Gut-Liver Axis as a Therapeutic Target for Drug-Induced Liver Injury.

Drug-induced liver injury (DILI) is a liver disease that remains difficult to predict and diagnose, and the underlying mechanisms are yet to be fully clarified. The gut-liver axis refers to the reciprocal interactions between the gut and the liver, and its homeostasis plays a prominent role in maintaining liver health. It has been recently reported that patients and animals with DILI have a disrupted gut-liver axis, involving altered gut microbiota composition, increased intestinal permeability and lipopolysaccharide translocation, decreased short-chain fatty acids production, and impaired bile acid metabolism homeostasis. The present review will summarize the evidence from both clinical and preclinical studies about the role of the gut-liver axis in the pathogenesis of DILI. Moreover, we will focus attention on the potential therapeutic strategies for DILI based on improving gut-liver axis function, including herbs and phytochemicals, probiotics, fecal microbial transplantation, postbiotics, bile acids, and Farnesoid X receptor agonists.

Nile Tilapia (Oreochromis niloticus) Patched1 Mutations Disrupt Cardiovascular Development and Vascular Integrity through Smoothened Signaling.

Hedgehog (Hh) signaling is crucial in cardiovascular development and maintenance. However, the biological role of Patched1 (Ptch1), an inhibitory receptor of the Hh signaling pathway, remains elusive. In this study, a Ptch1 ortholog was characterized in Nile tilapia (Oreochromis niloticus), and its function was investigated through CRISPR/Cas9 gene knockout. When one-cell embryos were injected with CRISPR/Cas9 targeting ptch1, the mutation efficiency exceeded 70%. During 0-3 days post fertilization (dpf), no significant differences were observed between the ptch1 mutant group and the control group; at 4 dpf (0 day after hatching), about 10% of the larvae showed an angiogenesis defect and absence of blood flow; from 5 dpf, most larvae exhibited an elongated heart, large pericardial cavity, and blood leakage and coagulation, ultimately dying during the 6-8 dpf period due to the lack of blood circulation. Consistently, multiple differentially expressed genes related to angiogenesis, blood coagulation, and heart development were enriched in the ptch1 mutants. Furthermore, Smoothened (Smo) antagonist (cyclopamine) treatment of the ptch1 mutants greatly rescued the cardiovascular disorders. Collectively, our study suggests that Ptch1 is required for cardiovascular development and vascular integrity via Smo signaling, and excessive Hh signaling is detrimental to cardiovascular development.

Disruption of Zar1 leads to arrested oogenesis by regulating polyadenylation via Cpeb1 in tilapia (Oreochromis niloticus).

Oogenesis is a complex process regulated by precise coordination of multiple factors, including maternal genes. Zygote arrest 1 (zar1) has been identified as an ovary-specific maternal gene that is vital for oocyte-to-embryo transition and oogenesis in mouse and zebrafish. However, its function in other species remains to be elucidated. In the present study, zar1 was identified with conserved C-terminal zinc finger domains in Nile tilapia. zar1 was highly expressed in the ovary and specifically expressed in phase I and II oocytes. Disruption of zar1 led to the failed transition from oogonia to phase I oocytes, with somatic cell apoptosis. Down-regulation and failed polyadenylation of figla, gdf9, bmp15 and wee2 mRNAs were observed in the ovaries of zar1-/- fish. Cpeb1, a gene essential for polyadenylation that interacts with Zar1, was down-regulated in zar1-/- fish. Moreover, decreased levels of serum estrogen and increased levels of androgen were observed in zar1-/- fish. Taken together, zar1 seems to be essential for tilapia oogenesis by regulating polyadenylation and estrogen synthesis. Our study shows that Zar1 has different molecular functions during gonadal development by the similar signaling pathway in different species.

Across two phylogeographic breaks: Quaternary evolutionary history of a mountain aspen (Populus rotundifolia) in the Hengduan Mountains.

Biogeographical barriers to gene flow are central to plant phylogeography. In East Asia, plant distribution is greatly influenced by two phylogeographic breaks, the Mekong-Salween Divide and Tanaka-Kaiyong Line, however, few studies have investigated how these barriers affect the genetic diversity of species that are distributed across both. Here we used 14 microsatellite loci and four chloroplast DNA fragments to examine genetic diversity and distribution patterns of 49 populations of Populus rotundifolia, a species that spans both the Mekong-Salween Divide and the Tanaka-Kaiyong Line in southwestern China. Demographic and migration hypotheses were tested using coalescent-based approaches. Limited historical gene flow was observed between the western and eastern groups of P. rotundifolia, but substantial flow occurred across both the Mekong-Salween Divide and Tanaka-Kaiyong Line, manifesting in clear admixture and high genetic diversity in the central group. Wind-borne pollen and seeds may have facilitated the dispersal of P. rotundifolia following prevalent northwest winds in the spring. We also found that the Hengduan Mountains, where multiple genetic barriers were detected, acted on the whole as a barrier between the western and eastern groups of P. rotundifolia. Ecological niche modeling suggested that P. rotundifolia has undergone range expansion since the last glacial maximum, and demographic reconstruction indicated an earlier population expansion around 600 Ka. The phylogeographic pattern of P. rotundifolia reflects the interplay of biological traits, wind patterns, barriers, niche differentiation, and Quaternary climate history. This study emphasizes the need for multiple lines of evidence in understanding the Quaternary evolution of plants in topographically complex areas.

