Genomic analyses of wild argali, domestic sheep, and their hybrids provide insights into chromosome evolution, phenotypic variation, and germplasm innovation.

Understanding the genetic mechanisms of phenotypic variation in hybrids between domestic animals and their wild relatives may aid germplasm innovation. Here, we report the high-quality genome assemblies of a male Pamir argali (O ammon polii, 2n = 56), a female Tibetan sheep (O aries, 2n = 54), and a male hybrid of Pamir argali and domestic sheep, and the high-throughput sequencing of 425 ovine animals, including the hybrids of argali and domestic sheep. We detected genomic synteny between Chromosome 2 of sheep and two acrocentric chromosomes of argali. We revealed consistent satellite repeats around the chromosome breakpoints, which could have resulted in chromosome fusion. We observed many more hybrids with karyotype 2n = 54 than with 2n = 55, which could be explained by the selfish centromeres, the possible decreased rate of normal/balanced sperm, and the increased incidence of early pregnancy loss in the aneuploid ewes or rams. We identified genes and variants associated with important morphological and production traits (e.g., body weight, cannon circumference, hip height, and tail length) that show significant variations. We revealed a strong selective signature at the mutation (c.334C > A, p.G112W) in TBXT and confirmed its association with tail length among sheep populations of wide geographic and genetic origins. We produced an intercross population of 110 F2 offspring with varied number of vertebrae and validated the causal mutation by whole-genome association analysis. We verified its function using CRISPR-Cas9 genome editing. Our results provide insights into chromosomal speciation and phenotypic evolution and a foundation of genetic variants for the breeding of sheep and other animals.

TNFAIP3 Derived from Skeletal Stem Cells Alleviated Rat Osteoarthritis by Inhibiting the Necroptosis of Subchondral Osteoblasts.

Recent investigations have shown that the necroptosis of tissue cells in joints is important in the development of osteoarthritis (OA). This study aimed to investigate the potential effects of exogenous skeletal stem cells (SSCs) on the necroptosis of subchondral osteoblasts in OA. Human SSCs and subchondral osteoblasts isolated from human tibia plateaus were used for Western blotting, real-time PCR, RNA sequencing, gene editing, and necroptosis detection assays. In addition, the rat anterior cruciate ligament transection OA model was used to evaluate the effects of SSCs on osteoblast necroptosis in vivo. The micro-CT and pathological data showed that intra-articular injections of SSCs significantly improved the microarchitecture of subchondral trabecular bones in OA rats. Additionally, SSCs inhibited the necroptosis of subchondral osteoblasts in OA rats and necroptotic cell models. The results of bulk RNA sequencing of SSCs stimulated or not by tumor necrosis factor α suggested a correlation of SSCs-derived tumor necrosis factor α-induced protein 3 (TNFAIP3) and cell necroptosis. Furthermore, TNFAIP3-derived from SSCs contributed to the inhibition of the subchondral osteoblast necroptosis in vivo and in vitro. Moreover, the intra-articular injections of TNFAIP3-overexpressing SSCs further improved the subchondral trabecular bone remodeling of OA rats. Thus, we report that TNFAIP3 from SSCs contributed to the suppression of the subchondral osteoblast necroptosis, which suggests that necroptotic subchondral osteoblasts in joints may be possible targets to treat OA by stem cell therapy.

Late Middle Pleistocene Levallois stone-tool technology in southwest China.

Levallois approaches are one of the best known variants of prepared-core technologies, and are an important hallmark of stone technologies developed around 300,000 years ago in Africa and west Eurasia1,2. Existing archaeological evidence suggests that the stone technology of east Asian hominins lacked a Levallois component during the late Middle Pleistocene epoch and it is not until the Late Pleistocene (around 40,000-30,000 years ago) that this technology spread into east Asia in association with a dispersal of modern humans. Here we present evidence of Levallois technology from the lithic assemblage of the Guanyindong Cave site in southwest China, dated to approximately 170,000-80,000 years ago. To our knowledge, this is the earliest evidence of Levallois technology in east Asia. Our findings thus challenge the existing model of the origin and spread of Levallois technologies in east Asia and its links to a Late Pleistocene dispersal of modern humans.

Complement system is overactivated in patients with IgA nephropathy after COVID-19.

