This study aimed to evaluate the efficacy and safety of fecal microbiota transplantation (FMT) as an adjunctive therapy for depressive episodes. This study recruited 46 participants aged 18–65 from January 2022 to December 2023 who were diagnosed with depression according to the International Classification of Diseases, 10th edition. They were randomly divided into two groups to receive different treatments, including FMT combined with medication group (test group, n = 23) and the medication-only group (control group, n = 23). Assessments were performed before and two weeks after treatment. Ten predominant gut microbiota species were analyzed, and the Hamilton’s Depression Scale-24(HAMD-24) was used to evaluate depressive symptoms. Adverse events related to treatment were assessed using an adverse event scale and laboratory tests. The main evaluation indicators included the reduction rate of HAMD-24 scores, treatment efficacy rate, and changes in the indicators of the ten predominant intestinal bacteria before and after transplantation. Safety assessment indicators included adverse events, blood routine, biochemistry, electrocardiogram, immunological parameters (immunoglobulins and complement), hypersensitive C-reactive protein(hs-CRP), thyroid function, and glycated hemoglobin. The rank-sum test was performed to compare differences in microbiota before and after FMT treatment. The relationship between gut microbiota and depression severity was examined by means of correlation analysis. The baseline HAMD-24 scores showed no significant difference between the test and control groups (P > 0.05). After two weeks treatment, the reduction in HAMD-24 scores (P = 0.048) and the HAMD-24 reduction rate (P = 0.016) were significantly higher in the test group than control group (P < 0.05). Following FMT treatment, Enterococcus, Lactobacillus, Bifidobacterium, and Butyricicoccus levels significantly increased compared to baseline (P < 0.05). Linear discriminant analysis(LDA) revealed a significant post-treatment increase in Enterococcus relative abundance (P = 0.02). In the test group, baseline-enriched Clostridium prausnitzii (P = 0.040), Butyricicoccus (P = 0.029), and Eubacterium rectale (P = 0.004) showed significant negative correlations with HAMD-24 scores, whereas post-treatment Enterococcus was correlated with HAMD-24 scores (P = 0.030). Adverse event incidence was 28.6% in the test group and 30% in the control group, with no significant difference (P = 0.928). Reported discomforts during FMT treatment—nausea, vomiting, and nasopharyngeal discomfort—were mild and self-resolving, with no serious adverse events observed. The administration of FMT as an adjunctive therapy demonstrates superior improvement in depressive symptoms and is deemed safe with no apparent adverse reactions. There was no change in the composition of gut microbiota structure before and after FMT in patients with depression. Enterococcus showed a significant relative abundance increase in the gut after FMT. The post-treatment Enterococcus was correlated with HAMD-24 scores.

Methylmercury (MeHg) is a potent neurotoxin and can lead to neurodegeneration in animals and humans. Fecal microbiota transplantation has been found to regulate the neurotoxicity of MeHg in rats. This study investigated the therapeutic potential of orally-given commercially-available probiotics (primarily Bifidobacterium and Lactobacillus acidophilus) against MeHg-poisoning in rats. It was found that probiotics intervention promoted the demethylation of MeHg in the liver and intestines, accompanied by upregulation of demethylating bacteria such as Desulfovibrionaceae and Geobacteraceae. It also reshaped the gut microbiota, significantly increasing beneficial short-chain fatty acids(SCFA)-producing bacteria like Ruminococcaceae and Lachnospiraceae. SCFA, amino acids and bile acids were found increased in feces. The expression of pro-inflammatory cytokines TNF-α and IL-6, and up-regulated IL-10 in the gut, serum and brain was found reduced, showing the decreased inflammation. Besides, the capability of spatial learning, memory, and motor coordination of MeHg-poisoned rats was improved as showed through Morris water maze test. Histologically, H&E staining revealed neatly arranged neurons with reduced nuclear condensation, while Nissl staining showed increased Nissl bodies and restored neuronal activity. In all, this study provides a simple and potentially translational strategy for MeHg-poisoning and sheds lights for the treatment of neurodegenerative diseases.

