Modulating the Coordination Chemistry of Co-N-C Catalytic Sites by Ru Species to Accelerate the Polysulfide Conversion Kinetics in Lithium-Sulfur Batteries.

The performance of lithium-sulfur batteries is compromised by the loss of sulfur as dissolved polysulfides in the electrolyte and consequently the polysulfide redox shutting effect. Accelerating the conversion kinetics of polysulfide intermediates into sulfur or lithium sulfide through electrocatalysis has emerged as a root-cause solution. Co-N-C composite electrocatalyst is commonly used for this purpose. It is illustrated here that how the effectiveness can be improved by modulating the coordination chemistry of Co-N-C catalytic sites through introducing Ru species (RuCo-NC). The well-dispersed Ru in the Co-NC carbon matrix altered the total charge distribution over the Co-N-C catalytic sites and led to the formation of electron-rich Co-N, which is highly active for the polysulfide conversion reactions. Using Ru to modulate the electronic structure in the Co-N-C configuration and the additional catalytic sites over the Ru-Nx species can manifest optimal adsorption behavior of polysulfides. Consequently, the sulfur cathode with RuCo-NC can reduce the capacity fade rate from 0.11% per cycle without catalyst (initial capacity of 701 mAh g-1) to 0.054% per cycle (initial capacity of 1074 mAh g-1) over 400 cycles at 0.2 C rate. The results of this study provide the evidence for a feasible catalyst modification strategy for the polysulfide electrocatalysis.

Extrachromosomal circular DNA landscape of breast cancer with lymph node metastasis.

Breast cancer (BC) is a complex disease with diverse manifestations, often resulting in lymph node metastasis (LNM) and impacting patient prognosis. Extrachromosomal circular DNA (eccDNA) has emerged as a key player in tumorigenesis, yet its contribution to BC LNM remains elusive. Here, we examined primary tumors and matched LNM tissues from 19 BC patients using the Circle-Seq method. We identified a median count of 44,682 eccDNA in primary tumor tissues and 38,057 in their paired LNM tissues. Furthermore, a ladder-like size distribution is observed in both primary tumor and LNM tissues. Meanwhile, similar repeat sequence distribution and GC content are identified from both primary tissue and LNM tissues. Finally, we found that eccDNA from both groups are flanked with palindromic trinucleotide motifs. These observations indicate that eccDNA of primary tumor and LNM tissues are from similar chromosomal origins. However, a subset of miRNA-associated eccDNA displayed selective enrichment in metastatic lesions, such as miR-6730 and miR-548AA1 genes. This observation implicates the function of miRNA-related eccDNA in the metastatic cascade. Our study uncovers the potential significance of these unique eccDNA molecules, shedding light on their role in cancer metastasis.

Correlation between severe attacks and serum aquaporin-4 antibody titer in neuromyelitis optica spectrum disorder.

Aquaporin 4-immunoglobulin G (AQP4-IgG) specifically targets aquaporin 4 in approximately 80% of Neuromyelitis Optica Spectrum Disorder (NMOSD) cases. NMOSD is presently categorized as anti-AQP4-antibody (Ab) positive or negative based on AQP4-Ab presence. The association between antibody titers and patient prognosis remains unclear. Therefore, the present study explores the correlation between severe attacks and serum AQP4 Ab titers in patients with neuromyelitis optica spectrum disorder. Data were gathered retrospectively from 546 patients with NMOSD between September 1, 2009, and December 1, 2021. Patients were categorized based on their AQP4-Ab titers: AQP4 titer ≥ 1:320 were classified as the high-titer group, AQP4 (+ +), and AQP4 titer of ≤ 1:100 were classified as the low-titer group, AQP4 ( +). Clinical characteristics and prognoses between the two groups were compared. Patients with AQP4 ( +) exhibited few severe optic neuritis (SON) attacks (false discovery rate [FDR] corrected p < 0.001), a reduced percentage experiencing SON attacks, and a lower incidence of visual disability than patients with AQP4 (+ +). Patients with AQP4 (+ +) and AQP4 ( +) NMOSD exhibited significant difference in annual recurrence rate (ARR) (FDR-corrected p < 0.001). The lower AQP4 Ab titer group demonstrated reduced susceptibility to severe relapse with conventional immunosuppressive agents and rituximab (RTX) than the higher titer group. No significant differences in sex, age at onset, coexisting connective tissue diseases, motor disability, or mortality rates were observed between the two groups. Higher AQP4 Ab titers correlated with increased disease severity and visual disability in patients with NMOSD.