IgA nephropathy (IgAN), which has been confirmed as a complement mediated autoimmune disease, is also one form of glomerulonephritis associated with COVID-19. Here, we aim to investigate the clinical and immunological characteristics of patients with IgAN after COVID-19. The level of plasma level of C5a (p < 0.001), soluble C5b-9 (p = 0.018), FHR5 (p < 0.001) were all significantly higher in Group CoV (33 patients with renal biopsy-proven IgAN experienced COVID-19) compared with Group non-CoV (44 patients with IgAN without COVID-19), respectively. Compared with Group non-CoV, the intensity of glomerular C4d (p = 0.017) and MAC deposition (p < 0.001) and Gd-IgA1 deposition (p = 0.005) were much stronger in Group CoV. Our finding revealed that for IgAN after COVID-19, mucosal immune responses to SARS-CoV-2 infection may result in the overactivation of systemic and renal local complement system, and increased glomerular deposition of Gd-IgA1, which may lead to renal dysfunction and promote renal progression in IgAN patients.

Donor memory-like NK cells persist and induce remissions in pediatric patients with relapsed AML after transplant.

Pediatric and young adult (YA) patients with acute myeloid leukemia (AML) who relapse after allogeneic hematopoietic cell transplantation (HCT) have an extremely poor prognosis. Standard salvage chemotherapy and donor lymphocyte infusions (DLIs) have little curative potential. Previous studies showed that natural killer (NK) cells can be stimulated ex vivo with interleukin-12 (IL-12), -15, and -18 to generate memory-like (ML) NK cells with enhanced antileukemia responses. We treated 9 pediatric/YA patients with post-HCT relapsed AML with donor ML NK cells in a phase 1 trial. Patients received fludarabine, cytarabine, and filgrastim followed 2 weeks later by infusion of donor lymphocytes and ML NK cells from the original HCT donor. ML NK cells were successfully generated from haploidentical and matched-related and -unrelated donors. After infusion, donor-derived ML NK cells expanded and maintained an ML multidimensional mass cytometry phenotype for >3 months. Furthermore, ML NK cells exhibited persistent functional responses as evidenced by leukemia-triggered interferon-γ production. After DLI and ML NK cell adoptive transfer, 4 of 8 evaluable patients achieved complete remission at day 28. Two patients maintained a durable remission for >3 months, with 1 patient in remission for >2 years. No significant toxicity was experienced. This study demonstrates that, in a compatible post-HCT immune environment, donor ML NK cells robustly expand and persist with potent antileukemic activity in the absence of exogenous cytokines. ML NK cells in combination with DLI present a novel immunotherapy platform for AML that has relapsed after allogeneic HCT. This trial was registered at https://clinicaltrials.gov as #NCT03068819.

Pleurotus eryngii root waste and soybean meal co-fermented protein improved the growth, immunity, liver and intestinal health of largemouth bass (Micropterus salmoides).

The present study aimed to evaluate the effect of king oyster mushroom (Pleurotus eryngii) root waste and soybean meal co-fermented protein (CFP) on growth performance, feed utilization, immune status, hepatic and intestinal health of largemouth bass (Micropterus salmoides). Largemouth bass (12.33 ± 0.18 g) were divided into five groups, fed with diets containing 0 %, 5 %, 10 %, 15 % and 20 % CFP respectively for 7 weeks. The growth performance and dietary utilization were slightly improved by the supplementation of CFP. In addition, improved immunoglobulin M (IgM) content and lysozyme activity in treatments confirm the enhancement of immunity in fish by the addition of CFP, especially in fish fed 20 % CFP (P < 0.05). Furthermore, CFP significantly improved liver GSH (glutathione) content in groups D10 and D15 (P < 0.05), and slightly improved total antioxidant capacity (T-AOC), superoxide dismutase (SOD) activity while slightly reduced malondialdehyde (MDA) content. Simultaneously, the upregulation of lipolysis-related genes (PPARα, CPT1 and ACO) expression and downregulation of lipid synthesis-related genes (ACC and DGAT1) expression was recorded in the group D20 compared with the control (P < 0.05), which were consistent with the decreased liver lipid contents, suggests that lipid metabolism was improved by CFP. In terms of intestinal structural integrity, ameliorated intestinal morphology in treatments were consistent with the upregulated Occludin, Claudin-1 and ZO-1 genes expression. The intestinal pro-inflammatory cytokines (TNF-α and IL-8) expression were suppressed while the anti-inflammatory cytokines (IL-10 and TGF-ß) were activated in treatments. The expression of antimicrobial peptides (Hepcidin-1, Piscidin-2 and Piscidin-3) and intestinal immune effectors (IgM and LYZ) were slightly up-regulated in treatments. Additionally, the relative abundance of intestinal beneficial bacteria (Firmicutes) increased while the relative abundance of potential pathogenic bacteria (Fusobacterium and Proteobacteria) decreased, which indicated that the intestinal microbial community was well-reorganized by CFP. In conclusion, dietary CFP improves growth, immunity, hepatic and intestinal health of largemouth bass, these data provided a theoretical basis for the application of this novel functional protein ingredient in fish.

