A feature extraction method based on noise reduction for circRNA-miRNA interaction prediction combining multi-structure features in the association networks.

MOTIVATION: A large number of studies have shown that circular RNA (circRNA) affects biological processes by competitively binding miRNA, providing a new perspective for the diagnosis, and treatment of human diseases. Therefore, exploring the potential circRNA-miRNA interactions (CMIs) is an important and urgent task at present. Although some computational methods have been tried, their performance is limited by the incompleteness of feature extraction in sparse networks and the low computational efficiency of lengthy data. RESULTS: In this paper, we proposed JSNDCMI, which combines the multi-structure feature extraction framework and Denoising Autoencoder (DAE) to meet the challenge of CMI prediction in sparse networks. In detail, JSNDCMI integrates functional similarity and local topological structure similarity in the CMI network through the multi-structure feature extraction framework, then forces the neural network to learn the robust representation of features through DAE and finally uses the Gradient Boosting Decision Tree classifier to predict the potential CMIs. JSNDCMI produces the best performance in the 5-fold cross-validation of all data sets. In the case study, seven of the top 10 CMIs with the highest score were verified in PubMed. AVAILABILITY: The data and source code can be found at https://github.com/1axin/JSNDCMI.

Longitudinal Analysis of Ocular Manifestation and Interleukin during Intravitreal Treatment of Vitreoretinal Lymphoma with Methotrexate.

PURPOSE: To explore the trend of ocular manifestations and interleukin (IL) during the treatment of vitreoretinal lymphoma (VRL), and to evaluate potential effects of different intravitreal administration schedules on the therapeutic response. DESIGN: Interventional comparative non-randomized clinical study. METHODS: Patients diagnosed with VRL from January 2011 to January 2022 were included. Intravitreal methotrexate (MTX) injections consisting induction, consolidation and maintenance were scheduled. At baseline and each visit, ocular manifestations and interleukin in aqueous humor were recorded. Effects of the variations (e.g. frequency and number) in the injection schedule on the therapeutic response were analyzed. RESULTS: Fifty-eight eyes of 33 patients were treated with intravitreal MTX chemotherapy. A mean (±SD) of 9±3 injections were given; 52 eyes achieved complete remission (CR). IL-10, keratic precipitates and sub-retinal lesions correlated well with the course of treatment (all P <0.001). Initial injection given twice weekly was correlated with a higher rate of CR (36/36) than given once weekly or less frequently (16/22, P=0.011). Ocular progression occurred in 13 eyes of 8 patients. The completion of schedule was correlated with PFS (induction + consolidation + maintenance: 547[335-874] days, induction + consolidation: 355[322-831] days, induction only: 147[116-187.5] days, P<0.001). IL-10 over 50 pg/mL was a feasible threshold for the detection of ocular relapse (sensitivity 100.0%, specificity 95.1%). CONCLUSION: Keratic precipitates, sub-retinal lesions and IL-10 could serve as indicators for therapeutic response. Intensive initial administration and adequate injection number would help to improve the response and prognosis. IL-10 over 50 pg/mL could help to detect ocular relapse.

Difference of anterior and posterior orbital development in patients with congenital microphthalmia: a retrospective cohort study from China.

AIM: To evaluate volume differences between anterior and posterior orbit and demographic characteristics of Chinese patients with congenital microphthalmia. METHODS: A retrospective cohort study, involving 169 unilateral congenital microphthalmia patients aged between 1 and 57 years old was conducted. Three-dimensional images of the orbit were generated from past CT scans, and digital orbital volume comprehensive measurement was done. The measured data included orbital volume (OBV), posterior orbital volume (POV), orbital width (OBW), orbital height (OBH), orbital depth (OBD), and posterior orbital area ratio. RESULTS: Significant differences were observed among OBV, POV, OBW, OBH, and OBD of the affected and unaffected eyes in different age-based groups (all P<0.001). Among them, OBH had the greatest different. The mean microphthalmic to contralateral ratio (MCR) of OBV, POV, OBW, and OBH continuously increased from 1 to 3 years old, whereas the MCR of POV decreased from 3 to 17 years old. The MCR of OBD was not found to be correlated to age. There was no significant difference between OBV, POV, OBW, and OBH in ages from 13 years old to adulthood (all P>0.05). The difference in posterior orbital area ratio between the affected and unaffected groups was not statistically significant (P>0.05). CONCLUSION: OBH is maximally affected, whereas OBD is minimally affected by microphthalmia. Posterior orbital retardation began 2y prior to orbital retardation and occurred at 3 years old in the affected eye, suggesting that intervention therapy should be done before the age of 4.

