Sources of Allergens Detected Through Allergen-Specific Serum IgE Antibody Test in Children with Suspected Allergic Diseases in Central China.

Purpose: Although allergic diseases in children are on the rise, there has been no comprehensive investigation of the allergens affecting children with allergic diseases in central China. Therefore, we aimed to analyze the distribution of serum allergen species among children with allergic conditions in central China to inform the prevention, diagnosis, and treatment of childhood allergies. Patients and Methods: A total of 9213 children (5543 males with 2.88 ± 0.04 years old and 3670 females with 2.91 ± 0.05 years old) underwent allergen screening, and serum allergen-specific IgE (sIgE) antibodies were detected using an automated fluorescent enzyme immunoassay system. Results: Our findings revealed a total sIgE-positive rate (sIgE-PR) of 57.83%, with mixed food (42.10%), egg whites (30.83%), milk (28.97%), mixed dust mites (24.57%), and mixed molds (23.20%) being the most prevalent source of allergens. The sIgE-PR for common sources of allergens exhibited significant sex-based differences, with males having greater susceptibility than females (p<0.05). Dust mites were the primary source of inhaled allergens, whereas egg white was the predominant source of food allergens. Sources of food allergens were most dominant among infants (0-3 years old); sIgE-PRs for most source of food allergens decreased with age, whereas those for most source of inhaled allergens increased. The autumn sIgE-PRs for mixed molds, weed pollen combinations, and tree pollen combinations were significantly higher than those found in other seasons (p<0.05). Conclusion: Our findings suggest that sources of allergens profiles in children with allergies vary across age groups and seasons. Understanding these patterns can improve the effective prevention of childhood allergies.

The interference of anti-TSH autoantibody on clinical TSH detection.

Objective: It is well known that macro-thyroid-stimulating hormone (macro-TSH) could interfere with the detection of TSH. The anti-TSH autoantibody is an essential component of macro-TSH. However, the epidemiological characteristics and the clinical interference of the anti-TSH autoantibody are unclear. Methods: In this study, the radioimmunoprecipitation technique was used to detect the anti-TSH autoantibody. Platforms with different detection mechanisms were applied to measure the TSH in patients with the anti-TSH autoantibody. Polyethylene glycol (PEG) precipitation was used to determine the immunoassay interference. Results: The prevalence of the anti-TSH autoantibody in patients with mild subclinical hypothyroidism (SCH) and autoimmune thyroiditis, but normal thyroid function, was 4.78%. All 10 patients with anti-TSH antibodies had autoimmune diseases, with five of them having significant clinical test interference. Conclusion: The appearance of the anti-TSH antibody is not associated with thyroid autoantibodies. The presence of the anti-TSH autoantibody can interfere with the detection of TSH and can affect clinical diagnosis and treatment.

Gender and tumor size-specific calcitonin cutoff value for diagnosing MTC in 10,618 patients with thyroid nodule surgery.

BACKGROUND: Calcitonin is a sensitive marker for medullary thyroid carcinoma (MTC) diagnosis and postsurgical follow-up. This study aimed to define the gender and tumor size-specific calcitonin cutoff values for diagnosing MTC. METHODS: This retrospective study recruited 95 MTC patients and 10,523 non-MTC patients who underwent thyroid nodule surgery at Zhongshan Hospital between January 2015 and June 2023. Receiver operating characteristic (ROC) curves were used to assess calcitonin cutoff values for diagnosing MTC. RESULTS: Calcitonin levels in non-MTC patients were influenced by gender, CKD stage and age, with gender being the highest ranked predictor. In MTC patients, calcitonin levels were associated with tumor diameter, lymph node metastasis, and TNM stage. In the entire study population, calcitonin cutoff values to diagnose MTC were 17.75 pg/mL for males (sensitivity: 97.60%, specificity: 99.40%) and 7.15 pg/mL for females (sensitivity: 94.34%, specificity: 99.22%). In patients with a thyroid nodule diameter ≤10 mm, the calcitonin cutoff values to diagnose MTC were 17.50 pg/mL for males (sensitivity: 95.00%, specificity: 99.27%) and 7.15 pg/mL for females (sensitivity: 90.91%, specificity: 99.04%). In patients with a thyroid nodule diameter >10 mm, the calcitonin cutoff values to diagnose MTC were 104.80 pg/mL for males (sensitivity: 100.00%, specificity: 100.00%) and 32.60 pg/mL for females (sensitivity: 96.77%, specificity: 100.00%). CONCLUSION: We have identified the gender and tumor size-specific cutoff values for the diagnosis of MTC. Cutoff values based on gender and tumor diameter may help to improve the accuracy of preoperative diagnosis of MTC, which is worth to be verified by future studies.

