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[4] We developed an innovative system for organ preservation using dextran-coated ceria nanoparticles (CeO2NPs) incorporated into the University of Wisconsin (UW) solution, aiming to enhance liver preservation by reducing oxidative stress and inflammation and adjusting macrophage polarization. Analytical techniques such as Fourier transform infrared spectroscopy, transmission electron microscopy, X-ray diffraction, and X-ray photoelectron spectroscopy can confirm nanoparticle size, valence states, and catalytic activities, which are critical for their effectiveness in reducing ROS levels during organ preservation [Supplementary Figure 1, http://links.lww.com/CM9/C364]. In addition to reducing liver enzyme levels and oxidative stress, CeO2NPs alleviated inflammation and cell death. [...]CeO2NPs appear to reduce donor liver injury and sterile inflammation by inhibiting M1 polarization through the STAT1/NF-κB-p65 pathway and promoting M2 polarization via STAT6.

ObjectiveHepatocellular carcinoma (HCC) poses a significant clinical challenge because the long-term benefits of immune checkpoint blockade therapy are limited. A comprehensive understanding of the mechanisms underlying immunotherapy resistance in HCC is imperative for improving patient prognosis.DesignIn this study, to systematically investigate the characteristics of cancer-associated fibroblast (CAF) subsets and the dynamic communication among the tumor microenvironment (TME) components regulated by CAF subsets, we generated an HCC atlas by compiling single-cell RNA sequencing (scRNA-seq) datasets on 220 samples from six datasets. We combined spatial transcriptomics with scRNA-seq and multiplexed immunofluorescence to identify the specific CAF subsets in the TME that determine the efficacy of immunotherapy in HCC patients.ResultsOur findings highlight the pivotal role of POSTN+ CAFs as potent immune response barriers at specific tumor locations, as they hinder effective T-cell infiltration and decrease the efficacy of immunotherapy. Additionally, we elucidated the interplay between POSTN+ CAFs and SPP1+ macrophages, whereby the former recruits the latter and triggers increased SPP1 expression via the IL-6/STAT3 signaling pathway. Moreover, we demonstrated a spatial correlation between POSTN+ CAFs and SPP1+ macrophages, revealing an immunosuppressive microenvironment that limits the immunotherapy response. Notably, we found that patients with elevated expression levels of both POSTN+ CAFs and SPP1+ macrophages achieved less therapeutic benefit in an immunotherapy cohort.ConclusionOur research elucidates light on the role of a particular subset of CAFs in immunotherapy resistance, emphasizing the potential benefits of targeting specific CAF subpopulations to improve clinical responses to immunotherapy.

Vitamin B2 (VB2) metabolism regulates numerous cellular processes, but its role in hepatocellular carcinoma (HCC) progression remains unclear. Here we show that HCC tumors are characterized by upregulation of a VB2 metabolism signature, and VB2 metabolism promotes HCC progression. Among VB2 metabolic enzymes, flavin adenine dinucleotide synthase (FADS) is the only one that is widely overexpressed in human HCC. Elevated FADS expression correlates with resistance to anti-PD-1 therapy and poor prognosis. In vivo, FADS facilitates HCC cell growth and suppresses T cell-mediated antitumor immunity. Single-cell transcriptomic analysis reveals that FADS-induced changes occur both in the tumor cells and the intra-tumoral CD8 + T cells. Knocking down FADS induces HCC cell death and increases CD8⁺ T cell infiltration. Mechanistically, FADS confers ferroptosis resistance on HCC cells via enzymatic function to produce FAD and non-enzymatic function to stabilize PCBP2. Moreover, FADS impairs CD8 + T cell recruitment by disrupting the cGAS-STING pathway. Hesperidin, a clinically approved FADS inhibitor, shows antitumor efficacy in a mouse model. Our study thus highlights the importance of VB2 metabolism in HCC and provides the proof of principle for targeting FADS as a therapeutic strategy for HCC. Vitamin B2 metabolism is important for essential biological processes, such as protection against oxidative damage and facilitating the immune response. Here authors show that contrary to its protective role in other contexts, upregulated Vitamin B2 metabolism via flavin adenine dinucleotide synthase propels the growth of tumour cells in hepatocellular cancer, while suppressing the anti-tumour CD8 +  T cell response.

The global incidence of biliary tract cancer (BTC) is on the rise, presenting a substantial healthcare challenge. The integration of immune checkpoint inhibitors (ICIs) with molecularly targeted therapies is emerging as a strategy to enhance immune responses. However, the efficacy and underlying mechanisms of these treatments in BTC are still largely unexplored. In this study, tissue samples from 19 BTC patients treated with camrelizumab and apatinib were analysed using the NanoString 289‐panel to identify key molecular biomarkers. Comparative analyses and subsequent experimental validations, including cell‐based assays and histopathological examinations, identified adrenomedullin (ADM) as a critical molecular marker associated with treatment efficacy and poor prognosis. ADM has been shown to promote BTC cell proliferation, migration and angiogenesis, primarily by interacting with vascular endothelial growth factor (VEGF) and increasing AKT phosphorylation. Furthermore, ADM disrupts endothelial cell barrier function via the calcitonin receptor‐like receptor (CRLR) and vascular endothelial (VE)‐cadherin signalling pathway. Preclinical inhibition of ADM or CRLR resulted in suppressed tumour growth. Additionally, elevated ADM expression was correlated with increased tumour‐infiltrating immune cells and higher immune checkpoint expression. These findings suggest that ADM plays a pivotal role in resistance to immunotherapy and anti‐angiogenic treatment in BTC, and thus, targeting ADM may offer a promising therapeutic approach to enhance treatment efficacy.