A molecular container providing supramolecular protection against acetylcholine hydrolysis.

Alzheimer's disease (AD) is characterized by cognitive decline, often attributed to the deficiency of acetylcholine, which can undergo hydrolysis by acetylcholinesterase (AChE) within the biological milieu. Here, we report a supramolecular strategy that takes advantage of confinement effects to inhibit such a hydrolysis process, shedding some light on AD therapy. A water-soluble and bowl-shaped molecule, hexacarboxylated tribenzotriquinacene (TBTQ-C6), was employed to shield acetylcholine (G1) from enzymatic degradation through host-guest binding interactions. Our study revealed highly efficient host-guest interactions with a binding ratio of 1 : 3, resulting in a significant reduction in acetylcholine hydrolysis from 91.1% to 7.4% in the presence of AChE under otherwise identical conditions. Furthermore, TBTQ-C6 showed potential for attenuating the degradation of butyrylcholine (G2) by butyrylcholinesterase (BChE). The broader implications of this study extend to the potential use of molecular containers in various biochemical and pharmacological applications, opening new avenues for research in the field of neurodegenerative diseases.

A Bibliometrics of the Treatment of Alopecia Areata in the Past Twenty Years.

BACKGROUND: Alopecia areata (AA) is an autoimmune disorder characterized by hair loss on the scalp, face, and other body areas. Despite affecting approximately 2% of the global population, there has been no previous bibliometric analysis specifically focusing on AA treatment that can guide researchers in exploring promising treatment options and directing future research efforts. SUMMARY: This study conducted a bibliometric analysis of AA treatment research, encompassing publications from 2003 to 2022. A total of 1,323 papers from 65 countries, predominantly led by the USA and China, were included in the analysis. The number of publications related to AA treatment showed a notable increase over the years. Prominent research institutions included the University of Manchester, Icahn School of Medicine at Mount Sinai, University of Miami, and Columbia University. Among the journals, Dermatologic Therapy stood out as the most popular, while the Journal of the American Academy of Dermatology appeared as the most frequently co-cited publication.

Development and validation of a multi-modal ultrasomics model to predict response to neoadjuvant chemoradiotherapy in locally advanced rectal cancer.

OBJECTIVES: To assess the performance of multi-modal ultrasomics model to predict efficacy to neoadjuvant chemoradiotherapy (nCRT) in patients with locally advanced rectal cancer (LARC) and compare with the clinical model. MATERIALS AND METHODS: This study retrospectively included 106 patients with LARC who underwent total mesorectal excision after nCRT between April 2018 and April 2023 at our hospital, randomly divided into a training set of 74 and a validation set of 32 in a 7: 3 ratios. Ultrasomics features were extracted from the tumors' region of interest of B-mode ultrasound (BUS) and contrast-enhanced ultrasound (CEUS) images based on PyRadiomics. Mann-Whitney U test, spearman, and least absolute shrinkage and selection operator algorithms were utilized to reduce features dimension. Five models were built with ultrasomics and clinical analysis using multilayer perceptron neural network classifier based on python. Including BUS, CEUS, Combined_1, Combined_2 and Clinical models. The diagnostic performance of models was assessed with the area under the curve (AUC) of the receiver operating characteristic. The DeLong testing algorithm was utilized to compare the models' overall performance. RESULTS: The AUC (95% confidence interval [CI]) of the five models in the validation cohort were as follows: BUS 0.675 (95%CI: 0.481-0.868), CEUS 0.821 (95%CI: 0.660-0.983), Combined_1 0.829 (95%CI: 0.673-0.985), Combined_2 0.893 (95%CI: 0.780-1.000), and Clinical 0.690 (95%CI: 0.509-0.872). The Combined_2 model was the best in the overall prediction performance, showed significantly better compared to the Clinical model after DeLong testing (P < 0.01). Both univariate and multivariate logistic regression analyses showed that age (P < 0.01) and clinical stage (P < 0.01) could be an independent predictor of efficacy after nCRT in patients with LARC. CONCLUSION: The ultrasomics model had better diagnostic performance to predict efficacy to nCRT in patients with LARC than the Clinical model.

