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The Farm Animal Genotype-Tissue Expression (FarmGTEx) project has been established to develop a public resource of genetic regulatory variants in livestock, which is essential for linking genetic polymorphisms to variation in phenotypes, helping fundamental biological discovery and exploitation in animal breeding and human biomedicine. Here we show results from the pilot phase of PigGTEx by processing 5,457 RNA-sequencing and 1,602 whole-genome sequencing samples passing quality control from pigs. We build a pig genotype imputation panel and associate millions of genetic variants with five types of transcriptomic phenotypes in 34 tissues. We evaluate tissue specificity of regulatory effects and elucidate molecular mechanisms of their action using multi-omics data. Leveraging this resource, we decipher regulatory mechanisms underlying 207 pig complex phenotypes and demonstrate the similarity of pigs to humans in gene expression and the genetic regulation behind complex phenotypes, supporting the importance of pigs as a human biomedical model.

目的 探讨颞浅动脉-大脑中动脉端侧吻合术中不同临时阻断技术的效果及可靠性。 方法 回顾性分析2015年1月—2023年4月南方医科大学南方医院神经外科收治的接受直接搭桥术治疗的烟雾病患者资料，根据临时阻断策略的不同将患者分为3组：①有垫片、多阻断夹阻断组（multi-clips+rubber pad group，M+R组）；②无垫片、多阻断夹阻断组（multi-clips group，M组）；③无垫片、单阻断夹阻断组（single-clip group，S组）。比较组间临时阻断时间、受体动脉切开后有无渗血、术中穿支血管损伤以及术后新发脑梗死情况。 结果 共355例患者、360个大脑半球纳入分析，按大脑半球统计患者360例，其中男性188例，女性172例，平均年龄为（43.8±0.7）岁。其中M+R组45例，M组191例，S组124例。3组平均阻断时间：M+R组为（37.9±9.8）min，M组为（20.9±9.0）min，S组为（11.0±3.5）min，组间差异有统计学意义（P＜0.001）。阻断后受体动脉管腔内渗血以及术中穿支血管损伤发生率：M+R组为8.89%（阻断后受体动脉渗血4例），M组为14.66%（阻断后受体动脉渗血19例，术中穿支血管损伤8例，临时阻断部位有血栓形成1例），S组为5.65%（阻断后受体动脉渗血7例），组间差异无统计学意义（P>0.05）。术后新发脑梗死发生率差异无统计学意义（P>0.05）。 结论 单阻断夹阻断策略安全、有效，能显著缩短临时阻断时间，可以优先考虑作为颞浅动脉-大脑中动脉端侧吻合过程中的临时阻断策略。 Abstract: Objective To investigate the effects and reliability of different temporary occlusion techniques in end-to-side anastomosis of the superficial temporal artery-middle cerebral artery. Methods A retrospective analysis was conducted on the data of patients with Moyamoya disease who underwent direct bypass surgery in the Department of Neurosurgery, Nanfang Hospital, Southern Medical University, from January 2015 to April 2023. The patients were divided into three groups according to the different temporary occlusion strategies: ①multi-clips+rubber pad group (M+R group); ②multi-clips group (M group); and ③single-clip group (S group). Temporary occlusion time, presence of errhysis after recipient artery incision, intraoperative perforator vessel injury, and postoperative novel cerebral infarction were compared among the three groups. Results A total of 355 patients and 360 cerebral hemispheres were included in the analysis, and 360 patients were counted according to the number of cerebral hemispheres, including 188 males and 172 females, with an average age of (43.8±0.7) years. There were 45 cases in the M+R group, 191 cases in the M group, and 124 cases in the S group. The average occlusion time were (37.9±9.8) minutes in the M+R group, (20.9±9.0) minutes in the M group, and (11.0±3.5) minutes in the S group, with significant differences between the groups (P0.05). There was no significant difference in the incidence of novel cerebral infarctions postoperatively (P>0.05). Conclusions The single-clip occlusion strategy is safe and effective, which significantly shortens the temporary occlusion time, and should be prioritized as the temporary occlusion technique in end-to-side anastomosis of the superficial temporal artery-middle cerebral artery.

The final step in the production of the human Sd(a) antigen is catalyzed by beta-1,4-N-acetyl-galactosamine transferase 2 (B4GALNT2). This is done by adding a N-acetylgalactosamine residue via a beta-1,4 linkage to a subterminal galactose residue that has been substituted with an alpha-2,3-linked sialic acid. The final stage of the production of the Cad antigen is also catalyzed by B4GALNT2. Knocking out pig B4GALNT2 gene decreased human serum antibodies binding to pig cells, which greatly reduces the immunological rejection in clinical xenotransplantation trials. Interestingly, gene region LOC110255214 (hereafter named B4GALNT2-like) showed high similarity with the B4GALNT2 gene in the pig genome in our previous work, but whether B4GALNT2-like shares similar biological properties like B4GALNT2 remains to be elucidated, whether B4GALNT2-like is a potential immune gene in xenotransplantation remains to be determined.

