Knockdown of fibrillin-1 suppresses retina-blood barrier dysfunction by inhibiting vascular endothelial apoptosis under diabetic conditions.

AIM: To investigate the effects of fibrillin-1 (FBN1) deletion on the integrity of retina-blood barrier function and the apoptosis of vascular endothelial cells under diabetic conditions. METHODS: Streptozotocin (STZ)-induced diabetic mice were used to simulate the diabetic conditions of diabetic retinopathy (DR) patients, and FBN1 expression was detected in retinas from STZ-diabetic mice and controls. In the Gene Expression Omnibus (GEO) database, the GSE60436 dataset was selected to analyze FBN1 expressions in fibrovascular membranes from DR patients. Using lentivirus to knock down FBN1 levels, vascular leakage and endothelial barrier integrity were detected by Evans blue vascular permeability assay, fluorescein fundus angiography (FFA) and immunofluorescence labeled with tight junction marker in vivo. High glucose-induced monkey retinal vascular endothelial cells (RF/6A) were used to investigate effects of FBN1 on the cells in vitro. The vascular endothelial barrier integrity and apoptosis were detected by trans-endothelial electrical resistance (TEER) assay and flow cytometry, respectively. RESULTS: FBN1 mRNA expression was increased in retinas of STZ-induced diabetic mice and fibrovascular membranes of DR patients (GSE60436 datasets) using RNA-seq approach. Besides, knocking down of FBN1 by lentivirus intravitreal injection significantly inhibited the vascular leakage compared to STZ-DR group by Evans blue vascular permeability assay and FFA detection. Expressions of tight junction markers in STZ-DR mouse retinas were lower than those in the control group, and knocking down of FBN1 increased the tight junction levels. In vitro, 30 mmol/L glucose could significantly inhibit viability of RF/6A cells, and FBN1 mRNA expression was increased under 30 mmol/L glucose stimulation. Down-regulation of FBN1 reduced high glucose (HG)-stimulated retinal microvascular endothelial cell permeability, increased TEER, and inhibited RF/6A cell apoptosis in vitro. CONCLUSION: The expression level of FBN1 increases in retinas and vascular endothelial cells under diabetic conditions. Down-regulation of FBN1 protects the retina of early diabetic rats from retina-blood barrier damage, reduce vascular leakage, cell apoptosis, and maintain vascular endothelial cell barrier function.

Transcriptome analysis reveals the synergistic involvement of MGLL and LPIN1 in fatty acid synthesis in broiler pectoral muscles.

Fatty acids (FAs) are one of the most important bioactive compounds affecting the quality of meat. In this study, we compared the expression profiles of genes involved in FA production in the breast muscle of Jingxing Yellow chickens at different days of age determined by transcriptomic analysis to identify key genes and pathways regulating the FA composition of the breast muscle. Through clustering analysis of gene expression data, the growth process of broiler chickens can be divided into two stages, namely the growth and development stage at the 35th and 63rd days of age (D35, D63), and the mature stage at the 119th day of age (D119). The content of some important unsaturated fatty acids (UFAs), such as C18:2n6c, C20:4n6, and C22:6n3, in the pectoral muscles, differed significantly between these two stages (p < 0.05). Therefore, we compared the gene expression profiles at D35 and D63 with those at D119, and identified differentially expressed genes (DEGs). The gene modules related to the five UFAs with significant changes were identified by weighted gene co-expression network analysis (WGCNA), and then 150 crossover genes were identified by crossover analysis of the detected DEGs and WGCNA. The results of the pathway enrichment analysis revealed the glycerolipid metabolism pathway related to lipid metabolism, in which the MGLL and LPIN1 genes were particularly enriched. In this study, the expression levels of MGLL and LPIN1 showed an increasing trend during the growth process of broilers, with a negative regulatory effect on the significantly reduced content of C18:2n6c in the pectoral muscle, and a positive regulatory effect on the significantly increased content of C20:4n6. These findings indicated that MGLL and LPIN1 synergistically promote the deposition of FAs, which may further promote the conversion of linoleic acid (C18:2n6c) to arachidonic acid (C20:4n6). Therefore, screening and identifying FA production-related functional genes are key to elucidate the regulatory molecular mechanism of production of FAs in chicken muscle, aiming to provide a theoretical basis for improving chicken meat quality.

