Combining bulk and scRNA-seq to explore the molecular mechanisms governing the distinct efferocytosis activities of a macrophage subpopulation in PDAC.

Pancreatic ductal adenocarcinoma (PDAC), a very aggressive tumour, is currently the third leading cause of cancer-related deaths. Unfortunately, many patients face the issue of inoperability at the diagnostic phase leading to a quite dismal prognosis. The onset of metastatic processes has a crucial role in the elevated mortality rates linked to PDAC. Individuals with metastatic advances receive only palliative therapy and have a grim prognosis. It is essential to carefully analyse the intricacies of the metastatic process to enhance the prognosis for individuals with PDAC. Malignancy development is greatly impacted by the process of macrophage efferocytosis. Our current knowledge about the complete range of macrophage efferocytosis activities in PDAC and their intricate interactions with tumour cells is still restricted. This work aims to resolve communication gaps and pinpoint the essential transcription factor that is vital in the immunological response of macrophage populations. We analysed eight PDAC tissue samples sourced from the gene expression omnibus. We utilized several software packages such as Seurat, DoubletFinder, Harmony, Pi, GSVA, CellChat and Monocle from R software together with pySCENIC from Python, to analyse the single-cell RNA sequencing (scRNA-seq) data collected from the PDAC samples. This study involved the analysis of a comprehensive sample of 22,124 cells, which were classified into distinct cell types. These cell types encompassed endothelial and epithelial cells, PDAC cells, as well as various immune cells, including CD4+ T cells, CD8+ T cells, NK cells, B cells, plasma cells, mast cells, monocytes, DC cells and different subtypes of macrophages, namely C0 macrophage TGM2+, C1 macrophage PFN1+, C2 macrophage GAS6+ and C3 macrophage APOC3+. The differentiation between tumour cells and epithelial cells was achieved by the implementation of CopyKat analysis, resulting in the detection and categorization of 1941 PDAC cells. The amplification/deletion patterns observed in PDAC cells on many chromosomes differ significantly from those observed in epithelial cells. The study of Pseudotime Trajectories demonstrated that the C0 macrophage subtype expressing TGM2+ had the lowest level of differentiation. Additionally, the examination of gene set scores related to efferocytosis suggested that this subtype displayed higher activity during the efferocytosis process compared to other subtypes. The most active transcription factors for each macrophage subtype were identified as BACH1, NFE2, TEAD4 and ARID3A. In conclusion, the examination of human PDAC tissue samples using immunofluorescence analysis demonstrated the co-localization of CD68 and CD11b within regions exhibiting the presence of keratin (KRT) and alpha-smooth muscle actin (α-SMA). This observation implies a spatial association between macrophages, fibroblasts, and epithelial cells. There is variation in the expression of efferocytosis-associated genes between C0 macrophage TGM2+ and other macrophage cell types. This observation implies that the diversity of macrophage cells might potentially influence the metastatic advancement of PDAC. Moreover, the central transcription factor of different macrophage subtypes offers a promising opportunity for targeted immunotherapy in the treatment of PDAC.

Biparametric MRI of the prostate radiomics model for prediction of pelvic lymph node metastasis in prostate cancers : a two-centre study.

