Identification of Susceptibility Genes Underlying Bovine Respiratory Disease in Xinjiang Brown Cattle Based on DNA Methylation.

DNA methylation is a form of epigenetic regulation, having pivotal parts in controlling cellular expansion and expression levels within genes. Although blood DNA methylation has been studied in humans and other species, its prominence in cattle is largely unknown. This study aimed to methodically probe the genomic methylation map of Xinjiang brown (XJB) cattle suffering from bovine respiratory disease (BRD), consequently widening cattle blood methylome ranges. Genome-wide DNA methylation profiling of the XJB blood was investigated through whole-genome bisulfite sequencing (WGBS). Many differentially methylated regions (DMRs) obtained by comparing the cases and controls groups were found within the CG, CHG, and CHH (where H is A, T, or C) sequences (16,765, 7502, and 2656, respectively), encompassing 4334 differentially methylated genes (DMGs). Furthermore, GO/KEGG analyses showed that some DMGs were involved within immune response pathways. Combining WGBS-Seq data and existing RNA-Seq data, we identified 71 significantly differentially methylated (DMGs) and expressed (DEGs) genes (p < 0.05). Next, complementary analyses identified nine DMGs (LTA, STAT3, IKBKG, IRAK1, NOD2, TLR2, TNFRSF1A, and IKBKB) that might be involved in the immune response of XJB cattle infected with respiratory diseases. Although further investigations are needed to confirm their exact implication in the involved immune processes, these genes could potentially be used for a marker-assisted selection of animals resistant to BRD. This study also provides new knowledge regarding epigenetic control for the bovine respiratory immune process.

Benefit finding in individuals undergoing maintenance hemodialysis in Shanghai: a latent profile analysis.

Objective: This multi-center cross-sectional study aimed to delineate latent profiles of benefit finding (BF) in individuals undergoing maintenance hemodialysis (MHD) in Shanghai and examine associations between these BF profiles, social support, and coping style. Methods: A total of 384 individuals undergoing MHD (mean age = 57.90, SD = 13.36) were assessed using the Benefit Finding Scale, Simplified Coping Style Questionnaire, and Perceived Social Support Scale. Latent profile analysis (LPA) identified distinct BF categories. Analysis of variance (ANOVA) evaluated the correlation between BF groups and demographic variables, while the relationship between BF, social support, and coping style was tested through correlation and multiple regression analyses. Results: LPA identified three BF groups: rich BF (54.17%), moderate BF (41.14%), and poor BF (4.69%). Regression analyses indicated that positive coping and social support are protective factors for BF. Additionally, older age and heightened understanding of MHD correlated with higher BF levels. Conclusion: The findings highlighted the importance of recognizing different BF profiles in individuals on MHD and working toward promoting BF levels in the rich BF and moderate BF groups, while helping the poor BF group to identify and address their challenges. Medical professionals should consider interventions tailored to individual psychological profiles to improve mental health and quality of life outcomes in this population.

Methanol-induced assembly and pyrolysis preparation of three-dimensional N-doped interconnected open carbon cages supported FeNb2O6 nanoparticles for boosting oxygen reduction reaction and Zn-air battery.

Three-dimensional (3D) hollow carbon is one of advanced nanomaterials widely applied in oxygen reduction reaction (ORR). Herein, iron niobate (FeNb2O6) nanoparticles supported on metal-organic frameworks (MOFs)-derived 3D N-doped interconnected open carbon cages (FeNb2O6/NICC) were prepared by methanol induced assembly and pyrolysis strategy. During the fabrication process, the evaporation of methanol promoted the assembly and cross linkage of ZIF-8, rather than individual particles. The assembled ZIF-8 particles worked as in-situ sacrificial templates, in turn forming hierarchically interconnected open carbon cages after high-temperature pyrolysis. The as-made FeNb2O6/NICC showed a positive onset potential of 1.09 V and a half-wave potential of 0.88 V for the ORR, outperforming commercial Pt/C under the identical conditions. Later on, the as-built Zn-air battery with the FeNb2O6/NICC presented a greater power density of 100.6 mW cm-2 and durable long-cycle stability by operating for 200 h. For preparing 3D hollow carbon materials, this synthesis does not require a tedious removal process of template, which is more convenient than traditional method with silica and polystyrene spheres as templates. This work affords an exceptional example of developing 3D N-doped interconnected hollow carbon composites for energy conversion and storage devices.