Identification of SNP loci and candidate genes genetically controlling norisoprenoids in grape berry based on genome-wide association study.

Obtaining new grapevine varieties with unique aromas has been a long-standing goal of breeders. Norisoprenoids are of particular interest to wine producers and researchers, as these compounds are responsible for the important varietal aromas in wine, characterized by a complex floral and fruity smell, and are likely present in all grape varieties. However, the single-nucleotide polymorphism (SNP) loci and candidate genes genetically controlling the norisoprenoid content in grape berry remain unknown. To this end, in this study, we investigated 13 norisoprenoid traits across two years in an F1 population consisting of 149 individuals from a hybrid of Vitis vinifera L. cv. Muscat Alexandria and V. vinifera L. cv. Christmas Rose. Based on 568,953 SNP markers, genome-wide association analysis revealed that 27 candidate SNP loci belonging to 18 genes were significantly associated with the concentrations of norisoprenoid components in grape berry. Among them, 13 SNPs were confirmed in a grapevine germplasm population comprising 97 varieties, including two non-synonymous mutations SNPs within the VvDXS1 and VvGGPPS genes, respectively in the isoprenoid metabolic pathway. Genotype analysis showed that the grapevine individuals with the heterozygous genotype C/T at chr5:2987350 of VvGGPPS accumulated higher average levels of 6-methyl-5-hepten-2-one and ß-cyclocitral than those with the homozygous genotype C/C. Furthermore, VvGGPPS was highly expressed in individuals with high norisoprenoids concentrations. Transient overexpression of VvGGPPS in the leaves of Vitis quinquangularis and tobacco resulted in an increase in norisoprenoid concentrations. These findings indicate the importance of VvGGPPS in the genetic control of norisoprenoids in grape berries, serving as a potential molecular breeding target for aroma.

Multipurpose ultrasonographic characteristics of primary uveal MALT lymphoma.

PURPOSE: To investigate the ultrasonographic features in patients with primary uveal mucosa-associated lymphoid tissue (MALT) lymphoma. METHODS: Medical records of 12 patients (13 eyes) diagnosed with primary uveal MALT lymphoma between September 2014 and September 2021 were retrospectively reviewed. Ultrasonography, B-scan ultrasonography, color Doppler flow imaging, and ultrasound biomicroscopy findings were retrieved from the medical records. RESULTS: Mean age of the included patients was 59.4 ± 8.6 years. Typical ultrasonographic features of the choroidal infiltrates were flat, diffuse, and thickened, with low and homogenous internal reflectivity and with rich arterial blood flow from posterior ciliary arterioles. The mean thickness of the choroidal infiltrates was 1.34 ± 0.68 mm (n = 13). Most of the affected eyes had posterior episcleral extensions, with a mean thickness of 1.66 ± 1.21 mm (n = 12). Typical crescent-like posterior episcleral extensions were detected in nine eyes (69.2%). In six eyes, the blood flow from the choroidal infiltrates communicated with the episcleral extensions. In the ciliary body, the mean thickness of the infiltrates was 1.08 ± 0.43 mm (n = 9), and seven eyes (77.8%) had 360° ring-like infiltrations. The initial best-corrected visual acuity (BCVA) was significantly correlated with the final BCVA after treatment (p < 0.001). CONCLUSION: Multipurpose ultrasonographic imaging revealed the unique characteristics of the primary uveal MALT lymphoma and is helpful in the diagnosis of this rare disease.

Volume-accumulated reflectivity of the outer retina (integral) on spectral domain optical coherence tomography as a predictor of cone cell density: a pilot study.

