SUMMARY Recent advances in three dimensional (3D) culture systems have led to the generation of brain organoids that resemble different human brain regions; however, a 3D organoid model of the midbrain containing functional midbrain dopaminergic (mDA) neurons has not been reported. We developed a method to differentiate human pluripotent stem cells into a large multicellular organoid-like structure that contains distinct layers of neuronal cells expressing characteristic markers of human midbrain. Importantly, we detected electrically active and functionally mature mDA neurons and dopamine production in our 3D midbrain-like organoids (MLOs). In contrast to human mDA neurons generated using 2D methods or MLOs generated from mouse embryonic stem cells, our human MLOs produced neuromelanin-like granules that were structurally similar to those isolated from human substantia nigra tissues. Thus our MLOs bearing features of the human midbrain may provide a tractable in vitro system to study the human midbrain and its related diseases.

Posttraumatic stress disorder (PTSD) is a common mental disorder caused by major psychological trauma. It could result in serious distress and disability. Previous epidemic studies report high prevalence rates among people exposed to the trauma resulted from an infectious disease epidemic. While the control of the epidemic and care of patients with COVID-19 are still the dominant task of the whole world, this commentary calls for attention to early intervention and prevention of PTSD among huge numbers of COVID-19 survivors, their family members, health care professionals and other first-line helpers.

We show that several well-known one-dimensional quantum systems possess a hidden nonlocal supersymmetry. The simplest example is the open XXZ spin chain with ∆ = − 1 2 . We use the supersymmetry to place lower bounds on the ground state energy with various boundary conditions. For an odd number of sites in the periodic chain, and with a particular boundary magnetic field in the open chain, we can derive the ground-state energy exactly. The supersymmetry thus explains why it is possible to solve the Bethe equations for the ground state in these cases. We also show that a similar space-time supersymmetry holds for the t-J model at its integrable ferromagnetic point, where the space-time supersymmetry and the Hamiltonian it yields coexist with a global u(1|2) graded Lie algebra symmetry. Possible generalizations to other algebras are discussed.

Gamma-aminobutyric acid (GABA)-releasing interneurons play an important modulatory role in the cortex and have been implicated in multiple neurological disorders. Patient-derived interneurons could provide a foundation for studying the pathogenesis of these diseases as well as for identifying potential therapeutic targets. Here, we identified a set of genetic factors that could robustly induce human pluripotent stem cells (hPSCs) into GABAergic neurons (iGNs) with high efficiency. We demonstrated that the human iGNs express neurochemical markers and exhibit mature electrophysiological properties within 6-8 weeks. Furthermore, in vitro, iGNs could form functional synapses with other iGNs or with human-induced glutamatergic neurons (iENs). Upon transplantation into immunodeficient mice, human iGNs underwent synaptic maturation and integration into host neural circuits. Taken together, our rapid and highly efficient single-step protocol to generate iGNs may be useful to both mechanistic and translational studies of human interneurons.