Adipocyte Rnf20 ablation increases the fast-twitch fibers of skeletal muscle via lysophosphatidylcholine 16:0.

Both adipose tissue and skeletal muscle are highly dynamic tissues and interact at the metabolic and hormonal levels in response to internal and external stress, and they coordinate in maintaining whole-body metabolic homeostasis. In our previous study, we revealed that adipocyte-specific Rnf20 knockout mice (ASKO mice) exhibited lower fat mass but higher lean mass, providing a good model for investigating the adipose-muscle crosstalk and exploring the effect of the adipocyte Rnf20 gene on the physiology and metabolism of skeletal muscle. Here, we confirmed that ASKO mice exhibited the significantly increased body weight and gastrocnemius muscle weight. Fiber-type switching in the soleus muscle of ASKO mice was observed, as evidenced by the increased number of fast-twitch fibers and decreased number of slow-twitch fibers. Serum metabolites with significant alteration in abundance were identified by metabolomic analysis and the elevated lysophosphatidylcholine 16:0 [LysoPC (16:0)] was observed in ASKO mice. In addition, lipidome analysis of gonadal white adipose tissue revealed a significant increase in LysoPCs and LysoPC (16:0) in ASKO mice. Furthermore, knockdown of Rnf20 gene in 3T3-L1 cells significantly increased the secretion of LysoPC, suggesting that LysoPC might be a critical metabolite in the adipose-muscle crosstalk of ASKO mice. Furthermore, in vitro study demonstrated that LysoPC (16:0) could induce the expression of fast-twitch muscle fibers related genes in differentiated C2C12 cells, indicating its potential role in adipose-muscle crosstalk. Taken together, these findings not only expand our understanding of the biological functions of Rnf20 gene in systemic lipid metabolism, but also provide insight into adipose tissue dysfunction-induced physiological alterations in skeletal muscle.

Bone Morphogenetic Protein 2 Enhances Porcine Beige Adipogenesis via AKT/mTOR and MAPK Signaling Pathways.

Bone morphogenetic protein 2 (BMP2) has been reported to regulate adipogenesis, but its role in porcine beige adipocyte formation remains unclear. Our data reveal that BMP2 is significantly induced at the early stages of porcine beige adipocyte differentiation. Additionally, supplementing rhBMP2 during the early stages, but not the late stages of differentiation, significantly enhances porcine SVF adipogenesis, thermogenesis, and proliferation. Furthermore, compared to the empty plasmid-transfected-SVFs, BMP2-overexpressed SVFs had the enhanced lipid accumulation and thermogenesis, while knockdown of BMP2 in SVFs exhibited the opposite effect. The RNA-seq of the above three types of cells revealed the enrichment of the annotation of thermogenesis, brown cell differentiation, etc. In addition, the analysis also highlights the significant enrichment of cell adhesion, the MAPK cascade, and PPARγ signaling. Mechanistically, BMP2 positively regulates the adipogenic and thermogenic capacities of porcine beige adipocytes by activating PPARγ expression through AKT/mTOR and MAPK signaling pathways.

SnRNA-Seq of Pancreas Revealed the Dysfunction of Endocrine and Exocrine Cells in Transgenic Pigs with Prediabetes.