BACKGROUND: The study aims to investigate the relationship between the volume-accumulated reflectivity (termed "integral") on spectral domain optical coherence tomography (SD-OCT) and cone density on adaptive optics (AO) imaging. METHODS: In this cross-sectional study, both eyes of 32 healthy subjects and 5 patients with inherited retinal diseases (IRD) were studied. The parameter, integral, was defined as the volume-accumulated reflectivity values in a selected region on OCT images; integrals of the ellipsoid zone (EZ) and interdigitation zone (IZ) were measured at 2°, 3°, 4°, 5°and 6° eccentricity along the four meridians on fovea-centered OCT B-scans. Cone density in the same region was measured using a flood illumination adaptive optics camera RTX1. RESULTS: Integrals of EZ, IZ and cone density shared similar distribution patterns. Integral of the IZ was better correlated with cone density in both healthy people (r = 0.968, p < 0.001) and those with IRD (r = 0.823, p < 0.001) than direct measurements of reflectivity on OCT images. A strong correlation was found between best corrected visual acuity (BCVA) and cone density at 2° eccentricity (r = -0.857, p = 0.002). BCVA was also correlated with the integral of the IZ at the foveola (r = -0.746, p = 0.013) and fovea (r = -0.822, p = 0.004). CONCLUSIONS: The new parameter "integral" of the photoreceptor outer segment measured from SD-OCT was noted to correlate with cone density and visual function in this pilot study.

MicroRNA-196a-5p targeting LRP1B modulates phenotype of thyroid carcinoma cells.

INTRODUCTION: Thyroid cancer (TC) is a common endocrine malignancy, comprising nearly one-third of all head and neck malignancies worldwide. MicroRNAs (miRNAs) have been implicated in the malignant progression of multiple cancers; however, their contribution to thyroid diseases has not been fully explored. MATERIAL AND METHODS: This study aimed to illustrate the regulatory mechanism of microRNA-196a-5p in TC progression and to investigate whether microRNA-196a-5p affects progression of TC cells by targeting low-density lipoprotein receptor-associated protein 1B (LRP1B). MicroRNA-196a-5p and LRP1B expression status in TC cells and normal human thyroid cells was detected by quantative reverse transcription polymerase chain reaction (qRT-PCR) and western blot. Dual-luciferase reporter assay, cell counting kit-8 (CCK-8) assay, scratch healing assay, and Transwell assay were also performed. RESULTS: The results showed that microRNA-196a-5p expression was up-regulated and LRP1B expression was down regulated in TC cells. In addition, the upregulation of microRNA-196a-5p facilitated progression of TC cells. Silencing microRNA-196a-5p led to the opposite results. Dual-luciferase reporter assay offered evidence for microRNA-196a-5p targeting LRP1B in TC. MicroRNA-196a-5p could target LRP1B to facilitate proliferation, invasion, and migration of TC cells. CONCLUSION: Overall, this study revealed that microRNA-196a-5p may be a cancer-promoting microRNA that plays an important role in TC progression.

Dairy product consumption was associated with a lower likelihood of non-alcoholic fatty liver disease: A systematic review and meta-analysis.

Background and aims: Non-alcoholic fatty liver disease (NAFLD) is one of the most common causes of chronic liver disease. Several epidemiological studies attempted to assess the association between dairy product and the likelihood of NAFLD, but the contribution of dairy consumption to NAFLD remains controversial. We conducted a meta-analysis to investigate the association between dairy product consumption and NAFLD. Methods: We conducted a literature search using the PubMed, Web of Science and Scopus databases, we conducted a thorough search of the literature published before January 5, 2023. Combined odds ratios (ORs) and 95% confidence intervals (CIs) of NAFLD in relation to dairy product intake were estimated using random-effects models. Subgroup analysis and meta-regression were performed according to the study design, region, sex, body mass index (BMI), type of exposure, NAFLD diagnostic criteria, and exposure assessment tools. Results: We initially identified 4,634 relevant studies, of which 25 complied with the inclusion criteria, including seven cross-sectional studies, six case-control studies and one cohort study. A total of 51,476 participants (14,546 patients with NAFLD) were included in the meta-analysis. There was an inverse association between dairy product consumption and NAFLD (OR = 0.97, 95% CI = 0.94-0.99). Subgroup analysis demonstrated that lower likelihood of NAFLD was associated with dairy product consumption in subgroups of Asian populations, women, patients diagnosed using NAFLD-related scores, patients with a BMI of 18.5-24.9 kg/m2, dairy intake assessed using a food frequency questionnaire, milk consumption, and yogurt consumption. No noteworthy connection was observed in the other subgroups. Conclusion: Our meta-analysis findings revealed that dairy product consumption is inversely associated with NAFLD. Consumption of dairy products could help prevent the development of non-alcoholic fatty liver disease.

