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Societal Impact Statement Crop wild relatives represent precious genetic resources for crop improvement. Investigating their local adaptation to marginal environments is important for the utilization of wild genetic resources. Oryza officinalis and Oryza granulata are wild relatives of cultivated rice and possess genes that convey resistance to insects, disease, and tolerance to shade and drought. The northern edge for the distribution of these two lies in China where populations are facing habitat destruction. This study found that the northern marginal populations of both species have adapted to local conditions, with specific implications for the conservation and utilization of wild rice. Summary O. officinalis and O. granulata, wild relatives of cultivated rice, represent important gene reservoirs with the potential to improve rice with respect to insect resistance and stress tolerance. However, the northern marginal populations of these two species in China are facing habitat destruction. Here, we investigated the genetic diversity and divergence of northern marginal populations of O. officinalis and O. granulata. The genomic variation of two species was examined by whole‐genome sequencing on 357 individuals. Generalized dissimilarity modeling was applied to investigate the effects of geographic and environmental isolation on population differentiation. Genetic‐environment association analysis and genome‐wide FST outlier scans were used to identify environmentally driven signals of selection. The marginal populations of both species exhibited low genetic diversity and obvious genetic differentiation stemmed from the joint effects of isolation by geographic distance and the environment. Both genomes exhibited specific signals of adaptation to cold environments in the north. Investigation of the divergence and adaptation of marginal populations of O. officinalis and O. granulata will help us to determine how wild rice can adapt to local environments, thus allowing for the development of scientific conservation policies and the identification of new genetic resources for rice with improved resistance.

Ethane, the second most abundant gaseous hydrocarbon in vast anoxic environments, is an overlooked greenhouse gas. Microbial anaerobic oxidation of ethane can be driven by available electron acceptors such as sulfate and nitrate. However, despite nitrite being a more thermodynamically feasible electron acceptor than sulfate or nitrate, little is known about nitrite-driven anaerobic ethane oxidation. In this study, a microbial culture capable of nitrite-driven anaerobic ethane oxidation was enriched through the long-term operation of a nitrite-and-ethane-fed bioreactor. During continuous operation, the nitrite removal rate and the theoretical ethane oxidation rate remained stable at approximately 25.0 mg NO2–N L−1 d−1 and 11.48 mg C2H6 L−1 d−1, respectively. Batch tests demonstrated that ethane is essential for nitrite removal in this microbial culture. Metabolic function analysis revealed that a species affiliated with a novel genus within the family Rhodocyclaceae, designated as 'Candidatus Alkanivoras nitrosoreducens', may perform the nitrite-driven anaerobic ethane oxidation. In the proposed metabolic model, despite the absence of known genes for ethane conversion to ethyl-succinate and succinate-CoA ligase, 'Ca. A. nitrosoreducens' encodes a prospective fumarate addition pathway for anaerobic ethane oxidation and a complete denitrification pathway for nitrite reduction to nitrogen. These findings advance our understanding of nitrite-driven anaerobic ethane oxidation, highlighting the previously overlooked impact of anaerobic ethane oxidation in natural ecosystems.

1-Naphthylamine (1NA), which is harmful to human and aquatic animals, has been used widely in the manufacturing of dyes, pesticides, and rubber antioxidants. Nevertheless, little is known about its environmental behavior and no bacteria have been reported to use it as the growth substrate. Herein, we describe a pathway for 1NA degradation in the isolate Pseudomonas sp. strain JS3066, determine the structure and mechanism of the enzyme NpaA1 that catalyzes the initial reaction, and reveal how the pathway evolved. From genetic and enzymatic analysis, a five gene-cluster encoding a dioxygenase system was determined to be responsible for the initial steps in 1NA degradation through glutamylation of 1NA. The γ-glutamylated 1NA was subsequently oxidized to 1,2-dihydroxynaphthalene which was further degraded by the well-established pathway of naphthalene degradation via catechol. A glutamine synthetase-like (GS-like) enzyme (NpaA1) initiates 1NA glutamylation, and this enzyme exhibits a broad substrate selectivity toward a variety of anilines and naphthylamine derivatives. Structural analysis revealed that the aromatic residues in the 1NA entry tunnel and the V201 site in the large substrate-binding pocket significantly influence NpaA1’s substrate preferences. The findings enhance understanding of degrading polycyclic aromatic amines, and will also enable the application of bioremediation at naphthylamine contaminated sites.

Summary: Biological nitrogen fixation catalyzed by nitrogenase contributes greatly to the global nitrogen cycle. Nitrogenase expression is subject to regulation in response to nitrogen availability. However, the mechanism through which the transcriptional activator NifA regulates nitrogenase expression by interacting with PII nitrogen regulatory proteins remains unclear in diazotrophic proteobacteria lacking NifL. Here, we demonstrate that in Rhodopseudomonas palustris grown with ammonium, NifA bound deuridylylated PII proteins to form an inactive NifA-PII complex, thereby inhibiting the expression of nitrogenase. Upon nitrogen limitation, the dissociation of uridylylated PII proteins from NifA resulted in the full restoration of NifA activity, and, simultaneously, uridylylation of the significantly up-regulated PII protein GlnK2 led to the increased expression of NifA in R. palustris. This insight into how NifA interacts with PII proteins and controls nitrogenase expression sets the stage for creating highly efficient diazotrophs, reducing the need for energy-intensive chemical fertilizers and helping to diminish carbon emissions.