Realize short-wave infrared luminescence in NaScP2O7:Cr3+,Yb3+ phosphor: Spectral and energy transfer.

Short-wave infrared emitting phosphors have extensive applications for spectroscopy technology. The near-infrared phosphor NaScP2O7:Cr3+ that we present in this work has a full width at half maximum (FWHM) of approximately 196 nm, which ranges from 700 to 1200 nm. To achieve efficient short-wave infrared, Yb3+ ions were co-doped. The NaScP2O7:Cr3+,Yb3+ material emitted infrared bands with peaks at 970 and 1003 nm upon excitation at450 nm. Benefitting from energy transfer (ET), the light in the 900-1200 nm from Yb3+ is effectively enhanced. Photoluminescence spectra, thermal quenching, and decay curves of Cr3+/Yb3+ single and codoped NaScP2O7 were investigated. An internal quantum yield of 29.6 % wasdemonstrated by the optimized phosphor NaScP2O7:Cr3+,Yb3+. Furthermore, The final fabrication of the short-wave infrared pc-LED was done through the combination of a blue-emitting chip and NaScP2O7:Cr3+,Yb3+ phosphor, thereby showing great promise for real implementations.

Role of Telemedicine Intervention in the Treatment of Patients with Chronic Heart Failure: A Systematic Review and Meta-analysis.

OBJECTIVE: Although telemedicine interventional therapy is an innovative method to reduce public medical burden and improve heart failure, its effectiveness is still controversial. This meta-analysis evaluates the role of telemedicine interventional therapy in the treatment of patients with chronic heart failure. METHODS: Relevant literature on telemedicine in chronic heart failure treatment was screened and extracted based on predefined criteria. Quality assessment used Cochrane Handbook 5.1.0 tool, and meta-analysis was conducted using R 4.2.2 software. RESULTS: Fifteen English-language articles were ultimately included in this meta-analysis. The risk bias evaluation determined that 4 articles were low-risk bias and 11 articles were unclear risk bias. The meta-analysis revealed that, compared to the routine intervention group, the all-cause hospitalization rate of patients in the telemedicine intervention group decreased [OR = 0.63, 95% CI (0.41; 0.96), P =.03], and the hospitalization rate of heart failure also decreased [OR = 0.70, 95% CI (0.48; 0.85), P <.01]. However, there were no differences in mortality [OR = 0.64, 95% CI (0.41; 1.01), P =.05], length of hospitalization [MD = -0.42, 95% CI (-1.22; 0.38), P =.31], number of emergency hospitalizations [MD = -0.09, 95% CI (-0.33; 0.15), P =.45], medication compliance [OR = 1.67, 95% CI (0.92; 3.02), P =.09], or MLHFQ scores [MD = -2.30, 95% CI (-6.16; 1.56), P =.24] among the patients. CONCLUSION: This meta-analysis showed that telemedicine reduced overall and heart failure-related hospitalizations in chronic heart failure patients, suggesting its value in clinical management. However, it did not significantly affect mortality, hospital stay length, emergency visits, medication adherence, or quality of life. This suggests the need to optimize specific aspects of telemedicine, identify key components, and develop strategies for better treatment outcomes.

Selection of key genes for dilated cardiomyopathy based on machine learning algorithms and assessment of diagnostic accuracy.