Disturbances in the gut microbiota (GM) contribute to the pathogenesis of various prevalent metabolic disorders. Short-chain fatty acids act as signaling molecules and donors for host post-translational modifications. Here, we report a novel type of lysine modification, phenylacetylation (Kpaa), derived from the phenylalanine-dependent phenylacetic acid (PAA) metabolic pathway of the GM. Hepatic Kpaa levels were significantly elevated in mice with high-fat-diet-induced obesity and were reduced by the deacetylase sirtuin 3 (SIRT3). Proteome-wide substrates were significantly associated with mitochondria. PAA disrupted mitochondrial function and impaired insulin signaling. Mechanistically, PAA-induced K481paa of HSP60 triggered the mitochondrial unfolded protein response, which could be reversed by SIRT3. Finally, relatively low levels of hepatic SIRT3 in adults with obesity and metabolic dysfunction-associated steatohepatitis (MASH) were negatively correlated with increased Kpaa levels. Together, our study uncovered a microbiota-derived lysine acylation modification underlying its biological relevance in the development of metabolic dysfunction-associated steatotic liver disease (MASLD)/MASH.

Accurate authentication of rice geographical origin is crucial for food safety and fraud prevention. Synchrotron radiation X-ray fluorescence (SR-XRF) spectroscopy was combined with deep learning to classify hulled rice (n = 903) and rice husks (n = 824) from 16 provinces in China. Distinct elemental fingerprints were observed, and PCA/t-SNE visualization confirmed clustering by origin. However, PCA-based discrimination was limited in resolving provinces with overlapping profiles, necessitating advanced nonlinear approaches. Three deep learning models-1D-CNN, 2D-VGG16, and 2D-AlexNet-were trained on SR-XRF spectra. 2D-AlexNet achieved the best results, with accuracies of 98.02% for hulled rice and 99.07% for husks, showing strong robustness across provinces. Husk-based classification outperformed hulled rice, highlighting rice husks as a reliable sample matrix. The SR-XRF-deep learning framework provides a rapid, non-destructive, scalable tool for rice traceability, surpassing conventional chemometric or isotope-based methods.

Einstein Telescope (ET) is the European project for a gravitational-wave (GW) observatory of third-generation. In this paper we present a comprehensive discussion of its science objectives, providing state-of-the-art predictions for the capabilities of ET in both geometries currently under consideration, a single-site triangular configuration or two L-shaped detectors. We discuss the impact that ET will have on domains as broad and diverse as fundamental physics, cosmology, early Universe, astrophysics of compact objects, physics of matter in extreme conditions, and dynamics of stellar collapse. We discuss how the study of extreme astrophysical events will be enhanced by multi-messenger observations. We highlight the ET synergies with ground-based and space-borne GW observatories, including multi-band investigations of the same sources, improved parameter estimation, and complementary information on astrophysical or cosmological mechanisms obtained combining observations from different frequency bands. We present advancements in waveform modeling dedicated to third-generation observatories, along with open tools developed within the ET Collaboration for assessing the scientific potentials of different detector configurations. We finally discuss the data analysis challenges posed by third-generation observatories, which will enable access to large populations of sources and provide unprecedented precision.

With the acceleration of global industrialization, water treatment has emerged as a critical environmental challenge demanding urgent resolution. Metal-organic frameworks (MOFs), characterized by their ultrahigh specific surface areas, tunable porous architectures, and multifunctional active sites, are regarded as highly promising materials for water-treatment applications. However, the practical implementation of MOFs and their derivatives remains constrained. Although recent advances in synthetic strategy optimization have significantly enhanced their water-treatment performance, precise elucidation of material intrinsic characteristics continues to pose challenges. Conventional characterization techniques struggle to reveal critical information regarding dynamic structural evolution in aqueous environments, local defect distribution, and electronic states of active sites, thereby hindering atomic/molecular-scale theoretical guidance for performance optimization. Synchrotron radiation techniques, leveraging their advantages of high flux, exceptional resolution, and element-specific detection capabilities, provide unique solutions to overcome these limitations. These advanced methodologies enable accurate correlation between MOF synthetic strategies and water treatment performance metrics, offering crucial experimental insights for rational material design. This review systematically compares the impact of synthesis and modification strategies on the water treatment performance of MOFs and their derivatives. By employing synchrotron radiation characterization techniques to elucidate the "structure-property" relationships relevant to water treatment, this work provides a theoretical foundation and technical support for the targeted synthesis, performance optimization, and industrial translation of high-performance MOF-based materials.

