Anthropogenic activities and climate change have accelerated biological invasions, leading to profound ecological, economic, social, and health impacts. The invasive species fall webworm (Hyphantria cunea) has been reported to have outbreaks in areas with climate anomalies and human settlements in recent years, highlighting the necessity to explore the species' suitable habitat and associated future changes. We built an ensemble species distribution model using Random Forest, MaxEnt, and Support Vector Machine, achieving excellent predictive performance (AUC = 0.996). Our results identify human settlement density as the dominant driving factor, with a contribution > 50%, far exceeding climatic and forest structure variables. Therefore, densely urbanized regions such as Beijing-Tianjin-Hebei, the Liaodong Peninsula, and the North China Plain comprise the current highly suitable areas. Future climate projections suggest a continued expansion of the suitable habitat for H. cunea, with the most pronounced growth expected under the high-emission pathway (SSP5-8.5), where human activity is greatest. Such a correlation indicates that highly urbanized regions should be given priority for corresponding monitoring and control measures. As climate warming continues, northeastern China will face escalating invasion risks. Conversely, some regions within the Yangtze River Delta may become less suitable for the habitation of H. cunea. These findings provide insightful guidance for region-specific surveillance, quarantine measures, and the precision management of H. cunea in China.

This study aims to fill the gaps in understanding the role of specific hydrolases (i.e., proteases and amylases) and substrates (e.g., starch, protein, and glucose) in enhancing carbamazepine (CBZ) degradation during anaerobic digestion (AD), where degradation efficiencies remain unsatisfactory, ranging from negligible to less than 10 %. This is the first study to confirm that anaerobic consortia can hydrolyze the amide bond in CBZ, facilitated by proteases through cometabolisation, and to evaluate the potential of polymeric substrates in promoting hydrolase activity for CBZ degradation. Furthermore, this study elucidates the transformation pathways of CBZ during AD, identifying amide bond hydrolysis as a key degradation mechanism. Batch experiments revealed that directly adding protease (activity of 360 U/g VS) achieved a CBZ removal efficiency of 68.3 %, which was significantly greater than that in the control reactors (18.3 %). Furthermore, the addition of polymeric substrates (starch and whey) and nonpolymeric substrates (glucose) resulted in CBZ removal efficiencies of 33.3 % and 51.4 %, respectively. Although polymeric substrates are less effective than nonpolymeric substrates for CBZ removal, they increase microbial diversity and are widely available in industrial waste, offering potential for sustainable larger-scale wastewater treatment applications. These findings provide new insights into the synergistic role of hydrolases and (non-) polymeric substrates, offering a promising approach for improving CBZ removal in AD systems.

Cheese whey wastewater (CWW) is an effluent stream with a high organic content produced by the dairy processing industry. Although anaerobic digestion (AD) is a promising process to treat CWW, it is prone to acidification caused by the accumulation of intermediate metabolites such as volatile fatty acids during AD because of CWW's high organic content. Our study explored how biochar (BC) and magnetite biochar (MBC) at concentrations of 2.5 and 5.0 g/L could play a role in relieving the acidification, and which mechanisms are at play. The results showed that at low anaerobic granular sludge (AGS) concentrations, biogas production in BC/MBC-assisted digestion could recover from acidification within 25∼44 days, while this issue pertained to the control reactor. As a result, BC and MBC-assisted systems led to a significantly higher biogas production of +119% ∼ +191%. The microbial community analysis showed that BC and MBC enriched the top 20 bacteria selected based on relative abundance and direct interspecies electron transfer (DIET)-related bacteria. Correlation plots of the material and AGS characterization showed that the main mechanism of action of BC and MBC at low AGS was pH regulation rather than DIET as reported in the literature. Alkaline earth metals such as Ca and Mg present in biochar-based materials increased alkalinity to provide buffering capacity and increase the pH. This study allows researchers to move away from the narrow perspective of overly focusing on DIET and expand to a more comprehensive look at the multiple mechanisms such as pH regulation, colonization, and DIET.