MyoD1 promotes the transcription of BIK and plays an apoptosis-promoting role in the development of gastric cancer.

Myogenic differentiation (MyoD) 1, which is known as a pivotal transcription factor during myogenesis, has been proven dysregulated in several cancers. However, litter is known about the precise role and downstream genes of MyoD1 in gastric cancer (GC) cells. Here, we report that MyoD1 is lowly expressed in primary GC tissues and cells. In our experiments, overexpression of MyoD1 inhibited cell proliferation. Downstream genes of MyoD1 regulation were investigated using RNA-Seq. As a result, 138 up-regulated genes and 20 down-regulated genes and 27 up-regulated lncRNAs and 20 down-regulated lncRNAs were identified in MyoD1 overexpressed MKN-45 cells, which participated in epithelial cell signaling in Helicobacter pylori infection, glycosaminoglycan biosynthesis (keratan sulfate), notch signaling pathway, and others. Among these genes, BIK was directly regulated by MyoD1 in GC cells and inhibited cancer cell proliferation. The BIK knockdown rescued the effects of MyoD1 overexpression on GC cells. In conclusion, MyoD1 inhibited cell proliferation via 158 genes and 47 lncRNAs downstream directly or indirectly that participated in multiple signaling pathways in GC, and among these, MyoD1 promotes BIK transcription by binding to its promoter, then promotes BIK-Bcl2-caspase 3 axis and regulates GC cell apoptosis.

Mitochondrial carrier homolog 2 increases malignant phenotype of human gastric epithelial cells and promotes proliferation, invasion, and migration of gastric cancer cells.

BACKGROUND: The precise role of mitochondrial carrier homolog 2 (MTCH2) in promoting malignancy in gastric mucosal cells and its involvement in gastric cancer cell metastasis have not been fully elucidated. AIM: To determine the role of MTCH2 in gastric cancer. METHODS: We collected 65 samples of poorly differentiated gastric cancer tissue and adjacent tissues, constructed MTCH2-overexpressing and MTCH2-knockdown cell models, and evaluated the proliferation, migration, and invasion of human gastric epithelial cells (GES-1) and human gastric cancer cells (AGS) cells. The mitochondrial membrane potential (MMP), mitochondrial permeability transformation pore (mPTP) and ATP fluorescence probe were used to detect mitochondrial function. Mitochondrial function and ATP synthase protein levels were detected via Western blotting. RESULTS: The expression of MTCH2 and ATP2A2 in gastric cancer tissues was significantly greater than that in adjacent tissues. Overexpression of MTCH2 promoted colony formation, invasion, migration, MMP expression and ATP production in GES-1 and AGS cells while upregulating ATP2A2 expression and inhibiting cell apoptosis; knockdown of MTCH2 had the opposite effect, promoting overactivation of the mPTP and promoting apoptosis. CONCLUSION: MTCH2 can increase the malignant phenotype of GES-1 cells and promote the proliferation, invasion, and migration of gastric cancer cells by regulating mitochondrial function, providing a basis for targeted therapy for gastric cancer cells.

Cloning and functional identification of apple LATERAL ORGAN BOUNDARY DOMAIN 3 (LBD3) transcription factor in the regulation of drought and salt stress.