Background: The mechanisms of the occurrence and progression of dilated cardiomyopathy are still unclear and further exploration is needed. The upgrading of programming languages and the improvement of biological databases have created conditions for us to explore the structural and functional information of biological molecules at the nucleic acid and protein levels, screen key pathogenic genes, and elucidate pathogenic mechanisms. This study aimed to screen key pathogenic genes using machine learning algorithms and explore the correlation between key genes and immune microenvironment through transcriptome sequencing data sets of myocardial samples from patients with dilated cardiomyopathy, providing new ideas for elucidating the pathogenesis of the disease. Methods: The transcriptome sequencing data sets of heart tissue from patients with dilated cardiomyopathy were downloaded from the Gene Expression Omnibus (GEO) database (GSE29819 and GSE21610). Differentially expressed genes (DEGs) were screened between pathological and normal tissues. The key genes were screened using least absolute shrinkage and selection operator (LASSO) regression analysis and random forest tree algorithms. The diagnostic efficiency of the key genes for the disease was evaluated using the receiver operating characteristic (ROC) curve. Results: Compared with the normal heart tissue (control group) samples, there were 213 DEGs in the heart tissue samples of patients with dilated cardiomyopathy (treat group), including 101 upregulated and 102 downregulated genes. CCL5 and CTGF were highly expressed in the treat group compared to the control group. The ROC curve showed that the areas under the curve (AUCs) of CCL5 and CTGF were 0.821 and 0.902, respectively (P<0.05). In the treat group samples, CCL5 was positively correlated with the infiltration content of most immune cell subtypes. Conclusions: CCL5 and CTGF are key disease-causing genes in dilated cardiomyopathy and have good diagnostic efficiency for the disease. CCL5 and CTGF may be related to immune cell enrichment and myocardial fibrosis, respectively.

The NF-κB/Relish Activates miR-308 to Negatively Regulate Imd Pathway Immune Signaling in Drosophila.

The strength and duration of the NF-κB signaling response must be tightly modulated to avoid an inadequate or excessive immune response. Relish, a core NF-κB transcription factor of the Drosophila Imd pathway, can control the expression of antimicrobial peptides, including Dpt and AttA, to defend against Gram-negative bacterial infections, but whether Relish may regulate miRNA expression to participate in the immune response remains unclear. In this study, taking advantage of Drosophila S2 cells and different overexpression/knockout/knockdown flies, we first found that Relish could directly activate the expression of miR-308 to negatively regulate the immune response and promote the survival of Drosophila during Enterobacter cloacae infection. Second, our results demonstrated that Relish-mediated expression of miR-308 could suppress target gene Tab2 to attenuate the Drosophila Imd pathway signal during the middle and late stages of the immune response. Third, we detected the dynamic expression patterns of Dpt, AttA, Relish, miR-308, and Tab2 in wild-type flies after E. coli infection, which further revealed that the feedback regulatory loop of Relish-miR-308-Tab2 plays a crucial role in the immune response and homeostasis maintenance of the Drosophila Imd pathway. Overall, our present study not only illustrates an important mechanism by which this Relish-miR-308-Tab2 regulatory axis can negatively control the Drosophila immune response and participate in homeostasis maintenance but also provides new insights into the dynamic regulation of the NF-κB/miRNA expression network of animal innate immunity.

Sex different effect of antibiotic and probiotic treatment on intestinal microbiota composition in chemically induced liver injury rats.

Differences in the gut microbiota and metabolic processes between males and females may explain differences in the risk of liver injury; however, the sex-specific effects of antibiotics and probiotics on these relationships are not clear. We evaluated differences in the gut microbiota and the risk of liver injury between male and female rats after the oral administration of antibiotics or probiotics followed by a period of diethylnitrosamine treatment to chemically induce liver injuryusing high-throughput sequencing of fecal microbiota combined with histological analyses of liver and colon tissues. Our results suggest that the ratio of gram-positive to gram-negative bacteria in kanamycin-treated rats was significantly higher than that of other groups, and this difference persisted for the duration of the experiment. Antibiotics significantly changed the composition of the gut microbiota of experimental rats. Clindamycin caused more diethylnitrosamine-induced damage to livers of male rats. Probiotics did not influencethe gut microbiota; however, they hadprotective effects against liver injury induced by diethylnitrosamine, especially in female rats. These results strengthen our understanding of sex differences in the indirect effects of antibiotics or probiotics on metabolism and liver injury in hosts via the gut microbiota.