OBJECTIVES: Exploring the value of adding correlation analysis (radiomic features (RFs) of pelvic metastatic lymph nodes and primary lesions) to screen RFs of primary lesions in the feature selection process of establishing prediction model. METHODS: A total of 394 prostate cancer (PCa) patients (263 in the training group, 74 in the internal validation group and 57 in the external validation group) from two tertiary hospitals were included in the study. The cases with pelvic lymph node metastasis (PLNM) positive in the training group were diagnosed by biopsy or MRI with a short-axis diameter ≥ 1.5 cm, PLNM-negative cases in the training group and all cases in validation group were underwent both radical prostatectomy (RP) and extended pelvic lymph node dissection (ePLND). The RFs of PLNM-negative lesion and PLNM-positive tissues including primary lesions and their metastatic lymph nodes (MLNs) in the training group were extracted from T2WI and apparent diffusion coefficient (ADC) map to build the following two models by fivefold cross-validation: the lesion model, established according to the primary lesion RFs selected by t tests and absolute shrinkage and selection operator (LASSO); the lesion-correlation model, established according to the primary lesion RFs selected by Pearson correlation analysis (RFs of primary lesions and their MLNs, correlation coefficient > 0.9), t test and LASSO. Finally, we compared the performance of these two models in predicting PLNM. RESULTS: The AUC and the DeLong test of AUC in the lesion model and lesion-correlation model were as follows: training groups (0.8053, 0.8466, p = 0.0002), internal validation group (0.7321, 0.8268, p = 0.0429), and external validation group (0.6445, 0.7874, p = 0.0431), respectively. CONCLUSION: The lesion-correlation model established by features of primary tumors correlated with MLNs has more advantages than the lesion model in predicting PLNM.

Leptin receptor Gln223Arg and Lys109Arg polymorphisms may be associated with HBV-related hepatocellular carcinoma risk: A system review and meta-analysis.

Increasing evidence has suggested a strong association of hepatocellular carcinoma (HCC) susceptibility and Gln223Arg (rs1137101) and Lys109Arg (rs1137100) polymorphisms in leptin receptor (LEPR) genes. To provide a quantitative assessment for such correlation, we reviewed all related systems and conducted meta-analysis for case and control researches. A literature search of Web of Science, EMBASE, PubMed, Scopus as well as China National Knowledge Infrastructure databases was collected. 95% confidence intervals (95% CIs) together with odds ratios (ORs) were calculated. Five case-control researches consisting of 1323 cases and 1919 control cases were incorporated into meta-analysis. Researches indicated A-allelic and AA genotype of rs1137101 were substantially related to boosted susceptibility of hepatitis B virus (HBV)-related HCC (mutant model, OR = 1.81, 95% CI = 1.36-2.41, p < .001; allelic model, OR = 1.55, 95% CI = 1.32-1.83, p < .001). On the contrary, we observed GG genotype of rs1137101 substantially related to reduced risk of HBV-related HCC (wild model, OR 0.59, 95%CI = 0.46-0.75, p < .001). We observed AA genotype of rs1137100 relevant to boosted HCC risk (mutant model, OR = 1.51, 95%CI = 1.14-2.01, p = .005) as well as in those with HBV-related HCCs (homozygous model, OR = 2.12, 95%CI = 1.49-3.02, p < .001; mutant model, OR = 1.67, 95%CI = 1.23-2.26, p = .001). G-allele and AA genotype of rs1137101 might be in connection with boosted HBV-related HCC susceptibility, and wild-type GG genotype might prevent diseases. AA genotype of rs1137100 might also improve HBV-related HCC susceptibility. Such conclusions ought to be validated by larger and better-designed researches.

Effect of Stepwise Exposure to High-Level Erythromycin on Anaerobic Digestion.

High-level erythromycin (ERY) fermentation wastewater will pose serious threats to lake environments. Anaerobic digestion (AD) has advantages in treating high-level antibiotic wastewater. However, the fate of antibiotic resistance genes (ARGs) and microbial communities in AD after stepwise exposure to high-level ERY remains unclear. In this study, an AD reactor was first exposed to 0, 5, 10, 50, 100 and 200 mg/L ERY and then re-exposed to 0, 50, 200 and 500 mg/L ERY to investigate the effect of ERY on AD. The results show that AD could adapt to the presence of high-level ERY (500 mg/L) and could maintain efficient CH4 production after domestication with low-level ERY (50 mg/L). The AD process could achieve higher removal of ERY (>94%), regardless of the initial ERY concentration. ErmB and mefA, conferring resistance through target alteration and efflux pumps, respectively, were dominant in the AD process. The first exposure to ERY stimulated an increase in the total ARG abundance, while the AD process seemed to discourage ARG maintenance following re-exposure to ERY. ERY inhibited the process of acetoclastic methanogenesis, but strengthened the process of hydrogenotrophic methanogenesis. This work provides useful information for treating high-level ERY fermentation wastewater by the AD process.