A systematic review on aquaculture wastewater: Pollutants, impacts, and treatment technology.

Aquaculture is the major way to solve the global food sacrcity. As the global population increases, the demand for aquaculture increases. Fish feed, drugs and chemicals, and metabolic waste or mortalities of aquatic organisms also increase, eventually resulting in the production of a large amount of aquaculture wastewater. These aquaculture discharges contain a variety of pollutants, such as conventional pollutants, organic compounds, heavy metals, and biological contaminants, inducing occupational hazards and risks, food security, the environment pollution. Proper wastewater treatment technologies are required to remove hazardous pollutants for minimizing their impacts on environmental and human health. Recirculating aquaculture systems, some biological and physicochemical methods have been applied to remove some pollutants from the aquaculture wastewater, but their efficiency in removing pollutants still requires to be further improved for achieving zero-waste discharge and ensuring sustainable aquaculture development. Meanwhile, sound regulation and legislation needs to be established for ensuring the normal operation of aquaculture industries and the standard discharge of wastewater. This review aims to provide comprehensive information of aquaculture wastewater for the researchers and promote the healthy development of aquaculture.

[Clinical and genetic analysis of three children with Legius syndrome due to variants of SPRED1 gene].

OBJECTIVE: To explore the clinical and genetic characteristics of three children with Leguis syndrome. METHODS: Three children suspected as Legius syndrome at the Henan Children's Hospital for precocious puberty or short stature from June 6, 2019 to August 25, 2022 were selected as the study subjects. Clinical data of the children were collected. All children were subjected to whole exome sequencing, and candidate variants were verified by Sanger sequencing. RESULTS: All of the children (including 2 females and 1 male, and aged 4 years and 6 months, 8 years, and 14 years and 8 months, respectively) had typical café de lait spots. Child 1 also had precocious puberty, and children 2 and 3 had short statures. Genetic testing revealed that all of them had harbored heterozygous variants of the SPRED1 gene, including c.751C>T (p.Arg251Ter194) in child 1, c.229A>T (p.Lys77Ter368) in child 2, and c.1044_1046delinsC (p.R349fs*11) in child 3. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the c.751C>T (p.Arg251Ter194) variant was predicted to be likely pathogenic, whilst the other two were known pathogenic variants. CONCLUSION: All of the three children were diagnosed with Leguis syndrome due to variants of the SPRED1 gene, which had manifested as multiple café de lait spots in conjunct with precocious puberty or short statures.

A Supramolecular Antibiotic Targeting Drug-Resistant Pseudomonas aeruginosa through the Inhibition of Virulence Factors and Activation of Acquired Immunity.

The bacterium Pseudomonas aeruginosa is an exceptionally resilient opportunistic pathogen, presenting formidable challenges for treatment due to its proclivity for developing drug resistance. To address this predicament, we have devised a self-assembled supramolecular antibiotic known as dHTSN1@pHPplus, which can circumvent the drug resistance mechanism of Pseudomonas aeruginosa and effectively combat Pseudomonas aeruginosa infection by impeding the secretion of key virulence factors through the inhibition of the type III secretion system while simultaneously mobilizing immune cells to eradicate Pseudomonas aeruginosa. Furthermore, dHTSN1@pHPplus was ingeniously engineered with infection-targeting capabilities, enabling it to selectively concentrate precisely at the site of infection. As anticipated, the administration of dHTSN1@pHPplus exhibited a remarkable therapeutic efficacy in combating dual resistance to Meropenem and imipenem in a mouse model of P. aeruginosa lung infection. The results obtained from metagenomic detection further confirmed these findings, demonstrating a significant reduction in the proportion of Pseudomonas aeruginosa compared to untreated mice with Pseudomonas aeruginosa-infected lungs. Additionally, no notable acute toxicity was observed in the acute toxicity experiments. The present study concludes that the remarkable efficacy of dHTSN1@pHPplus in treating drug-resistant P. aeruginosa infection confirms its immense potential as a groundbreaking antibiotic agent for combating drug-resistant P. aeruginosa.

Spatial patterning and species coexistence: A case study using concentric circular vegetation patches in saline land.