To achieve the UN Sustainable Development Goals (SDGs) and the China Toilet Revolution on a global scale, it is crucial to implement a decentralized sanitation management system in developing countries. Fecal slags (FS) generated from septic tanks of toilets pose a challenge for remote villages. This study sought to resourcefully utilize FS through co-digesting with food waste (FW) under high-solid anaerobic co-digestion (HSAD). Besides, two metallic nanomaterials, nano-zerovalent iron (nZVI) and magnetite (Fe3O4), were employed to demonstrate the practical improvement of HSAD. The results showed that nZVI-dosed digesters produced the highest cumulative methane of 295.72 mL/gVS, 371.36 mL/gVS, 360.53 mL/gVS and 296.64 mL/gVS in 10%, 15%, 20% and 25% TS content, respectively, which was 1.15, 1.22, 1.16, 1.12 times higher than Fe3O4 dosed digesters. This increment could be ascribed to the simultaneous production of H2 from Fe2+ release from nZVI and the enrichment of homoacetogen. Changes in carbon degradation and methanogenic pathways, which facilitated stability under high TS contents, were observed. At low solid digestion (10% TS), Syntrophomonas cooperated with Methanosarcina and Methanobacterium to metabolize butyrate and propionate. However, due to the buildup of total ammonia nitrogen and volatile fatty acids, acetoclastic methanogens were inhibited in the high-solid digesters (15%, 20% and 25% TS). Consequently, a more resilient and highly tolerant Syntrophaceticus, alongside hydrogenotrophic methanogens such as Methanoculleus and Methanobrevibacter, maintained stability in the harsh environment.

Uridine-disphosphate glucuronosyltransferase 1A9 (UGT1A9), an important detoxification and inactivation enzyme for toxicants, regulates the exposure level of environmental pollutants in the human body and induces various toxicological consequences. However, an effective tool for high-throughput monitoring of UGT1A9 function under exposure to environmental pollutants is still lacking. In this study, 1,3-dichloro-7-hydroxy-9,9-dimethylacridin-2(9H)-one (DDAO) was found to exhibit excellent specificity and high affinity towards human UGT1A9. Remarkable changes in absorption and fluorescence signals after reacting with UGT1A9 were observed, due to the intramolecular charge transfer (ICT) mechanism. Importantly, DDAO was successfully applied to monitor the biological functions of UGT1A9 in response to environmental pollutant exposure not only in microsome samples, but also in living cells by using a high-throughput screening method. Meanwhile, the identified pollutants that disturb UGT1A9 functions were found to significantly influence the exposure level and retention time of bisphenol S/bisphenol A in living cells. Furthermore, the molecular mechanism underlying the inhibition of UGT1A9 by these pollutant-derived disruptors was elucidated by molecular docking and molecular dynamics simulations. Collectively, a fluorescent probe to characterize the responses of UGT1A9 towards environmental pollutants was developed, which was beneficial for elucidating the health hazards of environmental pollutants from a new perspective.

The gut fungal community represents an essential element of human health, yet its functional and metabolic potential remains insufficiently elucidated, largely due to the limited availability of reference genomes. To address this gap, we presented the cultivated gut fungi (CGF) catalog, encompassing 760 fungal genomes derived from the feces of healthy individuals. This catalog comprises 206 species spanning 48 families, including 69 species previously unidentified. We explored the functional and metabolic attributes of the CGF species and utilized this catalog to construct a phylogenetic representation of the gut mycobiome by analyzing over 11,000 fecal metagenomes from Chinese and non-Chinese populations. Moreover, we identified significant common disease-related variations in gut mycobiome composition and corroborated the associations between fungal signatures and inflammatory bowel disease (IBD) through animal experimentation. These resources and findings substantially enrich our understanding of the biological diversity and disease relevance of the human gut mycobiome.