Sub-Regional Variation and Characteristics of Cabernet Sauvignon Wines in the Eastern Foothills of the Helan Mountain: A Perspective from Phenolics, Visual Properties and Mouthfeel.

As one of the most promising wine regions in China, the eastern foothills of the Helan Mountain (EFHM) in the Ningxia Hui Autonomous Region has attracted great attention recently. Geographically, EFHM is divided into six sub-regions, namely Shizuishan, Xixia, Helan, Qingtongxia, Yongning and Hongsipu. However, there have been few reports on the character and differences between wines in the six sub-regions. In this experiment, a total of 71 commercial Cabernet Sauvignon wines from six sub-regions were collected, and their phenolic compounds, visual properties and mouthfeel were investigated. The results showed that wines from the six sub-regions of EFHM showed distinctive phenolic profiles and could be distinguished through the OPLS-DA mode using 32 potential markers. In terms of color, Shizuishan wines showed higher a* values and lower b* values. The sensory evaluation showed that Hongsipu wines had higher astringency strength and lower tannin texture. The overall results implied that the phenolic compounds of wines in different sub-regions were affected by terroir conditions. To the best of our knowledge, this is the first time that a wide coverage of phenolic compounds has been analysed for wines from the sub-regions of EFHM, which could provide valuable information in deciphering the terroir of EFHM.

Whole genome sequencing of multidrug-resistant Proteus mirabilis strain PM1162 recovered from a urinary tract infection in China.

OBJECTIVES: Proteus mirabilis is an important opportunistic Gram-negative pathogen. This study reports the whole genome sequence of multidrug-resistant (MDR) P. mirabilis PM1162 and explores its antibiotic resistance genes (ARGs) and their genetic environments. METHODS: P. mirabilis PM1162 was isolated from a urinary tract infection in China. Antimicrobial susceptibility was determined, and whole genome sequencing (WGS) was performed. ARGs, insertion sequence (IS) elements, and prophages were identified using ResFinder, ISfinder, and PHASTER software, respectively. Sequence comparisons and map generation were performed using BLAST and Easyfig, respectively. RESULTS: On its chromosome, P. mirabilis PM1162 harboured 15 ARGs, including cat, tet(J), blaCTX-M-14 (three copies), aph(3')-Ia, qnrB4, blaDHA-1, qacE, sul1, armA, msr(E), mph(E), aadA1, and dfrA1. We focused our analysis on the four related MDR regions: (1) genetic contexts associated with blaCTX-M-14; (2) the prophage containing blaDHA-1, qnrB4, and aph(3')-Ia; (3) genetic environments associated with mph(E), msr(E), armA, sul, and qacE; and (4) the class II integron harbouring dfrA1, sat2, and aadA1. CONCLUSION: This study reported the whole genome sequence of MDR P. mirabilis PM1162 and the genetic context of its ARGs. This comprehensive genomic analysis of MDR P. mirabilis PM1162 provides a deeper understanding of its MDR mechanism and elucidates the horizontal spread of its ARGs, thus providing a basis for the containment and treatment of the bacteria.

The spatiotemporal matching pattern of Ezrin/Periaxin involved in myoblast differentiation and fusion and Charcot-Marie-Tooth disease-associated muscle atrophy.