Pyrolysis of antibiotic mycelial residue for biochar: Kinetic deconvolution, biochar properties, and heavy metal immobilization.

The safe disposal of antibiotic mycelial residue (AMR), a hazardous waste, is a pressing problem owing to the spread of antibiotic and heavy metal pollution. In this study, AMR pyrolysis at different temperatures and heating rates was investigated to prepare valuable biochar for heavy metal immobilization. The results showed that AMR decomposition mainly involved three pseudo-reactions, with average activation energies of 252.4, 149.8, and 219.7 kJ/mol, that fitted a three-dimensional diffusion model. Increasing the pyrolysis temperature and heating rate decreased the yield and volatile matter content of biochar, but the ash content, fixed carbon content, and aromaticity increased. The AMR-derived biochar had a favorable fuel property (18.1-19.8 MJ/kg) and stability against degradation in soil. Calcium oxalate hydrate, a major mineral in AMR, degraded during biochar formation. Furthermore, high pyrolysis temperature promoted the residual fractions of Cr, Cu, Zn, Cd, and Pb in biochar, more so than did the heating rate, inducing a low potential ecological risk. In particular, the leaching rate of Zn decreased from 46.9% in AMR to 0.3% in biochar obtained at 700 °C with a heating rate of 10 °C/min. This study elucidates the formation process and physicochemical properties of AMR biochar, which helps in the harmless utilization of AMR as a carbon resource.

Mechanistic insights into Fe3O4-modified biochar relieving inhibition from erythromycin on anaerobic digestion.

Anaerobic digestion (AD) of antibiotic manufacturing wastewater to degrade residual antibiotics and produce mixture of combustible gases has been investigated actively in the past decades. However, detrimental effect of residual antibiotic to microbial activities is commonly faced in AD process, leading to the reduction of treatment efficiency and energy recovery. Herein, the present study systematically evaluated the detoxification effect and mechanism of Fe3O4-modified biochar in AD of erythromycin manufacturing wastewater. Results showed that Fe3O4-modified biochar had stimulatory effect on AD at 0.5 g/L erythromycin existence. A maximum methane yield of 327.7 ± 8.0 mL/g COD was achieved at 3.0 g/L Fe3O4-modified biochar, leading to the increase of 55.7% compared to control group. Mechanistic investigation demonstrated that different levels of Fe3O4-modified biochar could improve methane yield via different metabolic pathways involved in specific bacteria and archaea. Low levels of Fe3O4-modified biochar (i.e., 0.5-1.0 g/L) led to the enrichment of Methanothermobacter sp., strengthening the hydrogenotrophic pathway. On the contrary, high levels of Fe3O4-modified biochar (2.0-3.0 g/L) favored the proliferation of acetogens (e.g., Lentimicrobium sp.) and methanogen (Methanosarcina sp.) and their syntrophic relations played vital role on the simulated AD performance at erythromycin stress. Additionally, the addition of Fe3O4-modified biochar significantly decreased the abundance of representative antibiotic resistant genes (ARGs), benefiting the reduction of environmental risk. The results of this study verified that the application of Fe3O4-modified biochar could be an efficient approach to detoxify erythromycin on AD system, which brings high impacts and positive implications for biological antibiotic wastewater treatment.

Highly Soluble and Stable, High Release Rate Nanocellulose Codrug Delivery System of Curcumin and AuNPs for Dual Chemo-Photothermal Therapy.

