Journal of advanced research最新文献

Background: Drought is a major constraint in arid and semi-arid regions, leading to a reduction in soil organic carbon (SOC) by suppressing microbial activities and limiting organic matter inputs. The decrease in soil health frequently threatens agricultural productivity and ecosystem sustainability. Arbuscular mycorrhizal fungi (AMF) and plant growth-promoting rhizobacteria (PGPR) can offer a sustainable strategy to enhance SOC in drylands.

Aim of review: While the sole effects of AMF or PGPR are often studied, their interactive effects on global SOC sequestration under drought conditions remain systematically unexplored. This review aims to address this critical knowledge gap by conducting, for the first time, a comprehensive meta-analysis of global studies from 1998 to 2025. The objective is to quantitatively evaluate the interaction effect of AMF and PGPR co-inoculation on SOC dynamics and its underlying mechanisms in adaptation to drought environments.

Key scientific concepts of review: Based on 989 observations, the meta-analysis reveals that both single and co-inoculation of AMF and PGPR significantly improve SOC levels. This increase is driven by enhancing key SOC fractions, including microbial biomass carbon, easily oxidizable carbon, dissolved, light fraction, and particulate organic carbon accumulation. The AMF-PGPR co-inoculation strategy is particularly effective across diverse conditions, significantly enhancing SOC in coarse (46%) and medium-textured (54%) soils across acidic (48%) and alkaline (48%) pH in various cropping systems by improving root and shoot traits. Different genera of AMF (Glomus, Rhizophagus) and PGPR (Bacillus, Pseudomonas) synergetically enhance SOC through glomalin production (48-51%), hyphal architecture (122%), phytochrome production (52%), and microbial enzymatic activities. AMF and PGPR co-inoculation enhances SOC accumulation by improving enzymatic activities (39-90%) and plant traits (44-251%). This meta-analysis concludes that AMF-PGPR co-incoulation is a sustainable strategy for increasing global soil carbon sequestration, thereby improving soil health and crop productivity in dryland ecosystems.

Introduction: Lithium manganate (LMO) is a new type of pollutant that is extensively applied in the manufacture of lithium-ion batteries. Accumulating evidence indicates that both manganese (Mn) and lithium (Li) can cross the blood-brain barrier and accumulate within the hippocampus. However, the neurotoxic effects of LMO on hippocampal core functions and the involved molecular mechanisms are still unclear.

Objectives: This study observed whether LMO exposure impairs hippocampus-dependent learning and memory in mice and investigated related mechanisms and intervention strategies.

Methods: A whole-body inhalation exposure system was employed to simulate occupationally relevant in vivo exposure to LMO, with mice exposed to concentrations of 0, 1.35, 13.5, and 135 mg/m³ for 28 and 45 days, corresponding approximately to 3 and 5 human years., In parallel, in vitro co-exposure models using HT-22 cells and primary hippocampal neurons treated with Mn and Li. Neurobehavioral, neuropathological, live-cell imaging-based assays were used to assess learning and memory impairment, neuronal damage, and retrograde axonal transport dysfunction. RNA-sequencing and molecular biology approaches were conducted to explore and validate mechanisms. Mid1 silencing/knockdown and valproic acid (VPA) treatment were used to assess whether modulation of Mid1-related changes attenuates LMO-induced neurotoxicity..

Results: The results demonstrated that LMO exposure impaired learning and memory in mice. Mechanistically, LMO or Mn and Li co-exposure up-regulates the E3 ubiquitin ligase Mid1 which promotes the degradation of dynein light chain family members Dynlrb2 and Dynlt4 through the ubiquitin-proteasome pathway. This disruption impairs retrograde axonal transport in hippocampal neurons, resulting in neuronal injury and ultimately compromising learning and memory function in mice. Suppression of Mid1 ,or VPA treatment significantly improved the observed neuronal damage and the expression levels of factors related to axonal retrograde transport.

Conclusion: This study indicates that LMO inhalation exposure is associated with learning and memory deficits and hippocampal neuronal injury, accompanied by Mid1-related ubiquitin-proteasome alterations and disrupted retrograde axonal transport.

Introduction: Osteoporosis, a "silent killer" among the elderly, is marked by progressive bone loss and microstructural deterioration. Oligopeptides derived from black bean, particularly tetrapeptides, have shown notable osteogenic potential, yet their therapeutic roles in regulating bone metabolism and preventing osteoporosis remain unclear.

Objectives: This study explored the osteoanabolic effects of black bean-derived tetrapeptides and elucidated their underlying mechanisms.

Methods: In vitro assays were conducted using MC3T3-E1 pre-osteoblasts derived from mouse calvaria to assess osteogenic differentiation upon tetrapeptide treatment. Six black bean tetrapeptides were evaluated, including KIGT, KGVG, KTGV, SIKL, KLGT, and SLKL. In vivo efficacy was evaluated in an ovariectomized mouse model of osteoporosis via intragastric administration. Based on molecular docking, the mechanisms were explored using Western blotting and immunofluorescence and validated through pathway inhibitor and siRNA knockdown experiments.