Ameliorative Role of Mitochondrial Therapy in Cognitive Function of Vascular Dementia Mice.

BACKGROUND: Mitochondrial dysfunction plays a vital role in the progression of vascular dementia (VaD). We hypothesized that transfer of exogenous mitochondria might be a beneficial strategy for VaD treatment. OBJECTIVE: The study was aimed to investigate the role of mitochondrial therapy in cognitive function of VaD. METHODS: The activity and integrity of isolated mitochondria were detected using MitoTracker and Janus Green B staining assays. After VaD mice were intravenously injected with exogenous mitochondria, Morris water maze and passive avoidance tests were used to detect cognitive function of VaD mice. Haematoxylin and eosin, Nissl, TUNEL, and Golgi staining assays were utilized to measure neuronal and synaptic injury in the hippocampus of VaD mice. Detection kits were performed to detect mitochondrial membrane potential (ΔΨ), SOD activity and the levels of ATP, ROS, and MDA in the brains of VaD mice. RESULTS: The results showed that isolated mitochondria were intact and active. Mitochondrial therapy could ameliorate cognitive performance of VaD mice. Additionally, mitochondrial administration could attenuate hippocampal neuronal and synaptic injury, improve mitochondrial ΔΨ, ATP level and SOD activity, and reduce ROS and MDA levels in the brains of VaD mice. CONCLUSIONS: The study reports profitable effect of mitochondrial therapy against cognitive impairment of VaD, making mitochondrial treatment become a promising therapeutic strategy for VaD.

Gliclazide Ameliorates Neuronal Injury by Attenuating Oxidative Stress in D-gal-Induced Senescent Cells and Aging Mice.

Enhancement of oxidative stress and resultant neuronal injury play important roles in initiating cognitive impairment during the aging process. Thus, attenuating oxidative injury is regarded as a profitable therapeutic strategy for age-associated cognitive impairment. Previous studies showed that gliclazide (Gli) had a protective role in neuronal injury from cerebral ischemia/reperfusion (I/R) injury. However, whether Gli has a profitable effect on age-associated cognitive impairment remains largely unclear. The present study showed that Gli held the potential to attenuate neuronal apoptosis in D-gal-induced senescent cells and aging mice. Additionally, Gli could alleviate synaptic injury and cognitive function in D-gal-induced aging mice. Further study showed that Gli could attenuate oxidative stress in D-gal-induced senescent cells and aging mice. The p38 MAPK pathway was predicted as the downstream target of Gli retarding oxidative stress using in silico analysis. Further studies revealed that Gli attenuated D-gal-induced phosphorylation of p38 and facilitated Nrf2 nuclear expression, indicating that the anti-oxidative property of Gli may be associated with the p38 MAPK pathway. The study demonstrates that Gli has a beneficial effect on ameliorating D-gal-induced neuronal injury and cognitive impairment, making this compound a promising agent for the prevention and treatment of age-associated cognitive impairment.

[Rapid detection technology of chemical component content in Lycii Fructus based on hyperspectral technology].

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STAT5 promotes PD-L1 expression by facilitating histone lactylation to drive immunosuppression in acute myeloid leukemia.