Diabetes poses a significant threat to human health. Exocrine pancreatic dysfunction is related to diabetes, but the exact mechanism is not fully understood. This study aimed to describe the pathological phenotype and pathological mechanisms of the pancreas of transgenic pigs (PIGinH11) that was constructed in our laboratory and to compare it with humans. We established diabetes-susceptible transgenic pigs and subjected them to high-fat and high-sucrose dietary interventions. The damage to the pancreatic endocrine and exocrine was evaluated using histopathology and the involved molecular mechanisms were analyzed using single-nucleus RNA-sequencing (SnRNA-seq). Compared to wild-type (WT) pigs, PIGinH11 pigs showed similar pathological manifestations to type 2 diabetes patients, such as insulin deficiency, fatty deposition, inflammatory infiltration, fibrosis tissue necrosis, double positive cells, endoplasmic reticulum (ER) and mitochondria damage. SnRNA-seq analysis revealed 16 clusters and cell-type-specific gene expression characterization in the pig pancreas. Notably, clusters of Ainar-M and Endocrine-U were observed at the intermediate state between the exocrine and endocrine pancreas. Beta cells of the PIGinH11 group demonstrated the dysfunction with insulin produced and secret decreased and ER stress. Moreover, like clinic patients, acinar cells expressed fewer digestive enzymes and showed organelle damage. We hypothesize that TXNIP that is upregulated by high glucose might play an important role in the dysfunction of endocrine to exocrine cells in PIGinH11 pigs.

Pnpla5-knockout rats exhibit reduced expression levels of proteins involved in steroid metabolism and wound healing compared to wild-type rats.

BACKGROUND: Patatin-like phospholipase domain containing 5 (PNPLA5) is a newly-discovered lipase. Although the PNPLA family plays critical roles in diverse biological processes, the biological functions of PNPLA5 mostly unknown. We previously found that the deletion of Pnpla5 in rats causes a variety of phenotypic abnormalities. In this study, we further explored the effects of Pnpla5 knockout (KO) on male rats. RESULTS: The body weight and testicular or epididymal tissue weight of three to six 3-month-old Pnpla5 KO or wild-type (WT) male Sprague-Dawley rats were measured. The protein expression levels were also measured via western blotting and iTRAQ (isobaric tags for relative and absolute quantitation) analyses. No significant difference between Pnpla5 KO and WT rats, regarding body weight, testicular or epididymal tissue weight, or hormone levels, were found. However, the relative testicular tissue weight of the KO (Pnpla5-/-) rats was higher (P < 0.05) than that of WT rats. Significant increases in apoptotic cells numbers (P < 0.001) and BAX and Caspase-9 expression levels were observed in the testicular tissue of Pnpla5-/- rats. Moreover, iTRAQ analysis revealed that the levels of proteins involved in steroid metabolism and wound healing were significantly decreased in Pnpla5-/- rats. CONCLUSION: This study revealed that Pnpla5 knockout induced apoptosis in rat testes. We also ascertained that Pnpla5 plays an important role in lipid metabolism, wound healing, and affects reproductive organs negatively, providing new target genes and pathways that can be analyzed to unravel the biological function of Pnpla5.

Enhancing Animal Disease Resistance, Production Efficiency, and Welfare through Precise Genome Editing.

The major goal of animal breeding is the genetic enhancement of economic traits. The CRISPR/Cas system, which includes nuclease-mediated and base editor mediated genome editing tools, provides an unprecedented approach to modify the mammalian genome. Thus, farm animal genetic engineering and genetic manipulation have been fundamentally revolutionized. Agricultural animals with traits of interest can be obtained in just one generation (and without long time selection). Here, we reviewed the advancements of the CRISPR (Clustered regularly interspaced short palindromic repeats)/Cas (CRISPR associated proteins) genome editing tools and their applications in animal breeding, especially in improving disease resistance, production performance, and animal welfare. Additionally, we covered the regulations on genome-edited animals (GEAs) and ways to accelerate their use. Recommendations for how to produce GEAs were also discussed. Despite the current challenges, we believe that genome editing breeding and GEAs will be available in the near future.

Rapid visual genotyping method for germline mutants with small genomic fragment deletion by allele-specific PCR and lateral flow nucleic acid biosensor.

