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Recent studies indicate that macrophages utilize NAD⁺-biosynthetic pathways to control inflammation and cell survival during the immune response and aging.

Chini et al. demonstrate that CD38⁺ expression in immune cells increases during aging, owing to the senescence-associated secretory phenotype of senescent cells, and the ecto-enzymatic activity of CD38⁺ affects intracellular NAD⁺ levels in vivo by hydrolyzing the NAD⁺ intermediate nicotinamide mononucleotide extracellularly.

Gender-based violence is widespread, affecting women and men worldwide. Stein et al. use a meta-analysis and the Burden of Proof methodology to evaluate associations between gender-based violence and eight health outcomes, including major depressive disorder, substance use and reproductive health.

Around the world, more than a billion children are regularly exposed to violence or neglect. Flor et al. systematically review evidence that links childhood physical violence, psychological violence and neglect to increased risks for 14 health outcomes.

Small molecule antagonists of CCR6 are potential drugs for autoimmune disorders. Here the authors present inactive structures of CCR6 bound by different allosteric antagonists from two series simultaneously, offering multiple approaches to inhibit CCR6.

The role of TREM1 in neurodegenerative diseases is unclear. Here the authors show that TREM1 promotes cognitive decline in aging and in the context of amyloid pathology in a mouse model of Alzheimer disease.

A meta-analysis using the burden of proof risk function identified consistent evidence supporting harmful associations between the exposure to intimate partner violence against women and childhood sexual abuse on health outcomes.

In aged mice, inhibition of prostaglandin E₂ (PGE₂) signalling through its receptor EP2 improves cellular bioenergetics, reduces inflammatory responses and restores hippocampal plasticity to youthful levels, resulting in an improvement in spatial memory and cognition.

Macrophages alter their metabolism in response to infection. The authors show that resting macrophages generate nicotinamide adenine dinucleotide via de novo synthesis, but activated and aged cells suppress the rate-limiting enzyme quinolinate phosphoribosyltransferase to regulate mitochondrial and immunological functions.

ALBATROSS is a deep-learning-based model for predicting ensemble properties of intrinsically disordered proteins and protein regions, such as radius of gyration, end-to-end distance, polymer-scaling exponent and ensemble asphericity, directly from sequences.

Redox signal transduction from the mitochondrial matrix to the cytosol is shown to be mediated through interaction between MIC60 and Miro, the disruption of which ameliorates oxidative stress in Drosophila.

Cerebral ischemia activates innate immune responses in injured brain lesions. Andreasson and colleagues show TREM1 is upregulated after stroke and amplifies these proinflammatory responses by peripheral CD11b⁺ myeloid cells in both the ischemic brain and distally in the intestine.

Microglia and astrocytes propagate neurodegeneration by releasing fragmented and dysfunctional mitochondria into the neuronal milieu. Inhibiting pathological fragmentation of glial mitochondria blunts neuroinflammation and increases neuroprotection.

Complex I (NADH:ubiquinone oxidoreductase) is the first enzyme of the respiratory chain in bacteria and mitochondria. Here, the authors present cryo-EM and crystal structures of T. thermophilus complex I in different conformational states and further analyse them by Normal Mode Analysis and molecular dynamics simulations and conclude that quinone redox reactions are important for the coupling mechanism of complex I.

The atomic-resolution structure of the entire respiratory complex I is reported, with the resolution high enough to map out the locations and orientations of nearly all amino-acid side chains—some of which link to human neurodegenerative diseases—and reveals which amino-acid interactions take place at the hydrophilic domain–membrane domain interface.

Delayed diagnosis and treatment of penile cancer often result in the development of advanced disease. Shabbir et al. highlight how pooling resources and expertise can help improve disease management and review remaining challenges in prevention, diagnosis, treatment and lymph node staging.

The profile of diseases that specifically affect men has increased in recent years, and charities have had a major role in raising public awareness and funding for these conditions. Now that these charities have gained attention, their influence in the field of men's health should be assessed.

When listening to a story, humans learn about its structure and content. Here the authors reveal the neural processes behind episodic memory and predictive recall at a fine temporal scale in this naturalistic setting

Machine learning is widely applied in various fields of genomics and systems biology. In this Review, the authors describe how responsible application of machine learning requires an understanding of several common pitfalls that users should be aware of (and mitigate) to avoid unreliable results.

Penile reconstructive surgery requires expertise in genital surgery, whether it is for traumatic injuries or penile cancer. The stages of initial assessment and management of traumatic penile injuries and penile cancer, and the different reconstructive techniques available, are described in this review by David Ralph and colleagues.

The mitochondrial respiratory chain comprises large multi-subunit protein complexes that generate ATP. The crystal structure of the entire bacterial complex I was recently solved, providing novel insights into its core architecture, as well as the electron transfer and proton translocation pathways and the coupling between them.

In this Review, Kayes and colleagues discuss the aetiology, diagnosis and treatment options for congenital micropenis, acquired micropenis and penile dysmorphic disorder, including both nonsurgical and surgical techniques. They evaluate the role of phalloplasty and penile replacement surgery including transplantation, in this challenging clinical area.

Transcranial alternating current stimulation (tACS) has been proposed to enhance neural rhythms supporting memory. Here, the authors leverage human intracranial recordings to show that low-frequency tACS does not entrain key rhythms in non-REM sleep or resting wakefulness.

In this Expert Recommendation, the most pressing questions related to male reproductive health, spanning the spectrum of andrology, are identified. These questions encompass and highlight many opportunities to influence the wellness of future generations.

The top 20 policy and research priorities for conditions such as diabetes, stroke and heart disease.