BACKGROUND: Clinically, Charcot-Marie-Tooth disease (CMT)-associated muscle atrophy still lacks effective treatment. Deletion and mutation of L-periaxin can be involved in CMT type 4F (CMT4F) by destroying the myelin sheath form, which may be related to the inhibitory role of Ezrin in the self-association of L-periaxin. However, it is still unknown whether L-periaxin and Ezrin are independently or interactively involved in the process of muscle atrophy by affecting the function of muscle satellite cells. METHOD: A gastrocnemius muscle atrophy model was prepared to mimic CMT4F and its associated muscle atrophy by mechanical clamping of the peroneal nerve. Differentiating C2C12 myoblast cells were treated with adenovirus-mediated overexpression or knockdown of Ezrin. Then, overexpression of L-periaxin and NFATc1/c2 or knockdown of L-periaxin and NFATc3/c4 mediated by adenovirus vectors were used to confirm their role in Ezrin-mediated myoblast differentiation, myotube formation and gastrocnemius muscle repair in a peroneal nerve injury model. RNA-seq, real-time PCR, immunofluorescence staining and Western blot were used in the above observation. RESULTS: For the first time, instantaneous L-periaxin expression was highest on the 6th day, while Ezrin expression peaked on the 4th day during myoblast differentiation/fusion in vitro. In vivo transduction of adenovirus vectors carrying Ezrin, but not Periaxin, into the gastrocnemius muscle in a peroneal nerve injury model increased the numbers of muscle myosin heavy chain (MyHC) I and II type myofibers, reducing muscle atrophy and fibrosis. Local muscle injection of overexpressed Ezrin combined with incubation of knockdown L-periaxin within the injured peroneal nerve or injection of knockdown L-periaxin into peroneal nerve-injured gastrocnemius muscle not only increased the number of muscle fibers but also recovered their size to a relatively normal level in vivo. Overexpression of Ezrin promoted myoblast differentiation/fusion, inducing increased MyHC-I+ and MyHC-II + muscle fiber specialization, and the specific effects could be enhanced by the addition of adenovirus vectors for knockdown of L-periaxin by shRNA. Overexpression of L-periaxin did not alter the inhibitory effects on myoblast differentiation and fusion mediated by knockdown of Ezrin by shRNA in vitro but decreased myotube length and size. Mechanistically, overexpressing Ezrin did not alter protein kinase A gamma catalytic subunit (PKA-γ cat), protein kinase A I alpha regulatory subunit (PKA reg Iα) or PKA reg Iß levels but increased PKA-α cat and PKA reg II α levels, leading to a decreased ratio of PKA reg I/II. The PKA inhibitor H-89 remarkably abolished the effects of overexpressing-Ezrin on increased myoblast differentiation/fusion. In contrast, knockdown of Ezrin by shRNA significantly delayed myoblast differentiation/fusion accompanied by an increased PKA reg I/II ratio, and the inhibitory effects could be eliminated by the PKA reg activator N6-Bz-cAMP. Meanwhile, overexpressing Ezrin enhanced type I muscle fiber specialization, accompanied by an increase in NFATc2/c3 levels and a decrease in NFATc1 levels. Furthermore, overexpressing NFATc2 or knocking down NFATc3 reversed the inhibitory effects of Ezrin knockdown on myoblast differentiation/fusion. CONCLUSIONS: The spatiotemporal pattern of Ezrin/Periaxin expression was involved in the control of myoblast differentiation/fusion, myotube length and size, and myofiber specialization, which was related to the activated PKA-NFAT-MEF2C signaling pathway, providing a novel L-Periaxin/Ezrin joint strategy for the treatment of muscle atrophy induced by nerve injury, especially in CMT4F.

Exposure to ambient air pollution and metabolic kidney diseases: evidence from the Northeast China Biobank.

BACKGROUND: At present, there is no epidemiological evidence of the association between metabolic kidney diseases (MKD)and exposure to air pollution. METHODS: We investigated the association between exposure to long-term air pollution and the risk of developing MKD using samples from the Northeast China Biobank. RESULTS: Data from 29191 participants were analyzed. MKD prevalence was 3.23%. Every standard deviation increments in PM2.5 increased the risk of MKD (OR = 1.37, 95% CI: 1.19-1.58), diabetic kidney disease ([DKD], OR = 2.03, 95% CI: 1.52-2.73), hypertensive kidney disease ([BKD], OR = 1.31, 95% CI: 1.11-1.56), hyperlipidemic kidney disease ([PKD], OR = 1.39, 95% CI: 1.19-1.63), and obese kidney disease ([OKD], OR = 1.34, 95% CI: 1.00-1.81). PM10 increased the risk of MKD (OR = 1.42, 95% CI: 1.20-1.67), DKD (OR = 1.38, 95% CI: 1.03-1.85), BKD (OR = 1.30, 95% CI: 1.07-1.58), and PKD (OR = 1.50, 95% CI: 1.26-1.80). SO2 increased the risk of MKD (OR = 1.57, 95% CI: 1.34-1.85), DKD (OR = 1.81, 95% CI: 1.36-2.40), BKD (OR = 1.44, 95% CI: 1.19-1.74), and PKD (OR = 1.72, 95% CI: 1.44-2.04). O3 decreased the risk of PKD (OR = 0.83, 95% CI: 0.70-0.99). Age, ethnicity, and air pollution interacted to affect the risk of MKD, BKD, and PKD. Association between air pollution and CKD or metabolic disease were weaker than those with MKD. Association between air pollution and MKD became stronger when compared with participant of non-metabolic disease. CONCLUSIONS: Air pollution may cause MKD or facilitate the progression from metabolic disease to renal failure.