As a natural antitumor drug, curcumin (CUR) has received increasing attention from researchers and patients due to its various medicinal properties. However, currently CUR is still restricted due to its low and stand-alone therapeutic effects that seriously limit its clinical application. Here, by using cellulose nanocrystals (CNCs) as a nanocarrier to load CUR and AuNPs simultaneously, we developed a hybrid nanoparticle as a codrug delivery system to enhance the low and stand-alone therapeutic effects of CUR. Aided with the encapsulation of ß-cyclodextrin (ßCD), both the solubility and the stability of CUR are greatly enhanced (solubility increased from 0.89 to 131.7 µg/mL). Owing to the unique rod-like morphology of CNCs, the system exhibits an outstanding loading capacity of 31.4 µg/mg. Under the heat effects of coloaded AuNPs, the system demonstrates a high release rate of 77.63%. Finally, with CNC as a bridge nanocarrier, all aforementioned functions were integrated into one hybrid nanoparticle. The all-in-one integration ensures CUR to have enhanced therapeutic effects and enables the delivery system to exhibit combined chemo-photothermal therapy outcomes. This work presents a significant step toward CUR's clinical application and provides a new strategy for effective and integrative treatment of tumor disease.

Inoculating indoleacetic acid bacteria promotes the enrichment of halotolerant bacteria during secondary fermentation of composting.

The secondary fermentation stage is critical for stabilizing composting products and producing various secondary metabolites. However, the low metabolic rate of mesophilic bacteria is regarded as the rate-limiting stage in composting process. In present study, two indoleacetic acid (IAA)-producing bacteria (Bacillus safensis 33C and Corynebacterium stationis subsp. safensis 29B) were inoculated to strengthen the secondary fermentation stage to improve the plant-growth promoting potential of composting products. The results showed that the addition of IAA-producing bacteria promoted the assimilation of soluble salt, the condensation and aromatization of humus, and the accumulation of dissolved organic nitrogen (DON) and dissolved organic carbon (DOC). The bioaugmentation strategy also enabled faster microbial community succession during the medium-late phase of secondary fermentation. However, the colonization of Bacillus and Corynebacterium could not explain the disproportionate increase of IAA yield, which reached up to 5.6 times compared to the control group. Deeper analysis combined with physicochemical properties and microbial community structure suggested that IAA-producing bacteria might induce the increase of salinity, which enriched halotolerant bacteria capable of producing IAA, such as Halomonas, Brachybacterium and Flavobacterium. In addition, the results also proved that it was necessary to shorten secondary fermentation time to avoid IAA degradation without affecting composting maturity. In summary, enhancing secondary fermentation of composting via adding proper IAA-producing bacteria is an efficient strategy for upgrading the quality of organic fertilizer.

Manganese and dysprosium codoped carbon quantum dots as a potential fluorescent/T1/T2/CT quadri-modal imaging nanoprobe.

It has been challenging to integrate various medical imaging modalities into an ultra-small nanoparticle with good biocompatibility to build highly efficient multimodal imaging nanoprobes. A new manganese and dysprosium codoped carbon quantum dots (Mn,Dy-CQDs) with a mean diameter of 1.77 nm was synthesized for fluorescence imaging,T1/T2-weighted magnetic resonance imaging (T1/T2-weighted MRI), and x-ray computed tomography (CT) imaging using a simple one-step hydrothermal approach. The obtained Mn,Dy-CQDs showed good water solubility, long-term stability, strong stable fluorescence property (fluorescence quantum yield of 31.62%), and excellent biocompatibility. The cell imaging verified that the Mn,Dy-CQDs have high efficiency of fluorescence imaging. The Mn,Dy-CQDs, on the other hand, had a superior x-ray absorption performance (47.344 HU l g-1), a higher longitudinal relaxivity (r1 = 7.47 mM-1s-1), a higher transverse relaxivity (r2 = 42.686 mM-1s-1).In vitroT1/T2-weighted MRI and CT imaging showed that Mn,Dy-CQDs can produce a strong contrast enhancement impact. To summarise, the Mn,Dy-CQDs may be used as aT1/T2-weighted MRI/CT/fluorescent quadri-modal imaging nanoprobe, indicating that they have a lot of uses in biomedical multimode imaging and clinics.