Effects of organic and inorganic nitrogen sources on the transcriptome of gellan gum biosynthesis by Sphingomonas paucimobilis.

AIM: Investigate the effects of different nitrogen sources on the metabolic characteristics of Sphingomonas paucimobilis during gellan gum (GG) production was helpful for developing optimized conditions that are widely applicable to all GG production processes. METHODS AND RESULTS: We compared the effects of organic nitrogen (ON) and inorganic nitrogen (IN) sources during GG production using transcriptome sequencing. Our results showed that compared with the IN source, the ON source effectively improved the cell number and GG production of S. paucimobilis during fermentation. There were significant differences in gene transcription levels between the ON and IN groups at different fermentation times. CONCLUSIONS: The transcriptional levels of multiple genes in the pathways from α-D-glucose-1P to glyceraldehyde-3P were reduced in the ON group, whereas those of multiple genes in the pathways from glyceraldehyde-3P to acetyl-CoA were significantly enhanced in the ON group after 12 h of fermentation. The transcription levels of multiple genes participating in the citrate cycle and upstream of fatty acid metabolism pathways were significantly enhanced in the ON group after 12 h of fermentation. Except for the transcripts per million (TPMs) of pgm and rfbA genes in ON, which were significantly higher than those in IN at 12 h after fermentation, the TPMs of the majority of genes in ON were significantly lower than those in IN. The transcription levels of genes participating in the transformation of N-acetyl-D-glucosamine (GlcNAc) to UDP-N-acetyl-alpha-D-glucosamine (UDP-GlcNAc) were enhanced in the ON group during the fermentation process.

Complete genome analysis of Pseudomonas furukawaii ZS1 isolated from grass carp (Ctenopharyngodon idellus) culture water.

Pseudomonas furukawaii ZS1, isolated from grass carp (Ctenopharyngodon idellus) culture water, exhibits efficient aerobic nitrate reduction without nitrite accumulation; however, the molecular pathway underlying this aerobic nitrate reduction remains unclear. In this study, we constructed a complete genome map of P. furukawaii ZS1 and performed a comparative genomic analysis with a reference strain. The results showed that P. furukawaii ZS1 genome was 6 026 050 bp in size and contained 5427 predicted protein-coding sequences. The genome contained all the necessary genes for the dissimilatory nitrate reduction to ammonia pathway but lacked those for the assimilatory nitrate reduction pathway; additionally, genes that convert ammonia to organic nitrogen were also identified. The presence of putative genes associated with the nitrogen and oxidative phosphorylation pathways implied that ZS1 can perform respiration and nitrate reduction simultaneously under aerobic conditions, so that nitrite is rapidly consumed for detoxication by denitrification. The aim of this study is to indicate the great potential of strain ZS1 for future full-scale applications in aquaculture. This work provided insights at the molecular level on the nitrogen metabolic pathways in Pseudomonas species. The understanding of nitrogen metabolic pathways also provides significant molecular information for further Pseudomonas species modification and development.

Renal function damage in children with duplex kidneys.

PURPOSE: To evaluate renal function damage in children with duplex kidneys. METHODS: A total of 355 duplex kidneys, 110 urinary tract infection (UTI) kidneys without abnormalities, and 104 kidneys with primary unilateral vesicoureteral reflux (VUR) were reviewed. Clinical data including age at diagnosis, body weight, history of UTI, ureteroceles, ectopic ureteral opening, VUR grade, serum creatinine level, cystatin C level, renal scarring, split renal function in dimercaptosuccinic acid scans, and effective renal plasma flow (ERPF) were analyzed. RESULTS: Duplex kidneys had a higher grade of VUR and renal scarring. Split renal function in unilateral duplex kidneys (45.58 ± 12.85%) was much lower than that in contralateral duplex kidneys (56.33 ± 11.90%) and controls (50.00 ± 11.38%) (P < 0.001 and P = 0.014, respectively). Both left and right split renal functions in bilateral duplex kidneys were similar to those ipsilateral to the controls (P = 0.906 and P = 0.932, respectively). However, the total ERPFs in the left, right, and bilateral duplex kidneys were significantly lower than that in the control group (P = 0.003, P = 0.001, and P = 0.003, respectively). The total ERPFs in the left and right unilateral duplex kidneys were similar. ERPF in unilateral duplex kidneys (106.70 ± 48.05 mL/min/m2) was significantly lower than that in contralateral duplex kidneys (150.18 ± 49.01 mL/min/m2) or those ipsilateral to controls (145.98 ± 41.16 mL/min/m2) (P < 0.001 and P < 0.001, respectively). CONCLUSION: Duplex kidneys are usually accompanied by a higher grade of VUR, more severe renal scarring, and renal function impairment. Split renal function in duplex kidneys often declines significantly. Notably, the evaluation of split renal function in bilateral duplex kidneys should be performed cautiously.