Identification of m6A regulator-mediated RNA methylation modification patterns and key immune-related genes involved in atrial fibrillation.

The role of m6A in the regulation of the immune microenvironment in atrial fibrillation (AF) remains unclear. This study systematically evaluated the RNA modification patterns mediated by differential m6A regulators in 62 AF samples, identified the pattern of immune cell infiltration in AF and identified several immune-related genes associated with AF. A total of six key differential m6A regulators between healthy subjects and AF patients were identified by the random forest classifier. Three distinct RNA modification patterns (m6A cluster-A, -B and -C) among AF samples were identified based on the expression of 6 key m6A regulators. Differential infiltrating immune cells and HALLMARKS signaling pathways between normal and AF samples as well as among samples with three distinct m6A modification patterns were identified. A total of 16 overlapping key genes were identified by weighted gene coexpression network analysis (WGCNA) combined with two machine learning methods. The expression levels of the NCF2 and HCST genes were different between controls and AF patient samples as well as among samples with the distinct m6A modification patterns. RT-qPCR also proved that the expression of NCF2 and HCST was significantly increased in AF patients compared with control participants. These results suggested that m6A modification plays a key role in the complexity and diversity of the immune microenvironment of AF. Immunotyping of patients with AF will help to develop more accurate immunotherapy strategies for those with a significant immune response. The NCF2 and HCST genes may be novel biomarkers for the accurate diagnosis and immunotherapy of AF.

The Role of Widefield Optical Coherence Tomography Angiography in the Diagnosis and Management of Acute Vogt-Koyanagi-Harada Disease.

PURPOSE: We explore the choroid vasculature changes of acute Vogt-Koyanagi-Harada (VKH) disease using widefield optical coherence tomography angiography (OCTA). METHODS: In this retrospective, observational, longitudinal study, 16 patients with acute VKH disease (32 eyes, mean age: 42.19 ±13.66 years) were measured using widefield OCTA. RESULTS: In this study, we first described the multiple dark foci in choriocapillaris and Sattler's layer in the panoramic montage of the five 12x12mm images in 30 eyes (93.8%) of acute VKH disease. OCTA follow-up in these 30 eyes demonstrated the diminished size and number of these dark foci in choriocapillaris and Sattler's layer after the initiation of treatment. CONCLUSIONS: Widefield OCTA enables noninvasive identification of characteristics of flow void at the level of superficial choroidal vessels in the acute phase and may be a novel valuable tool for diagnosis and monitoring of disease progression in VKH disease in the future.

Safety, tolerability, and pharmacokinetics of a single ascending subcutaneous dose of GSK3772847 in healthy participants.

The aim of this study was to evaluate the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of GSK3772847, compared with placebo administered subcutaneously (SC) in healthy participants, including cohorts of Japanese and Chinese participants. This was a single-center, randomized, placebo-controlled, double-blind, single ascending dose study. Following a screening period of up to 28 days, eligible participants were assigned to one of four cohorts receiving a single dose of GSK3772847 70 mg (cohort 1) or 140 mg (cohorts 2, 3, and 4) or placebo SC. In cohorts 1 and 2, participants were randomly assigned to one of three injection sites (upper arm, abdomen, or thigh), while cohorts 3 and 4 included Japanese and Chinese participants, respectively, assigned to receive GSK3772847 or placebo SC (upper arm). Participants attended follow-up visits on Days 9, 15, 29, 43, 57, 71, and 85 before final analysis. GSK3772847 was generally well tolerated. Most adverse events (AEs) were mild, resolved without treatment and were considered not related to study treatment by the investigator. There were no serious AEs or deaths during the study. The PK and PD were dose dependent, with negligible differences across injection sites or ethnicities. Target engagement was demonstrated by reduced free soluble interleukin 33 (sIL-33) concentrations and substantially increased total sIL-33 concentrations compared with baseline. Subcutaneously administered GSK3772847 was well tolerated in healthy participants, including cohorts of Japanese and Chinese participants, and shows consistent PK and PD across injection sites and ethnicities.

LPIH2V: LncRNA-protein interactions prediction using HIN2Vec based on heterogeneous networks model.