Endoscopic Rectal Ultrasound-Based Radiomics Analysis for the Prediction of Synchronous Liver Metastasis in Patients With Primary Rectal Cancer.

OBJECTIVES: To develop and validate an ultrasound-based radiomics model to predict synchronous liver metastases (SLM) in rectal cancer (RC) patients preoperatively. METHODS: Two hundred and thirty-nine RC patients were included in this study and randomly divided into training and validation cohorts. A total of 5936 radiomics features were calculated on the basis of ultrasound images to build a radiomic model and obtain a radiomics score (Rad-score) using logistic regression. Meanwhile, clinical characteristics were collected to construct a clinical model. The radiomics-clinical model was developed and validated by integrating the radiomics features with the selected clinical characteristics. The performances of three models were evaluated and compared through their discrimination, calibration, and clinical usefulness. RESULTS: The radiomics model was developed based on 13 radiomic features. The radiomics-clinical model, which incorporated Rad-score, CEA, and CA199, exhibited favorable discrimination and calibration with areas under the receiver operating characteristic curve (AUC) of 0.920 (95% CI: 0.874-0.965) in the training cohorts and 0.855 (95% CI: 0.759-0.951) in the validation cohorts. And the AUC of the radiomics-clinical model was 0.849 (95% CI: 0.771-0.927) for the training cohorts and 0.780 (95% CI: 0.655-0.905) for the validation cohorts, the clinical model was 0.811 (95% CI: 0.718-0.905) for the training cohorts and 0.805 (95% CI: 0.645-0.965) for the validation cohorts. Moreover, decision curve analysis (DCA) further confirmed the clinical utility of the radiomics-clinical model. CONCLUSIONS: The radiomics-clinical model performed satisfactory predictive performance, which can help improve clinical diagnosis performance and outcome prediction for SLM in RC patients.

Application of thifluzamide to stem rot in peppers: Infection and control mechanisms of sclerotium rolfsii.

In recent years, the fungal disease 'pepper stem rot', contracted from the soil-borne pathogen sclerotium rolfsii, has been increasing year by year, causing significant losses to the pepper (Capsicum annuum L.) industry. To investigate the infection mechanism of stem rot, the fungus S. rolfsii was used to infect the roots of pepper plants, and was found to affect root morphology and reduce root activity, which subsequently inhibited root growth and development. With fungal infestation, its secretions (oxalic acid, PG and PMG enzyme) were able to break normal tissues in the stem base and induced the burst of the active oxygen, which leads to injury aggravation. Morphological observations of the site of damage at the base of the stem using SEM revealed that the vascular bundles and stomata were completely blocked by hyphae, resulting in a blockade of material exchange in the plant. It was subsequently found that most of the stomata in the leaves were closed, which caused the leaves to lose their ability to photosynthesize, then turned yellow, wilt, shed, and the plant died. Commercialized fungicide thifluzamide with excellent in vitro (EC50 = 0.1 µg/mL) and in vivo curative (EC50 = 29.2 µg/mL) antifungal activity was selected to control the stem rot disease in peppers. The results demonstrated that it was able to suppress the secretion of associated pathogenic factors and reduce the outbursts of reactive oxygen species, thus reducing the damage caused by S. rolfsii at the base of the plant's stem and also enhancing the root activity of the infected plant, thereby promoting root growth. It could also inhibit fungal growth, unblock the vascular bundles and stomata, maintain a balance of material and energy exchange within the plant, and thus restore the damaged plant to its normal growth capacity. All the results will provide an adequate reference for the prevention and control of stem rot disease on peppers with thifluzamide.

PTPN7 mediates macrophage-polarization and determines immunotherapy in gliomas: A single-cell sequencing analysis.