Spatial patterns in plant community structures within stressed ecosystems have drawn much attention in the field of ecology. However, the mechanisms underlying spatial formation and its impact on species coexistence and diversity remain controversial. In this study, we investigated concentric circular vegetation patches in coastal saline land, and analysed the spatial patterning of plant communities and associated soil physicochemical properties. Thereafter, we tested how the soil conditioned by plant communities from different locations within the vegetation patches influence the species growth and inter-specific competition. Our results show soil salinity enlarges in a centrifugal manner in horizontal direction in all patches. Soil salinity decreased and species diversity increased along with the increase of patch size. In addition, we found significant shifts in both the composition of plant communities and in soil physicochemical properties from outer to center. The results indicate that the pioneer species Suaeda salsa facilitated the subsequent species. However Suaeda salsa was inhibited and became inferior competitor in the soil conditioned by the subsequent species. We infer that the less-visible spatial patterns of soil physicochemical properties at small scales create ecological niches for specialized species, allowing them to coexist but not mix. We suggest that a trade-off between tolerance to salt stress and competitive ability under ameliorated conditions may underlie mechanisms of pattern formation in small scale. Our findings lend support to the idea that soil stress constraints community assembly and triggers spatial patterns, which, in turn, buffer the stress on plant communities and enhance species diversity.

Enhanced immunochromatographic assay using multifunctional gold@iridium nanoflower with colorimetric photothermal catalytic activity for the detection of staphylococcal enterotoxin B.

The development of a rapid, sensitive, and accurate screening method for staphylococcal enterotoxin B (SEB) in food is urgently needed because trace amounts of SEB can pose a serious threat to human health. Here, we developed a ultrasensitive triple-modal immunochromatographic assay (ICA) for SEB detection. The AuNFs@Ir nanoflowers exhibited enhanced colorimetric, photothermal, and catalytic performance by modulating the sharp branching structure of the gold nanoflowers and depositing high-density Ir atoms. Subsequently, the combination of AuNFs@Ir and ICA promoted colorimetric, catalytic amplified colorimetric, and photothermal-assisted quantitative detection. The results showed detection limits of 0.175, 0.0188, and 0.043 ng mL-1 in the colorimetric/photothermal/catalytic mode, which increased the sensitivity by 16.5-fold, 153.7-fold, and 67.2-fold, respectively, compared with the AuNPs-ICA. Furthermore, the proposed strategy was verified in milk, milk powder, pork, and beef successfully. This strategy improves significantly the sensitivity, accuracy, flexibility and offers an effective insight for foodborne bacterial toxin monitoring.

Glyco-signatures in patients with advanced lung cancer during anti-PD-1/PD-L1 immunotherapy.

Immune checkpoint inhibitors (ICIs) targeting programmed cell death 1/programmed cell death ligand-1 (PD-1/PD-L1) have significantly prolonged the survival of advanced/metastatic patients with lung cancer. However, only a small proportion of patients can benefit from ICIs, and clinical management of the treatment process remains challenging. Glycosylation has added a new dimension to advance our understanding of tumor immunity and immunotherapy. To systematically characterize anti-PD-1/PD-L1 immunotherapy-related changes in serum glycoproteins, a series of serum samples from 12 patients with metastatic lung squamous cell carcinoma (SCC) and lung adenocarcinoma (ADC), collected before and during ICIs treatment, are firstly analyzed with mass-spectrometry-based label-free quantification method. Second, a stratification analysis is performed among anti-PD-1/PD-L1 responders and non-responders, with serum levels of glycopeptides correlated with treatment response. In addition, in an independent validation cohort, a large-scale site-specific profiling strategy based on chemical labeling is employed to confirm the unusual characteristics of IgG N-glycosylation associated with anti-PD-1/PD-L1 treatment. Unbiased label-free quantitative glycoproteomics reveals serum levels' alterations related to anti-PD-1/PD-L1 treatment in 27 out of 337 quantified glycopeptides. The intact glycopeptide EEQFN 177STYR (H3N4) corresponding to IgG4 is significantly increased during anti-PD-1/PD-L1 treatment (FC=2.65, P=0.0083) and has the highest increase in anti-PD-1/PD-L1 responders (FC=5.84, P=0.0190). Quantitative glycoproteomics based on protein purification and chemical labeling confirms this observation. Furthermore, obvious associations between the two intact glycopeptides (EEQFN 177STYR (H3N4) of IgG4, EEQYN 227STFR (H3N4F1) of IgG3) and response to treatment are observed, which may play a guiding role in cancer immunotherapy. Our findings could benefit future clinical disease management.