Abstract Background Tandem C2 domains, nuclear (TC2N) is a C2 domain-containing protein that belongs to the carboxyl-terminal type (C-type) tandem C2 protein family, and acts as an oncogenic driver in several cancers. Previously, we preliminarily reported that TC2N mediates the PI3K-Akt signaling pathway to inhibit tumor growth of breast cancer (BC) cells. Beyond that, its precise biological functions and detailed molecular mechanisms in BC development and progression are not fully understood. Methods Tumor tissues of 212 BC patients were subjected to tissue microarray and further assessed the associations of TC2N expression with pathological parameters and FASN expression. The protein levels of TC2N and FASN in cell lines and tumor specimens were monitored by qRT-PCR, WB, immunofluorescence and immunohistochemistry. In vitro cell assays, in vivo nude mice model was used to assess the effect of TC2N ectopic expression on tumor metastasis and stemness of breast cancer cells. The downstream signaling pathway or target molecule of TC2N was mined using a combination of transcriptomics, proteomics and lipidomics, and the underlying mechanism was explored by WB and co-IP assays. Results Here, we found that the expression of TC2N remarkedly silenced in metastatic and poorly differentiated tumors. Function-wide, TC2N strongly inhibits tumor metastasis and stem-like properties of BC via inhibition of fatty acid synthesis. Mechanism-wise, TC2N blocks neddylated PTEN-mediated FASN stabilization by a dual mechanism. The C2B domain is crucial for nuclear localization of TC2N, further consolidating the TRIM21-mediated ubiquitylation and degradation of FASN by competing with neddylated PTEN for binding to FASN in nucleus. On the other hand, cytoplasmic TC2N interacts with import proteins, thereby restraining nuclear import of PTEN to decrease neddylated PTEN level. Conclusions Altogether, we demonstrate a previously unidentified role and mechanism of TC2N in regulation of lipid metabolism and PTEN neddylation, providing a potential therapeutic target for anti-cancer.

Advancements in understanding the pathogenesis mechanisms underlying gastrointestinal diseases, encompassing inflammatory bowel disease, gastrointestinal cancer, and gastroesophageal reflux disease, have led to the identification of numerous novel therapeutic targets. These discoveries have opened up exciting possibilities for developing gene therapy strategies to treat gastrointestinal diseases. These strategies include gene replacement, gene enhancement, gene overexpression, gene function blocking, and transgenic somatic cell transplantation. In this review, we introduce the important gene therapy targets and targeted delivery systems within the field of gastroenterology. Furthermore, we provide a comprehensive overview of recent progress in gene therapy related to gastrointestinal disorders and shed light on the application of innovative gene-editing technologies in treating these conditions. These developments are fueling a revolution in the management of gastrointestinal diseases. Ultimately, we discuss the current challenges (particularly regarding safety, oral efficacy, and cost) and explore potential future directions for implementing gene therapy in the clinical settings for gastrointestinal diseases.

Abstract Plant-derived exosome-like nanoparticles (PDENs) have been paid great attention in the treatment of ulcerative colitis (UC). As a proof of concept, we isolated and identified Portulaca oleracea L-derived exosome-like nanoparticles (PELNs) from edible Portulaca oleracea L, which exhibited desirable nano-size (~ 160 nm) and a negative zeta potential value (-31.4 mV). Oral administration of PELNs effectively suppressed the expressions of pro-inflammatory cytokines (TNF-α, IL-6, IL-12, and IL-1β) and myeloperoxidase (MPO), increased levels of the anti-inflammatory cytokine (IL-10), and alleviated acute colitis in dextran sulfate sodium (DSS)-induced C57 mice and IL-10−/− mice. Notably, PELNs exhibited excellent stability and safety within the gastrointestinal tract and displayed specific targeting to inflamed sites in the colons of mice. Mechanistically, oral administration of PELNs played a crucial role in maintaining the diversity and balance of gut microbiota. Furthermore, PELNs treatment enhanced Lactobacillus reuteri growth and elevated indole derivative levels, which might activate the aryl-hydrocarbon receptor (AhR) in conventional CD4+ T cells. This activation downregulated Zbtb7b expression, leading to the reprogramming of conventional CD4+ T cells into double-positive CD4+CD8+T cells (DP CD4+CD8+ T cells). In conclusion, our findings highlighted the potential of orally administered PELNs as a novel, natural, and colon-targeted agent, offering a promising therapeutic approach for managing UC. Graphic abstract Schematic illustration of therapeutic effects of oral Portulaca oleracea L -derived natural exosome-like nanoparticles (PELNs) on UC. PELNs treatment enhanced Lactobacillus reuteri growth and elevated indole derivative levels, which activate the aryl-hydrocarbon receptor (AhR) in conventional CD4+ T cells leading to downregulate the expression of Zbtb7b, reprogram of conventional CD4+ T cells into double-positive CD4+CD8+T cells (DP CD4+CD8+ T cells), and decrease the levels of pro-inflammatory cytokines.

Abstract The organoids represent one of the greatest revolutions in the biomedical field in the past decade. This three-dimensional (3D) micro-organ cultured in vitro has a structure highly similar to that of the tissue and organ. Using the regeneration ability of stem cells, a 3D organ-like structure called intestinal organoids is established, which can mimic the characteristics of real intestinal organs, including morphology, function, and personalized response to specific stimuli. Here, we discuss current stem cell-based organ-like 3D intestinal models, including understanding the molecular pathophysiology, high-throughput screening drugs, drug efficacy testing, toxicological evaluation, and organ-based regeneration of inflammatory bowel disease (IBD). We summarize the advances and limitations of the state-of-the-art reconstruction platforms for intestinal organoids. The challenges, advantages, and prospects of intestinal organs as an in vitro model system for precision medicine are also discussed. Key applications of stem cell-derived intestinal organoids. Intestinal organoids can be used to model infectious diseases, develop new treatments, drug screens, precision medicine, and regenerative medicine.