Cytochrome P450 2D6 (CYP2D6) is a key enzyme that mediates the metabolism of various drugs and endogenous substances in humans. However, its biological role in drug-drug interactions especially mechanism-based inactivation (MBI), and various diseases remains poorly understood, owing to the lack of molecular tools suitable for selectively monitoring CYP2D6 in complex biological systems. Herein, using a tailored molecular strategy, we developed a fluorescent probe BDPM for CYP2D6. BDPM exhibits excellent specificity and imaging capability for CYP2D6, making it suitable for the real-time monitoring of endogenous CYP2D6 activity in living bio-samples. Therefore, our tailored strategy proved useful for constructing the highly selective and enzyme-activated fluorescent probes. BDPM as a molecular tool to explore the critical roles of CYP2D6 in the pathogenesis of diseases, high-throughput screening of inhibitors and intensive investigation of CYP2D6-induced MBI in natural systems.

We present a visual analytics (VA) framework for the comprehensive exploration and integrated analysis of radiogenomic and clinical data from a cancer cohort. Our framework aims to support the workflow of cancer experts and biomedical data scientists as they investigate cancer mechanisms. Challenges in the analysis of radiogenomic data, such as the heterogeneity and complexity of the data sets, hinder the exploration and sensemaking of the available patient information. These challenges can be answered through the field of VA, but approaches that bridge radiogenomic and clinical data in an interactive and flexible visual framework are still lacking. Our approach enables the integrated exploration and joint analysis of radiogenomic data and clinical information for knowledge discovery and hypothesis assessment through a flexible VA dashboard. We follow a user-centered design strategy, where we integrate domain knowledge into a semi-automated analytical workflow based on unsupervised machine learning to identify patterns in the patient data provided by our collaborating domain experts. An interactive visual interface further supports the exploratory and analytical process in a free and a hypothesis-driven manner. We evaluate the unsupervised machine learning models through similarity measures and assess the usability of the framework through use cases conducted with cancer experts. Expert feedback indicates that our framework provides suitable and flexible means for gaining insights into large and heterogeneous cancer cohort data, while also being easily extensible to other data sets.

Symbiotic microorganisms are ubiquitous on the body surface or internal tissues of invertebrates, providing them with benefits. Developing symbiotic relationships requires synchronization of developmental stages and physical proximity of partners. Therefore, the identification of metabolites that coordinate the reproduction of symbiotic partners is essential. This study demonstrates that palmitoleic acid (C16: 1) coordinates bilateral propagation by regulating the synchronization of reproduction between the invasive pinewood nematode (PWN) and its newly associated blue-stain fungus, Sporothrix sp.1. When the PWN fed on Sporothrix sp.1, there was a significant increase in lipid metabolism gene expression and metabolite abundance. Through further investigations, it highlighted a significant enhancement in the reproduction of the PWN through direct acquisition of C16: 1, which was abundantly present in Sporothrix sp.1. Furthermore, the PWN biosynthesized C16: 1 through the involvement of the stearoyl-CoA 9-desaturase gene fat-5 and its hormone nuclear receptor nhr-80, which was clarified to promote the egg-laying capacity of females. Moreover, it is worth noting that the production of C16: 1 was significantly higher by the associated fungus Sporothrix sp.1 to enhance sporulation during the spore formation phase compared to the hypha growth phase. Thus, by coordinating the fecundity and spore production, the key lipid metabolite C16: 1 facilitates the rapid and successful colonization of a mutually beneficial symbiotic relationship between the invasive PWN and the native Sporothrix sp.1 within the host. This finding emphasizes the significant role of metabolite sharing and its function in promoting partner synchronization within symbiotic relationships.

We report a fluorescent dye TM by incorporating the tetraphenylethylene (TPE) and cholesterol components into perylene bisimides (PBI) derivative. Fluorescence emission spectrum shows that the dye has stable red emission and aggregation‐induced emission (AIE) characteristics. The incorporation of cholesterol components triggers TM to show induced chirality through supramolecular self‐assembly. The cRGD‐functionalized nanoparticles were prepared by encapsulating fluorescent dyes with amphiphilic polymer matrix. The functionalized fluorescent organic nanoparticles exhibit excellent biocompatibility, large Stokes’ shift and good photostability, which make them effective fluorescent probes for targeting cancer cells with high fluorescence contrast.