Advanced Lung Adenocarcinoma with EGFR 19-del Mutation Transformed into SCC after EGFR-tyrosine Kinase inhibitors Treatment: A Case report.

BACKGROUND: Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) significantly improve the survival of patients with Epidermal growth factor receptor (EGFR) sensitive mutations in non-small cell lung cancer (NSCLC). CASE SUMMARY: A 67-year-old female patient in advanced lung adenocarcinoma suffered from drug resistance after EGFR-TKIs treatment. Secondary pathological tissue biopsy confirmed squamous cell carcinoma (SCC) transformation. Patients inevitably encountered drug resistance issues after receiving EGFR-TKIs treatment for a certain period of time, while EGFR-TKIs can significantly improve the survival of patients with EGFR-sensitive mutations in NSCLC. Notably, EGFR-TKIs resistance includes primary and acquired. Pathological transformation is one of the mechanisms of acquired resistance in EGFR-TKIs, with SCC transformation being relatively rare. Our results provide more detailed results of the patient's diagnosis and treatment process on SCC transformation after EGFR-TKIs treatment for lung adenocarcinoma. CONCLUSION: Squamous cell carcinoma transformation is one of the acquired resistance mechanisms of EGFR-TKIs in advanced lung adenocarcinoma with EGFR mutations.

Arterial stiffness in subclinical atherosclerosis quantified with ultrafast pulse wave velocity measurements: a comparison with a healthy population using propensity score matching.

PURPOSE: This study aimed to evaluate changes in ultrafast pulse wave velocity (ufPWV) in individuals with arterial stiffness and subclinical atherosclerosis (subAS), and to provide cutoff values. METHODS: This retrospective study recruited 231 participants, including 67 patients with subAS. The pulse wave velocity was measured at the beginning and end of systole (PWV-BS and PWVES, respectively) using ultrafast ultrasonography to assess arterial stiffness. The right and left common carotid arteries were measured separately, and laboratory metabolic parameters were also collected. Participants were balanced between groups using propensity score matching (PSM) at a 1:1 ratio, adjusting for age, sex, and waist-to-hip ratio as potential confounders. Cutoff values of ufPWV for monitoring subAS were determined via receiver operating characteristic (ROC) curve analysis. RESULTS: PWV-ES, unlike PWV-BS, was higher in the subAS subgroup than in the subAS-free group after PSM (all P<0.05). For each 1 m/s increase in left, right, and bilateral mean PWV-ES, the risk of subAS increased by 23% (95% confidence interval [CI], 1.04 to 1.46), 26% (95% CI, 1.07 to 1.52), and 38% (95% CI, 1.12 to 1.72), respectively. According to ROC analyses, predictive potential was found for left PWV-ES (cutoff value=7.910 m/s, P=0.002), right PWV-ES (cutoff value=6.615 m/s, P=0.003), and bilateral mean PWV-ES (cutoff value=7.415 m/s, P<0.001), but not for PWV-BS (all P>0.05). CONCLUSION: PWV-ES measured using ultrafast ultrasonography was significantly higher in individuals with subAS than in those without. Specific PWV-ES cutoff values showed potential for predicting an increased risk of subAS.

Systematic comparison of sequencing-based spatial transcriptomic methods.

Recent developments of sequencing-based spatial transcriptomics (sST) have catalyzed important advancements by facilitating transcriptome-scale spatial gene expression measurement. Despite this progress, efforts to comprehensively benchmark different platforms are currently lacking. The extant variability across technologies and datasets poses challenges in formulating standardized evaluation metrics. In this study, we established a collection of reference tissues and regions characterized by well-defined histological architectures, and used them to generate data to compare 11 sST methods. We highlighted molecular diffusion as a variable parameter across different methods and tissues, significantly affecting the effective resolutions. Furthermore, we observed that spatial transcriptomic data demonstrate unique attributes beyond merely adding a spatial axis to single-cell data, including an enhanced ability to capture patterned rare cell states along with specific markers, albeit being influenced by multiple factors including sequencing depth and resolution. Our study assists biologists in sST platform selection, and helps foster a consensus on evaluation standards and establish a framework for future benchmarking efforts that can be used as a gold standard for the development and benchmarking of computational tools for spatial transcriptomic analysis.

