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A 57-year-old man with nonischemic cardiomyopathy who was dependent on venoarterial extracorporeal membrane oxygenation (ECMO) and was not a candidate for standard therapeutics, including a traditional allograft, received a heart from a genetically modified pig source animal that had 10 individual gene edits. Immunosuppression was based on CD40 blockade. The patient was weaned from ECMO, and the xenograft functioned normally without apparent rejection. Sudden diastolic thickening and failure of the xenograft occurred on day 49 after transplantation, and life support was withdrawn on day 60. On autopsy, the xenograft was found to be edematous, having nearly doubled in weight. Histologic examination revealed scattered myocyte necrosis, interstitial edema, and red-cell extravasation, without evidence of microvascular thrombosis — findings that were not consistent with typical rejection. Studies are under way to identify the mechanisms responsible for these changes. (Funded by the University of Maryland Medical Center and School of Medicine.) In this report, a porcine-to-human heart transplantation is described. Videos show transthoracic echocardiography in the patient who received the heart.

A raft of alterations to the pig genome — removing three antigen-encoding genes, adding seven human genes and eliminating a retrovirus — allows kidneys to be transplanted into monkeys, with implications for clinical trials. Genetic engineering for pig-to-primate kidney transplants. Credit: Cristine Heaps, PhD, Texas A&M University Yucatán miniature pigs in a research facility at Texas A&M university

A genetically engineered pig cardiac xenotransplantation was done on Jan 7, 2022, in a non-ambulatory male patient, aged 57 years, with end-stage heart failure, and on veno-arterial extracorporeal membrane oxygenation support, who was ineligible for an allograft. This report details our current understanding of factors important to the xenotransplantation outcome. Physiological and biochemical parameters critical for the care of all heart transplant recipients were collected in extensive clinical monitoring in an intensive care unit. To ascertain the cause of xenograft dysfunction, we did extensive immunological and histopathological studies, including electron microscopy and quantification of porcine cytomegalovirus or porcine roseolovirus (PCMV/PRV) in the xenograft, recipient cells, and tissue by DNA PCR and RNA transcription. We performed intravenous immunoglobulin (IVIG) binding to donor cells and single-cell RNA sequencing of peripheral blood mononuclear cells. After successful xenotransplantation, the graft functioned well on echocardiography and sustained cardiovascular and other organ systems functions until postoperative day 47 when diastolic heart failure occurred. At postoperative day 50, the endomyocardial biopsy revealed damaged capillaries with interstitial oedema, red cell extravasation, rare thrombotic microangiopathy, and complement deposition. Increased anti-pig xenoantibodies, mainly IgG, were detected after IVIG administration for hypogammaglobulinaemia and during the first plasma exchange. Endomyocardial biopsy on postoperative day 56 showed fibrotic changes consistent with progressive myocardial stiffness. Microbial cell-free DNA testing indicated increasing titres of PCMV/PRV cell-free DNA. Post-mortem single-cell RNA sequencing showed overlapping causes. Hyperacute rejection was avoided. We identified potential mediators of the observed endothelial injury. First, widespread endothelial injury indicates antibody-mediated rejection. Second, IVIG bound strongly to donor endothelium, possibly causing immune activation. Finally, reactivation and replication of latent PCMV/PRV in the xenograft possibly initiated a damaging inflammatory response. The findings point to specific measures to improve xenotransplant outcomes in the future. The University of Maryland School of Medicine, and the University of Maryland Medical Center.

Preventing xenograft rejection is one of the greatest challenges of transplantation medicine. Here, we describe a reproducible, long-term survival of cardiac xenografts from alpha 1-3 galactosyltransferase gene knockout pigs, which express human complement regulatory protein CD46 and human thrombomodulin ( GTKO.hCD46.hTBM ), that were transplanted into baboons. Our immunomodulatory drug regimen includes induction with anti-thymocyte globulin and αCD20 antibody, followed by maintenance with mycophenolate mofetil and an intensively dosed αCD40 (2C10R4) antibody. Median (298 days) and longest (945 days) graft survival in five consecutive recipients using this regimen is significantly prolonged over our recently established survival benchmarks (180 and 500 days, respectively). Remarkably, the reduction of αCD40 antibody dose on day 100 or after 1 year resulted in recrudescence of anti-pig antibody and graft failure. In conclusion, genetic modifications ( GTKO.hCD46.hTBM ) combined with the treatment regimen tested here consistently prevent humoral rejection and systemic coagulation pathway dysregulation, sustaining long-term cardiac xenograft survival beyond 900 days. Tweaking immune characteristics of donors and recipients could allow for successful cross-species organ transplantation. Here, the authors show that an anti-CD40 antibody therapy of baboons that received heart transplants from genetically modified pigs is key to their long-term survival.