Immunotherapy is a revolutionized therapeutic strategy for tumor treatment attributing to the rapid development of genomics and immunology, and immune checkpoint inhibitors have successfully achieved responses in numbers of tumor types, including hematopoietic malignancy. However, acute myeloid leukemia (AML) is a heterogeneous disease and there is still a lack of systematic demonstration to apply immunotherapy in AML based on PD-1/PD-L1 blockage. Thus, the identification of molecules that drive tumor immunosuppression and stratify patients according to the benefit from immune checkpoint inhibitors is urgently needed. Here, we reported that STAT5 was highly expressed in the AML cohort and activated the promoter of glycolytic genes to promote glycolysis in AML cells. As a result, the increased-lactate accumulation promoted E3BP nuclear translocation and facilitated histone lactylation, ultimately inducing PD-L1 transcription. Immune checkpoint inhibitor could block the interaction of PD-1/PD-L1 and reactive CD8+ T cells in the microenvironment when co-culture with STAT5 constitutively activated AML cells. Clinically, lactate accumulation in bone marrow was positively correlated with STAT5 as well as PD-L1 expression in newly diagnosed AML patients. Therefore, we have illustrated a STAT5-lactate-PD-L1 network in AML progression, which demonstrates that AML patients with STAT5 induced-exuberant glycolysis and lactate accumulation may be benefited from PD-1/PD-L-1-based immunotherapy.

Pediatric hypereosinophilic syndrome associated with liver damage, portal vein, splenic vein and superior mesenteric vein thromboses: a case report.

BACKGROUND: The hypereosinophilic syndrome (HES) is a group of rare blood disorders characterized by persistent eosinophilia and damage to multiple organs. HES can be either primary, secondary or idiopathic. Secondary HES are commonly caused by parasitic infections, allergic reactions or cancer. We described a pediatric case of HES associated with liver damage and multiple thrombi. A 12-year-old boy with eosinophilia was complicated with severe thrombocytopenia, liver damage, portal vein, splenic vein, and superior mesenteric vein thromboses. The thrombi recanalized after treatment with methylprednisolone succinate and low molecular weight heparin. No side effects appeared after 1-month. CONCLUSIONS: Corticosteroids should be used at an early stage of HES to prevent further damage to vital organs. Anticoagulants should be recommended only in cases with thrombosis which should be actively screened as a part of evaluation of end organ damage.

A Genome-Wide Association Study of the Chest Circumference Trait in Xinjiang Donkeys Based on Whole-Genome Sequencing Technology.

Animal genotyping by means of genome-wide association studies is important for connecting phenotypes of interest with their underlying genetics in livestock. However, the use of whole genome sequencing to investigate chest circumference (CC) in donkeys has rarely been reported. We aimed to use the genome-wide association study approach to detect significant single nucleotide polymorphisms (SNPs) and key genes associated with chest circumference traits in Xinjiang donkeys. We assessed 112 Xinjiang donkeys in this study. The chest circumference of each was measured 2 h before milking. We re-sequenced blood samples from the Xinjiang donkeys, and genome-wide association study analyses were performed using a mixed model with the PLINK, GEMMA, and REGENIE programs. We tested 38 donkeys for candidate SNPs for genome-wide association study using three software programs. Additionally, 18 SNP markers reached genome-wide significance (p < 1.61 × 10-9). On the basis of these, 41 genes were identified. Previously proposed candidate genes for CC traits were supported by this study, including NFATC2 (Nuclear Factor of Activated T Cells 2), PROP1 (PROP Paired-Like Homeobox 1), UBB (Ubiquitin B), and HAND2 (Heart and Neural Crest Derivatives Expressed 2). These promising candidates provide a valuable resource for validating potential meat production genes and will facilitate the development of high-yielding Xinjiang donkey breeds through marker-assisted selection or gene editing.

Transcript Characteristics on the Susceptibility Difference of Bovine Respiratory Disease.