MAIN CONCLUSION: Overexpression of MdLBD3 in Arabidopsis reduced sensitivity to salt and drought stresses and was instrumental in promoting early flowering. Salt and drought stresses have serious effects on plant growth. LATERAL ORGAN BOUNDARY DOMAIN (LBD) proteins are a plant-specific transcription factors (TFs) family and play important roles in plants in resisting to abiotic stress. However, about the function of LBDs in apple and other woody plants is little known. In this study, protein sequences of the LBD family TFs in apples were identified which contained conserved LOB domains. The qRT-PCR analysis showed that the MdLBD3 gene was widely expressed in various tissues and organs. The subcellular localization assay showed that the MdLBD3 protein was localized in the nucleus. Ectopic expression of MdLBD3 in Arabidopsis positively regulated its salt and drought resistance, and promoted early flowering. Collectively, these results showed that MdLBD3 improved the abiotic stress resistance, plant growth and development. Overall, this study provided a new gene for breeding that can increase the abiotic stress tolerance in apple.

Pan-cancer analysis of ARFs family and ARF5 promoted the progression of hepatocellular carcinoma.

Background: ARF family proteins are a kind of small GTPases, which are involved in regulating a variety of basic functions of cells. In recent years, the role and molecular regulatory mechanisms of ARFs in tumor progression have received increasing attention, and research reports on most of their family members are increasing. However, research on the clinical and pathological relevance of ARF5 in cancer, especially in hepatocellular carcinoma, still needs to be improved. Methods: RNA-seq data in the Cancer Genome Atlas (TCGA) and genome tissue expression (GTEx) databases were used to analyze the expression and pathological data of ARFs family in Pan-cancer. Kaplan-Meier and Cox regression were used for prognostic analysis of ARF5 and Pan-cancer. Combined with ImmuCellAI database and TIMER2 database, the relationship between ARF5 expression and immune cell tumor infiltration in hepatocellular carcinoma (HCC) was analyzed. WGCNA is used to construct the co-expression gene network related to ARF5 expression in HCC and screen important modules and central genes. GO and KEGG path enrichment analysis were carried out for the genes in the modules with clinical significance. GSEA analysis was performed to take into account the role of genes with small differences. Finally, ceRNA network analysis was used to explore the molecular mechanism of miRNAs and lncRNAs regulating ARF5 expression. Results: ARFs family (ARF1, ARF3, ARF4, ARF5, ARF6) are generally highly expressed in Pan-cancer. ARF5 is significantly highly expressed in 29 cancers, and the high expression of ARF5 in HCC patients is significantly negatively correlated with OS, DFI, PFI and DSS, which may lead to cancer deterioration by participating in tumor immune infiltration of HCC. Through WGCNA analysis, the expression of ARF5 in HCC may be involved in many cellular processes that consume a lot of energy, such as ribosome formation, RNA and protein synthesis and lipids, as well as COVID-19, nonalcoholic fatty liver, neurodegenerative diseases and other disease pathways. Conclusion: ARFs, especially ARF5, are overexpressed in many human tumors. This study shows for the first time that ARF5 is significantly correlated with the poor prognosis of HCC patients, which may play a role as an oncogene, suggesting that ARF5 has the potential as a biomarker for the diagnosis and treatment of HCC.

Tandem transcription factors PpNAC1 and PpNAC5 synergistically activate the transcription of the PpPGF to regulate peach softening during fruit ripening.

Peach fruit rapidly soften after harvest, a significant challenge for producers and marketers as it results in rotting fruit and significantly reduces shelf life. In this study, we identified two tandem genes, PpNAC1 and PpNAC5, within the sr (slow ripening) locus. Phylogenetic analysis showed that NAC1 and NAC5 are highly conserved in dicots and that PpNAC1 is the orthologous gene of Non-ripening (NOR) in tomato. PpNAC1 and PpNAC5 were highly expressed in peach fruit, with their transcript levels up-regulated at the onset of ripening. Yeast two-hybrid and bimolecular fluorescence complementation assays showed PpNAC1 interacting with PpNAC5 and this interaction occurs with the tomato and apple orthologues. Transient gene silencing experiments showed that PpNAC1 and PpNAC5 positively regulate peach fruit softening. Yeast one-hybrid and dual luciferase assays and LUC bioluminescence imaging proved that PpNAC1 and PpNAC5 directly bind to the PpPGF promoter and activate its transcription. Co-expression of PpNAC1 and PpNAC5 showed higher levels of PpPGF activation than expression of PpNAC1 or PpNAC5 alone. In summary, our findings demonstrate that the tandem transcription factors PpNAC1 and PpNAC5 synergistically activate the transcription of PpPGF to regulate fruit softening during peach fruit ripening.

genRCT: a statistical analysis framework for generalizing RCT findings to real-world population.