Synthesis of an easily recyclable and safe adsorbent from sludge pyrochar for ciprofloxacin adsorption.

Utilization of sludge pyrochar (SP) is the terminal step to loop the entire harmless disposal process of sewage sludge with pyrolysis. A new, easily recyclable, and safe adsorbent with well-immobilized heavy metals (HMs) was prepared from SP for ciprofloxacin (CIP) adsorption. The operational conditions for the adsorbent preparation were systematically optimized based on recycling rate and adsorption performance. Additionally, the adsorption conditions, adsorption kinetics, isotherms, and regeneration of adsorbents were further investigated in the present study. The results showed that easily recyclable and safe adsorbents were successfully prepared at 1100 °C under N2 atmospheric conditions (SPA-N-1100) with a maximum CIP adsorption capacity of 10.42 mg/g. SPA-N-1100 exhibited good CIP adsorption performance at an adsorption temperature of 45 °C and pH between 8.0 and 9.0. The adsorbents were regenerated by thermal desorption at 450 °C with a thorough decomposition of CIP. The adsorption mechanism was mainly dominated by its special porous microspheres-accumulation structure and surface species (e.g., FeP and graphite). Moreover, HMs in the adsorbents were well immobilized in SPA-N-1100 by the generation of new metal mineral phases and encapsulation of melting minerals, which had an ultralow potential for ecological risk during application.

Chemical speciation and distribution of potentially toxic elements in soilless cultivation of cucumber with sewage sludge biochar addition.

Potentially toxic elements in municipal sewage sludge can be effectively immobilized during biochar production via pyrolysis. However, the bioavailability of these elements when biochar is applied in soilless cultivation to improve substrate quality has yet to be sufficiently established. In this study, we investigated the chemical speciation and cucumber plant uptake of potentially toxic elements in soilless cultivation when the growth substrate was amended with sewage sludge biochar (0, 5, 10, 15, and 20 wt%). It was found that the addition of 10 wt% biochar was optimal with respect to obtaining a high cucumber biomass and achieving low environmental risk considering the occurrence of hormesis. When the substrate was amended with 10 wt% biochar, cucumber fruit contained lower concentrations of As, Cr, and Zn and smaller bioavailable fractions of As, Cd, Cr, Ni, Cu, and Zn compared with the fruit of control plants, thereby meeting national safety requirements (standard GB 2762-2012, China). Most of the As and Cd taken up by cucumbers accumulated in the leaves and fruit, whereas Cr was found primarily in the roots, and most Ni, Cu, and Zn was detected in the fruit. Importantly, only small proportions of the potentially toxic elements in biochar were taken up by cucumber plants (As: 0.0075%; Cd: 0.038%; Ni: 0.0064%; Cu: 0.0016%; and Zn: 0.0015%). Given that the As, Cd, Ni, and Zn speciation in sewage sludge biochar was effectively immobilized after cultivation, the findings of this study indicate that sewage sludge biochar is a suitable substrate amendment in terms of the risk posed by potentially toxic elements.

Effect of pyrolysis temperature on characteristics, chemical speciation and risk evaluation of heavy metals in biochar derived from textile dyeing sludge.