BACKGROUND: Genome-editing techniques incorporating artificial nucleases develop rapidly and enable efficient and precise modification of genomic DNA of numerous organisms. The present research aimed to establish a rapid, sensitive and visual method for genotyping of germline genome-edited mutants with small genomic fragment deletion. METHODS AND RESULTS: The genome-edited pigs with 2-bp deletion and 11-bp deletion of Myostatin (MSTN) gene generated by TALENs system were used as test materials to check the proposed allele-specific PCR (AS-PCR) and lateral flow nucleic acid biosensor (LFNAB) cascade method. AS-PCR can produce products with different tags to distinguish genome-edited alleles and wild-type alleles. A LFNAB was applied to do visual detection of AS-PCR products without using additional instruments. Furthermore, we demonstrated that AS-PCR and LFNAB cascade could accurately and visually distinguish genome-edited pigs with small genomic fragment deletion of Myostatin (MSTN) gene and wild-type pigs with limit of detection (LOD) of 0.1 ng. CONCLUSION: The proposed AS-PCR and LFNAB cascade can do rapid and visual genotyping of genome-edited mutants with small genomic fragment deletion, serving as a platform for genome-edited animal genotyping.

CRH/CRHR1 mediates prenatal synthetic glucocorticoid programming of depression-like behavior across 2 generations.

Pregnant women at risk of preterm labor usually receive synthetic glucocorticoids (sGCs) to promote fetal lung development. Emerging evidence indicates that antenatal sGC increases the risk of affective disorders in offspring. Data from animal studies show that such disorders can be transmitted to the second generation. However, the molecular mechanisms underlying the intergenerational effects of prenatal sGC remain largely unknown. Here we show that prenatal dexamethasone (Dex) administration in late pregnancy induced depression-like behavior in first-generation (F1) offspring, which could be transmitted to second-generation (F2) offspring with maternal dependence. Moreover, corticotropin-releasing hormone (CRH) and CRH receptor type 1 (CRHR1) expression in the hippocampus was increased in F1 Dex offspring and F2 offspring from F1 Dex female rats. Administration of a CRHR1 antagonist to newborn F1 Dex offspring alleviated depression-like behavior in these rats at adult. Furthermore, we demonstrated that increased CRHR1 expression in F1 and F2 offspring was associated with hypomethylation of CpG islands in Crhr1 promoter. Our results revealed that prenatal sGC exposure could program Crh and Crhr1 gene expression in hippocampus across 2 generations, thereby leading to depression-like behavior. Our study indicates that prenatal sGC can cause epigenetic instability, which increases the risk of disease development in the offspring's later life.-Xu, Y.-J., Sheng, H., Wu, T.-W., Bao, Q.-Y., Zheng, Y., Zhang, Y.-M., Gong, Y.-X., Lu, J.-Q., You, Z.-D., Xia, Y., Ni, X. CRH/CRHR1 mediates prenatal synthetic glucocorticoid programming of depression-like behavior across 2 generations.

Comparative profiling of small RNAs of pig seminal plasma and ejaculated and epididymal sperm.

The similarities and differences of small RNAs in seminal plasma, epididymal sperm and ejaculated sperm remain largely undefined. We conducted a systematic comparative analysis of small RNA profiles in pig ejaculated sperm, epididymal sperm and seminal plasma and found that the diversity distribution of small RNA species was generally similar, whereas the abundance of small RNAs is dramatically different across the three libraries; miRNAs and small RNAs derived from rRNA, tRNA, small nuclear RNA, 7SK RNA, NRON RNA and cis-regulatory RNA were enriched in the three libraries, but piRNA was absent. A large population of small RNAs from ejaculated sperm are ejaculated sperm specific, and only 8-30% of small RNAs overlapped with those of epididymal sperm or seminal plasma and a small proportion (5-18%) of small RNAs were shared in the three libraries, suggesting that, in addition to the testes, sperm RNAs may also originate from seminal plasma, epididymis as well as other resources. Most miRNAs were co-distributed but differentially expressed across the three libraries, with epididymal sperm exhibiting the highest abundance, followed by ejaculated sperm and seminal plasma. The prediction of target genes of the top 10 highly expressed miRNAs across the three libraries revealed that these miRNAs may be involved in spermatogenesis, zygote development and the interaction between the environment and animals. Our study provides the first description of the similarities and differences of small RNA profiles in ejaculated sperm, epididymal sperm and seminal plasma and indicates that sperm RNA may have origins other than the testes.