The interferon (IFN) response is vital for the effectiveness of immune checkpoint inhibition (ICI) therapy. Our previous research showed that KRAS (Kirsten rat sarcoma viral) mutation impairs the IFN response in colorectal cancer (CRC), with an unclear mechanism. Here, we demonstrate that KRAS accelerates double-stranded RNA (dsRNA) degradation, impairing dsRNA sensing and IFN response by down-regulating DExD/H-box helicase 6 (DDX60). DDX60 was identified as a KRAS target here and could bind to dsRNAs to protect against RNA-induced silencing complex (RISC)–mediated degradation. Overexpressing DDX60 induced dsRNA accumulation, reactivated IFN signaling, and increased CRC sensitivity to ICI therapy. Mechanistically, KRAS engaged the AKT (also known as protein kinase B)–GSK3β (glycogen synthase kinase-3 beta) pathway to suppress STAT3 phosphorylation, thereby inhibiting STAT3-driven DDX60 transcription. Our findings reveal a role for KRAS in dsRNA homeostasis, suggesting potential strategies to convert "cold" tumors to "hot" and to overcome ICI resistance in CRC with KRAS mutations. Editor's summary: Mutations in the KRAS (Kirsten rat sarcoma viral) oncogene have been linked to impaired IFN responses and limited efficacy of immune checkpoint inhibition (ICI) in colorectal cancer (CRC). Zhou et al. show that oncogenic KRAS promotes double-stranded RNA degradation in CRC cells, which inhibits RIG-I–like receptor (RLR)–mediated signaling, normally needed for antiviral responses and downstream IFN responses. The RNA binding protein DExD/H-box helicase 6 (DDX60) was shown to be suppressed by oncogenic KRAS via AKT-GSK3β-STAT3 signaling, but overexpression of DDX60 could overcome IFN inhibition by oncogenic KRAS by protecting dsRNA from degradation and could sensitize tumors to ICI. —Christiana Fogg [ABSTRACT FROM AUTHOR]

China has the largest pork consumption worldwide. However, the high incidence of piglet fetal mummification (3%-5%) is an important factor that causes the slow improvement of pig reproductive capacity, and the genetic mechanism is still unclear. This study aimed to identify candidate genes associated with piglet fetal mummification. RNA-seq technology was used to compare transcriptome profiling of blood from healthy and mummified piglets at different stages of pregnancy (35, 56, 77, and 98 days). A total of 137-420 differentially expressed genes (DEGs) were detected at each stage. Seven DEGs were significantly differentially expressed at various stages. IL-9R, TLR8, ABLIM3, FSH-a, ASCC1, PRKCZ, and GCK may play important roles in the course of piglet fetal mummification. The differential genes we identified between the groups were mainly enriched in immune and inflammation regulation, while others were mainly enriched in reproduction. Considering the function of candidate genes, IL-9R and TLR8 were suggested as the most promising candidate genes involved in mummified piglet traits. We speculate that during pregnancy, it may be the combined effects of the above-mentioned inflammation, immune response, and reproduction-related signaling pathways that affect the occurrence of mummified piglets and further affect pig reproduction. Key words: transcriptome, pregnancy, piglet, fetal mummification, blood. La Chine est le pays dont la consommation de porc est la plus elevee au monde. Cependant, la forte incidence de porcelets momifies (3-5 %) est l'un des facteurs importants qui retardent les avancees en matiere de capacite reproductive des porcs. Le mecanisme genetique expliquant ce phenomene n'est pas encore clair. Cette etude visait a identifier des genes candidats associes a une frequence elevee de porcelets momifies. La technologie RNA-seq a ete employee pour realiser un profil transcriptomique du sang a differents stades de la gestation (35, 56, 77 et 98 jours) chez des truies en sante et celles produisant un nombre eleve de porcelets momifies. Au total, de 137 a 420 genes exprimes de maniere differentielle (DEG) ont ete detectes a ces stades. Les genes IL-9R, TLR8, ABLIM3, FSH-a, ASCC1, PRKCZ et GCK pourraient jouer des roles importants dans ce processus. Les genes impliques dans la regulation de l'immunite et de l'inflammation ainsi que ceux impliques dans la reproduction etaient surrepresentes parmi les DEG entre les deux groupes de truies. Sur la base de la fonction des genes candidats, les auteurs proposent que les genes IL-9R et TLR-8 seraient les plus prometteurs en tant que genes impliques dans la momification des porcelets. Les auteurs speculent que, lors de la gestation, les effets combines des genes impliques dans les voies de signalisation de l'inflammation, de la reponse immunitaire et de la reproduction affecteraient l'occurrence de porcelets momifies et donc la reproduction des porcs. [Traduit par la Redaction] Mots-cles : transcriptome, gestation, porcelet, momification foetale, sang., Introduction Reproductive traits are one of the most important economic traits that affect the economic benefits of pig production. Living piglets have the greatest potential for the economic benefits of [...]

Cetaceans (whales, dolphins, and porpoises) are a group of mammals adapted to various aquatic habitats, from oceans to freshwater rivers. We report the sequencing, de novo assembly and analysis of a finless porpoise genome, and the re-sequencing of an additional 48 finless porpoise individuals. We use these data to reconstruct the demographic history of finless porpoises from their origin to the occupation into the Yangtze River. Analyses of selection between marine and freshwater porpoises identify genes associated with renal water homeostasis and urea cycle, such as urea transporter 2 and angiotensin I-converting enzyme 2, which are likely adaptations associated with the difference in osmotic stress between ocean and rivers. Our results strongly suggest that the critically endangered Yangtze finless porpoises are reproductively isolated from other porpoise populations and harbor unique genetic adaptations, supporting that they should be considered a unique incipient species.