Assessment of the safety of Roxadustat for cardiovascular events in chronic kidney disease-related anemia using meta-analysis and bioinformatics.

Objective: This study compares the cardiovascular risk in anemic chronic kidney disease patients treated with Roxadustat versus erythropoietin stimulating agents (ESAs). It also explores the cardiovascular impact of Roxadustat. Methods: We searched PubMed, EMBASE, Cochrane, Scopus, and Web of Science databases up to 13 August 2023, using terms such as "ESA," "Roxadustat," "MACE," "stroke," "death," "myocardial infarction," and "heart failure." Two researchers independently selected and extracted data based on predefined criteria. We assessed the risk of bias with the Cochrane tool and analyzed statistical heterogeneity using the Q and I2 tests. We conducted subgroup analyses by geographical region and performed data analysis with Stata 14.0 and RevMan 5.4 software. Data were sourced from the NCBI database by filtering for "Roxadustat" and "human," and differentially expressed genes were identified using R software, setting the significance at p < 0.01 and a 2-fold logFC, followed by GO enrichment analysis, KEGG pathway analysis, and protein interaction network analysis. Results: A total of 15 articles encompassing 1,43,065 patients were analyzed, including 1,38,739 patients treated with ESA and 4,326 patients treated with Roxadustat. In the overall population meta-analysis, the incidences of Major Adverse Cardiovascular Events (MACE), death, and heart failure (HF) were 13%, 8%, and 4% in the Roxadustat group, compared to 17%, 12%, and 6% in the ESA group, respectively, with P-values greater than 0.05. In the subgroup analysis, the incidences were 13%, 11%, and 4% for the Roxadustat group versus 17%, 15%, and 5% for the ESA group, also with p-values greater than 0.05. Bioinformatics analysis identified 59 differentially expressed genes, mainly involved in the inflammatory response. GO enrichment analysis revealed that these genes are primarily related to integrin binding. The main pathways identified were the TNF signaling pathway, NF-κB signaling pathway, and lipid metabolism related to atherosclerosis. The protein interaction network highlighted IL1B, CXCL8, ICAM1, CCL2, and CCL5 as the top five significantly different genes, all involved in the inflammatory response and downregulated by Roxadustat, suggesting a potential role in reducing inflammation. Conclusion: The meta-analysis suggests that the use of Roxadustat and ESA in treating anemia associated with chronic kidney disease does not significantly alter the likelihood of cardiovascular events in the overall and American populations. However, Roxadustat exhibited a safer profile with respect to MACE, death, and heart failure. The bioinformatics findings suggest that Roxadustat may influence integrin adhesion and affect the TNF and NF-κB signaling pathways, along with lipid and atherosclerosis pathways, potentially reducing inflammation.

Effects of postbiotic products from Saccharomyces cerevisiae fermentation on lactation performance, antioxidant capacities, and blood immunity in transition dairy cows.