The convergence of blockchain and metaverse technologies is poised to redefine how Global Value Chains (GVCs) create, capture, and distribute value, yet scholarly insight into their joint impact remains scattered. Addressing this gap, the present study aims to clarify where, how, and under what conditions blockchain-enabled transparency and metaverse-enabled immersion enhance GVC performance. A systematic literature review (SLR), conducted according to PRISMA 2020 guidelines, screened 300 articles from ABI Global, Business Source Premier, and Web of Science records, yielding 65 peer-reviewed articles for in-depth analysis. The corpus was coded thematically and mapped against three theoretical lenses: transaction cost theory, resource-based view, and network/ecosystem perspectives. Key findings reveal the following: 1. digital twins anchored in immersive platforms reduce planning cycles by up to 30% and enable real-time, cross-border supply chain reconfiguration; 2. tokenized assets, micro-transactions, and decentralized finance (DeFi) are spawning new revenue models but simultaneously shift tax triggers and compliance burdens; 3. cross-chain protocols are critical for scalable trust, yet regulatory fragmentation—exemplified by divergent EU, U.S., and APAC rules—creates non-trivial coordination costs; and 4. traditional IB theories require extension to account for digital-capability orchestration, emerging cost centers (licensing, reserve backing, data audits), and metaverse-driven network effects. Based on these insights, this study recommends that managers adopt phased licensing and geo-aware tax engines, embed region-specific compliance flags in smart-contract metadata, and pilot digital-twin initiatives in sandbox-friendly jurisdictions. Policymakers are urged to accelerate work on interoperability and reporting standards to prevent systemic bottlenecks. Finally, researchers should pursue multi-case and longitudinal studies measuring the financial and ESG outcomes of integrated blockchain–metaverse deployments. By synthesizing disparate streams and articulating a forward agenda, this review provides a conceptual bridge for international business scholarship and a practical roadmap for firms navigating the next wave of digital GVC transformation.

Following our previous experience with cardiac xenotransplantation of a genetically modified porcine heart into a live human, we sought to achieve improved results by selecting a healthier recipient and through more sensitive donor screening for potential zoonotic pathogens. Here we transplanted a 10-gene-edited pig heart into a 58-year-old man with progressive, debilitating inotrope-dependent heart failure due to ischemic cardiomyopathy who was not a candidate for standard advanced heart failure therapies. He was maintained on a costimulation (anti-CD40L, Tegoprubart) blockade-based immunomodulatory regimen. The xenograft initially functioned well, with excellent systolic and diastolic function during the first several weeks posttransplantation. Subsequently, the xenograft developed rapidly progressing diastolic heart failure, biventricular wall thickening and, ultimately, near-complete loss of systolic function necessitating initiation of extracorporeal membranous oxygenation on day 31. Given these setbacks, the patient chose to transition to comfort care after 40 days. As with our first patient, histology did not reveal substantial immune cell infiltration but suggested capillary endothelial injury with interstitial edema and early fibrosis. No evidence of porcine cytomegalovirus replication in the xenograft was observed. Strategies to overcome the obstacle of antibody-mediated rejection are needed to advance the field of xenotransplantation. In the second case in which a genetically modified pig heart was transplanted into a living person, the xenografted heart functioned well initially, but antibody-mediated rejection occurred thereafter, pointing to the need for improved strategies to avoid this complication.

Nitrate (NO 3 -1 ) leaching from soils results in the lower soil fertility, reduced crop productivity and increased water pollution. The effects of bentonite clay mixed with various nitrogen (N) fertilizers on NO 3 -1 leaching from sandy soils haven’t been extensively studied. Therefore, the present lysimetric study determined NO 3 -1 leaching from bentonite [0, 2 and 4% (m/m)] treated sandy soil under three N sources (calcium nitrate [Ca(NO 3 ) 2 ], ammonium chloride [NH 4 Cl], and urea [CO(NH 2 ) 2 ] at the rate of 300 kg N ha -1 ). Results showed that bentonite markedly reduced NO 3 -1 release in the leachate, while 4% bentonite retained higher NO 3 in the soil. The NO 3 -1 leaching from sandy soil varied with N sources as Ca(NO 3 ) 2 > NH 4 Cl > (CO(NH 2 ) 2 . At early stages of leaching, higher concentrations of NO 3 -1 were detected in leachate with both NH 4 Cl and Ca(NO 3 ) 2 , but leaching of NO 3 -1 increased with urea at later leaching stages. The amount of total NO 3 -1 retained in soil was conversely related to the amount of NO 3 -1 in the leachate. This study indicated that soil amendment with bentonite could efficiently mitigate NO 3 -1 leaching from sandy soil and hence prevent N fertilizer losses and groundwater pollution.

Purpose of Review The first successful pig to human cardiac xenotransplantation in January 2022 represented a major step forward in the fields of heart failure, immunology, and applied genetic engineering, using a 10-gene edited (GE) pig. This review summarizes the evolution of preclinical modelling data which informed the use of each of the 10 genes modified in the 10-GE pig: GGTA1, Β4GalNT2, CMAH, CD46, CD55, TBM, EPCR, CD47, HO-1, and growth hormone receptor. Recent Findings The translation of the 10-GE pig from preclinical modelling to clinical compassionate xenotransplant use was the culmination of decades of research combating rejection, coagulopathy, inflammation, and excessive xenograft growth. Summary Understanding these 10 genes with a view to their combinatorial effects will be useful in anticipated xenotransplant clinical trials.