain was required for VP3 to downregulate MDA5-mediated IFN-ß production. A ubiquitination assay showed that lysine-155 of TRAF3 was the critical residue for K33-linked polyubiquitination, which contributes to the formation of a TRAF3-TBK1 complex. Subsequently, we revealed that VP3 blocked TRAF3-TBK1 complex formation through reducing K33-linked polyubiquitination of lysine-155 on TRAF3. Taken together, our data reveal that VP3 inhibits MDA5-dependent IRF3-mediated signaling via blocking TRAF3-TBK1 complex formation, which improves our understanding of the interplay between RNA virus infection and the innate host antiviral immune response.IMPORTANCE Type I interferon plays a critical role in the host response against virus infection, including Avibirnavirus. However, many viruses have developed multiple strategies to antagonize the innate host antiviral immune response during coevolution with the host. In this study, we first identified that K33-linked polyubiquitination of lysine-155 of TRAF3 enhances the interaction with TBK1, which positively regulates the host IFN immune response. Meanwhile, we discovered that the interaction of the CC1 domain of the Avibirnavirus VP3 protein and the residue lysine-155 of TRAF3 reduced the K33-linked polyubiquitination of TRAF3 and blocked the formation of the TRAF3-TBK1 complex, which contributed to the downregulation of host IFN signaling, supporting viral replication.