Textile dyeing sludge (TDS) was pyrolyzed at temperature ranging from 300 to 700 °C to investigate characteristics and to evaluate the risk of heavy metals (Zn, Cu, Cr, Ni, Cd, and Mn) in biochar derived from the TDS. The analyzation of characteristics and potential environmental risk evaluation of heavy metals were conducted by the BET-N2, FTIR, and BCR sequential extraction procedure. The results showed that the pyrolysis treatment of the TDS contributed to the improvement of the pH value and specific surface areas with increasing pyrolysis temperature. Conversion of the TDS to biochar significantly decreased the H/C and O/C ratios, resulting in a far stronger carbonization and a higher aromatic condensation for the TDS derived biochar. The total contents of Zn, Cu, Cr, Ni and Mn in biochar increased with pyrolysis temperature owing to the thermal decomposition of organic matter in the TDS; but for Cd, the portion distributed in the biochars decreased significantly when the temperature increased up to 600 °C. However, using BCR sequential extraction procedure and analysis, it was found that pyrolysis process promoted changes in the chemical speciation and biochar matrix characteristics, leading to reduce bio-available fractions of heavy metals in the biochars. The potential environmental risk of heavy metals decreased from considerable risk in the TDS to low risk or no risk in biochar after pyrolysis above 400 °C. This work demonstrated that the pyrolysis process was a promising method for disposing of the TDS with acceptable environment risk.

Study of ciprofloxacin removal by biochar obtained from used tea leaves.

In this study, used tea leaves (UTLs) were pyrolyzed to obtain used tea-leaf biochar (UTC), and then the UTC was used as an adsorbent to remove ciprofloxacin (CIP) from aqueous solutions. Batch experiments were conducted to investigate the CIP adsorption performance and mechanism. The results showed that the CIP-adsorbing ability first increased and then declined as the UTC pyrolysis temperature increased. The UTC obtained at 450°C presented excellent CIP-absorbing ability at pH6 and 40°C. The maximum monolayer adsorption capacity was 238.10mg/g based on the Langmuir isotherm model. The pseudo-second-order kinetic equation agreed well with the CIP adsorption process, which was controlled by both external boundary layer diffusion and intra-particle diffusion. The characterization analysis revealed that the OH groups, CC bonds of aromatic rings, CH groups in aromatic rings and phenolic CO bonds play vital roles in the CIP adsorption process, and that the NC, NO, OCO and COH groups of UTC were consumed in large quantities. π-π interactions, hydrogen bonding and electrostatic attraction are inferred as the main adsorption mechanisms. The present work provides not only a feasible and promising approach for UTLs utilization but also a potential adsorbent material for removing high concentrations of CIP from aqueous solutions.

Biodegradation of sulfamethazine by an isolated thermophile-Geobacillus sp. S-07.

Sulfamethazine (SM2) is an antimicrobial drug that is frequently detected in manure compost, is difficult to degrade at high temperatures and is potentially threatening to the environment. In this study, a thermophilic bacterium was isolated from the activated sludge of an antibiotics pharmaceutical factory; this bacterium has the ability to degrade SM2 at 70 °C, which is higher than the traditional manure composting temperature. The strain S-07 is closely related to Geobacillus thermoleovorans based on its 16S rRNA gene sequence. The optimal conditions for the degradation of SM2 are 70 °C, pH 6.0, 50 rpm rotation speed and 50 mL of culture volume. More than 95% of the SM2 contained in media was removed via co-metabolism within 24 h, which was a much higher percentage than that of the type strain of G. thermoleovorans. The supernatant from the S-07 culture grown in SM2-containing media showed slightly attenuated antibacterial activity. In addition, strain S-07 was able to degrade other sulfonamides, including sulfadiazine, sulfamethoxazole and sulfamerazine. These results imply that strain S-07 might be a new auxiliary bacterial resource for the biodegradation of sulfonamide residue in manure composting.

[Advance in studies on anti-inflammatory and immunoregulatory monomers of Tripterygium wilfordii].

Tripterygium wilfordii has complex chemical components. To study and summarize the advance in studies on the anti-inflammatory and immunoregulatory activities and toxicology of known monomers of T. wilfordii, the pertinent literatures related to the studies on the pharmacology, toxicology and pharmacokinetics of T. wilfordii over past 30 years were searched. According to the findings, more than ten anti-inflammatory and immunoregulatory monomers were found in T. wilfordii. The pharmacology and toxicology of wilforidine, triptolidenol, triptonide, demethylzeylasteral shall be further studied.

Novel strategy for efficient energy recovery and pollutant control from sewage sludge and food waste treatment.