Mercury sulfide nanoparticles (HgSNPs) are widespread yet poorly understood Hg species in contaminated areas. Here, we present a 2.5-year simulated experiment tracking the persistence, transformation, and bioavailability of HgSNPs relative to larger HgS forms in soil-rice systems. We demonstrate that HgSNPs persist in soils with minimal physicochemical change but exhibit high methylation potential and rice uptake. Soil amended with HgSNPs yielded 13- to 26-fold higher methylmercury (MeHg) concentrations than bulk HgS treatments, resulting in 14- to 92-fold and 5.6- to 68-fold increases in MeHg and inorganic Hg in brown rice, respectively. Mechanistically, this sustained bioavailability arises from the synergistic effects of HgSNPs translocation within rice tissues, reactive Hg release, and enhanced methylation. Our findings identify HgSNPs as a persistent and highly bioavailable Hg pool in paddies, fundamentally driving long-term Hg transformation and accumulation in rice. This work redefines Hg biogeochemical cycling in agricultural ecosystems and underscores the critical need to incorporate HgSNPs into food safety assessments.

This study investigates the accumulation characteristics and cost-benefit evaluation of the monoculture modes of Pteris vittata (MP) and Hylotelephium spectabile (MH), as well as their intercropping with peach (LP and LH) in arsenic (As)- or cadmium (Cd)-contaminated orchards. The intercropping modes exhibited remediation efficiencies comparable to those of their respective monocultures. Soil As/Cd concentrations were projected to fall below risk intervention values in the 21st, 22nd, 34th, and 30th years for MP, LP, MH, and LH, respectively. The gross ecosystem product (GEP) of the intercropping modes significantly exceeded that of the corresponding monoculture, with peach profits contributing 85.8

Neurodegenerative diseases bring heavy burden to our society. Methylmercury (MeHg) is a potent neurotoxin and causes neurodegenerative diseases like Minamata Disease. Therefore, finding ways to combat MeHg-induced neurodegeneration may shed light on the treatment of neurodegenerative diseases. This study investigated the efficacy of bismuth selenide nanoparticles (Bi2Se3NPs, nBS) in treating MeHg-induced neurodegeneration. MeHg-poisoned rats were orally given nBS (4 mg/kg) every other day for 21 days and then sacrificed. It was found that nBS improved neurobehavioral performance, alleviated hippocampus damage and intestinal barrier damage, reduced Hg accumulation, and promoted MeHg demethylation in MeHg-poisoned rats. In addition, nBS up-regulated the abundance of gut microbes such as Faecalibacterium, Bifidobacterium and Akkermansiaceae, and increased the levels of butyric acid in feces while reduced the concentration of isobutyric acid in the brains. At the same time, nBS reduced the secretion of inflammatory factors IL-6 and TNF-α in the brains, guts and serum, and regulated AHR/IDO expression in the guts and brains. In all, nBS treatment improved the health status of MeHg-poisoned rats through enhancing Hg excretion and MeHg demethylation, reshaping gut microbiota, and reducing neuroinflammation. These findings suggested that nBS supplementation is a promising approach to treat MeHg-induced neurodegeneration, which may shed lights on the treatment of neurodegenerative diseases.

Approximately 367 million metric tons of plastic were produced globally in 2020, and it is projected that the global plastic waste will reach around 12,000 metric tons by 2050. Plastic waste can be fragmented into nanoplastics (NPs). Despite their widespread presence in the environment and even within the human body, the long-term risks of NPs to plants, animals, and humans remain poorly understood. This study investigated the life-long impacts of nano polyethylene terephthalate (nPET) on rice (Oryza sativa L.), which is a staple food for a significant portion of the global population. We found that nPET exposure at environmentally relevant concentrations negatively affected rice growth, compromising grain quality and yield. nPET exposure disrupted the metallome, interfered with chlorophyll synthesis, and induced oxidative stress in rice plants. Additionally, nPET exposure influenced soil health, as evidenced by increased soil organic matter (SOM) during the tillering and flowering stages. The soil microbial community were significantly perturbed, with distinct β-diversity observed between nPET-exposed and control soils, including variations in species abundance at the phylum and family levels. Moreover, nPET exposure affected soil microbiota involved in carbon, nitrogen, and sulfur cycles, with specific species capable of degrading PET being identified. Overall, exposure to environmentally relevant concentrations of nPET led to reduced rice grain yield and compromised soil health, characterized by perturbed metallome and soil microbiome. Therefore, effective management of NPs in soils is urgently needed to ensure food safety and soil health.