Bovine respiratory disease (BRD) is one of the major health issues in the cattle industry, resulting in significant financial crises globally. There is currently no good treatment, and cattle are made resistant to pneumonia through disease-resistant breeding. The serial blood samples from six Xinjiang brown (XJB) calves were collected for the RNA sequencing (RNA-seq). The obtained six samples were grouped into two groups, in each group as infected with BRD and healthy calves, respectively. In our study, the differential expression mRNAs were detected by using RNA-seq and constructed a protein-protein interaction (PPI) network related to the immunity in cattle. The key genes were identified by protein interaction network analysis, and the results from RNA-seq were verified using reverse transcription-quantitative polymerase chain reaction (RT-qPCR). A total of 488 differentially expressed (DE) mRNAs were identified. Importantly, the enrichment analysis of these identified DEGs classified them as mainly enriched in the regulation and immune response processes. The 16 hub genes were found to be related to immune pathways categorized by PPIs analysis. Results revealed that many hub genes were related to the immune response to respiratory disease. These results will provide the basis for a better understanding of the molecular mechanism of bovine resistance to BRD.

Surface Electromyography of Pharyngeal Swallowing in Healthy Chinese Individuals: Establishment of a Timing and Amplitude Database.

This study determined the surface electromyography (sEMG) characteristics of healthy Chinese adults during swallowing to provide a reference for the clinical differential diagnosis of swallowing and dysphagia. sEMG was performed on 187 healthy adults to obtain quantitative information on normal pharyngeal swallowing. The evaluated parameters included the timing and amplitude of sEMG activity in the submental and infrahyoid muscles. A normative database was constructed for the timing and amplitude of muscle activity during pharyngeal swallowing. Results indicated that the duration of sEMG activity was related to the age of the patient; the duration gradually increasing with age. Similarly, the duration of the sEMG activity was associated with the type of swallowing. The duration of the sEMG activity was similar for dry and wet swallowing but was significantly different for excessive swallowing. The mean amplitude of sEMG activity for the submental and infrahyoid muscles was not significantly associated with patient age. A significant correlation between the mean amplitude of sEMG activity and the types of normal swallowing was observed in infrahyoid, but not in submental muscle activity. This study is the first report on the establishment of a normative database for the duration and amplitude of muscle activity based on sEMG analysis of pharyngeal swallowing in healthy Chinese adults.

Evaluation of Doppler indices (MCA & UA) and fetal outcomes: a retrospective case-control study in women with hypertensive disorders of pregnancy.

BACKGROUND: Hypertensive disorders of pregnancy (HDP) is associated with an increased risk of adverse outcomes. The fetal middle cerebral artery (MCA) and umbilical artery (UA) blood flow detected by ultrasound are recommended to evaluate the oxygenation of the fetus. It is necessary to analyze the relationship between MCA & UA doppler indices or cerebroplacental ratio (CPR) and fetal outcomes and describe MCA and UA blood flow values across gestation. METHODS: Hospital-based retrospective case-control study during 2016 to 2020. 800 singleton pregnant women: 400 normotensive control, 219 gestational hypertension (GH), and 181 preeclampsia (PE)/eclampsia (EC). An analysis of the outcomes of mothers and neonates was performed. The fetal MCA and UA blood flow values across gestation were established, and MCA-resistance index (RI) and CPR were used to predict fetal distress and small for gestational age (SGA). RESULTS: In the normotensive control, GH and PE/EC groups, the mean gestational age (GA) was 38.9 ± 1.2 weeks, 39.0 ± 1.0 weeks, and 38.6 ± 1.3 weeks respectively, and the mean birth weight (BW) was 3.195 ± 0.387 kilograms, 3.198 ± 0.428 kilograms, and 2.987 ± 0.544 kilograms respectively. There were differences in GA, BW, fetal distress, SGA and intraventricular hemorrhage I-II between the hypertension group and normotensive control group (p < 0.05). The MCA-RI (sensitivity: 70.1%, specificity: 64.3%) and MCA-RI (sensitivity: 52.4%, specificity: 84.6%) were the best indices to predict fetal distress and SGA, respectively during GA of 35-40 weeks. CONCLUSIONS: Fetal MCA blood flow values and CPR are of great benefit for obstetricians to evaluate the status of fetus evidentially in singleton pregnancy.

