Physiological basis for xenotransplantation from genetically modified pigs to humans.

The collective efforts of scientists over multiple decades have led to advancements in molecular and cellular biology-based technologies including genetic engineering and animal cloning that are now being harnessed to enhance the suitability of pig organs for xenotransplantation into humans. Using organs sourced from pigs with multiple gene deletions and human transgene insertions, investigators have overcome formidable immunological and physiological barriers in pig-to-nonhuman primate (NHP) xenotransplantation and achieved prolonged pig xenograft survival. These studies informed the design of Revivicor's (Revivicor Inc, Blacksburg, VA) genetically engineered pigs with 10 genetic modifications (10 GE) (including the inactivation of 4 endogenous porcine genes and insertion of 6 human transgenes), whose hearts and kidneys have now been studied in preclinical human xenotransplantation models with brain-dead recipients.

Research opportunities and ethical considerations for heart and lung xenotransplantation research: A report from the National Heart, Lung, and Blood Institute workshop.

Xenotransplantation offers the potential to meet the critical need for heart and lung transplantation presently constrained by the current human donor organ supply. Much was learned over the past decades regarding gene editing to prevent the immune activation and inflammation that cause early organ injury, and strategies for maintenance of immunosuppression to promote longer-term xenograft survival. However, many scientific questions remain regarding further requirements for genetic modification of donor organs, appropriate contexts for xenotransplantation research (including nonhuman primates, recently deceased humans, and living human recipients), and risk of xenozoonotic disease transmission.

Genetic Engineering of Donor Pig for the First Human Cardiac Xenotransplantation: Combatting Rejection, Coagulopathy, Inflammation, and Excessive Growth.

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.

Effective altruism and the dark side of entrepreneurship.

Purpose: Effective Altruism (EA) has become one of the most prominent socio-philosophical movements of recent years. EA is also facing intense scrutiny due to the business practices of some of its most prominent adherents. On the other hand, the dark triad traits of Machiavellianism, narcissism and psychopathy have been getting increasing attention in entrepreneurship research.

Graft dysfunction in compassionate use of genetically engineered pig-to-human cardiac xenotransplantation: a case report.

Background: 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.

Methods: Physiological and biochemical parameters critical for the care of all heart transplant recipients were collected in extensive clinical monitoring in an intensive care unit.

Antecedents of immigrants' entrepreneurial intention formation process: an empirical study of immigrant entrepreneurs in Canada.

Economic integration of ever-increasing number of immigrants in the host country is a challenge both for the immigrant and their host government. Immigrant entrepreneurship can be one of the solutions to this challenge. However, little is known about how immigrant entrepreneurship intention formation process takes place.

Partial heart xenotransplantation: A research protocol in non-human primates.

Partial heart transplantation is a new type of transplant that delivers growing heart valve replacements for babies. Partial heart transplantation differs from orthotopic heart transplantation because only the part of the heart containing the heart valve is transplanted. It also differs from homograft valve replacement because viability of the graft is preserved by tissue matching, minimizing donor ischemia times, and recipient immunosuppression.

Willingness to pay premium prices for green buildings: evidence from an emerging economy.

The building sector is one of the major contributors to greenhouse gas (GHG) emissions, which may impede the achievement of Malaysia's intended nationally determined contribution (INDC) by 2030. Therefore, this paper is aimed at identifying the underlying factors that affect working adults' willingness to pay (WTP) premium prices for green buildings. Data were collected from a total of 1198 respondents and analyzed using structural equitation modeling partial least square (SEM-PLS) to measure the willingness to pay for green buildings among working adults in Malaysia.

The immunobiology and clinical use of genetically engineered porcine hearts for cardiac xenotransplantation.

A summary of the scientific rationale of the advancements that led to the first genetically modified pig-to-human cardiac xenotransplantation is lacking in a complex and rapidly evolving field. Here, we aim to aid the general readership in the understanding of the gradual progression of cardiac (xeno)transplantation research, the immunobiology of cardiac xenotransplantation (including the latest immunosuppression, cardiac preservation and genetic engineering required for successful transplantation) and the regulatory landscape related to the clinical application of cardiac xenotransplantation for people with end-stage heart failure. Finally, we provide an overview of the outcomes and lessons learned from the first genetically modified pig-to-human cardiac heart xenotransplantation.

Characterizing stomatal attributes and photosynthetic induction in relation to biochemical changes in L. by foliar-applied zinc oxide nanoparticles under drought conditions.

Abiotic stress, particularly drought, will remain an alarming challenge for sustainable agriculture. New approaches have been opted, such as nanoparticles (NPs), to reduce the negative impact of drought stress and lessen the use of synthetic fertilizers and pesticides that are an inevitable problem these days. The application of zinc oxide nanoparticles (ZnO NPs) has been recognized as an effective strategy to enhance plant growth and crop production during abiotic stress.

A Standardized Approach to Orthotopic (Life-supporting) Porcine Cardiac Xenotransplantation in a Nonhuman Primate Model.

Cardiac xenotransplantation from swine has been proposed to "bridge the gap" in supply for heart failure patients requiring transplantation. Recent preclinical success using genetically modified pig donors in baboon recipients has demonstrated survival greater than 6 mo, with a modern understanding of xenotransplantation immunobiology and continued experience with large animal models of cardiac xenotransplantation. As a direct result of this expertise, the Food and Drug Administration approved the first in-human transplantation of a genetically engineered cardiac xenograft through an expanded access application for a single patient.

Intraoperative Management of an Orthotopic Porcine-to-Human Cardiac Xenotransplant.

We report the intraoperative management of an orthotopic cardiac xenotransplant in a 57-year-old man with nonischemic cardiomyopathy requiring venoarterial extracorporeal membrane oxygenation. Transesophageal echocardiography was used for preharvest assessment. Continuous ex vivo perfusion of the heart was performed.

CD40-CD40L Blockade: Update on Novel Investigational Therapeutics for Transplantation.

Effective immune responses require antigen presentation by major histocompatibility complexes with cognate T-cell receptor and antigen-independent costimulatory signaling for T-cell activation, proliferation, and differentiation. Among several costimulatory signals, CD40-CD40L is of special interest to the transplantation community because it plays a vital role in controlling or regulating humoral and cellular immunity. Blockade of this pathway has demonstrated inhibition of donor-reactive T-cell responses and prolonged the survival of transplanted organs.

Bentonite clay with different nitrogen sources can effectively reduce nitrate leaching from sandy soil.

Nitrate (NO3-1) 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 NO3-1 leaching from sandy soils haven't been extensively studied. Therefore, the present lysimetric study determined NO3-1 leaching from bentonite [0, 2 and 4% (m/m)] treated sandy soil under three N sources (calcium nitrate [Ca(NO3)2], ammonium chloride [NH4Cl], and urea [CO(NH2)2] at the rate of 300 kg N ha-1).