Oral administration of grape seed polyphenol extract restores memory deficits in chronic cerebral hypoperfusion rats.

Chronic cerebral hypoperfusion (CCH) has been recognized as an important cause of both vascular dementia and Alzheimer's disease (AD), the two most prominent neurodegenerative diseases causing memory impairment in the elderly. However, an effective therapy for CCH-induced memory impairment has not yet been established. Grape seed polyphenol extract (GSPE) has powerful antioxidant properties and protects neurons and glia during ischemic injury, but its potential use in the prevention of CCH-induced memory impairment has not yet been investigated. Here, CCH-related memory impairment was modeled in rats using permanent bilateral occlusion of the common carotid artery. A Morris water maze task was used to evaluate memory, the levels of acetylcholinesterase, choline acetyltransferase, acetylcholine were used to evaluate cholinergic function, and oxidative stress was assessed by measuring the enzyme activity of superoxide dismutase, glutathione peroxidase, malonic dialdehyde, and catalase. We found that oral administration of GSPE for 1 month can rescue memory deficits. We also found that GSPE restores cholinergic neuronal function and represses oxidative damage in the hippocampus of CCH rats. We propose that GSPE protects memory in CCH rats by reducing ischemia-induced oxidative stress and cholinergic dysfunction. These findings provide a novel application of GSPE in CCH-related memory impairments.

A case of rapid-onset dystonia-parkinsonism accompanied by pyramidal tract impairment.

BACKGROUND: Rapid-onset dystonia-parkinsonism (RDP) is a rare autosomal dominant disorder that is caused by mutations in the ATP1A3 gene and is characterized by an acute onset of asymmetric dystonia and parkinsonism. To date, fewer than 75 RDP cases have been reported worldwide. Clinical signs of pyramidal tract involvement have been reported in several RDP cases, and none of them included the Babinski sign. CASE PRESENTATION: We report a 24-year-old Chinese female with RDP who exhibited a strikingly asymmetric, predominantly dystonic movement disorder with a rostrocaudal gradient of involvement and parkinsonism. Physical examiniations revealed hyperactive reflexes, bilateral ankle clonus and positive Babinski sign in the right. DTI showed reduced white matter integrity of the corticospinal tract in the frontal lobe and subpontine plane. Genetic testing revealed a missense mutation of the ATP1A3-gene (E277K) in the patient. CONCLUSION: We suggest that pyramidal tract impairment could be involved in rapid-onset dystonia-parkinsonism and the pyramidal tract impairment in RDP needs to be differentiated from HSP.

Wip1 knockout inhibits the proliferation and enhances the migration of bone marrow mesenchymal stem cells.

Mesenchymal stem cells (MSCs), a unique population of multipotent adult progenitor cells originally found in bone marrow (BM), are extremely useful for multifunctional therapeutic approaches. However, the growth arrest and premature senescence of MSCs in vitro prevent the in-depth characterization of these cells. In addition, the regulatory factors involved in MSCs migration remain largely unknown. Given that protein phosphorylation is associated with the processes of MSCs proliferation and migration, we focused on wild-type p53-inducible phosphatase-1 (Wip1), a well-studied modulator of phosphorylation, in this study. Our results showed that Wip1 knockout significantly inhibited MSCs proliferation and induced G2-phase cell-cycle arrest by reducing cyclinB1 expression. Compared with WT-MSCs, Wip1(-/-) MSCs displayed premature growth arrest after six passages in culture. Transwell and scratch assays revealed that Wip1(-/-) MSCs migrate more effectively than WT-MSCs. Moreover, the enhanced migratory response of Wip1(-/-) MSCs may be attributed to increases in the induction of Rac1-GTP activity, the pAKT/AKT ratio, the rearrangement of filamentous-actin (f-actin), and filopodia formation. Based on these results, we then examined the effect of treatment with a PI3K/AKT and Rac1 inhibitor, both of which impaired the migratory activity of MSCs. Therefore, we propose that the PI3K/AKT/Rac1 signaling axis mediates the Wip1 knockout-induced migration of MSCs. Our findings indicate that the principal function of Wip1 in MSCs transformation is the maintenance of proliferative capacity. Nevertheless, knocking out Wip1 increases the migratory capacity of MSCs. This dual effect of Wip1 provides the potential for purposeful routing of MSCs.

