Global burden and trends of acute viral hepatitis among children and adolescents from 1990 to 2019: a systematic analysis of the Global Burden of Disease Study 2019.

BACKGROUND: Children and adolescents are at high risk for acute viral hepatitis (AVH), but epidemiological research focusing on them has been overshadowed by adult chronic B and C. We provide global, regional, and national estimates of the AVH burden and their trends on people under 20 years from 1990 to 2019. METHODS: AVH data from Global Burden of Disease Study (GBD) 2019 was used. Incidence and disability-adjusted life years (DALYs) were calculated, analyzing trends with estimated annual percentage change (EAPC) and Joinpoint regression. RESULTS: In 2019, 156.39 (95% uncertainty interval 145.20-167.16) million new cases of AVH were reported among children and adolescents globally, resulting in 1.98 (1.50-2.55) million DALYs. Incidence rates for young children (< 5 years), older children (5-9 years), and adolescents (10-19 years) were 12,799 (11,068-14,513), 5,108 (4829-5411), and 3020 (2724-3339) per 100,000 population, respectively. The global AVH incidence displayed a linear decline with an EAPC of - 0.66 (- 0.68 to - 0.65). High-incidence regions included sub-Saharan Africa, Oceania, South Asia, and Central Asia, with India, Pakistan, and Nigeria facing the greatest burden. Leading causes were hepatitis A, followed by hepatitis E, B, and C. All hepatitis types showed declining trends, especially hepatitis B. Furthermore, we confirmed the association between the AVH incidence and the socioeconomics, vaccine, and advanced liver diseases. CONCLUSION: Effective vaccines and treatments for hepatitis B and C offer eradication opportunities. Broadening diagnostic and therapeutic coverage is vital to address disparities in service provision for children and adolescents.

Unravelling the role of NFE2L1 in stress responses and related diseases.

The nuclear factor erythroid 2 (NF-E2)-related factor 1 (NFE2L1, also known as Nrf1) is a highly conserved transcription factor that belongs to the CNC-bZIP subfamily. Its significance lies in its control over redox balance, proteasome activity, and organ integrity. Stress responses encompass a series of compensatory adaptations utilized by cells and organisms to cope with extracellular or intracellular stress initiated by stressful stimuli. Recently, extensive evidence has demonstrated that NFE2L1 plays a crucial role in cellular stress adaptation by 1) responding to oxidative stress through the induction of antioxidative responses, and 2) addressing proteotoxic stress or endoplasmic reticulum (ER) stress by regulating the ubiquitin-proteasome system (UPS), unfolded protein response (UPR), and ER-associated degradation (ERAD). It is worth noting that NFE2L1 serves as a core factor in proteotoxic stress adaptation, which has been extensively studied in cancer and neurodegeneration associated with enhanced proteasomal stress. In these contexts, utilization of NFE2L1 inhibitors to attenuate proteasome "bounce-back" response holds tremendous potential for enhancing the efficacy of proteasome inhibitors. Additionally, abnormal stress adaptations of NFE2L1 and disturbances in redox and protein homeostasis contribute to the pathophysiological complications of cardiovascular diseases, inflammatory diseases, and autoimmune diseases. Therefore, a comprehensive exploration of the molecular basis of NFE2L1 and NFE2L1-mediated diseases related to stress responses would not only facilitate the identification of novel diagnostic and prognostic indicators but also enable the identification of specific therapeutic targets for NFE2L1-related diseases.

Thermotaxis of mammalian sperm.

Sperm are guided through the female reproductive tract. A temperature difference of about 2°C exists between the storage site and fertilization site of the mammalian oviduct, leading to the hypothesis that sperm can sense and swim towards the oocyte along a rising temperature gradient, known as thermotaxis. Research over the past two decades has reported that sperm feature a sophisticated thermal detection system to detect and track ambient temperature gradients. More recently, thermotaxis is expected to be added to the microfluidic isolation method based on sperm tactic responses for sperm selection. In this article, mammalian sperm thermotaxis is discussed, explaining the underlying behavioural mechanisms and molecular basis, according to the latest research. Finally, this article explores the possible application of sperm thermotaxis in ART.

TRPV1 in male reproductive system: focus on sperm function.

The transient receptor potential vanilloid 1 (TRPV1) is a receptor used to perceive external noxious stimuli and participates in the regulation of various pathophysiological mechanisms in vivo by integrating multiple signals. The explosive growth in knowledge of TRPV1 stemmed from research on neuronal pain and heat sensation over the last decades and is being expanded tremendously in peripheral tissue research. The discovery that TRPV1 is functionally active in male animal and human reproductive tissues have attracted increasing attention in recent years. Indeed, many studies have indicated that TRPV1 is an endocannabinoid receptor that mediates Anandamide's regulation of sperm function. Other characteristics of the TRPV1 channel itself, such as calcium penetration and temperature sensitivity, have also been investigated, especially the possibility that TRPV1 could act as a mediator for sperm thermotaxis. In addition, some reproductive diseases appear to be related to the protective effects of TRPV1 on oxidative stress and heat stress. A better understanding of TRPV1 in these areas should provide strategies for tackling male infertility. This paper is the first to review the expression and mechanism of TRPV1 in the male reproductive system from molecular and cellular perspectives. A focus is given on sperm function, including calcium homeostasis, crosstalk with endocannabinoid system, participation in cholesterol-related sperm maturation, and thermotaxis, hoping to capture the current situation of this rapidly developing field.