IntroductionMicroplastics (MPs), as emerging environmental contaminants, pose a significant threat to global food security. In order to rapidly screen and diagnosis rice seedling under MPs stress at an early stage, it is essential to develop efficient and non-destructive detection methods.MethodsIn this study, rice seedlings exposed to different concentrations (0, 10, and 100 mg/L) of polyethylene terephthalate (PET), polystyrene (PS), and polyvinyl chloride (PVC) MPs stress were constructed. Two complementary spectroscopic techniques, visible/near-infrared hyperspectral imaging (VNIR-HSI) and synchrotron radiation-based Fourier Transform Infrared spectroscopy (SR-FTIR), were employed to capture the biochemical changes of leaf organic molecules.ResultsThe spectral information of rice seedlings under MPs stress was obtained by using VNIR-HSI, and the low-dimensional clustering distribution analysis of the original spectra was conducted. An improved SE-LSTM full-spectral detection model was proposed, and the detection accuracy rate was greater than 93.88%. Characteristic wavelengths were extracted to build a simplified detection model, and the SHapley Additive exPlanations (SHAP) framework was applied to interpret the model by identifying the bands associated with chlorophyll, carotenoids, water content, and cellulose. Meanwhile, SR-FTIR spectroscopy was used to investigate compositional changes in both leaf lamina and veins, and two-dimensional correlation spectroscopy (2DCOS) was employed to reveal the sequential interactions among molecular components.DiscussionIn conclusion, the combination of spectral technology and deep learning to capture the physiological and biochemical reactions of leaves could provide a rapid and interpretable method for detecting rice seedlings under MPs stress. This method could provide a solution for the early detection of external stress on other crops.

Sepsis-induced acute lung injury (ALI) represents a severe pathological state marked by uncontrolled inflammation, redox imbalance, and alveolar-capillary barrier breakdown. Here, we evaluated the therapeutic potential of pituitary adenylate cyclase-activating polypeptide (PACAP) in a murine sepsis-ALI model. PACAP treatment notably ameliorated histological damage, reduced oxidative stress biomarkers, and mitigated inflammatory processes, including neutrophil accumulation and pro-inflammatory cytokine release. Molecular analysis revealed PACAP-mediated downregulation of Aquaporin-1 (AQP1) and specificity protein 1 (Sp1), key regulators of alveolar fluid homeostasis and inflammatory signaling. Genetic Sp1 overexpression abrogated PACAP-induced AQP1 suppression, validating the Sp1/AQP1 signaling pathway as a critical mediator of PACAP's protective effects. Additionally, in vitro MTT assays on RAW 264.7 macrophages demonstrated that PACAP has low toxicity at biologically relevant levels. These findings demonstrate PACAP's therapeutic promise for sepsis-ALI through modulation of the Sp1/AQP1 axis.

Nanoplastics are increasingly detected in human tissues, yet their biological interactions and health effects remain poorly understood. Here, we show that polyvinyl chloride (PVC) nanoplastics change lipid metabolism of macrophages such as the induced formation of foam cells through a lipoprotein-mediated mechanism. Using transmission electron microscope, scattering light-confocal imaging, and soft X-ray nano-computed tomography, we visualize intracellular PVC nanoplastics and extensive lipid droplet accumulation in macrophages. Proteomic profiling reveals that PVC nanoplastics acquire apolipoproteins enriched protein corona, particularly ApoA1, imparting them with a lipoprotein-like identity. In response, macrophages selectively upregulate scavenger receptor class B type 1 (SR-B1), a key high density lipoprotein (HDL) receptor involved in cholesterol uptake and lipid homeostasis. These findings uncover a receptor-specific pathway by which apolipoprotein-coated nanoplastics mimic endogenous lipoproteins, disrupt lipid metabolism, and drive foam cell-like transformation. This work highlights uncovered links of the exposure of nanoplastics to cardiovascular risk through metabolic reprogramming.