When evaluating the real-world treatment effect, the analysis based on randomized clinical trials (RCTs) often introduces generalizability bias due to the difference in risk factors between the trial participants and the real-world patient population. This problem of lack of generalizability associated with the RCT-only analysis can be addressed by leveraging observational studies with large sample sizes that are representative of the real-world population. A set of novel statistical methods, termed "genRCT", for improving the generalizability of the trial has been developed using calibration weighting, which enforces the covariates balance between the RCT and observational study. This paper aims to review statistical methods for generalizing the RCT findings by harnessing information from large observational studies that represent real-world patients. Specifically, we discuss the choices of data sources and variables to meet key theoretical assumptions and principles. We introduce and compare estimation methods for continuous, binary, and survival endpoints. We showcase the use of the R package genRCT through a case study that estimates the average treatment effect of adjuvant chemotherapy for the stage 1B non-small cell lung patients represented by a large cancer registry.

ATP Citrate Lyase is a General Tumour Biomarker and Contributes to the Development of Cutaneous Squamous Cell Carcinoma.

ATP citrate lyase, the first rate-limiting enzyme in de novo lipogenesis, plays a crucial role in tumour progression. This study explores ATP citrate lyase's potential as a tumour biomarker and its role in cutaneous squamous cell carcinoma. ATP citrate lyase expression patterns were analysed using TCGA and TIMER databases, and patient skin specimens were collected for immunohistochemistry to determine ATP citrate lyase levels. Cell proliferation, cell cycle, apoptosis, and c-Myc expression were assessed in A431 and SCL-1 cells. Stable cell lines with reduced ATP citrate lyase expression were obtained and subcutaneously implanted into nude mice to evaluate in vivo tumour growth. Ki67, c-Myc expression and TUNEL staining were analysed in subcutaneous tumours. ATP citrate lyase exhibited upregulation in various tumours, and showed significant associations with prognosis and immune infiltrate. Moreover, ATP citrate lyase was highly expressed in cutaneous squamous cell carcinoma. After ATP citrate lyase silencing, cutaneous squamous cell carcinoma cell growth decelerated, the cell cycle halted, cell apoptosis increased, and c-Myc expression decreased. Animal experiments revealed that, following ATP citrate lyase knockdown, tumour tissue growth slowed down, and there was a reduction in Ki-67 and c-Myc expression, accompanied by enhanced TUNEL staining. In conclusion, ATP citrate lyase may serve as a tumour biomarker. It is highly expressed in cutaneous squamous cell carcinoma and may serve as a therapeutic target.

Impact of specific electromagnetic radiation on wakefulness in mice.

Electromagnetic radiation (EMR) in the environment, particularly in the microwave range, may constitute a public health concern. Exposure to 2.4 GHz EMR modulated by 100 Hz square pulses was recently reported to markedly increase wakefulness in mice. Here, we demonstrate that a similar wakefulness increase can be induced by the modulation frequency of 1,000 Hz, but not 10 Hz. In contrast to the carrier frequency of 2.4 GHz, 935 MHz EMR of the same power density has little impact on wakefulness irrespective of modulation frequency. Notably, the replacement of the 100 Hz square-pulsed modulation by sinusoidal-pulsed modulation of 2.4 GHz EMR still allows a marked increase of wakefulness. In contrast, continuous sinusoidal amplitude modulation of 100 Hz with the same time-averaged power output fails to trigger any detectable change of wakefulness. Therefore, alteration of sleep behavior by EMR depends upon not just carrier frequency but also frequency and mode of the modulation. These results implicate biological sensing mechanisms for specific EMR in animals.