Results: All six tetrapeptides significantly stimulated the osteogenic differentiation of MC3T3-E1 pre-osteoblasts, particularly during early osteogenesis. Notably, the peptides all exhibited osteogenic effects at low doses (0.1 μM), although their optimal concentrations varied. Mechanistic studies revealed a shared anabolic pathway among the tetrapeptides, in which lysine residues may play a pivotal role in mediating their similar interactions with bone morphogenetic protein-2 (BMP-2), thereby activating the BMP-2/Smad signaling. Furthermore, this potent osteoanabolic efficacy was confirmed in osteoporotic mice, where a 10-week treatment with black bean oligopeptides (<1 kD), KIGT, and KGVG (100 mg/kg) markedly attenuated bone loss.

Conclusion: Lysine-containing tetrapeptides derived from black bean exert direct osteoanabolic activity by targeting BMP-2/Smad signaling in osteoblasts. These findings support their potential as novel anabolic candidates against osteoporosis, paving the way for the development of oligopeptide-based therapies targeting bone health.

Introduction: Rapeseed (Brassica napus L.) is a major oilseed crop with considerable potential for improving saline-alkali soils, yet the molecular mechanisms underlying its salt tolerance remain unclear.

Objectives: This study investigates the functional roles and regulatory mechanisms of glycine-rich protein 3 (BnaGRP3) in rapeseed under salt stress.

Methods: We employed molecular genetics, phenotypic and biochemical evaluation of transgenic rapeseed and Arabidopsis, transcriptome sequencing, protein interaction assays including immunoprecipitation-mass spectrometry (IP-MS), yeast two-hybrid (Y2H), luciferase complementation (LCA), and bimolecular fluorescence complementation (BiFC) assays, gene expression analysis by RT-qPCR, and hydrogen peroxide (H₂O₂) permeability assays conducted in yeast.

Results: BnaGRP3 was induced by salt stress and enhanced salt tolerance. Transcriptome analysis revealed that BnaGRP3 modulated expression of ion transporters under salt stress, especially NHX1 and SKOR. BnaGRP3 physically interacted with four plasma membrane intrinsic proteins (BnaPIPs). Overexpression of these BnaPIPs improved salt tolerance in Arabidopsis and increased H₂O₂ tolerance when expressed in yeast. In addition, these BnaPIPs formed both homomeric and heteromeric complexes, suggesting they may facilitate H₂O₂ permeability.

Conclusions: BnaGRP3 enhances salt tolerance by maintaining Na⁺/K⁺ homeostasis and, through its interactions with BnaPIPs, may participate in the regulation of H₂O₂ balance·H₂O₂ potentially serves as a bridge linking BnaGRP3-mediated ion homeostasis and redox regulation. The previously uncharacterized BnaGRP3-BnaPIP module broadens the mechanistic framework of GRP-mediated salt stress responses, thereby expanding our understanding of salt tolerance mechanisms in Brassica napus.

Introduction: Viruses are abundant biological entities within the gastrointestinal tract (GIT) of ruminants. Current understanding is extensive for bacterial and archaeal communities, but limited for viral communities.

Objectives: The study aimed to investigate viral diversity, virus-host interactions and ecological functions of viruses across GIT regions and ruminant species.

Methods: We collected 373 short-read and long-read metagenomes from 10 GIT regions of seven ruminant species, combining Illumina, PacBio HiFi, and Nanopore sequencing. Viral contigs were identified using sequence homology, viral hallmark gene and machine learning, and employed to uncover community assembly of spatial heterogeneity by analyzing virus-host linkage, lifestyle, and auxiliary metabolic genes (AMGs).

Results: We constructed a Ruminant Gastrointestinal Virome Catalog (RGVC) comprising 43,981 vOTUs, revealing that viral communities were remarkably diverse and mainly driven by the GIT regions rather than by the ruminant species. Virus-host linkage analysis identified 4603 putative prokaryotic hosts across 34 classes for 5954 host-linked viruses, along with robust correlation (R² = 0.91) observed between abundances of prokaryotic hosts and host-linked viruses across GIT regions. The lysogenic lifestyle was a dominant feature, with integrases being the predominant lysogenic-specific genes. We identified 864 high-confidence AMGs in lysogenic viruses that are annotated as key genes for polysaccharide degradation, glycolysis, and the Wood-Ljungdahl pathway, indicating a putative role for the viruses in supporting these host metabolic functions. The metabolic features of host-linked viruses were further verified by genomic context of selected AMGs of GH10, GPI and FHS with target function.

Conclusion: These findings suggest that the GIT viral communities exhibit spatial heterogeneity with distinct virus-host interactions, and offer new perspectives on maintenance of complex ecological and nutritional functions in ruminant GIT.

Background: Tryptophan (Trp) catabolism has been recognized as a key immunosuppressive axis in cancer. However, this largely centered on indoleamine-2,3-dioxygenase 1 (IDO1). The clinical failure of IDO1 inhibitors has exposed the limitations of this reductionist view.