FeCo alloy entrapped in N-doped graphitic carbon nanotubes-on-nanosheets prepared by coordination-induced pyrolysis for oxygen reduction reaction and rechargeable Zn-air battery.

Oxygen reduction reaction (ORR) on cathode severely suffers from sluggish kinetics in zinc-air batteries. Therefore, substantial efforts have been made to prepare advanced electrocatalysts for facilitating the ORR. Herein, we synthesized FeCo alloyed nanocrystals entrapped in N-doped graphitic carbon nanotubes on nanosheets (FeCo-N-GCTSs) by 8-aminoquinoline coordination-induced pyrolysis, whose morphology, structures, and property were characterized in details. Impressively, the obtained FeCo-N-GCTSs catalyst showed a positive onset potential (Eonset = 1.06 V) and half-wave potential (E1/2 = 0.88 V), revealing excellent ORR activity. Further, the FeCo-N-GCTSs assembled zinc-air battery displayed the maximum power density of 133 mW cm-2 and negligible gap change in the discharge-charge voltage plot over 288 h (ca. 864 cycles) at 5 mA cm-2, outperforming the Pt/C + RuO2 based counterpart. This work provides a facile route for construction of high-efficiency, durable and low-cost nanocatalysts for the ORR in fuel cells and rechargeable Zn-air batteries.

Synthesis of graphene oxide grafted by diazanyl groups and its application in recovery of lead from lead-acid wastewater.

Heavy metal ion (HMI) in wastewater is a kind of resource that is wrongly placed. Recovery of heavy metal from lead-acid wastewater desires efficient and reusable functional materials. In this paper, graphene oxide-like with diazanyl groups (GOLA) was synthesized by a nucleophilic substitution reaction of graphene oxide-like with hydroxyl groups (GOLH) with diazane. GOLA exhibited good stability and recyclability in wastewater. The maximal adsorption capacity (qmax) values of GOLA for Pb(II), Cd(II), Cu(II), Ni(II), and Cr(III) ions were 505.80, 401.99, 83.48, 82.29, and 147.77 mg/g, respectively. The equilibrium time of GOLA adsorbing HMIs was 20 min. GOLA was employed to recover lead ions from lead-acid wastewater to give Pb(OH)2 and reusable water. Therefore, this paper provides a useful method of recycling lead from lead-acid wastewater.

Alpha lipoamide inhibits diabetic kidney fibrosis via improving mitochondrial function and regulating RXRα expression and activation.