Fluorescence image for accurate tumor label still faces challenges in cancer detection and diagnostics.Emerging evidence is indicating that glucose-regulated protein 78（GRP78）, a stress-inducible protein chaperone, is a great potential biomarker and therapeutic target for cancer. However, currently available probe for image tumor based on GRP78 has not been reported, owning to no obvious strategy in probe design towards this protein. In this paper, a hairpin-shaped peptidyl probe（pep FAM） conjugated with a 5-FAM fluorophore and a dabcyl quencher at both ends was developed, respectively. The probe was designed by performing a traditional fluorescence resonance energy transfer mechanism and employing a GRP78 specifically-binding peptide. Furthermore, the probe was used to specifically image cancer cells,and accurately image xenograft tumors in mice models. The novel fluorescent probe is expected to be a useful tool for the diagnostics of cancer.

Soluble epoxide hydrolase (sEH) plays a critical role in inflammation by modulating levels of epoxyeicosatrienoic acids (EETs) and other epoxy fatty acids (EpFAs). Here, we investigate the possible role of sEH in lipopolysaccharide (LPS)-mediated macrophage activation and acute lung injury (ALI). In this study, we found that a small molecule, wedelolactone (WED), targeted sEH and led to macrophage inactivation. Through the molecular interaction with amino acids Phe362 and Gln384, WED suppressed sEH activity to enhance levels of EETs, thus attenuating inflammation and oxidative stress by regulating glycogen synthase kinase 3beta (GSK3β)-mediated nuclear factor-kappa B (NF-κB) and nuclear factor E2-related factor 2 (Nrf2) pathways in vitro. In an LPS-stimulated ALI animal model, pharmacological sEH inhibition by WED or sEH knockout (KO) alleviated pulmonary damage, such as the increase in the alveolar wall thickness and collapse. Additionally, WED or sEH genetic KO both suppressed macrophage activation and attenuated inflammation and oxidative stress in vivo. These findings provided the broader prospects for ALI treatment by targeting sEH to alleviate inflammation and oxidative stress and suggested WED as a natural lead candidate for the development of novel synthetic sEH inhibitors.

Cytochrome P450 1A is one of the vital subfamilies of heme-containing cytochrome P450 enzymes belonging to an important exogenous metabolizing CYP in human. The abnormal of endoplasmic reticulum (ER) may directly affect the functional activity of ER-located CYP1A and be associated with the occurrence and development of various diseases. In the present study, we constructed a selective two-photon fluorescent probe ERNM for rapid and visual detection of endogenous CYP1A that was localized in the ER. ERNM could target the ER and detect the enzymatically active CYP1A in living cells and tissues. The monitoring ability of ERNM for the fluctuations in functionality level of CYP1A was confirmed using ER stressed A549 cell. Based on the ER-targeting two-photon probe for CYP1A, the close association of ER state and the functional activity of ER-locating CYP1A was confirmed, which would promote the deep understanding of the biofunction of CYP1A in various ER-related diseases.

Fast and selective fluorescence imaging for a biomarker to related-disease diagnosis remains a significant challenge due to complex physical environment. Human carboxylesterase (CE) is expected to be a potential biomarker of hepatocellular carcinoma (HCC) to improve the accuracy of diagnosis. However, existing probes for CE has slow response rate and low selectivity. Herein, the amide group is selected as CE-responsive sites based on the "substrate-hydrolysis enzymatic reaction" approach. From a series of off-on probes with leave groups in the amide unit, probe J(Fast) is screened with the optimal combination of rapid response rate and high selectivity toward CE. J(Fast) requires only 150 s to reach the maximum fluorescence at 676 nm in the presence of CE and free from the interference of other esterase. Computational docking simulations indicate the shortest distance between the CE and active site of J(Fast). Cell and in vivo imaging present that the probe can turn on the liver cancer cells and tumor region precisely. Importantly, J(Fast) is allowed to specifically image orthotopic liver tumor rather than metastatic tumor and distinguish human primary liver cancer tissue from adjacent ones. This study provides a new tool for CE detection and promotes advancements in accurate HCC diagnosis.