BACKGROUND: Protein tyrosine phosphatase non-receptor type 7 (PTPN7) is a signaling molecule that regulates a multitude of cellular processes, spanning cell proliferation, cellular differentiation, the mitotic cycle, and oncogenic metamorphosis. However, the characteristic of PTPN7 in the glioma microenvironment has yet to be elucidated. METHODS: The prognostic value, genomic features, immune characteristics, chemotherapy prediction, and immunotherapy prediction of PTPN7 were systematically explored at the bulk sequencing level. The cell evolution trajectory, cell communication pattern, and cell metabolic activity related to PTPN7 were systematically explored at the single-cell sequencing level. HMC3 and M0 cells were cocultured with U251 and T98G cells, and flow cytometry was carried out to investigate the polarization of HMC3 and M0. Transwell assay and CCK-8 assay were performed to explore the migration and proliferation activity of U251 and T98G. RESULTS: The expression level of PTPN7 is significantly elevated in glioma and indicates malignant features. PTPN7 expression predicts worse prognosis of glioma patients. PTPN7 is associated with genome alteration and immune infiltration. Besides, PTPN7 plays a crucial role in modulating metabolic and immunogenic processes, particularly by influencing the activity of microglia and macrophages through multiple signaling pathways involved in cellular communication. Specifically, PTPN7 actively mediates inflammation-resolving-polarization of macrophages and microglia and protects glioma from immune attack. PTPN7 could also predict the response of immunotherapy. CONCLUSIONS: PTPN7 is critically involved in inflammation-resolving-polarization mediated by macrophage and microglia and promotes the immune escape of glioma cells.

Application of Independent Component Analysis and Nelder-Mead Particle Swarm Optimization Algorithm in Non-Contact Blood Pressure Estimation.

In recent years, hypertension has become one of the leading causes of illness and death worldwide. Changes in lifestyle among the population have led to an increasing prevalence of hypertension. This study proposes a non-contact blood pressure estimation method that allows patients to conveniently monitor their blood pressure values. By utilizing a webcam to track facial features and the region of interest (ROI) for obtaining forehead images, independent component analysis (ICA) is employed to eliminate artifact signals. Subsequently, physiological parameters are calculated using the principle of optical wave reflection. The Nelder-Mead (NM) simplex method is combined with the particle swarm optimization (PSO) algorithm to optimize the empirical parameters, thus enhancing computational efficiency and accurately determining the optimal solution for blood pressure estimation. The influences of light intensity and camera distance on the experimental results are also discussed. Furthermore, the measurement time is only 10 s. The superior accuracy and efficiency of the proposed methodology are demonstrated by comparing them with those in other published literature.

Whole-Genome Resequencing of Worldwide Wild and Domestic Sheep Elucidates Genetic Diversity, Introgression, and Agronomically Important Loci.

Domestic sheep and their wild relatives harbor substantial genetic variants that can form the backbone of molecular breeding, but their genome landscapes remain understudied. Here, we present a comprehensive genome resource for wild ovine species, landraces and improved breeds of domestic sheep, comprising high-coverage (∼16.10×) whole genomes of 810 samples from 7 wild species and 158 diverse domestic populations. We detected, in total, ∼121.2 million single nucleotide polymorphisms, ∼61 million of which are novel. Some display significant (P < 0.001) differences in frequency between wild and domestic species, or are private to continent-wide or individual sheep populations. Retained or introgressed wild gene variants in domestic populations have contributed to local adaptation, such as the variation in the HBB associated with plateau adaptation. We identified novel and previously reported targets of selection on morphological and agronomic traits such as stature, horn, tail configuration, and wool fineness. We explored the genetic basis of wool fineness and unveiled a novel mutation (chr25: T7,068,586C) in the 3'-UTR of IRF2BP2 as plausible causal variant for fleece fiber diameter. We reconstructed prehistorical migrations from the Near Eastern domestication center to South-and-Southeast Asia and found two main waves of migrations across the Eurasian Steppe and the Iranian Plateau in the Early and Late Bronze Ages. Our findings refine our understanding of genome variation as shaped by continental migrations, introgression, adaptation, and selection of sheep.

Exosomal hsa_circ_000200 as a potential biomarker and metastasis enhancer of gastric cancer via miR-4659a/b-3p/HBEGF axis.