Gas transmitters in female reproductive system.

Nitric oxide, carbon monoxide and hydrogen sulfide synthesized endogenously in living organisms produce an array of disparate biological effects, so as to be considered as gas transmitters. These three gaseous molecules play important roles in many physiological and pathological processes in the bodies, such as the regulation of vascular tone and inflammatory responses as well as reproductive function. This review mainly focuses on the distribution and biological functions of these three gas transmitters in female reproductive tissues.

Improved beluga whale optimization algorithm based cluster routing in wireless sensor networks.

Cluster routing is a critical routing approach in wireless sensor networks (WSNs). However, the uneven distribution of selected cluster head nodes and impractical data transmission paths can result in uneven depletion of network energy. For this purpose, we introduce a new routing strategy for clustered wireless sensor networks that utilizes an improved beluga whale optimization algorithm, called tCBWO-DPR. In the selection process of cluster heads, we introduce a new excitation function to evaluate and select more suitable candidate cluster heads by establishing the correlation between the energy of node and the positional relationship of nodes. In addition, the beluga whale optimization (BWO) algorithm has been improved by incorporating the cosine factor and t-distribution to enhance its local and global search capabilities, as well as to improve its convergence speed and ability. For the data transmission path, we use Prim's algorithm to construct a spanning tree and introduce DPR for determining the optimal route between cluster heads based on the correlation distances of cluster heads. This effectively shortens the data transmission path and enhances network stability. Simulation results show that the improved beluga whale optimization based algorithm can effectively improve the survival cycle and reduce the average energy consumption of the network.

Single-nucleus transcriptomics reveal cardiac cell type-specific diversification in metabolic disease transgenic pigs.

Cardiac damage is widely present in patients with metabolic diseases, but the exact pathophysiological mechanisms involved remain unclear. The porcine heart is an ideal material for cardiovascular research due to its similarities to the human heart. This study evaluated pathological features and performed single-nucleus RNA sequencing (snRNA-seq) on myocardial samples from both wild-type and metabolic disease-susceptible transgenic pigs (previously established). We found that transgenic pigs exhibited lipid metabolism disturbances and myocardial injury after a high-fat high-sucrose diet intervention. snRNA-seq reveals the cellular landscape of healthy and metabolically disturbed pig hearts and identifies the major cardiac cell populations affected by metabolic diseases. Within metabolic disorder hearts, metabolically active cardiomyocytes exhibited impaired function and reduced abundance. Moreover, massive numbers of reparative LYVE1+ macrophages were lost. Additionally, proinflammatory endothelial cells were activated with high expression of multiple proinflammatory cytokines. Our findings provide insights into the cellular mechanisms of metabolic disease-induced myocardial injury.

Deficiency of SLC26A3 promotes jejunal barrier damage in metabolic disease-susceptible transgenic pigs.