Comparative proteomic analysis of children FSGS FFPE tissues.

BACKGROUND: In children, focal segmental glomerulosclerosis (FSGS) is the main cause of steroid resistant nephrotic syndrome (SRNS). To identify specific candidates and the mechanism of steroid resistance, we examined the formalin-fixed paraffin embedded (FFPE) renal tissue protein profiles via liquid chromatography tandem mass spectrometry (LC-MS/MS). METHODS: Renal biopsies from seven steroid-sensitive (SS) and eleven steroid-resistant (SR) children FSGS patients were obtained. We examined the formalin-fixed paraffin embedded (FFPE) renal tissue protein profiles via liquid chromatography tandem mass spectrometry (LC-MS/MS). Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment and Gene Ontology (GO) analysis, as well as the construction of protein-protein interaction (PPI) network were performed. Two proteins were further valiadated by immunohistochemistry staining in FSGS patients and mice models. RESULTS: In total, we quantified more than 4000 proteins, of which 325 were found to be differentially expressed proteins (DEPs) between the SS and SR group (foldchange ≥2, P<0.05). The results of GO revealed that the most significant up-regulated proteins were primarily related to protein transportation, regulation of the complement activation process and cytolysis. Moreover, clustering analysis showed differences in the pathways (lysosome, terminal pathway of complement) between the two groups. Among these potential candidates, validation analyses for LAMP1 and ACSL4 were conducted. LAMP1 was observed to have a higher expression in glomerulus, while ACSL4 was expressed more in tubular epithelial cells. CONCLUSIONS: In this study, the potential mechanism and candidates related to steroid resistance in children FSGS patients were identified. It could be helpful in identifying potential therapeutic targets and predicting outcomes with these proteomic changes for children FSGS patients.

A novel CLCN5 frame shift mutation responsible for Dent disease 1: Case report.

Background: Dent disease is a group of inherited X-linked recessive renal tubular disorders. This group of disorders is characterized by low molecular weight proteinuria (LMWP), nephrocalcinosis, hypercalciuria and renal failure. Case presentation: Here we report one 11-year-old Chinese boy (proband) and one 13-year-old Chinese boy who was proband's cousin, both presented with massive proteinuria. Further laboratory examinations revealed a lack of nephrocalcinosis, nor any other signs of tubular dysfunction, but only LMWP and hypercalciuria. There was no abnormality in growth, renal function or mineral density of the bones. A novel deletion (c.1448delG) in the CLCN5 gene was identified, resulting in a frame shift mutation (p.Gly483fs). The proband's and his cousin's mothers were found to be the carrier of this mutation. Conclusions: In this study, we have found a novel frameshift mutation (c. 1448delG) at exon 11 of the CLCN5 gene which leads to Dent disease 1, expanding the spectrum of CLCN5 mutations.

SFA-Net: Scale and Feature Aggregate Network for Retinal Vessel Segmentation.

A U-Net-based network has achieved competitive performance in retinal vessel segmentation. Previous work has focused on using multilevel high-level features to improve segmentation accuracy but has ignored the importance of shallow-level features. In addition, multiple upsampling and convolution operations may destroy the semantic feature information contained in the decoder layer. To address these problems, we propose a scale and feature aggregate network (SFA-Net), which can make full use of multiscale high-level feature information and shallow features. In this paper, a residual atrous spatial feature aggregate block (RASF) is embedded at the end of the encoder to learn multiscale information. Furthermore, an attentional feature module (AFF) is proposed to enhance the effective fusion between shallow and high-level features. In addition, we designed the multi-path feature fusion (MPF) block to fuse high-level features of different decoder layers, which aims to learn the relationship between the high-level features of different paths and alleviate the information loss. We apply the network to the three benchmark datasets (DRIVE, STARE, and CHASE_DB1) and compare them with the other current state-of-the-art methods. The experimental results demonstrated that the proposed SFA-Net performs effectively, indicating that the network is suitable for processing some complex medical images.