MRCT and CT in the diagnosis of pediatric disease imaging: assessing imaging performance and clinical effects.

OBJECTIVE: This study focused on analyzing the clinical value and effect of magnetic resonance imaging plus computed tomography (MRCT) and CT in the clinical diagnosis of cerebral palsy in children. METHODS: From February 2021 to April 2023, 94 children diagnosed with cerebral palsy were selected from our hospital for study subjects. These patients were divided into CT and MRI groups, with CT examination given to the CT group and MRI examination given to the MRI group. The positive rate of the two examination methods in the diagnosis of cerebral palsy was compared, different imaging signs in two groups of children with cerebral palsy were compared, and the diagnostic test typing results between two groups were further analyzed. RESULTS: The diagnostic positivity rate of the children in the MRI group was 91.49%, which was significantly higher than that of the children in the CT group (70.21%) (P < 0.05). In both groups, encephalomalacia, bilateral frontal subdural effusions, and gray-white matter atrophy of the brain were the main signs, and the difference in the proportion of these three imaging signs between the two groups was not significant (P > 0.05). Differences between the two groups examined for cerebral palsy subtypes were not significant (P > 0.05). CONCLUSION: The positive rate of pediatric cerebral palsy examined by MRI is higher than that of CT diagnosis, but the clinic should organically combine the two to further improve the detection validity and accuracy.

Effects of Active Ingredients in Alcoholic Beverages and Their De-Alcoholized Counterparts on High-Fat Diet Bees: A Comparative Study.

The mechanisms by which alcohol, alcoholic beverages, and their de-alcoholized derivatives affect animal physiology, metabolism, and gut microbiota have not yet been clarified. The polyphenol, monosaccharide, amino acid, and organic acid contents of four common alcoholic beverages (Chinese Baijiu, beer, Chinese Huangjiu, and wine) and their de-alcoholized counterparts were analyzed. The research further explored how these alcoholic beverages and their non-alcoholic versions affect obesity and gut microbiota, using a high-fat diet bee model created with 2% palm oil (PO). The results showed that wine, possessing the highest polyphenol content, and its de-alcoholized form, particularly when diluted five-fold (WDX5), markedly improved the health markers of PO-fed bees, including weight, triglycerides, and total cholesterol levels in blood lymphocytes. WDX5 treatment notably increased the presence of beneficial microbes such as Bartonella, Gilliamella, and Bifidobacterium, while decreasing Bombilactobacillus abundance. Moreover, WDX5 was found to closely resemble sucrose water (SUC) in terms of gut microbial function, significantly boosting short-chain fatty acids, lipopolysaccharide metabolism, and associated enzymatic pathways, thereby favorably affecting metabolic regulation and gut microbiota stability in bees.

A new surface plasmon resonance-based immunoassay for rapid and sensitive quantification of D-dimer in human plasma for thrombus screening.

D-dimer is a protein fragment generated during the fibrin breakdown by plasmin, and it serves as a mature biomarker for diagnosing thrombotic disorders. A novel immunoassay method based on surface plasmon resonance (SPR) has been developed, validated, and successfully applied for the quantification of D-dimer in human plasma with high sensitivity and rapidity. In this methodological study, we investigated the activity and stability of the SPR biosensor, sample pre-processing, washing conditions, intra-day and inter-day precision and accuracy and detection parameters, including a limit of detection of 8.3 ng/mL, a detection range spanning from 31.25 to 4000 ng/mL, and a detection time of 20 min. We compared D-dimer plasma concentration determination results using SPR with a classical latex-enhanced immunoturbidimetric immunoassay in 29 healthy individuals and thrombotic patients, and both methods exhibited consistency. Furthermore, we propose a hypothesis about the relationship between the concentration of D-dimer and its molecular weight. With an increase in the D-dimer concentration in plasma, the D-dimer approaches its simplest form (190 kDa).