This study aimed to evaluate the effects of dietary supplementation with different types of Saccharomyces cerevisiae fermentation products (SCFP) on lactational performance, metabolism, acute phase protein response, and antioxidant capacities in dairy cows from -21 to 56 d in milk (DIM). One hundred and 80 multiparous Holstein dairy cows were blocked by parity, expected calving date, pre-trial body condition score, and previous 305-d ME yield, and then randomly assigned to 1 of 3 dietary treatments: basal diet (CON; n = 60), basal diet supplemented with 40 g/d of SCFP1 (XPC; n = 60; XPC, Diamond V, Cedar Rapids, IA), and basal diet supplemented with 19 g/d of SCFP2 (NTK; n = 60, NutriTek®, Diamond V, Cedar Rapids, IA). Blood (n = 15, 13 and 12 in the CON, XPC and NTK groups, respectively) was sampled at -7 ± 3, + 3, + 7, + 21, and + 28 d, and milk samples (n = 19, 18 and 15 in the CON, XPC and NTK groups, respectively) was sampled during 1-8 wk from a subset of cows from -21 to 56 d relative to calving. Data were analyzed using the MIXED procedure in SAS (SAS Institute Inc.). All data were subjected to repeated measures ANOVA. Dietary treatment (TRT), time, and their interaction (TRT × time) were considered as fixed effects and cow as the random effect. Cows fed XPC and NTK had greater energy-corrected milk (ECM). Supplementing NTK increased milk fat content and yield, and 3.5% fat-corrected milk (FCM) yield compared with CON. Milk urea nitrogen (MUN) was lower in XPC cows than CON. SCFP supplementation decreased plasma ß-hydroxybutyrate (BHB), ceruloplasmin (CER), haptoglobin (HPT), and interleukin-1ß (IL-1ß) concentrations, whereas increased plasma phosphorus (P) concentrations. In addition, cows fed NTK showed lower creatinine (CR) and cortisol (COR) concentrations but increased plasma calcium (Ca) and myeloperoxidase (MPO) concentrations than those in the CON cows. In addition, cows fed NTK and XPC both had reduced plasma concentrations of serum amyloid-A (SAA) at 3 DIM of lactation compared with CON fed cows. Furthermore, SCFP cows had greater concentrations of plasma glucose (GLU) and calcium (Ca) than CON cows at 7 DIM, and greater concentrations of plasma phosphorus (P) at 21 DIM. Between different SCFP type fed groups, plasma concentrations of nonesterified fatty acids (NEFA), MDA, creatinine (CR), SAA, and HPT were lower in cows fed NTK compared with cows fed XPC at 7 DIM. Overall, our results indicate the potential benefits of supplementing SCFP in transition dairy cows by modulating immunity, liver metabolic function and supporting ECM yield. The results also suggest that NutriTek at 19 g/d appears to support the performance and health of dairy cows better compared with XPC at 40 g/d, based on improved metabolic and inflammatory status during the transition period.

Spiky tubular nanoparticles with low protein corona can realize efficient and non-destructive penetration through endothelial barrier.

Upon intravascular applications, i.e., cancer treatment, nanoparticles (NPs) are required to deliver through blood circulation, sustain serum protein interactions, before they penetrate the blood vessels and reach targeted sites for payload drug release. For a delivery process as such, it is elusive and difficult to comprehend the morphological change of NP surface and evaluate associated effects on its targeted delivery. Herein, we used silica NPs with different surface modifications to demonstrate the morphological impact of NPs during the application of the NP-blood protein interaction, vascular endothelial cell penetration, subsequent targeted delivery and photodynamic therapy efficacy, and pursue high drug-load NPs with surface designs. Compared to solid and mesoporous NPs, we found the spiky tubular NPs reserved the NPs' antifouling properties (or shedding of "protein corona"), promoted better endothelial penetration and less destruction in vitro and in vivo. Such effects could be attributed to their spiky surface structures, which can limit the NP-protein interaction area and promote the NP-protein steric hindrance. Further in molecular simulations, we determined that the spiky tubular morphological modification on NPs enhanced the interaction free energy and lowered the amino acids number and the subsequent frequency in contacting with VE-cadherin of vascular endothelia. As a result, the spiky tubular NPs demonstrated its advantages in mitigating damages to VE-cadherin stability and endothelial cell integrity. Exploiting such spiky tubular surface modification, we can improve the NP delivery efficiency and prohibit the leakiness of vascular endothelia, helping address challenges faced by tumor migration in nanomedicine applications for cancer therapy.

Comparative efficacy and safety of systemic steroids, oral JAK inhibitors and Contact Immunotherapy in the Treatment of severe alopecia areata: a systematic review and network meta-analysis.

Severe alopecia areata (AA) is a nonscarring hair loss for immune disorder and SALT score ≥ 50%. The guidelines for managing patients with severe AA suggest treatments: systemic steroids, JAK inhibitors, and contact immunotherapy. However, there is a lack of evidence indicating the superiority of one treatment over another. Therefore, this study aimed to identify the most effective treatment for severe AA through network meta-analysis. Following the PRISMA guidelines, we conducted a network meta-analysis. The literature search was retrieved across four databases. The Cochrane 5.1 risk of bias assessment tool and ROBINS-I tool assessed quality of the included studies. Subsequently, efficacy and safety comparisons among the three treatments were conducted using Stata 14.0 on account of the frequency method. The SUCRA rank indicated that oral dexamethasone (95.9%) > diphenylcyclopropenone(DPCP) (74.5%) > oral ritlecitinib (62.6%) > oral baricitinib (46.9%) > squaric acid dibutyl ester(SADBE) (20.1%) > placebo (0.0%) from high to low in the aspect of improving efficacy. As for safety, placebo(88.4%) > oral ritlecitinib (86.5%) > oral baricitinib (62.1%) > SADBE (37.0%) > oral dexamethasone(22.3%) > DPCP(3.8%) in the aspect of decreasing adverse events. Oral dexamethasone and DPCP showed superior efficacy compared to oral ritlecitinib and oral baricitinib. However, in terms of safety, oral ritlecitinib was preferable. Some adverse events associated with oral dexamethasone and DPCP were intolerable to patients, whereas those related to oral ritlecitinib and oral baricitinib were more manageable. Overall, ritlecitinib and baricitinib remain promising drugs in the future treatment of severe AA.