Contrasting range changes and drivers of four forest foundation species under future climate change in China.

Forest foundation species, vital for shaping community structure and dynamics through non-trophic level interactions, are key to forest succession and sustainability. Despite their ecological importance, the habitat ranges of these species in China and their responses to future climate change remain unclear. Our study employed the optimal MaxEnt model to assess the range shifts and their essential drivers of four typical forest foundation species from three climatic zones in China under climate scenarios, including Acer tegmentosum, Acer pseudo-sieboldianum (temperate zone), Quercus glandulifera (subtropical zone), and Ficus hispida (tropical zone). The optimal MaxEnt model exhibited high evaluation indices (AUC values > 0.90) for the four foundation species, indicating excellent predictive performance. Currently, we observed that A. tegmentosum and A. pseudo-sieboldianum are predominantly inhabited temperate forest areas in northeastern China, Q. glandulifera is primarily concentrated in subtropical forests in southeastern China, and F. hispida is mainly distributed across the tropical forests in southern China. Climate factors, particularly temperature, emerged as the primary environmental factors influencing the potential range of forest foundation species. Moreover, precipitation strongly influenced the potential range of A. tegmentosum and A. pseudo-sieboldianum, while elevation exhibited a greater impact on the range of Q. glandulifera and F. hispida. Under future climate scenarios, suitable areas for A. tegmentosum and A. pseudo-sieboldianum tend to expand southward, F. hispida tends to expand northward, while Q. glandulifera exhibited a tendency to contract towards the center. This study advances our understanding of the spatial and temporal dynamics of forest foundation species in China under climate change, providing critical insights for conservation efforts and sustainable forest management practices.

Nuclear accumulation of rice UV-B photoreceptors is UV-B- and OsCOP1-independent for UV-B responses.

In plants, the conserved plant-specific photoreceptor UV RESISTANCE LOCUS 8 (UVR8) perceives ultraviolet-B (UV-B) light and mediates UV-B-induced photomorphogenesis and stress acclimation. In this study, we reveal that UV-B light treatment shortens seedlings, increases stem thickness, and enhances UV-B stress tolerance in rice (Oryza sativa) via its two UV-B photoreceptors OsUVR8a and OsUVR8b. Although the rice and Arabidopsis (Arabidopsis thaliana) UVR8 (AtUVR8) photoreceptors all form monomers in response to UV-B light, OsUVR8a, and OsUVR8b function is only partially conserved with respect to AtUVR8 in UV-B-induced photomorphogenesis and stress acclimation. UV-B light and CONSTITUTIVELY PHOTOMORPHOGENIC 1 (COP1) promote the nuclear accumulation of AtUVR8; by contrast, OsUVR8a and OsUVR8b constitutively localize to the nucleus via their own nuclear localization signals, independently of UV-B light and the RING-finger mutation of OsCOP1. We show that OsCOP1 negatively regulates UV-B responses, and shows weak interaction with OsUVR8s, which is ascribed to the N terminus of OsCOP1, which is conserved in several monocots. Furthermore, transcriptome analysis demonstrates that UV-B-responsive gene expression differs globally between Arabidopsis and rice, illuminating the evolutionary divergence of UV-B light signaling pathways between monocot and dicot plants.

A new species of Megastigmus (Hymenoptera, Megastigmidae) from China.

Background: Most species of Megastigmus are considered important economic pests that grow in seeds, especially of conifers. Accurate identification of species is a crucial step for the biological research of parasitic pests and the further application of biological control. However, their large variety, small size, similar morphology and different growth and development stages have brought great challenges to taxonomic research. Traditional morphological identification often takes a long time and this requires us to seek a new method for rapid and accurate identification. Therefore, the better identification of Megastigmus urgently needs to be combined with molecular methods to help taxonomic development. New information: Here, Megastigmusdaduheensis sp. n. (Chalcidoidea: Megastigmidae) was identified, based on morphology and molecular markers, such as COI and Cytb. M.daduheensis sp. n. is distinct from other known species of the same genus in the morphology. The results of the molecular phylogenetic tree, similarity alignment and genetic distance indicate that the COI and Cytb sequences of M.daduheensis sp. n. are highly similar to M.sobinae and M.duclouxiana, but there are some genetic differences. The genetic distances of M.daduheensis sp. nov. with M.duclouxiana and M.sabinae were 0.34 and 0.33 and the percentages of shared base pairs were 76.3% and 76.8%, respectively. Both morphological and molecular data classified M.daduheensis sp. n. as a new species. The obtained COI and Cytb sequences of M.daduheensis sp. n. can be used as DNA barcodes, providing molecular data for rapid and accurate identification of this species in the future.