Intestinal disorders are common in metabolic syndrome. However, their pathogenesis is still not fully understood. Pig and human intestines are highly similar in terms of associated metabolic processes. Here, we successfully constructed a metabolic disease-susceptible transgenic (TG) Bama pig model by knocking in three humanized disease risk genes with the CRISPR/Cas9 technique to assess its potential as a model for human intestinal diseases and explore the possible pathological mechanisms involved. We found that jejunal barrier integrity was disrupted and that the infiltration of inflammatory cells increased in TG pigs after high-fat and high-sucrose diet (HFHSD) treatment. We revealed significant differences in the transcriptome, associated microbiome profiles and microbial metabolite short-chain fatty acid (SCFA) content of the jejunum of TG pigs. Notably, we found that SLC26A3 was significantly downregulated in TG pigs. Knockdown or overexpression of the SLC26A3 gene in IPEC-J2 cells significantly affected the expression of MUC2, MUC13 and occludin. Furthermore, in vitro experiments further verified that CDX2 directly regulated the expression of SLC26A3. Mechanistically, CDX2 mediated intestinal barrier function by enhancing the expression of SLC26A3 by binding to its promoter region between -1120 and - 1070 bp. TG pigs represent a promising model that provides new insights into preclinical research on human intestinal metabolic diseases associated with metabolic disorders and revealed that SLC26A3 may be a potential therapeutic target for intestinal metabolic diseases.

Alterations in serum metabolomics during the first seizure and after effective control of epilepsy.

The existing diagnostic methods of epilepsy have great limitations, and more reliable and less difficult diagnostic methods are needed. We collected serum samples of adult patients with first-diagnosed epilepsy (EPs) and seizure control patients (EPRs) for non-targeted metabolomics detection and found that they were both significantly altered, with increased expression of nicotine addiction, linoleic acid metabolism, purine metabolism, and other metabolic pathways. The diagnostic model based on 4 differential metabolites achieved a diagnostic efficiency of 99.4% in the training cohort and 100% in the validation cohort. In addition, the association analysis of oral flora, serum metabolism, and clinical indicators also provided a new angle to analyze the mechanism of epilepsy. In conclusion, this study characterized the serum metabolic characteristics of EPs and EPRs and the changes before and after epilepsy control based on a large cohort, demonstrating the potential of metabolites as non-invasive diagnostic tools for epilepsy.

Glucose restriction enhances oxidative fiber formation: A multi-omic signal network involving AMPK and CaMK2.

Skeletal muscle is a highly plastic organ that adapts to different metabolic states or functional demands. This study explored the impact of permanent glucose restriction (GR) on skeletal muscle composition and metabolism. Using Glut4m mice with defective glucose transporter 4, we conducted multi-omics analyses at different ages and after low-intensity treadmill training. The oxidative fibers were significantly increased in Glut4m muscles. Mechanistically, GR activated AMPK pathway, promoting mitochondrial function and beneficial myokine expression, and facilitated slow fiber formation via CaMK2 pathway. Phosphorylation-activated Perm1 may synergize AMPK and CaMK2 signaling. Besides, MAPK and CDK kinases were also implicated in skeletal muscle protein phosphorylation during GR response. This study provides a comprehensive signaling network demonstrating how GR influences muscle fiber types and metabolic patterns. These insights offer valuable data for understanding oxidative fiber formation mechanisms and identifying clinical targets for metabolic diseases.

Oral microbiome alterations in epilepsy and after seizure control.

Background: The existing diagnostic methods of epilepsy such as history collection and electroencephalogram have great limitations in practice, so more reliable and less difficult diagnostic methods are needed. Methods: By characterizing oral microbiota in patients diagnosed with epilepsy (EPs) and patients whose seizures were under control (EPRs), we sought to discover biomarkers for different disease states. 16S rRNA gene sequencing was performed on 480 tongue swabs [157 EPs, 22 EPRs, and 301 healthy controls (HCs)]. Results: Compared with normal individuals, patients with epilepsy exhibit increased alpha diversity in their oral microbiota, and the oral microbial communities of the two groups demonstrate significant beta diversity differences. EPs exhibit a significant increase in the abundance of 26 genera, including Streptococcus, Granulicatella, and Kluyvera, while the abundance of 14 genera, including Peptostreptococcus, Neisseria, and Schaalia, is significantly reduced. The area under the receiver operating characteristic curve (AUC) of oral microbial markers in the training cohort and validation cohort was 98.85% and 97.23%, respectively. Importantly, the AUC of the biomarker set achieved 92.44% of additional independent validation sets. In addition, EPRs also have their own unique oral community. Conclusion: This study describes the characterization of the oral microbiome in EP and EPR and demonstrates the potential of the specific microbiome as a non-invasive diagnostic tool for epilepsy.