Repetitive Sequences, Codon Usage Bias and Phylogenetic Analysis of the Plastome of Miliusa glochidioides.

Annonaceae is the largest family in Magnoliales, exhibiting the greatest diversity among and within genera. In this study, we conducted an analysis of repetitive sequences and codon usage bias in the previously acquired plastome of Miliusa glochidioides. Using a concatenated dataset of shared genes, we constructed the phylogenetic relationships among 27 Annonaceae species. The results showed that the size of the plastomes in the Annonaceae ranged from 159 to 202 kb, with the size of the inverted repeat region ranging from 40 to 65 kb. Within the plastome of M. glochidioides, we identified 42 SSRs, 36 tandem repeats, and 9 dispersed repeats. These SSRs consist of three nucleotide types and eight motif types, with a preference for A/T bases, primarily located in the large single-copy regions and intergenic spacers. Tandem and dispersed repeat sequences were predominantly detected in the IR region. Through codon usage bias analysis, we identified 30 high-frequency codons and 11 optimal codons. The plastome of M. glochidioides demonstrated relatively weak codon usage bias, favoring codons with A/T endings, primarily influenced by natural selection. Phylogenetic analysis revealed that all four subfamilies formed monophyletic groups, with Cananga odorata (Ambavioideae) and Anaxagorea javanica (Anaxagoreoideae) successively nested outside Annonoideae + Malmeoideae. These findings improve our understanding of the plastome of M. glochidioides and provide additional insights for studying plastome evolution in Annonaceae.

Plasmonic trimers designed as SERS-active chemical traps for subtyping of lung tumors.

Plasmonic materials can generate strong electromagnetic fields to boost the Raman scattering of surrounding molecules, known as surface-enhanced Raman scattering. However, these electromagnetic fields are heterogeneous, with only molecules located at the 'hotspots', which account for ≈ 1% of the surface area, experiencing efficient enhancement. Herein, we propose patterned plasmonic trimers, consisting of a pair of plasmonic dimers at the bilateral sides and a trap particle positioned in between, to address this challenge. The trimer configuration selectively directs probe molecules to the central traps where 'hotspots' are located through chemical affinity, ensuring a precise spatial overlap between the probes and the location of maximum field enhancement. We investigate the Raman enhancement of the Au@Al2O3-Au-Au@Al2O3 trimers, achieving a detection limit of 10-14 M of 4-methylbenzenethiol, 4-mercaptopyridine, and 4-aminothiophenol. Moreover, single-molecule SERS sensitivity is demonstrated by a bi-analyte method. Benefiting from this sensitivity, our approach is employed for the early detection of lung tumors using fresh tissues. Our findings suggest that this approach is sensitive to adenocarcinoma but not to squamous carcinoma or benign cases, offering insights into the differentiation between lung tumor subtypes.

LncRNA LINC01278 Regulates the Prognosis and Related Mechanisms of Gastric Cancer by Targeting miR-129-5p.

Gastric cancer, a prevalent malady within the digestive tract, has a complex pathological mechanism and numerous patients. The regulation of gastric cancer process by long non-coding RNA (lncRNA) presented new prospects for the study of its molecular mechanism and the treatment of patients. The abnormal expressed genes in gastric cancer were screened by GSE193109 dataset. The correlation between LINC01278 and the likelihood of survival in patients suffering from gastric cancer was investigated by Kaplan-Meier survival curve and multivariate Cox analysis. LINC01278 in gastric cancer tissue samples and cells was verified via RT-qPCR. The cell counting kit-8 (CCK-8) and transwell assay were selected to detect the growth activity of gastric cancer cells. The association between LINC01278 and miR-129-5p was validated through luciferase reporter assay and RNA-binding protein immunoprecipitation (RIP) assay. Correlation analysis of clinical features revealed an association between LINC01278 and the prognosis in gastric cancer patients. LINC01278 was actively expressed in gastric cancer, which exerts a tumor-promoting effect. Silencing LINC01278 suppressed the biological function of tumor cells through spongiform miR-129-5p. LINC01278 has the potential to serve as a novel biomarker, offering new avenues of research for the prognosis and treatment of gastric cancer.

