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We recommend upgrading to the latest version of Internet Explorer , Google Chrome , or Firefox × Issue published May 1, 2024 Previous issue Volume 134, Issue 9 Go to section: 100th Anniversary Viewpoints Reviews Commentaries Research Letters Research Articles Erratum Corrigenda On the cover: Compromised hypothermic cardioprotection in aged donor heart Zhu et al. report that reduced expression of cold-inducible RNA-binding protein (CIRBP) in aged donor hearts promotes ferroptosis and blunts cardioprotective effects of hypothermia during heart transplantation in a rat model. Image credit: Shanghai Bangtu Culture Media Co. 100th Anniversary Viewpoints Life-saving effect of pulmonary surfactant in premature babies J. Usha Raj, … , Marlene Rabinovitch, Michael A. Matthay J. Usha Raj, … , Marlene Rabinovitch, Michael A. Matthay Published May 1, 2024 Citation Information: J Clin Invest. 2024; 134(9) :e179948. https://doi.org/10.1172/JCI179948 . View: Text | PDF Life-saving effect of pulmonary surfactant in premature babies Text PDF Abstract Authors J. Usha Raj, Richard D. Bland, Jahar Bhattacharya, Marlene Rabinovitch, Michael A. Matthay × Reviews Complement regulation in the eye: implications for age-related macular degeneration Georgia A. Wilke, Rajendra S. Apte Georgia A. Wilke, Rajendra S. Apte Published May 1, 2024 Citation Information: J Clin Invest. 2024; 134(9) :e178296. https://doi.org/10.1172/JCI178296 . View: Text | PDF Complement regulation in the eye: implications for age-related macular degeneration Text PDF Abstract Careful regulation of the complement system is critical for enabling complement proteins to titrate immune defense while also preventing collateral tissue damage from poorly controlled inflammation. In the eye, this balance between complement activity and inhibition is crucial, as a low level of basal complement activity is necessary to support ocular immune privilege, a prerequisite for maintaining vision. Dysregulated complement activation contributes to parainflammation, a low level of inflammation triggered by cellular damage that functions to reestablish homeostasis, or outright inflammation that disrupts the visual axis. Complement dysregulation has been implicated in many ocular diseases, including glaucoma, diabetic retinopathy, and age-related macular degeneration (AMD). In the last two decades, complement activity has been the focus of intense investigation in AMD pathogenesis, leading to the development of novel therapeutics for the treatment of atrophic AMD. This Review outlines recent advances and challenges, highlighting therapeutic approaches that have advanced to clinical trials, as well as providing a general overview of the complement system in the posterior segment of the eye and selected ocular diseases. Authors Georgia A. Wilke, Rajendra S. Apte × Therapeutic vaccines for herpesviruses Jeffrey I. Cohen Jeffrey I. Cohen Published May 1, 2024 Citation Information: J Clin Invest. 2024; 134(9) :e179483. https://doi.org/10.1172/JCI179483 . View: Text | PDF Therapeutic vaccines for herpesviruses Text PDF Abstract Herpesviruses establish latent infections, and most reactivate frequently, resulting in symptoms and virus shedding in healthy individuals. In immunocompromised patients, reactivating virus can cause severe disease. Persistent EBV has been associated with several malignancies in both immunocompromised and nonimmunocompromised persons. Reactivation and shedding occur with most herpesviruses, despite potent virus-specific antibodies and T cell immunity as measured in the blood. The licensure of therapeutic vaccines to reduce zoster indicates that effective therapeutic vaccines for other herpesviruses should be feasible. However, varicella-zoster virus is different from other human herpesviruses in that it is generally only shed during varicella and zoster. Unlike prophylactic vaccines, in which the correlate of immunity is antibody function, T cell immunity is the correlate of immunity for the only effective therapeutic herpesvirus vaccine–zoster vaccine. While most studies of therapeutic vaccines have measured immunity in the blood, cellular immunity at the site of reactivation is likely critical for an effective therapeutic vaccine for certain viruses. This Review summarizes the status of therapeutic vaccines for herpes simplex virus, cytomegalovirus, and Epstein-Barr virus and proposes approaches for future development. Authors Jeffrey I. Cohen × Commentaries A therapeutic leap: how myosin inhibitors moved from cardiac interventions to skeletal muscle myopathy solutions Julius Bogomolovas, Ju Chen Julius Bogomolovas, Ju Chen Published May 1, 2024 Citation Information: J Clin Invest. 2024; 134(9) :e179958. https://doi.org/10.1172/JCI179958 . View: Text | PDF A therapeutic leap: how myosin inhibitors moved from cardiac interventions to skeletal muscle myopathy solutions Text PDF Abstract The myosin inhibitor mavacamten has transformed the management of obstructive hypertrophic cardiomyopathy (HCM) by targeting myosin ATPase activity to mitigate cardiac hypercontractility. This therapeutic mechanism has proven effective for patients with HCM independent of having a primary gene mutation in myosin. In this issue of the JCI, Buvoli et al. report that muscle hypercontractility is a mechanism of pathogenesis underlying muscle dysfunction in Laing distal myopathy, a disorder characterized by mutations altering the rod domain of β myosin heavy chain. The authors performed detailed physiological, molecular, and biomechanical analyses and demonstrated that myosin ATPase inhibition can correct a large extent of muscle abnormalities. The findings offer a therapeutic avenue for Laing distal myopathy and potentially other myopathies. This Commentary underscores the importance of reevaluating myosin activity’s role across myopathies in general for the potential development of targeted myosin inhibitors to treat skeletal muscle disorders. Authors Julius Bogomolovas, Ju Chen × A step closer to understanding how a diet high in simple carbohydrates may cause dysbiosis Shrinivas Bishu, John Y. Kao Shrinivas Bishu, John Y. Kao Published May 1, 2024 Citation Information: J Clin Invest. 2024; 134(9) :e180001. https://doi.org/10.1172/JCI180001 . View: Text | PDF A step closer to understanding how a diet high in simple carbohydrates may cause dysbiosis Text PDF Abstract The gut microbiota is an integral part of the human metaorganism that is required to shape physiologic...