The interaction between herbs and clinical drugs is one of the risk factors for adverse drug reactions. In the present study, the inhibitory effects of 47 tetracyclic triterpenoids toward the main drug-metabolizing CYPs in humans were investigated. Most of the evaluated tetracyclic triterpenoids (TT) exhibited strong inhibitory effects toward CYP3A4 compared with other CYP subtypes. The inhibition kinetics of compounds 9 (23-acetyl alisol C), 44 (hemslecin A), and 47 (cu-curbitacin E) against CYP3A4 were studied, and inhibition constant (Ki) was determined as 2.12, 0.196, and 0.162 mM, respectively. Some representative TT exhibited significant inhibitory effects toward the metabolism of gefitinib, atorvastatin, and quetiapine, indicating a potential interaction between TT derivatives and clinical drugs. Additionally, a quantitative structure-activity relation-ship (QSAR) study of a series of TT as inhibitors of CYP3A4 was performed. The present study provided key information to guide the rational use of herbs rich in TT.& COPY; 2023 The Authors. Published by Elsevier B.V. on behalf of King Saud University. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

Currently, the development of selective fluorescent probes toward targeted enzymes is still a great challenge, due to the existence of numerous isoenzymes that share similar catalytic capacity. Herein, a double-filtering strategy was established to effectively develop isoenzyme-specific fluorescent probe(s) for cytochrome P450 (CYP) which are key enzymes involving in metabolism of endogenous substances and drugs. In the first-stage of our filtering approach, near-infrared (NIR) fluorophores with alkoxyl group were prepared for the screening of CYP-activated fluorescent substrates using a CYPs-dependent incubation system. In the second stage of our filtering approach, these candidates were further screened using reverse protein-ligand docking to effectively determine CYP isoenzyme-specific probe(s). Using our double-filtering approach, probes S9 and S10 were successfully developed for the real-time and selective detection of CYP2C9 and CYP2J2, respectively, to facilitate high-throughput screening and assessment of CYP2C9-mediated clinical drug interaction risks and CYP2J2-associated disease diagnosis. These observations suggest that our strategy could be used to develop the isoform-specific probes for CYPs.

Dimethomorph (DMM), an effective and broad-spectrum fungicide applied in agriculture, is toxic to environments and living organisms due to the hazardous nature of its toxic residues. This study aims to investigate the human cyto-chrome P450 enzyme (CYP)-mediated oxidative metabolism of DMM by combining experimental and computational approaches. Dimethomorph was metabolized predominantly through a two-step oxidation process mediated by CYPs, and CYP3A was identified as the major contributor to DMM sequential oxidative metabolism. Meanwhile, DMM elic-ited the mechanism-based inactivation (MBI) of CYP3A in a suicide manner, and the iminium ion and epoxide reactive intermediates generated in DMM metabolism were identified as the culprits of MBI. Furthermore, three common pes-ticides, prochloraz (PCZ), difenoconazole (DFZ) and chlorothalonil (CTL), could significantly inhibit CYP3A-mediated DMM metabolism, and consequently trigger elevated exposure to DMM in vivo. Computational studies elucidated that the differentiation effects in charge distribution and the interaction pattern played crucial roles in DMM-induced MBI of CYP3A4 during sequential oxidative metabolism. Collectively, this study provided a global view of the two-step met-abolic activation process of DMM mediated by CYP3A, which was beneficial for elucidating the environmental fate and toxicological mechanism of DMM in humans from a new perspective.