Pulmonary infection and baseline mRS scores predict poor prognosis in anti-GABABR encephalitis.

Purpose: Anti-gamma-aminobutyric-acid type B receptor (anti-GABABR) encephalitis is a rare autoimmune condition caused by the presence of GABABR antibodies in the limbic system. However, its clinical features and prognostic factors are poorly understood. In this study, we aimed to explore factors that affect the response to first-line treatment in patients with anti-GABABR encephalitis. Methods: Thirty-four patients with an initial diagnosis of anti-GABABR encephalitis were retrospectively enrolled from December 2015 to June 2021. Clinical features and experimental data recorded within 24 h of admission were extracted from the patients' medical records. The modified Rankin Scale (mRS) was utilized to assess disease severity at admission and functional recovery after immunotherapy. Independent prognostic factors were determined by ordinal logistic regression analysis. Results: Of the 34 anti-GABABR encephalitis patients, 12 (35%) presented with cancer; all of these patients had lung cancer. According to multivariate regression analysis, the cancer group exhibited a decrease in the peripheral blood absolute lymphocyte count (ALC) (odds ratio [OR]: 0.063, 95% confidence interval [CI]: 0.006-0.639, P=0.019) and hyponatremia (OR: 9.268, 95% CI: 1.054-81.502, 0.045). In addition, the neutrophil/lymphocyte ratio (NLR), monocyte/lymphocyte ratio (MLR) and platelet/lymphocyte ratio (PLR) did not significantly differ according to mRS scores in patients receiving first-line treatment. No patients with mild or moderate mRS scores (0-2) at admission developed symptoms after treatment; in contrast, only 11 patients with a severe mRS scores (≥3, 11/18) experienced symptom alleviation. Ordinal regression analysis indicated that worse prognosis was associated with pulmonary infection (OR=9.885, 95% CI: 1.106-88.323, P=0.040) and baseline mRS scores (OR= 24.047, 95% CI: 3.294-175.739, P=0.002) in the adjusted model. Conclusion: Our findings demonstrate that pulmonary infection and baseline mRS scores are independent risk factors for poor prognosis in patients with anti-GABABR encephalitis after first-line treatment. ALC and hyponatremia are potential biomarkers for anti-GABABR encephalitis cases accompanied by lung cancer.

Long-term, multidomain analyses to identify the breed and allelic effects in MSTN-edited pigs to overcome lameness and sustainably improve nutritional meat production.

Beef and mutton production has been aided by breeding to integrate allelic diversity for myostatin (MSTN), but a lack of diversity in the MSTN germplasm has limited similar advances in pig farming. Moreover, insurmountable challenges with congenital lameness and a dearth of data about the impacts of feed conversion, reproduction, and meat quality in MSTN-edited pigs have also currently blocked progress. Here, in a largest-to-date evaluation of multiple MSTN-edited pig populations, we demonstrated a practical alternative edit-site-based solution that overcomes the major production obstacle of hindlimb weakness. We also provide long-term and multidomain datasets for multiple breeds that illustrate how MSTN-editing can sustainably increase the yields of breed-specific lean meat and the levels of desirable lipids without deleteriously affecting feed-conversion rates or litter size. Apart from establishing a new benchmark for the data scale and quality of genome-edited animal production, our study specifically illustrates how gene-editing site selection profoundly impacts the phenotypic outcomes in diverse genetic backgrounds.