Anti-ANGPTL3-FLD monoclonal antibody treatment ameliorates podocyte lesions through attenuating mitochondrial damage.

Proteinuria, an indication of kidney disease, is caused by the malfunction of podocytes, which play a key role in maintaining glomerular filtration. Angiopoietin-like 3 (ANGPTL3) has been documented to have a cell-autonomous involvement in podocytes, and deletion of Angptl3 in podocytes reduced proteinuria in adriamycin-induced nephropathy. Here, we developed a monoclonal antibody (mAb) against ANGPTL3 to investigate its effects on podocyte injury in an ADR nephropathy mouse model and puromycin (PAN) induced podocyte damage in vitro. The mAb against the human ANGPTL3-FLD sequence (5E5F6) inhibited the binding of ANGPTL3-FLD to integrin ß3. Treatment with the 5E5F6 mAb in ADR nephropathy mice mitigated proteinuria and led to a significant decline in podocyte apoptosis, reactive oxygen species (ROS) generation and mitochondrial fragmentation. In PAN-induced podocyte damage in vitro, the 5E5F6 mAb blocked the ANPGPLT3-mediated activation of integrin αvß3 and Rac1, which regulated the mitochondrial homeostasis. Altogether, anti-ANGPLT3-FLD mAb attenuates proteinuria and podocyte lesions in ADR mice models, as well as PAN-induced podocyte damage, in part through regulating mitochondrial functions. Our study provides a therapeutic approach for targeting ANGPTL3 in proteinuric kidney disease.

Systemic Lupus Erythematosus Patients With Related Organic Damage Are at High Risk of Hypothyroidism.

Purpose: The aim of this study included determining the prevalence of hypothyroidism in patients with systemic lupus erythematosus (SLE), clarifying the clinical characteristics of SLE patients with hypothyroidism, and identifying the relationship between hypothyroidism and SLE-related organic damage. Another purpose was to analyze the relationship between SLE and thyroid autoantibody. We also intended to discuss the pathogenesis of hypothyroidism in SLE patients, which would provide clues for further investigation. Methods: This study recruited 856 SLE patients and 856 age- and sex-matched healthy population and compared the prevalence of hypothyroidism between the cases and controls. Univariate and multivariate logistic analyses were applied to identify risk factors for hypothyroidism in SLE patients. Results: SLE patients had higher prevalence of clinical hypothyroidism (9.10%) and TgAb+TPOAb- (10.40%) than controls. The prevalence of hypothyroidism was the highest in SLE patients aged 16-26 years (18.9%) and decreased with age. The prevalence of autoimmune hypothyroidism in SLE group was higher than that in the control group (64.4% vs. 51.5%, P=0.042), which was mainly due to TgAb; the prevalence of non-autoimmune hypothyroidism in SLE group was also significantly higher than that in the control group (67.3% vs. 47.8%, P<0.001). Based on multivariate analysis, the use of glucocorticoids/immunosuppressants, liver abnormality, lupus nephritis (LN), and cardiac insufficiency were independently associated with hypothyroidism in SLE patients. Conclusion: The prevalence of hypothyroidism in SLE patients was higher than that in controls and decreased with age. The results suggested that young SLE patients combined with LN, liver abnormality and cardiac insufficiency were at higher risk of hypothyroidism. According to the results of this study, we speculated that SLE might have impact on thyroid, and SLE might be one of the causes of hypothyroidism.

A New Perspective on the Antimicrobial Mechanism of Berberine Hydrochloride Against Staphylococcus aureus Revealed by Untargeted Metabolomic Studies.