Primary liver cancer (PLC) is a primary cause of cancer-related death worldwide, and novel treatments are needed due to the limited options available for treatment and tumor heterogeneity. 66 surgically removed PLC samples were cultured using the self-developed 2:2 method, and the final success rate for organoid culture was 40.9%. Organoid performance has been evaluated using comprehensive molecular measurements, such as whole-exome and RNA sequencing, as well as anticancer drug testing. Multiple organoids and their corresponding tumor tissues contained several of the same mutations, with all pairs sharing conventional TP53 mutations. Regarding copy number variations and gene expression, significant correlations were observed between the organoids and their corresponding parental tumor tissues. Comparisons at the molecular level provided us with an assessment of organoid-to-tumor concordance, which, in combination with drug sensitivity testing provided direct guidance for treatment selection. Finally, we were able to determine an appropriate pharmacological regimen for a patient with ICC, demonstrating the clinical practicality in tailoring patient-specific drug regimens. Our study provides an organoid culture technology that can cultivate models that retain most of the molecular characteristics of tumors and can be used for drug sensitivity testing, demonstrating the broad potential application of organoid technology in precision medicine for liver cancer treatment.

A modified QuEChERS (Quick, Easy, Cheap, Effective, Rugged and Safe) -LC-MS/MS method was developed for the determination of hexachlorophene in fruits and vegetables. Samples were extracted by acetonitrile and then salted with an acetate buffer system. Extractants neutral alumina (Al-N), strong cation exchange silica gel bonded adsorbent (SCX) and graphitized carbon black (GCB) were used for sample purification. The method demonstrates excellent accuracy and reproducibility. Under optimized conditions, the correlation coefficients of hexachlorophene were higher than 0.995 in the range of 0.5–20 ng/mL. The limit of quantification (LOQ) was 2.0 μg/kg. The average recoveries, assessed at three spiked levels (2.0, 4.0, and 20.0μg/kg) across various matrices including cabbage, celery, tomato, eggplant, potato, radish, cowpea, chives, apple, peach, grape, citrus, bitter melon, banana and hami melon ranged from 72.0 to 100.5% with relative standard deviations from 3.2 to 9.8% (n = 6).

The urgency of reducing pollution and developing clean energy storage requires efficient photocatalytic hydrogen evolution (PHE) tactics. To improve solar conversion efficiency, it is highly imperative to accelerate the photocarriers separation and transport through materials design. A stable hydrogen evolution photocatalyst based on TpPa-COFs (triformylphloroglucinol phenylenediamine covalent organic frameworks) was developed by a molecular-level design strategy. The study successfully introduced a molecular-scale Ir active site onto the surface of TpPa-COFs via coordination bonds. It verified the structural integrity of TpPa-COFs and the existence of Ir through the basic structural characterizations, such as Fourier transform infrared spectroscopy (FT-IR), X-ray photoelectron spectroscopy (XPS), and transmission electron microscopy (TEM). After the Ir-based coordination compound joining, the absorption edge of TpPa-COF-M1 and TpPa-COF-M2 was extended to 750 nm. The TpPa-COF + M1 exhibited the highest photocatalytic H2 evolution rate of 662 µmol/h (10 mg catalyst) under visible-light (λ ≥ 420 nm) irradiation. The apparent quantum yield (AQY) of TpPa-COF-M1 is calculated to be 1.9%, 3.8%, 4.8%, 2.8%, 1.8%, and 0.3% at monochromatic wavelengths of 420, 450, 470, 500, 550, and 600 nm, respectively. Our findings confirm that the molecular-level design of photocatalysts can effectively boost performance and reduce cost in photocatalytic reactions and provide an important strategy for designing efficient photocatalysts.

Background This study aimed to investigate the impacts of guar gum and cellulose as the source of dietary fiber during gestation on the reproductive performance of sows. Methods A total of 210 sows (parities 3–6) were randomly allocated into six diets ( n  = 35) throughout gestation to feed graded levels of dietary fiber (DF), including a corn-soybean meal-based control diet with no wheat bran inclusion (CON, 12.5% DF), a wheat bran-rich diet (DF1, 17.4% DF), and another 4 diets (DF2, 17.7% DF; DF3, 18.1% DF; DF4, 18.4% DF; DF5, 18.8% DF) in which wheat bran were equally substituted by 1%, 2%, 3% and 4% purified FIBER MIX (guar gum and cellulose, 1:4). All sows received similar DE and other nutrients throughout gestation. Results DF treatment during gestation resulted in normal fecal score (1 to 5 with 1 = dry and 5 = watery) in sows compared with those received the CON diet ( P  <  0.05). The number of total born piglets had a tendency to be affected by dietary treatment ( P  = 0.07), and correlation analysis revealed a linear response of total born to dietary fiber levels during gestation ( P <  0.01). Sows received the DF2, DF3, and DF5 diets during gestation had a greater ADFI during lactation compared with those in the CON group ( P <  0.05) without affecting the daily body weight gain of suckling piglets. Gut microbiota compositions were dramatically changed by the gestation stage and some of those were changed by DF inclusion. Fecal acetate, propionate, and butyrate of sows were markedly increased in late gestation, and butyrate contents in feces of gestating sows were significantly affected by DF levels ( P <  0.01). Serum concentrations of pro-inflammatory TNF-α were decreased and anti-inflammatory IL-10 was increased on day 30 of gestation by DF levels ( P <  0.05). Conclusions In summary, increasing dietary fiber levels by guar gum and cellulose during gestation improved the reproductive performance of sows, which might be related to changes in immunity and gut microbiota of sows.