LncRNA-protein interaction plays an important role in the development and treatment of many human diseases. As the experimental approaches to determine lncRNA-protein interactions are expensive and time-consuming, considering that there are few calculation methods, therefore, it is urgent to develop efficient and accurate methods to predict lncRNA-protein interactions. In this work, a model for heterogeneous network embedding based on meta-path, namely LPIH2V, is proposed. The heterogeneous network is composed of lncRNA similarity networks, protein similarity networks, and known lncRNA-protein interaction networks. The behavioral features are extracted in a heterogeneous network using the HIN2Vec method of network embedding. The results showed that LPIH2V obtains an AUC of 0.97 and ACC of 0.95 in the 5-fold cross-validation test. The model successfully showed superiority and good generalization ability. Compared to other models, LPIH2V not only extracts attribute characteristics by similarity, but also acquires behavior properties by meta-path wandering in heterogeneous networks. LPIH2V would be beneficial in forecasting interactions between lncRNA and protein.

Pathogenic free-living amoebic encephalitis from 48 cases in China: A systematic review.

Background: Free-living amoebae (FLA) including Naegleria fowleri, Acanthamoeba spp., and Balamuthia mandrillaris can become pathogenic and cause severe cerebral infections, named primary amoebic meningoencephalitis (PAM), granulomatous amoebic encephalitis (GAE), and balamuthia amoebic encephalitis (BAE), respectively. FLA encephalitis has been reported across China, but the clinical data descriptions and analytical results of these different reports vary widely. Currently, no consensus treatment has been established. We conduct a systematic review to evaluate the exposure location, clinical symptoms, diagnosis, treatment, and prognosis of three FLA encephalitis and aim to reveal the differences between three FLA encephalitis in China. Methods: We used MEDLINE (PubMed interface), EMBASE, China National Knowledge Infrastructure (CNKI), Wanfang database, and China Biology Medicine disc (CBMdisc) databases for literatures published and manually retrieve the hospital records of our hospital. The search time was up to August 30, 2022, with no language restrictions. Results: After excluding possible duplicate cases, a total of 48 patients of three FLA encephalitis were collected. One from the medical records of our hospital and 47 patients from 31 different studies. There were 11 patients of PAM, 10 patients of GAE, and 27 patients of BAE. The onset of PAM is mostly acute or subacute, and the clinical symptoms are acute and fulminant hemorrhagic meningoencephalitis. Most patients with GAE and BAE have an insidious onset and a chronic course. A total of 21 BAE patients (77.8%) had skin lesions before onset of symptoms. Additionally, 37 cases (77.1%) were diagnosed with FLA encephalitis before death. And there were 4 of PAM, 2 of GAE, and 10 of BAE diagnosed using next generation sequencing. No single agent can be proposed as the ideal therapy by itself. Only 6 cases were successfully treated. Conclusions: This review provides an overview of the available data and studies of FLA encephalitis in China and identify some potential differences. FLA encephalitis is a rare but pathogenic infection, and physicians should early identify this encephalitis to improve survival.

Novel diagnostic biomarkers of T cell-mediated tumor killing characteristics for early-stage triple negative breast cancer: A SEER analysis and molecular portraits.