BACKGROUND: Exosome, a component of liquid biopsy, loaded protein, DNA, RNA and lipid gradually emerges as biomarker in tumors. However, exosomal circRNAs as biomarker and function mechanism in gastric cancer (GC) are not well understood. METHODS: Differentially expressed circRNAs in GC and healthy people were screened by database. The identification of hsa_circ_000200 was verified by RNase R and sequencing, and the expression of hsa_circ_000200 was evaluated using qRT-PCR. The biological function of hsa_circ_000200 in GC was verified in vitro. Western blot, RIP, RNA fluorescence in situ hybridization, and double luciferase assay were utilized to explore the potential mechanism of hsa_circ_000200. RESULTS: Hsa_circ_000200 up-regulated in GC tissue, serum and serum exosomes. Hsa_circ_000200 in serum exosomes showed better diagnostic ability than that of tissues and serum. Combined with clinicopathological parameters, its level was related to invasion depth, TNM staging, and distal metastasis. Functionally, knockdown of hsa_circ_000200 inhibited GC cells proliferation, migration and invasion in vitro, while its overexpression played the opposite role. Importantly, exosomes with up-regulated hsa_circ_000200 promoted the proliferation and migration of co-cultured GC cells. Mechanistically, hsa_circ_000200 acted as a "ceRNA" for miR-4659a/b-3p to increase HBEGF and TGF-ß/Smad expression, then promoted the development of GC. CONCLUSIONS: Our findings suggest that hsa_circ_000200 promotes the progression of GC through hsa_circ_000200/miR-4659a/b-3p/HBEGF axis and affecting the expression of TGF-ß/Smad. Serum exosomal hsa_circ_000200 may serve as a potential biomarker for GC.

Formation of Rogue Waves and Modulational Instability with Zero-Wavenumber Gain in Multicomponent Systems with Coherent Coupling.

It is known that rogue waves (RWs) are generated by the modulational instability (MI) of the baseband type. Starting with the Bers-Kaup-Reiman system for three-wave resonant interactions, we identify a specific RW-building mechanism based on MI which includes zero wavenumber in the gain band. An essential finding is that this mechanism works solely under a linear relation between the MI gain and a vanishingly small wavenumber of the modulational perturbation. The same mechanism leads to the creation of RWs by MI in other multicomponent systems-in particular, in the massive Thirring model.

Experimental Investigation on Laser-Induced Electrochemical Silver Plating Technology.

The silver coating is widely used in electronic device manufacturing due to its excellent conductivity and soldering properties. Conventional preparation of local silver coating often uses the preplated silver, mask high-speed silver plating, and deplated silver processes. In this paper, the laser-induced electrodeposition technique is used to perform maskless laser-induced localized electrodeposition on a copper substrate preplated with a layer of silver. After the deplated silver process, ultrathin silver coatings with high dimensional accuracy, good corrosion resistance, and good bonding were obtained. The spatial distribution of the transient temperature field under laser irradiation is studied, the variation pattern of cathode substrate current under laser irradiation is tested, and finally, the spatial distribution of the pressure field under laser irradiation is simulated by Comsol. The effect of different laser scanning methods on the coating morphology was investigated, and the experimental study of the different single pulse energy-induced localized silver coatings was systematically carried out. The results show that the localized coating obtained by cross-line scanning with a laser single pulse energy of 93 µJ is flat with a film thickness of 0.23 µm, high dimensional accuracy, and good bonding force and corrosion resistance properties. This method provides a new approach for the preparation of a localized silver coating.

Urine Galectin-3 binding protein reflects nephritis activity in systemic lupus erythematosus.

BACKGROUND: Lupus nephritis (LN) is a major and severe organ involvement in systemic lupus erythematosus (SLE), whose diagnosis and treatment necessitate to perform kidney biopsy, which is an invasive procedure. Non-invasive urine biomarkers are an active area of investigation to support LN diagnosis and management. OBJECTIVE: To investigate the role of urinary galectin-3 binding protein (u-Gal-3BP) as a candidate biomarker of renal disease in biopsy proven LN. PATIENTS AND METHODS: Levels of u-Gal-3BP were investigated in a cross-sectional fashion by ELISA in 270 subjects: 86 LN patients, 63 active SLE patients with no kidney involvement, 73 SLE patients with inactive disease and 48 age and sex-matched population-based controls (PBC). Moreover, urine samples were analysed separately by ELISA for additional markers of kidney pathology: neutrophil gelatinase-associated lipocalin (NGAL), osteopontin (OPN), kidney injury molecule-1 (KIM-1) and galectin-3 (Gal-3). The concentrations of all studied molecules were normalized to urine creatinine levels. In 10 patients, post-treatment levels of the biomarkers were measured. RESULTS: Normalized u-Gal-3BP levels were higher in LN patients compared to the other groups (p < .0001). Comparing different LN classes, u-Gal-3BP levels were higher among patients with proliferative (class III/IV) and membranous (class V) as compared to mesangial (class II) forms (p = .04). In proliferative forms, u-Gal-3BP levels correlated with the activity index in renal biopsies (r = 0.42, p = .004). Moreover, in a subset of 10 patients with repeated kidney biopsy and urine sampling before and after induction treatment, a significant decrease of u-Gal-3BP was observed (p = .03). Among the other markers, KIM-1 was also able to discriminate LN from the other groups, while NGAL, OPN and Gal-3 could not in this cohort. CONCLUSION: Given its ability to discriminate LN patients from active non-renal and inactive SLE patients, the observed correlation with the activity index in renal biopsies, and its levels declining following treatment, u-Gal-3BP shows promise as a non-invasive urinary biomarker to help detecting and to monitor renal involvement in SLE patients and should be validated in larger cohorts.