Previous studies have shown mitochondrial dysfunction in various acute kidney injuries and chronic kidney diseases. Lipoic acid exerts potent effects on oxidant stress and modulation of mitochondrial function in damaged organ. In this study we investigated whether alpha lipoamide (ALM), a derivative of lipoic acid, exerted a renal protective effect in a type 2 diabetes mellitus mouse model. 9-week-old db/db mice were treated with ALM (50 mg·kg-1·d-1, i.g) for 8 weeks. We showed that ALM administration did not affect blood glucose levels in db/db mice, but restored renal function and significantly improved fibrosis of kidneys. We demonstrated that ALM administration significantly ameliorated mitochondrial dysfunction and tubulointerstitial fibrotic lesions, along with increased expression of CDX2 and CFTR and decreased expression of ß-catenin and Snail in kidneys of db/db mice. Similar protective effects were observed in rat renal tubular epithelial cell line NRK-52E cultured in high-glucose medium following treatment with ALM (200 µM). The protective mechanisms of ALM in diabetic kidney disease (DKD) were further explored: Autodock Vina software predicted that ALM could activate RXRα protein by forming stable hydrogen bonds. PROMO Database predicted that RXRα could bind the promoter sequences of CDX2 gene. Knockdown of RXRα expression in NRK-52E cells under normal glucose condition suppressed CDX2 expression and promoted phenotypic changes in renal tubular epithelial cells. However, RXRα overexpression increased CDX2 expression which in turn inhibited high glucose-mediated renal tubular epithelial cell injury. Therefore, we reveal the protective effect of ALM on DKD and its possible potential targets: ALM ameliorates mitochondrial dysfunction and regulates the CDX2/CFTR/ß-catenin signaling axis through upregulation and activation of RXRα. Schematic figure illustrating that ALM alleviates diabetic kidney disease by improving mitochondrial function and upregulation and activation of RXRα, which in turn upregulated CDX2 to exert an inhibitory effect on ß-catenin activation and nuclear translocation. RTEC renal tubular epithelial cell. ROS Reactive oxygen species. RXRα Retinoid X receptor-α. Mfn1 Mitofusin 1. Drp1 dynamic-related protein 1. MDA malondialdehyde. 4-HNE 4-hydroxynonenal. T-SOD Total-superoxide dismutase. CDX2 Caudal-type homeobox transcription factor 2. CFTR Cystic fibrosis transmembrane conductance regulator. EMT epithelial mesenchymal transition. α-SMA Alpha-smooth muscle actin. ECM extracellular matrix. DKD diabetic kidney disease. Schematic figure was drawn by Figdraw ( www.figdraw.com ).

Circular RNAs: emerging players in brain aging and neurodegenerative diseases.

Brain aging is closely related to neurodegenerative diseases. Circular RNAs (circRNAs) are a type of conserved RNAs with covalently closed continuous loops. Emerging evidence has shown that circRNAs are implicated in the biology of brain aging and the pathology of age-related neurodegenerative diseases. Here, we summarize current studies on circRNAs associated with brain aging and neurodegenerative diseases by discussing their expression features, pathophysiological roles, and mechanisms of action. We also discuss the potential challenges of circRNA-based therapy against brain aging and neurodegenerative diseases, as well as their potential as diagnostic biomarkers of neurodegenerative diseases. The review provides insights into current progress in the functions of circRNAs in the process of brain aging and neurodegenerative diseases. © 2022 The Pathological Society of Great Britain and Ireland.

Candidate genes for litter size in Xinjiang sheep identified by Specific Locus Amplified Fragment (SLAF) sequencing.

The aim of this study was to investigate the selection signatures at a genome-wide level in 'Pishan' sheep using Specific Locus Amplified Fragment (SLAF)-seq. Blood samples from 126 ewes were sequenced using SLAF tags, and the ovarian tissues from 8 ewes (Bashbay sheep, a single litter size group (SG group); 'Pishan' sheep, double litter size group (DG group)) were collected to detect expression levels by quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR). Selection signature analysis was performed using global fixation index (Fst) and nucleotide diversity (π) ratio. A total of 1,192,168 high-quality SLAFs were identified. Notably, 2380 candidate regions under selection using two approaches were identified. A total of 2069 genes were identified, which were involved in dopaminergic synapses, thyroid hormone synthesis, ovarian steroidogenesis and thyroid hormone signalling pathways. Furthermore, Growth Differentiation Factor 9 (GDF9), Period Circadian Regulator 2 (PER2), Thyroid Stimulating Hormone Receptor (TSHR), and Nuclear Receptor Coactivator 1 (NCOA1) reside within these regions and pathways. The expression levels of GDF9 and PER2 genes in sheep tissue of the DG group were significantly higher than those in the SG group. These genes are interesting candidates for litter size and provide a starting point for further identification of conservation strategies for 'Pishan' sheep.

Transcriptome profiling of LncRNAs in sheep tail fat deposition.