The primary objective was to investigate the epidemiology, molecular characteristics, and clinical survival to identify potential transcriptome biomarkers to promote early diagnosis and screening of triple-negative breast cancer patients. Early-stage triple-negative breast cancer patients (E-TNBC) and late-stage triple-negative breast cancer patients (L-TNBC) were identified from the Surveillance, Epidemiology, and End Results database from 2010 to 2019. The difference in cancer specific survival (CSS) and overall survival (OS) between E-TNBC and L-TNBC was analyzed via a Kaplan-Meier plotter. 118 triple-negative breast cancer samples and 114 normal samples with the RNA sequencing expression data were selected from the cohort of TCGA breast cancer from UCSC Xena Database. The study involved 13,690 patients with L-TNBC and 44,994 patients with E-TNBC. L-TNBC patients were more frequently to be ≤ 60 years old (54.9% vs 52.2%), multiple primary site (44.0% vs 30.1%), and were more likely to receive radiotherapy (49.6% vs 47.4%) and chemotherapy (81.1% vs 72.1%), while L-TNBC patients were less likely to be white (68.7% vs 73.0%), married or with domestic partner (46.7% vs 54.7%), poorly differentiated grade (54.0% vs 61.9%), < 3 months from diagnosis to treatment (91.6% vs 96.4%), and were less likely to receive surgery (72.3% vs 95.4%). Stage-stratified survival analysis revealed that the prognosis of L-TNBC was worse when compared to E-TNBC, Kaplan-Meier analysis demonstrated that there were striking differences in OS and CSS between E-TNBC and L-TNBC. In the multivariable regression models, L-TNBC was the single highest risk factor, with a death risk that was 4.741 and 6.074 times higher than E-TNBC in terms of OS and CSS, respectively. The results also showed that treatment with surgery, radiation, or chemotherapy was effective for a better prognosis. Transcriptome analyses revealed that the top 5 upregulated genes in L-TNBC were, respectively, ISX, ALOX15B, MADCAM1, TP63, and ARG1 compared with E-TNBC. And the top 5 downregulated genes were, respectively, CTAG1B, CT45A1, MAGEC2, TFF2, and TNFRSF11B. The L-TNBC exhibited a lower rate of survival than E-TNBC, and the 2 groups differed in terms of transcriptome characteristics. To date, the diagnostic value of T cell-mediated tumor killing portraits on E-TNBC may not be completely recognized.

Regulating conduction and polarization losses by adjusting bonded N in N-doped Cu/CuO/C composites.

Conduction and polarization losses are the main forms of dielectric loss, and regulating these mechanisms is key to obtaining favorable electromagnetic wave absorption performance. In this study, the conversion of graphite N and pyridine N in Cu-based metal-organic framework (MOF)-derived composites was adopted to modulate conduction and polarization losses by tuning the pyrolysis temperature and Cu salt concentration. The results show that increasing the pyrolysis temperature facilitates the conversion of pyridine N to graphite N, which is beneficial for conduction loss. Moreover, increasing the Cu concentration promotes the transformation of pyridine N to graphite N as well as, and then promotes the reverse conversion of graphite N to pyridine N, which is conducive to defect-induced polarization. The unique layered Cu/CuO/C composite obtained at 700 °C with a moderate Cu content exhibited the optimal performance with an effective absorption bandwidth of 5.5 GHz (11.6 âˆ¼ 17.1 GHz) at an ultra-thin thickness of 1.56 mm. This is owed to its favorable impedance matching, significant conduction loss, and polarization loss (defect-induced polarization and interfacial polarization). This study provides a novel strategy for regulating conduction and polarization losses.

Constructing a thyroid cancer prognostic risk model based on CD8+ T cell associated genes.

Thyroid cancer (TC) is a common and curable endocrine tumor occurring in the head and neck characterized by a low mortality rate compared to other malignancies. In this study, the immune microenvironment of TC was investigated to identify biomarkers. The mRNA and clinical data available in this study were accessed from The Cancer Genome Atlas-Thyroid Cancer (TCGA-THCA) dataset. Differences in immune infiltration levels of TC and normal samples were assessed by CIBERSORT. Thyroid cancer samples were classified into high- and low-abundance groups according to the median abundance of immune cell infiltration, and CD8+ T cells were notably correlated with the survival status. Differential expression analysis was conducted on CD8+ T cells to obtain immune-related differentially expressed genes (DEGs). Subsequently, a prognostic risk model was established through Cox regression analysis. According to the median risk score, samples in the training set and validation set were assigned to high- and low-risk groups. The survival and ROC curves demonstrated that the model possesses favorable prognostic prediction ability. Furthermore, the results of gene set enrichment analysis (GSEA) indicated differences between the high- and low-risk groups in terms of ECM receptor interaction and transforming growth factor ß (TGF-ß) signaling pathways. The tumor microenvironment of TC samples was evaluated by ESTIMATE, which showed that stromal scores were higher in the high-risk group. Finally, simple-sample GSEA (ssGSEA) was performed on TC samples. The results indicated a higher infiltration level of NK cells in the low-risk group, as well as a lower level in the high-risk group. In terms of immune function-related gene sets, genes related to APC co-inhibition, cytolytic activity, HLA and T cell co-inhibition were observed to present higher expression levels in the low-risk group. In general, this study built a 6-gene prognostic risk assessment model based on CD8+ T cells through bioinformatics analysis, which is expected to be a reference for clinicians to judge the prognosis of TC patients.