Berberine hydrochloride (BBR) is a natural product widely used in clinical medicine and animal production. It has a variety of antimicrobial effects, but its complex antimicrobial mechanism has not been clarified. This study aimed to discover the metabolic markers and gain a new perspective on the antibacterial mechanism of BBR. The effects of different inhibitory concentrations of BBR on the survival and growth of standard strain Staphylococcus aureus ATCC 25923 were analyzed by the bacteriostatic activity test. Differences in intracellular metabolites of S. aureus following 19 µg/ml BBR exposure for 1 h were investigated by combining non-targeted metabolomics techniques of gas chromatography-mass spectrometry (GC-MS) and liquid chromatography-mass spectrometry (LC-MS). The results showed that the minimum inhibitory concentration of BBR against S. aureus was 51 µg/ml. A total of 368 and 3,454 putative metabolites were identified by GC-MS and LC-MS analyses, respectively. Principal component analysis showed the separation of intracellular metabolite profiles between BBR-exposed samples and non-exposed controls. Pathway activity profiling analysis indicated a global inhibition of metabolisms by BBR exposure, while enhancement was also found in nucleic acid metabolism, amino sugar, and nucleotide sugar metabolism. Several metabolic markers were screened out mainly based on their variable importance of projection values. Two pyridine dicarboxylic acids were significantly downregulated, suggesting the reduction of stress resistance. The oxidized phospholipid (PHOOA-PE) was accumulated, while lipid antioxidant gamma-tocopherol was decreased, and farnesyl PP, the synthetic precursor of another antioxidant (staphyloxanthin), was decreased below the detection threshold. This evidence indicates that BBR reduced the antioxidant capacity of S. aureus. Accumulation of the precursors (UDP-GlcNAc, CDP-ribitol, and CDP-glycerol) and downregulation of the key metabolite D-Ala-D-Ala suggest the inhibition of cell wall synthesis, especially the peptidoglycan synthesis. Metabolites involved in the shikimate pathway (such as 3-dehydroshikimate) and downstream aromatic amino acid synthesis were disturbed. This study provides the first metabolomics information on the antibacterial mechanism of BBR against S. aureus. The key metabolic markers screened in this study suggest that the shikimate pathway, staphyloxanthin synthesis, and peptidoglycan biosynthesis are new directions for further study of BBR antibacterial mechanism in the future.

DNL-Net: deformed non-local neural network for blood vessel segmentation.

BACKGROUND: The non-local module has been primarily used in literature to capturing long-range dependencies. However, it suffers from prohibitive computational complexity and lacks the interactions among positions across the channels. METHODS: We present a deformed non-local neural network (DNL-Net) for medical image segmentation, which has two prominent components; deformed non-local module (DNL) and multi-scale feature fusion. The former optimizes the structure of the non-local block (NL), hence, reduces the problem of excessive computation and memory usage, significantly. The latter is derived from the attention mechanisms to fuse the features of different levels and improve the ability to exchange information across channels. In addition, we introduce a residual squeeze and excitation pyramid pooling (RSEP) module that is like spatial pyramid pooling to effectively resample the features at different scales and improve the network receptive field. RESULTS: The proposed method achieved 96.63% and 92.93% for Dice coefficient and mean intersection over union, respectively, on the intracranial blood vessel dataset. Also, DNL-Net attained 86.64%, 96.10%, and 98.37% for sensitivity, accuracy and area under receiver operation characteristic curve, respectively, on the DRIVE dataset. CONCLUSIONS: The overall performance of DNL-Net outperforms other current state-of-the-art vessel segmentation methods, which indicates that the proposed network is more suitable for blood vessel segmentation, and is of great clinical significance.

Associations Between Cessation of Second-Line Therapies and Relapse Rates of Childhood Refractory Minimal-Change Nephrotic Syndrome: A Single-Center, Retrospective Chart Review.