The objective of this state-of-the-art review is to summarize contemporary data on the potential toxic effects of aluminum nanoparticles (AlNPs) and discuss the underlying molecular mechanisms. In vivo studies using laboratory rodents demonstrate that lungs, liver, brain, and the immune system are the primary targets for AlNPs toxicity. Specifically, inhalation exposure to AlNPs induces lung damage by promoting inflammatory infiltration, airway remodeling, septal thickening, and bronchial hyperresponsiveness. AlNPs-induced liver damage is characterized by hepatocyte degeneration and necrosis, liver sinusoid congestion, inflammation, and fibrosis. AlNPs induces neurotoxicity resulting in neurodegeneration, neuroinflammation, altered neurotransmitter metabolism, and subsequent adverse neurobehavioral outcome. In turn, immunotoxicity of AlNPs is characterized by promotion of systemic inflammation along with impaired phagocytosis. In addition to the toxicity exerted by Al2O3NPs itself, the observed toxic effects of AlNPs may be attributed to Al3+ release from the particles with the subsequent induction of oxidative stress, inflammation, mitochondrial dysfunction, genotoxicity, cell cycle dysregulation, and cell death due to apoptosis, necrosis, and ferroptosis. It is also evident that both the size and the form of AlNPs significantly affect its cytotoxicity. However, further studies are required to explore the mechanisms of toxic effects of AlNPs, as well as its potential adverse effects on human health.

Luanhe River is one of the important parts in Northern China hydrographic nets, which has been seriously impacted by industrialization. However, the heavy metal pollution caused by the production activities across the basin remains poorly understood, which may pose health risks to local residents. The study aims to address this gap by focusing on heavy metal pollution in sediments from 41 sampling sites along the Luanhe River basin evaluating the potential ecological risks. The results showed that, due to varying local industries, geography, and human activities, different sections exhibited distinct contamination patterns. The upper reach showed predominant pollution by Mn (up to 4305.59 mg kg-1) and As (59.92 mg kg-1), the middle reach by Mn (4305.59 mg kg-1), Cu (692.88 mg kg-1), As, and Hg (3.48 mg kg-1), and the lower reach by Mn and Hg. Thereinto, the particular concern was the moderate to serious ecological risk posed by Hg across most of the river basin, as indicated by the potential ecological risk indices. For most of the identified heavy metals along the Luanhe River basin, the ecological risk assessed by the geo-accumulation index and potential ecological risk index indicated a moderate to serious pollution level. Overall, this work systematically depicted the heavy metal pollution map across the Luanhe River basin, revealed and discussed the relationship between industrialization and heavy metal pollution in this district. This study highlights that practical policy and technical measures should be taken to cope with the heavy metal pollution and associated ecological risks in this area.

ABSTRACT The emergence of novel variants of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) continues to pose an ongoing challenge for global public health services, highlighting the urgent need for effective therapeutic interventions. Neutralizing monoclonal antibodies (mAbs) are a major therapeutic strategy for the treatment of COVID-19 and other viral diseases. In this study, we employed hybridoma technology to generate mAbs that target the BA.5 receptor-binding domain (RBD) of the SARS-CoV-2 spike protein. Through a comprehensive screening process, we identified four mAbs capable of effectively neutralizing BA.5, XBB.1.16, and related variant infections in vitro , among which ORB10 was found to neutralize BA.5 variants with a plaque reduction neutralization test (PRNT 50 ) of 8.7 ng/mL. Additionally, competitive binding assays, sequencing of heavy and light chain variable regions, and binding kinetics characterization provided insights into the epitopes and binding affinities of the identified mAbs. Moreover, in vivo experiments in the K18-hACE2 mouse model demonstrated the protective efficacy of ORB10 against both BA.5 and XBB.1.16 variants. Finally, cryo-electron microscopy structural analysis of the ORB10–RBD complex identified key residues involved in the antibody–antigen interactions, providing insights into the molecular mechanisms of neutralization and immune escape of SARS-CoV-2 Omicron variants from mAbs. IMPORTANCE The ongoing evolution of SARS-CoV-2 has led to the emergence of variants capable of evading immune responses elicited by natural infection and vaccination, especially the highly transmissible and immune-evasive Omicron variants. This study generated and characterized a panel of monoclonal antibodies (mAbs) specifically targeting the RBD of the Omicron BA.5 variant, of which the ORB10 showed efficacy against Omicron BA.5 and XBB.1.16 variants both in vitro and in vivo . Cryo-EM structural analysis further elucidated the binding epitope interactions and neutralization mechanism between ORB10 and the BA.5 RBD protein. This study enhances our understanding of antibody-mediated neutralization of SARS-CoV-2 and provides valuable insights into the development of effective therapeutic strategies to combat ongoing SARS-CoV-2 variant infections.