Effect of myristic acid supplementation on triglyceride synthesis and related genes in the pectoral muscles of broiler chickens.

Fatty acids (FAs) can serve as energy for poultry, maintain normal cell structure and function, and support a healthy immune system. Although the addition of polyunsaturated fatty acids (PUFAs) to the diet has been extensively studied and reported, the mechanism of action of saturated fatty acids (SFAs) remains to be elucidated. We investigated the effect of 0.04% dietary myristic acid (MA) on slaughter performance, lipid components, tissue FAs, and the transcriptome profile in chickens. The results showed that dietary MA had no effect on slaughter performance (body weight, carcass weight, eviscerated weight, and pectoral muscle weight) (P > 0.05). Dietary MA enrichment increased MA (P < 0.001) and triglycerides (TGs) (P < 0.01) levels in the pectoral muscle. The levels of palmitic acid, linoleic acid (LA), arachidonic acid (AA), SFAs, monounsaturated fatty acids (MUFAs), and PUFAs were significantly higher (P < 0.01) in the MA supplementation group compared to the control group. However, there were no significant differences in the ratios of PUFA/SFA and n6/omega-3 (n3) between the two groups. The MA content was positively correlated with the contents of palmitic acid, LA, linolenic acid (ALA), n3, n6, SFAs, and unsaturated fatty acids (UFA). DHCR24, which is known to be involved in steroid metabolism and cholesterol biosynthesis pathways, was found to be a significantly lower in the MA supplementation group compared to the control group (P < 0.05, log2(fold change) = -0.85). Five overlapping co-expressed genes were identified at the intersection between the differential expressed genes and Weighted Gene Co­expression Network Analysis-derived hub genes associated with MA phenotype, namely BHLHE40, MSL1, PLAGL1, SRSF4, and ENSGALG00000026875. For the TG phenotype, a total of 28 genes were identified, including CHKA, KLF5, TGIF1, etc. Both sets included the gene PLAGL1, which has a negative correlation with the levels of MA and TG. This study provides valuable information to further understand the regulation of gene expression patterns by dietary supplementation with MA and examines at the molecular level the phenotypic changes induced by supplementation with MA.

Atomic-level tailoring of single-atom tungsten catalysts for optimized electrochemical nitrate-to-ammonia conversion.

Nitrate contamination of water resources poses significant health and environmental risks, necessitating efficient denitrification methods that produce ammonia as a desirable product. The electrocatalytic nitrate reduction reaction (NO3RR) powered by renewable energy offers a promising solution, however, developing highly active and selective catalysts remains challenging. Single-atom catalysts (SACs) have shown impressive performance, but the crucial role of their coordination environment, especially the next-nearest neighbor dopant atoms, in modulating catalytic activity for NO3RR is underexplored. This study aims to optimize the NO3RR performance of tungsten (W) single atoms anchored on graphene by precisely engineering their coordination environment through first and next-nearest neighbor dopants. The stability, reaction paths, activity, and selectivity of 43 different nitrogen and boron doping configurations were systematically studied using density functional theory. The results reveal W@C3, with W coordinated to three carbon atoms, exhibits outstanding NO3RR activity with a low limiting potential of -0.36 V. Intriguingly, introducing next-nearest neighbor B and N dopants further enhances the performance, with W@C3-BN achieving a lower limiting potential of -0.26 V. This exceptional activity originates from optimal nitrate adsorption strengths facilitated by orbital hybridization and charge modulation effects induced by the dopants. Furthermore, high energy barriers for NO2 and NO formation on W@C3 and W@C3-BN ensure their selectivity towards NO3RR products. These findings provide crucial atomic-level insights into rational design strategies for high-performance single-atom NO3RR catalysts via coordination environment engineering.