A Case of Fetal Familial Hemophagocytic Lymphohistiocytosis Type 5 caused by STXBP2 Gene Mutation.

BACKGROUND: Familial hemophagocytic lymphohistiocytosis type 5 (FHL-5) is a rare hyper-inflammatory syndrome caused by mutations in STXBP2. Most cases present at 2 - 6 months of age, and FHL-5 is extremely rare in neonates. METHODS: Appropriate laboratory tests, abdominal ultrasonography and whole exome sequencing were carried out. Respiratory support, antibiotics, and transfusion of blood products were done. RESULTS: Laboratory tests revealed metabolic acidosis, thrombocytopenia, mild anemia, and low fibrinogen level. Blood culture, metagenomics, and TORCH screening were negative. Liver and spleen enlargements were confirmed by abdominal ultrasonography. Whole exome sequencing identified a homozygous mutation in STXBP2 c. 1432del G (p. V478Sfs*5). The heterozygous STXBP2 mutation was identified in the paternal grandfather, maternal grandfather, and parents. CONCLUSIONS: Here we report a case with a novel homozygous deletion in exon 16 of STXBP2, which caused the earliest reported case of FHL-5 in a neonate. Our results identify a new pathogenic variant for the early identification and clinical consultation of FHL-5.

Differences between CEUS LI-RADS and CECT LI-RADS in the diagnosis of focal liver lesions in patients at risk for HCC.

OBJECTIVES: To compare the inter-modality consistency and diagnostic performances of the contrast-enhanced ultrasound (CEUS) Liver Imaging Reporting and Data System (LI-RADS) and contrast-enhanced computed tomography (CECT) LI-RADS in patients at risk for hepatocellular carcinoma (HCC), so as to help clinicians to select a more appropriate modality to follow the focal liver lesions (FLLs). METHODS: This retrospective study included untreated 277 FLLs from 247 patients who underwent both CEUS and CECT within 1 month. The ultrasound contrast medium used was SonoVue. FLL categories were independently assigned by two ultrasound physicians and two radiologists using CEUS LI-RADS v2017 and CECT LI-RADS v2018, respectively. The diagnostic performances of CEUS and CECT LI-RADS were evaluated using sensitivity, specificity, positive predictive value (PPV), and negative predictive value. Cohen's Kappa was employed to evaluate the concordance of the LI-RADS category. RESULTS: The inter-modality consistency for CEUS and CECT LI-RADS was 0.31 (p < 0.001). HCC was more frequently observed in CECT LR-3 and LR-4 hepatic lesions than in CEUS (7.3% vs. 19.5%, p < 0.001). The specificity and PPV of CEUS and CECT LR-5 for the diagnosis of HCC were 89.5%, 95.0%, and 82.5%, 94.4%, respectively. The sensitivity of CEUS LR-5 + LR-M for the diagnosis of hepatic malignancies was higher than that of CECT (93.7% vs. 82.7%, p < 0.001). The specificity and PPV of CEUS LR-M for the diagnosis of non-HCC malignancies were lower than those of CECT (59.7% vs. 95.5%, p < 0.001; 23.4% vs. 70.3%, p < 0.001). CONCLUSIONS: The inter-modality consistency between the CEUS and CECT LI-RADS categories is fair. CEUS LI-RADS was more sensitive than CECT LI-RADS in terms of identifying hepatic malignancies, but weaker in terms of separating HCC from non-HCC malignancies.