The National Institute for Environmental Studies (NIES) developed the NIES CRM No. 13-a, a new certified reference material for human hair, using scalp hair from Asian females. This CRM represents a significant advancement in support of global mercury exposure assessments and offers unparalleled reliability and scope compared with existing materials. We aimed to provide a comprehensive overview of the preparation, certification, and application of NIES CRM No. 13-a. In total, 806 bottles (3 g each) were produced, with thorough homogenization ensured through sieving and blending. Certified values for total mercury (1.06 ± 0.07 mg/kg), methylmercury (0.858 ± 0.075 mg/kg), and key trace elements (arsenic, cadmium, lead, selenium, and zinc) were determined through extensive collaborative analyses involving 20 laboratories. Additional reference values were provided for calcium, magnesium, sodium, sulfur, antimony, barium, copper, iron, and manganese. Rigorous stability and homogeneity assessments demonstrated the stability of the CRM for over 10 years and consistency across sample units, even for challenging elements such as selenium. The CRM also includes information values of stable mercury isotope ratios, reflecting their growing importance as exposure tracers. This enhancement in accuracy and traceability facilitates accurate mercury and trace element assessments in human hair, enabling improved biomonitoring of mercury exposure, dietary studies, toxicological evaluations, human health risk evaluations, and regulatory compliance.

The intestinal barrier is crucial for homeostasis. This study aimed to investigate the protective effects of earthworm protein hydrolysates (EWPH) on the intestinal mucosal barrier and elucidate the underlying mechanisms. We first hydrolyzed earthworm protein using alcalase and identified the primary peptide components of EWPH through Nano LC-MS/MS analysis. Network pharmacology and bioinformatics approaches were employed to predict potential targets associated with the intestinal mucosal barrier. Experimentally, we demonstrated that EWPH effectively protects against dextran sulfate sodium (DSS)-induced intestinal barrier damage in mice. The protective mechanisms involve not only the inhibition of the Toll-like receptor 4 (TLR4)-nuclear factor-kappa (NF-kappa)/mitogen-activated protein kinases (MAPK) signaling pathway in the intestinal epithelium but also the suppression of other key molecules implicated in intestinal mucosal barrier damage, including phosphorylated-SRC proto-oncogene (p-SRC), phosphorylated-signal transducer and activator of transcription 3 (p-STAT3), Caspase-3, and matrix metalloproteinase-9 (MMP9), thereby mitigating intestinal inflammation and mucosal barrier injury. This study provides evidence that EWPH have the potential to safeguard the intestinal barrier hemostasis.

The widespread use of plastic products in daily life has raised concerns about the health hazards associated with nanoplastics (NPs). When exposed, NPs are likely to infiltrate the bloodstream, interact with plasma proteins, and trigger macrophage recognition and clearance. In this study, we focused on establishing a correlation between the unique protein coronal signatures of high-density (HDPE) and low-density (LDPE) polyethylene (PE) NPs with their ultimate impact on macrophage recognition and cytotoxicity. We observed that low-density and high-density lipoprotein receptors (LDLR and SR-B1), facilitated by apolipoproteins, played an essential role in PE-NP recognition. Consequently, PE-NPs activated the caspase-3/GSDME pathway and ultimately led to pyroptosis. Advanced imaging techniques, including label-free scattered light confocal imaging and cryo-soft X-ray transmission microscopy with 3D-tomographic reconstruction (nano-CT), provided powerful insights into visualizing NPs-cell interactions. These findings underscore the potential risks of NPs to macrophages and introduce analytical methods for studying the behavior of NPs in biological systems.