Theoretical Insights into the Photophysical Properties of 4CzIPN Doped in Different Hosts: A Multiscale Study.

As a typical thermally activated delayed fluorescence (TADF) emitter with green emission, 4CzIPN has attracted much attention recently. Most studies indicated that 4CzIPN doped in different hosts presented different performances; thus, the hosts should have an obvious influence on its photophysical properties. Herein, the influence of four kinds of hosts, including m-CzPym, m-CzTrz, p-CzPym, and p-CzTrz, on the photophysical properties of 4CzIPN is investigated. Molecular dynamics simulations were performed to simulate the host-guest conformations, and the photophysical properties were studied using the combined quantum mechanics/molecular mechanics method coupled with the thermal-vibration correlation function method. It is found that 4CzIPN in doped films has larger transition dipole moments and spin-orbital coupling constants compared to that in nondoped films. Faster radiative decay, intersystem crossing rates, and higher fluorescence efficiency could be obtained in doped films. Our work helps to better understand the photophysical properties of 4CzIPN in doped films and may favor the design of new hosts.

MdTPR16, an apple tetratricopeptide repeat (TPR)-like superfamily gene, positively regulates drought stress in apple.

The Tetratricopeptide repeat (TPR)-like superfamily with TPR conserved domains is widely involved in the growth and abiotic stress in many plants. In this report, the gene MdTPR16 belongs to the TPR family in apple (Malus domestica). Promoter analysis reveal that MdTPR16 incorporated various stress response elements, including the drought stress response elements. And different abiotic stress treatments, drought especially, significantly induce the response of MdTPR16. Overexpression of MdTPR16 result in better drought tolerance in apple and Arabidopsis by up-regulating the expression levels of drought stress-related genes, achieving a higher chlorophyll content level, more material accumulation, and overall better growth compared to WT in the drought. Under drought stress, the overexpressed MdTPR16 also mitigate the oxidative damage in cells by reducing the electrolyte leakage, malondialdehyde content, and the H2O2 and O2- accumulation in apples and Arabidopsis. In conclusion, MdTPR16 act as a beneficial regulator of drought stress response by regulating the expression of related genes and the cumulation of reactive oxygen species (ROS).

Prognostic model on pregnancy outcomes for women with recurrent spontaneous abortions treated with cyclosporin A: A single-institution experience.

BACKGROUND: This study aimed to identify prognostic factors for pregnancy outcomes and construct a prognostic model for pregnancy outcomes in women with Recurrent Spontaneous Abortions (RSA) treated with cyclosporin A. METHODS: A total of 154 RSA patients treated with cyclosporin A between October 2016 and October 2018 were retrospectively recruited. Multivariate logistic regression was applied to identify the prognostic factors for pregnancy success in RSA women treated with cyclosporin A. The Receiver Operating Characteristic (ROC) curve was applied to construct prognostic value, and the prognostic performance was assessed using area under the ROC. RESULTS: After adjusting potential confounding factors, the authors noted increased age (OR = 0.771; 95 % CI 0.693‒0.858; p < 0.001) and positive antinuclear antibodies (OR = 0.204; 95 % CI 0.079‒0.526; p = 0.001) were associated with a reduced incidence of pregnancy success, while positive anti-ß2 glycoprotein-I-antibody (OR = 21.941; 95 % CI 1.176‒409.281; p = 0.039) was associated with an increased incidence of pregnancy success after treated with cyclosporin A. The AUC of combining these variables for predicting pregnancy failure was 0.809 (95 % CI 0.735‒0.880). CONCLUSIONS: This study systematically identified the prognostic factors for pregnancy success in women treated with cyclosporin A, and the constructed prognostic model based on these factors with relatively higher prognostic value. Further large-scale prospective studies should be performed to validate the prognostic value of the constructed model.

Availability of genome-matched therapy based on clinical practice.