Considering the high organic matter contents and pollutants in sewage sludge (SS) and food waste (FW), seeking green and effective technology for energy recovery and pollutant control is a big challenge. In this study, we proposed a integrated technology combing SS mass separation by hydrothermal pretreatment, methane production from co-digestion of hydrothermally treated sewage sludge (HSS) centrate and FW, and biochar production from co-pyrolysis of HSS cake and digestate with heavy metal immobilization for synergistic utilization of SS and FW. The results showed that the co-digestion of HSS centrate with FW reduced the NH4+-N concentration and promoted volatile fatty acids conversion, leading to a more robust anaerobic system for better methane generation. Among the co-pyrolysis of HSS cake and digestate, digestate addition improved biochar quality with heavy metals immobilization and toxicity reduction. Following the lab-scale investigation, the pilot-scale verification was successfully performed (except the co-digestion process). The mass and energy balance revealed that the produced methane could supply the whole energy consumption of the integrated system with 26.2 t biochar generation for treating 300 t SS and 120 t FW. This study presents a new strategy and technology validation for synergistic treatment of SS and FW with resource recovery and pollutants control.

MC1R regulates T regulatory cell differentiation through metabolic reprogramming to promote colon cancer.

BACKGROUND: Until 2021, colon cancer was a leading cancer globally. Early detection improves outcomes; however, advanced cases still having poor prognosis. Therefore, an understanding of associated molecular mechanisms is crucial for developing new preventive and therapeutic strategies for colon cancer. METHODS: The TCGA database was analyzed to assess melanocortin 1receptor (MC1R) expression in colon cancer and its link with patient prognosis. Further, models and diverse experimental techniques were employed to investigate the impact of MC1R on colon cancer progression and its underlying mechanism was elucidated. RESULTS: In a follow-up study of clinical patients, the important role of MC1R was identified in the development of colon cancer. First, MC1R was expressed more highly in colon tumor tissues than in adjacent tissues. In addition, MC1R was associated with colon cancer prognosis, and higher expression of MC1R tended to predict a worse prognosis. This conclusion was verified in MC1R-/- mice, which showed a greater resistance to tumor growth than wild-type mice, as expected. Further investigation revealed a significant change in the portion of Tregs in MC1R-/- mice, while the portion of CD4 + and CD8 + T cells remained unchanged. The in vitro experiments revealed a weaker ability of the MC1R-/- T cells to differentiate into Tregs. Previous studies report that the functional integrity of Tregs is interwoven with cellular metabolism. Therefore, MC1R was deduced to regulate the differentiation of Tregs by reprogramming the metabolism. As expected, MC1R-/- T cells exhibited weaker mitochondrial function and a lower aerobic oxidation capacity. Concurrently, the MC1R-/- T cells had stronger limiting effects on colon cancer cells. According to these results, the MC1R inhibitor was hypothesized as a potential therapeutic agent to suppress colon cancer. The results showed that upon MC1R suppression, the tumors in the mice developed more slowly, and the mice survived longer, potentially providing a novel strategy to treat clinical colon cancer. CONCLUSION: By regulating Tregs differentiation, MC1R overexpression in colon cancer correlates with poor prognosis, while MC1R inhibition shows potential as a therapeutic approach to slow tumor growth and enhance survival.

Relationship of black soldier fly larvae (BSFL) gut microbiota and bioconversion efficiency with properties of substrates.

