Palmitic acid (PA), the main component of dietary saturated fat, has been known to increase in patients with obesity, and PA-induced lipotoxicity may contribute to obesity-related male infertility. Melatonin has beneficial effects on reproductive processes; however, the effect and the underlying molecular mechanism of melatonin's involvement in PA-induced cytotoxicity in the testes are poorly understood. Our findings showed that lipotoxicity was observed in mouse testes after long-term PA treatment and that melatonin therapy restored spermatogenesis and fertility in these males. Moreover, melatonin therapy suppressed PA-induced apoptosis by modulating apoptosis-associated proteins such as Bcl2, Bax, C-Caspase3, C-Caspase12, and CHOP in type B spermatogonial stem cells. Changes in the expression of endoplasmic reticulum (ER) stress markers (p-IRE1, p-PERK, ATF4) and intracellular Ca 2+ levels showed that melatonin relieved PA-induced ER stress. Mechanistically, melatonin stimulated the expression and nuclear translocation of SIRT1 through its receptors and prevented PA-induced ROS production and mitochondrial dysfunction via SIRT1 signaling pathway. Furthermore, melatonin promoted SIRT1-mediated p53 deacetylation, thereby relieving G2/M arrest in response to PA-stimulated DNA damage. Collectively, these findings indicate that melatonin protects the testes from PA-induced lipotoxicity through the activation of SIRT1, which alleviates oxidative stress, ER stress, mitochondrial dysfunction, and DNA damage.
P robabilistic selling-the sale of synthetic products consisting of a lottery between two distinct goods-has been extensively analyzed in horizontal markets. In this research, we investigate probabilistic selling in quality-differentiated markets. This is an important new dimension of inquiry because of the widespread prevalence of quality-differentiated markets as well as significant differences in the preference structure across these markets. In fact, this latter consideration casts doubt as to whether probabilistic selling will even emerge in quality-differentiated markets. We find that probabilistic selling emerges in quality-differentiated markets as a way to profitably dispose excess capacity; moreover, probabilistic selling remains viable even under endogenous quality choice. In addition, in markets where sellers employ "strong" quality differentiation, the introduction of an intermediate probabilistic good actually causes closer quality levels in a product line and enhances consumer welfare. In contrast, in markets where sellers employ "weak" quality differentiation, the introduction of an intermediate probabilistic good increases quality separation and degrades consumer welfare. Overall, we view our contribution as one of characterizing the optimality, implementation, and policy implications of probabilistic selling in quality-differentiated markets.
Currently studied carbon nanotube‐silicon (CNT‐Si) solar cells are based on relatively small active areas (typically <0.15 cm2); increasing the active area generally leads to reduced power conversion efficiencies. This study reports CNT‐Si solar cells with active areas of more than 2 cm2 for single cells, yet still achieving cell efficiencies of about 10%, which is the first time for CNT‐Si solar cells with an active area more than 1 cm2 to reach the level for real applications. In this work, a controlled number of flattened highly conductive CNT strips is added, in simple arrangement, to form a CNT‐Si solar cell with CNT strips in which the middle film makes heterojunctions with Si while the top strips act as self‐similar top electrodes, like conventional metal grids. The CNT strips, directly condensed from as‐grown CNT films, not only improve the CNT‐Si junctions, but also enhance the conductivity of top electrodes without introducing contact barrier when the CNT strips are added onto the film. This property may facilitate the development of large‐area high‐performance CNT or graphene‐Si solar cells.
Mycobacterium tuberculosis, which primarily infects mononuclear phagocytes, remains the leading bacterial cause of enormous morbidity and mortality because of bacterial infections in humans throughout the world. The IL-1 family of cytokines is critical for host resistance to M. tuberculosis. As a newly discovered subgroup of the IL-1 family, although IL-36 cytokines have been proven to play roles in protection against M. tuberculosis infection, the antibacterial mechanisms are poorly understood. In this study, we demonstrated that IL-36γ conferred to human monocyte-derived macrophages bacterial resistance through activation of autophagy as well as induction of WNT5A, a reported downstream effector of IL-1 involved in several inflammatory diseases. Further studies showed that WNT5A could enhance autophagy of monocyte-derived macrophages by inducing cyclooxygenase-2 (COX-2) expression and in turn decrease phosphorylation of AKT/mTOR via noncanonical WNT signaling. Consistently, the underlying molecular mechanisms of IL-36γ function are also mediated by the COX-2/AKT/mTOR signaling axis. Altogether, our findings reveal a novel activity for IL-36γ as an inducer of autophagy, which represents a critical inflammatory cytokine that control the outcome of M. tuberculosis infection in human macrophages.
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