BACKGROUND: Comprehensive genomic profiling (CGP) provides new opportunities for patients with advanced cancer to receive genome-matched therapies, but the availability rate of these remains low. We reviewed our CGP cases and suggested possible strategies to improve the current status from a clinical perspective. METHODS: Druggable genomic alterations and barriers to accessing genome-matched therapies were investigated in 653 patients with 30 various types of cancers who underwent CGP. RESULTS: While the availability rate of genome-matched therapies as a whole was 9.5%, CGP was useful in some cancer types. Patients with thyroid cancer and lung cancer harbored druggable genomic alterations at high rates, while sarcoma rarely harbored these alterations (100%, 76%, and 15.2%, respectively). In contrast, the availability rate of genome-matched therapies was highest in patients with sarcoma and head and neck cancer (HNC) (60% and 40%, respectively). One hundred thirteen patients (63.5%) had multiple barriers to accessing genome-matched therapy. Of 178 patients, 21 patients (11.8%) could not be considered for genome-matched therapies solely because of the deterioration of their performance status. CONCLUSION: This study demonstrated the usefulness of CGP for patients with sarcoma and HNC in addition to lung cancer in clinical practice. Performing CGP at the front line has the potential to improve the availability of genome-matched therapy.

AQP4-DARPin1: A Chimeric Antigen Based on Scaffold Protein DARPin for Efficient Detection of AQP4-IgG in NMOSD.

AQP4-IgG is an autoantibody associated with neuromyelitis optica spectroscopic disorder (NMOSD), a central nervous system inflammatory disease that requires early diagnosis and treatment. We designed two fusion proteins, AQP4-DARPin1 and AQP4-DARPin2, comprising the complete antigenic epitopes of aquaporin-4 (AQP4) and the constant region of the scaffold protein DARPin. These fusion proteins were expressed and purified from Escherichia coli and coated on microplates to develop an efficient method for detecting AQP4-IgG. Molecular dynamics simulation revealed that the fusion of AQP4 extracellular epitopes with DARPin did not alter the main structure of DARPin. The purified AQP4-DARPins bound recombinant antibody rAb-53 (AQP4-IgG) with affinities of 135 and 285 nM, respectively. Enzyme-linked immunosorbent assay (ELISA) and immunoprecipitation demonstrated that AQP4-DARPin1 specifically recognized AQP4-IgG in the NMOSD patient serum. AQP4-DARPin1 as a coated antigen showed higher ELISA signal and end point dilution ratio than full-length AQP4. Our AQP4-DARPin1-coated AQP4-IgG ELISA had 100% specificity and 90% sensitivity. These results indicate that AQP4-DARPin1, compared to existing detection strategies that use full-length or extracellular loop peptides of AQP4, provides a new and more effective approach to the ELISA detection of NMOSD.

Integration Analysis of Hair Follicle Transcriptome and Proteome Reveals the Mechanisms Regulating Wool Fiber Diameter in Angora Rabbits.

Fiber diameter is an important characteristic that determines the quality and economic value of rabbit wool. This study aimed to investigate the genetic determinants of wool fiber diameter through an integration analysis using transcriptomic and proteomic datasets from hair follicles of coarse and fine wool from Angora rabbits. Using a 4D label-free technique, we identified 423 differentially expressed proteins (DEPs) in hair follicles of coarse and fine wool in Angora rabbits. Eighteen DEPs were examined using parallel reaction monitoring, which verified the reliability of our proteomic data. Functional enrichment analysis revealed that a set of biological processes and signaling pathways related to wool growth and hair diameter were strongly enriched by DEPs with fold changes greater than two, such as keratinocyte differentiation, skin development, epidermal and epithelial cell differentiation, epidermis and epithelium development, keratinization, and estrogen signaling pathway. Association analysis and protein-protein interaction network analysis further showed that the keratin (KRT) family members, including KRT77, KRT82, KRT72, KRT32, and KRT10, as well as CASP14 and CDSN, might be key factors contributing to differences in fiber diameter. Our results identified DEPs in hair follicles of coarse and fine wool and promoted understanding of the molecular mechanisms underlying wool fiber diameter variation among Angora rabbits.