Treating food waste using black soldier fly larvae (BSFL) is widely regarded as a promising nature-based measure. This study explored the influence of food waste particle sizes on substrate properties and its subsequent effects on bioconversion efficiency and gut microbiota. The results indicated that particle sizes mainly ranging from 4 mm to 10 mm (T1) significantly increased the weight loss rate of food waste by 35 % and larval biomass by 38 % compared to those in T4 (particle sizes mostly less than 2 mm) and promoted the bioconversion of carbon and nitrogen into larvae and gases. Investigation of substrates properties indicated that the final pH value of T1 was 7.79 ± 0.10, with Anaerococcus as the predominant substrate microorganism (relative abundance: 57.4 %), while T4 exhibited a final pH value of 5.71 ± 0.24, with Lactobacillus as the dominant microorganism (relative abundance: 95.2 %). Correlation analysis between substrate chemical properties and microbial community structure unveiled a strong relationship between substrate pH and the relative abundance of Anaerococcus and Lactobacillus. Furthermore, beneficial microorganisms such as Lactobacillus and Enterococcus colonized the BSFL gut of T1, while pathogenic bacterium Morganella, detrimental to BSFL gut function, was enriched in T4 (relative abundance: 60.9 %). Nevertheless, PCA analysis indicated that alterations in the gut microbial community structure may not be attributed to the substrate microorganisms. This study establishes particle size as a crucial parameter for BSFL bioconversion and advances understanding of the relationship between gut microbiota and substrate microbiota.

Mechanistic exploration of COVlD-19 antiviral drug ritonavir on anaerobic digestion through experimental validation coupled with metagenomics analysis.

Aggregation of antiviral drugs (ATVs) in waste activated sludge (WAS) poses considerable environmental risk, so it is crucial to understand the behavior of these agents during WAS treatment. This study investigated the effects of ritonavir (RIT), an ATV used to treat human immunodeficiency virus infection and coronavirus disease 2019, on anaerobic digestion (AD) of WAS to reveal the mechanisms by which it interferes with anaerobic flora. The dosage influence results showed that methane production in AD of WAS decreased by 46.56 % when RIT concentration was increased to 1000 µg/kg total suspended solids (TSS). The AD staging test revealed that RIT mainly stimulated microbial synthesis of the extracellular polymeric substance (EPS), limiting organic matter solubilization. At 500 µg/kg TSS, RIT decreased CHO and CHON levels in dissolved organic matter by 23.12 % and 56.68 %, respectively, significantly reducing substrate availability to microorganisms. Metagenomic analysis of microbial functional gene sets revealed that RIT had greater inhibitory effects on protein and amino acid metabolism than on carbohydrate metabolism. Under RIT stress, methanogens switched from hydrogenotrophic and acetotrophic methanogenesis to methylotrophic and acetotrophic methanogenesis.

Revealing the effects of fermented food waste on the growth and intestinal microorganisms of black soldier fly (Hermetia illucens) larvae.

The escalating global food waste (FW) issues necessitate sustainable management strategies. Black soldier fly larvae (BSFL) offer a promising solution for FW management by converting organic matter into insect protein. However, the fermentation of FW during production, collection, and transportation induces changes in FW's physicochemical properties and bacterial communities, requiring further exploration of its impact on BSFL growth and gut microbiota. The results showed that feeding FW fermented for different durations (0-10 d) slightly affected the BSFL yield. Feeding FW fermented for 8 d, characterized by a lower pH and higher biodiversity, resulted in a slight increase in larval biomass (222 mg/larvae). Nearly all groups harvested the peak larval biomass after 10 day's bioconversion. The fermentation significantly altered the microbial community of FW, with an increase in the abundance of unclassified_f_Clostridiaceae and a decrease in Lactobacillus abundance. As bioconversion progressed, intricate and mutualistic microbial interactions likely occurred between the BSFL gut and FW substrate, restructuring each other's microbial community. Specifically, the abundance of unclassified_f_Clostridiaceae increased in the BSFL gut, while its abundance in the initial larval gut was extremely low (<1 %). Despite the substrate microbial changes and interactions, a stable core gut microbiota was identified across all BSFL samples, primarily composed of nine genera dominated by Enterococcus and Klebsiella. This core gut microbiome may play a crucial role in facilitating the adaptation of BSFL to various environmental conditions and maintaining efficient FW bioconversion. These findings enhance our understanding of the role of BSFL gut microbiota in FW bioconversion.