LncRNAs have recently received special attention due to their critical role in many important biological processes. There are few reports on its regulatory function in sheep fat deposition. In this study, two sheep populations with different tail types in Xinjiang, Bashibai sheep (fat-tailed) and the hybrid population of Bashibai sheep and wild argali (small-tailed) were selected for whole transcriptome sequencing from their tail tissues. First, 728 differentially expressed LncRNAs of tail fat between Bashibai and F2 sheep were identified by RNA-seq. Second, the tissue expression profile and relative expression difference between Bashibai and F2 sheep of 2 of 728 DE LncRNAs were analyzed by RT-PCR. LncRNA-MSTRG.24995 was highly expressed in tail fat, while lncRNA-MSTRG.36913 was highly expressed in subcutaneous fat. In addition, the expressions of LncRNA-MSTRG.24995 and LncRNA-MSTRG.36913 in tail fat of F2 sheep were significantly lower than that of Bashibai sheep, while those patterns in longissimus dorsi, quadriceps femoris and rumen were reversed. Third, the expression pattern of target genes FASN and THRSP in each tissue was similar with that of corresponding LncRNAs. The LncRNA-MSTRG.24995 directly affects tail fat deposition by FASN gene, while the LncRNA-MSTRG.36913 indirectly affects that by THRSP gene. This will help us to understand molecular mechanism of fat tail deposition from transcriptomic perspectives.

Study on lactation performance and development of KASP marker for milk traits in Xinjiang donkey (Equus asinus).

Donkey milk has high nutritional and medicinal value, but there are few researches in donkey milk traits, especially on genome. The whole lactation of 89 donkeys was recorded and it was found that Xinjiang donkey had good lactation performance while great differences among individuals. In our previous study, four genes including LGALS2, NUMB, ADCY8 and CA8 were identified as milk-associated with Chinese Kazakh house, based on Equine 670k Chip genomic analysis. And then 15 SNPs of the four key genes were conducted for genotyping in Xinjiang donkey in this study, one of Chinese indigenous breed, 14 SNPs were successful classified. And those SNPs were correlation analysis with milk yield of Xinjiang donkeys. The results showed that NUMB g.46709914T > G was significantly correlated with daily milk yield of Xinjiang donkey in the early, middle, and late periods, while ADCY8 g.48366302T > C, CA8 g.89567442T > G and CA8 g.89598328T > A were significantly correlated with lactation in the late periods. These results indicate that NUMB g.46709914T > G can be as markers of candidate genes for lactating traits in donkeys, SNPs of ADCY8 and CA8 as potential. Our findings will not only help confirm key genes for donkey milk traits, but also provide future for genomic selection in donkeys.

Coexistence of multiple anti-neuronal antibodies in autoimmune encephalitis in China: A multi-center study.

Background: Given that the combination of multiple antibodies in autoimmune encephalitis (AE) is rare and its clinical significance is unclear, this study aimed to investigate the clinical characteristics and significance of overlapping multiple anti-neuronal antibodies in patients with AE. Methods: We conducted a retrospective analysis of the clinical characteristics, treatment, and prognostic details of 22 patients with multiple coexisting antibodies from multiple clinical centers in China. Results: Among the 276 patients who were AE antibody-positive, 22 (7.97%) had two or more antibodies. Among the 22 patients with coexisting AE-related antibodies, 14 patients (63.63%) were combined of cell surface and intracellular antibody, and the remaining 8 patients (36.36%) were detected to be cell surface antibody positive only. The main symptoms of the 22 patients in this cohort included fever, seizures, memory impairment, cognitive decline, and sleep disorders. Five (22.73%) patients had tumors, among whom four had small-cell lung cancers, and one had mediastinal tumors. A total of 20 patients were treated with steroids and intravenous immunoglobulin, and 18 showed varying degrees of symptomatic improvement after first-line immunotherapy. Three patients died of tumor progression or chemotherapy complications. Conclusion: The coexistence of multiple anti-neuronal antibodies in patients with AE may cause a superimposition and diversification of clinical manifestations. Combined paraneoplastic antibody positivity may be suggestive of an underlying malignancy.