Aim of review: To re-synthesize current knowledge into a further understanding of Trp metabolism, and propose biomarker-guided, multi-node intervention strategies that can resurrect Trp metabolism as a precision immuno-oncology target. Key Scientific Concepts of Review: This review comprehensively describes the pathways of Trp metabolism in the human body and the key enzymes that can serve as therapeutic targets, thus proposing the possibility of multi enzyme combined inhibition. Second, we synthesize how Trp metabolites can modulate the functionality of immune cells, mainly T cells, within the tumor microenvironment, thereby affecting tumor immune surveillance and the efficacy of immunotherapy. Then we discuss how tumor cells manipulate Trp metabolic pathways to enhance their survival and metastasis. We also propose a new framework for targeting Trp metabolism, such as combining enzymes inhibitors or Aryl hydrocarbon receptor (AhR) antagonists with immune checkpoint blockade. By shifting from "IDO1-focus" paradigms to comprehensive metabolic interventions, we may release more potential of Trp modulation in cancer immunotherapy.

Introduction: Autoimmune uveitis (AU) is an autoimmune disease of the eye that can lead to irreversible vision loss. Current therapies are limited by suboptimal efficacy and substantial side effects, highlighting the urgent need for the discovery of novel therapeutic targets. Nicotinamide phosphoribosyltransferase (NAMPT) is a key enzyme controlling the NAD⁺ salvage pathway and also exerts immunoregulatory and anti-inflammatory effects. However, its role in AU remains unclear.

Objective: To investigate NAMPT's effects on AU and underlying mechanisms.

Methods: Single-cell RNA sequencing (scRNA-seq) was performed on cervical draining lymph node (CDLN) cells from normal, experimental autoimmune uveitis (EAU), and NAMPT inhibitor-treated EAU mice. The influence of NAMPT inhibition on immune cell subsets, transcriptional programs, and intercellular communication networks was comprehensively analyzed. Additionally, scRNA-seq was performed on peripheral blood mononuclear cells (PBMCs) collected from Vogt-Koyanagi-Harada (VKH) disease patients and healthy controls (HC) to assess NAMPT expression and its modulation in human CD4⁺ T cells. In vivo and in vitro experiments, flow cytometry, and adoptive transfer experiments confirmed NAMPT's role in uveitis.

Results: NAMPT inhibition significantly ameliorated the clinical and histopathological manifestations of EAU. scRNA-seq revealed that NAMPT blockade reshaped immune cell composition and reversed disease-associated transcriptional programs, particularly within CD4⁺ T cells. It suppressed pro-inflammatory T helper (Th)-17 and Th1 responses while promoting regulatory T cell (Treg) populations. Mechanistically, NAMPT inhibition modulated the Th17/Treg balance by downregulation of Hif1α expression. In VKH patients, CD4⁺ T cells exhibited elevated NAMPT expression, which led to increased Th17 and Th1 cells and reduced Tregs. NAMPT knockdown reproduced the protective phenotype observed with FK866 treatment, suggesting a conserved NAMPT-Hif1α axis in human uveitis.

Conclusions: Inhibiting NAMPT can reverse the imbalance of effector T (Teff)/Treg cells by suppressing the expression of Hif1α in CD4⁺T cells, thereby effectively alleviating the symptoms of EAU. Therefore, NAMPT might be a potential target for AU.

Introduction: The widespread presence of antibiotic pollutants, such as tetracycline hydrochloride (TCH), causes significant environmental and public health concerns. Biochar-based photocatalysts derived from renewable biomass have attracted increasing attention due to their low cost, structural tunability, and environmental sustainability. However, their photocatalytic performance is often limited by poor charge separation and a lack of active sites.

Objectives: This study aims to construct a visible-light-responsive Cu/Fe co-doped biochar composite using Sphagnum palustre as a biomass precursor for the synergistic adsorption and photocatalytic removal of TCH from aqueous environments.

Methods: The Cu/Fe co-doped photocatalyst (CFO/S) was synthesized via a hydrothermal method by integrating Cu-Fe oxides with Sphagnum-derived biochar. The composite was comprehensively characterized, and its visible-light performance was evaluated. The photocatalytic mechanism was elucidated through radical trapping experiments and DFT+U simulations.

Results: The CFO/S-10 composite achieved a TCH removal efficiency of 94.56% within 60 min under visible-light irradiation. Adsorption was identified as the primary removal mechanism, while photocatalysis contributed to the degradation of adsorbed molecules. A layered FeO/CuFe₂O₄/S structure promoted charge separation and intermediate desorption. Multiple degradation products were detected, involving demethylation, hydroxylation, and ring-opening reactions.

Conclusion: The Cu/Fe co-doped biochar composite exhibited excellent removal performance through a synergistic adsorption-photocatalysis mechanism. Photogenerated electrons were the dominant reactive species, supported by •OH, •O₂^-, and h⁺. An S-scheme charge transfer mechanism was proposed to explain the enhanced redox capability. These findings demonstrate the potential of CFO/S as a promising candidate for visible-light-driven removal of antibiotic contaminants in water.