Background: Most patients (≥85%) with minimal-change nephrotic syndrome (MCNS) respond to corticosteroid treatment. However, about 10% to 20% of patients with MCNS have steroid-resistant nephrotic syndrome and 25% to 43% of patients have steroid-dependent nephrotic syndrome or frequent-relapse steroid-sensitive nephrotic syndrome. Patients with refractory MCNS are treated with various second-line therapies. Objectives: This study aimed to evaluate the associations between the use of various second-line therapies and relapse rates in Chinese patients with childhood refractory MCNS. Methods: In this study, patients with childhood nephrotic syndrome renal biopsy proved to be "minimal change" from a single tertiary-care center between January 2002 and July 2018 were identified. A Total of 56 medical charts of patients treated with 1 of these second-line immunosuppressors: cyclophosphamide (CYC), mycophenolate mofetil (MMF), or tacrolimus (TAC) were reviewed. Patients were divided into CYC (n = 24), MMF (n = 20), and TAC (n = 12) groups according to the second-line therapy administered. Baseline characteristics, immune status, immunocomplex deposition in the renal tissue, and treatment outcomes were analyzed. Results: The ratio of patients with steroid-resistant nephrotic syndrome and steroid-dependent nephrotic syndrome in the CYC, MMF, and TAC groups did not differ significantly (P = 0.721). The immunofluorescence assay did not show any significant differences in immunocomplex deposition identified in renal biopsy specimens among the 3 groups. The rate of steroid-free remission in the TAC group (75%) was higher than that in the MMF (55%) and CYC (25%) groups (P = 0.012). At the last follow-up, two-thirds of children in the TAC group had a relapse following discontinuation of therapy. In the TAC group, patients for whom steroids were withdrawn had significantly higher levels of immunoglobulin G at the onset of nephrotic syndrome than those for whom steroids were continued (P = 0.017). In the MMF group, children with relapse had a significantly higher percentage of CD16+CD56+-positive cells than those without relapse (P = 0.042). The relapse rate after treatment discontinuation was significantly different among the 3 groups (P = 0.035). Notably, the relapse rate after treatment discontinuation in the CYC group was lower than those in the other 2 groups (P = 0.035). Conclusions: In this small population of Chinese patients with childhood refractory MCNS, the relapse rate following TAC therapy was higher than that following MMF or CYC therapy. Different proportions of CD16+CD56+-positive cells might be associated with relapse rates in patients with MCNS receiving MMF treatment. (Curr Ther Res Clin Exp. 2022; 83:XXX-XXX).

Probiotic Bacillus Alleviates Oxidative Stress-Induced Liver Injury by Modulating Gut-Liver Axis in a Rat Model.

Emerging evidence suggests a key role of gut microbiota in maintaining liver functions through modulating the gut-liver axis. In this study, we investigated whether microbiota alteration mediated by probiotic Bacillus was involved in alleviating oxidative stress- induced liver injury. Sprague-Dawley rats were orally administered Bacillus SC06 or SC08 for a 24-day period and thereafter intraperitoneally injected diquat (DQ) to induce oxidative stress. Results showed that Bacillus, particularly SC06 significantly inhibited hepatic injuries, as evidenced by the alleviated damaged liver structure, the decreased levels of ALT, AST, ALP and LDH, and the suppressed mitochondrial dysfunction. SC06 pretreatment markedly enhanced the liver antioxidant capacity by decreasing MDA and p47, and increasing T-AOC, SOD and HO-1.16S rRNA sequencing analysis revealed that DQ significantly changed the diversities and composition of gut microbiota, whereas Bacillus pretreatments could attenuate gut dysbiosis. Pearson's correlation analysis showed that AST and MDA exerted a positive correlation with the opportunistic pathogenic genera and species (Escherichia and Shigella), and negatively correlated with the potential probiotics (Lactobacillus), while SOD exerted a reverse trend. The microbial metagenomic analysis demonstrated that Bacillus, particularly SC06 markedly suppress the metabolic pathways such as carbohydrate metabolism, lipid metabolism, amino acid metabolism and metabolism of cofactors and vitamins. Furthermore, SC06 decreased the gene abundance of the pathways mediating bacterial replication, secretion and pathogenicity. Taken together, Bacillus SC06 alleviates oxidative stress-induced liver injuries via optimizing the composition, metabolic pathways and pathogenic replication and secretion of gut microbiota. These findings elucidate the mechanisms of probiotics in alleviating oxidative stress and provide a promising strategy for preventing liver diseases by targeting gut microbiota.