Conductive material assisted anaerobic digestion presented much interest and promising prospect in pollutant removal during wastewater treatment. The present study deeply investigated the effect iron/carbon in anaerobic digestion for dichlorophen (DCP) degradation and methane production in synthetic DCP wastewater treatment. Results showed that nano-zero valent iron/activated carbon (nZVI/AC) and zero valent iron/activated carbon (ZVI/AC) gave higher chemical oxygen demand (COD) conversion (42.18% and 42.61%) and DCP removal (98.49 wt% and 99.00 wt%) in acidification step with better methane production from anaerobic digestion of the pretreated effluent. Same phenomenon occurred in the direct anaerobic degradation process due to the formation of galvanic cells between iron and carbon. In comparison, applying iron/carbon in acidification as pretreatment strategy plus following effluent anaerobic degradation showed higher efficiency in methane production and DCP removal than that of direct anaerobic degradation. Specifically, the methane production was 253.70 mL and 253.41 mL in subsequent anaerobic digestion system after nZVI/AC and ZVI/AC acidification pre-treatment, which was higher than 224.37 mL and 246.31 mL in direct anaerobic digestion system. Microbial community analysis showed that Clostridium_sensu_stricto_1 was the dominated bacteria due to its important role in DCP wastewater treatment. Both acetoclastic and hydrogenotrophic methanogens were enhanced in iron/carbon added systems, which was also agreement with the strengthen in related genes involved in methanogenesis. In conclusion, the present work systematically investigated the enhancement role of iron/carbon system in anaerobic digestion for DCP wastewater treatment and paved way for future application.

: Anaerobic digestion (AD) is one of the most widely used bioconversion technologies for renewable energy production from wet biowaste. However, such AD system is so complicated that it is challenging to fully comprehend this process and design the operational conditions for a specific biowaste to achieve CH 4 -rich biogas. In this context, ensemble machine learning (ML) algorithms were employed to develop multi-task models for jointly predicting the CH 4 yield and content in biogas and understanding this complicated process. Based on the best ensemble model with the R 2 of 0.82 and 0.86 for the multi-task prediction of CH 4 yield and content, the top-three critical factors for CH 4 yield/contents were identified and their interactions with process acid generation and microbial community in the AD process were comprehensively interpreted to unveil their importance on CH 4 generation. Moreover, the well-developed ensemble model was integrated with an optimization algorithm to inversely design the AD process for a real-world food waste, in which the CH 4 yield was as high as 468.7 mL/gVS and the calculation results were experimentally validated with relative errors of 9-16%. This work provides a creative approach to gain insights and inverse design for AD reactors, which is helpful to waste-to-energy technologists and practitioners.

Background: Acute lung injury (ALI) is a life-threatening lung disease and characterized by pulmonary edema and atelectasis. Inula japonica Thunb. is a commonly used traditional Chinese medicine for the treatment of lung diseases. However, the potential effect and mechanism of total terpenoids of I. japonica (TTIJ) on ALI remain obscure. Purpose: This study focused on the protective effect of TTIJ on lipopolysaccharide (LPS)-induced ALI in mice and its potential mechanism. Study design and methods: A mouse model of ALI was established by intratracheal instillation of LPS to investigate the protective effect of TTIJ. RNA-seq and bioinformatics were then performed to reveal the underlying mechanism. Finally, western blot and real-time qPCR were used to verify the effects of TTIJ on the inflammation and oxidative stress. Results: TTIJ notably attenuated LPS-induced histopathological changes of lung. The RNA-seq result suggested that the protective effect of TTIJ on LPS-induced ALI were associated with the Toll-like receptor 4 (TLR4) and nuclear factor-erythroid 2-related factor 2 (Nrf2) signaling pathways. Pretreatment with TTIJ significantly reduced the inflammation and oxidative stress via regulating levels of pro-inflammatory and anti-oxidative cytokines, such as tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), superoxide dismutase (SOD), and glutathione (GSH), in LPS-induced ALI mice. TTIJ treatment could suppress the cyclooxygenase-2 (COX-2) expression level and the phosphorylation of p65, p38, ERK, and JNK through the inactivation of the MAPK/NF-kappa B signaling pathway in a TLR4-independent manner. Meanwhile, TTIJ treatment upregulated expression levels of proteins involved in the Nrf2 signaling pathway, such as heme oxygenase-1 (HO-1), NAD(P)H: quinoneoxidoreductase-1 (NQO-1), glutamate-cysteine ligase catalytic subunit (GCLC), and glutamate-cysteine ligase modifier subunit (GCLM), via activating the Nrf2 receptor, which was confirmed by the luciferase assay. Conclusion: TTIJ could activate the Nrf2 receptor to alleviate the inflammatory response and oxidative stress in LPS-induced ALI mice, which suggested that TTIJ could serve as the potential agent in the treatment of ALI.