Developing colorimetric ammonia-sensing nanocomposite films based on potato starch/PVA and ZnCu-BTC nanorods for real-time monitoring food freshness.

Smart packaging material capable of real-time monitoring of food freshness is essential for ensuring food safe. At present, colorimetric ammonia-sensing smart film often possesses issues with complicated production, high cost, and inferior long-term colour stability. Herein, Zinc­copper bimetallic organic framework (ZnCu-BTC, BTC = 1,3,5-benzenetricarboxylate acid) nanorods with colorimetric ammonia-responsiveness were synthesized by adopting facile aqueous solution method, which were then explored as nano inclusions in potato starch/polyvinyl alcohol (PS/PVA) composite film towards developing high-performance smart packaging material. The results demonstrated that the introduction of ZnCu-BTC nanorods within PS/PVA brought about remarkable improvement in blend compatibility, accompanied by a boost in tensile strength to 47.2 MPa, as well as enhanced ultraviolet (UV) blocking efficacy (over 95.0 %). Additionally, the barrier properties of PS/PVA film against water vapor and oxygen were fortified due to the addition of ZnCu-BTC. More importantly, the developed PS/PVA/ZnCu-BTC nanocomposite film displayed satisfactory antibacterial activity (over 99 %) against Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus), favorable colorimetric ammonia-sensing ability, and long-term colour stability. The ZnCu-BTC incorporated PS/PVA nanocomposite film could grant real-time detection of prawn freshness decline via remarkable colour change, indicating vast promise for smart food packaging applications.

An experimental study to estimate the early postmortem interval based on the degradation of lncRNAs in rat brain tissue.

To study the degradation of lncRNAs in EPMI in rat brain tissue, this study provides a new direction for the estimation of EPMI. LncRNA high-throughput sequencing was performed on the brain tissues of hemorrhagic shock model rats at 0 h and 24 h, and the target lncRNAs were screened. Samples at 0, 1, 3, 6, 12, 18 and 24 h after death were collected, and miRNA-9 and miRNA-125b were used as reference genes. The relative expression levels of lncRNAs at each PMI were detected by RT-qPCR, and a functional model involving lncRNAs and EPMI was established. Samples were collected at 6, 9, 15, and 21 h after death for functional model verification. The expression of several lncRNAs decreased with the prolongation of EPMI, and the mathematical model established by several lncRNA indices exhibited good fit. The verification results of the multi-index joint function model are significantly better than those of the single-index function model, and the established model is more practical. There is a linear relationship between lncRNAs and EPMI, and the multi-index function model is significantly better than the single-index function model, which is important for EPMI inference in forensic pathology practice.

Structures of LIG1 uncover the mechanism of sugar discrimination against 5'-RNA-DNA junctions during ribonucleotide excision repair.

Ribonucleotides in DNA cause several types of genome instability and can be removed by ribonucleotide excision repair (RER) that is finalized by DNA ligase 1 (LIG1). However, the mechanism by which LIG1 discriminates the RER intermediate containing a 5'-RNA-DNA lesion generated by RNase H2-mediated cleavage of ribonucleotides remains unknown. Here, we determine X-ray structures of LIG1/5'-rG:C at the initial step of ligation where AMP is bound to the active site of the ligase, and uncover a large conformational change downstream the nick resulting in a shift at Arg(R)871 residue in the Adenylation domain of the ligase. Furthermore, we demonstrate a diminished ligation of the nick DNA substrate with a 5'-ribonucleotide in comparison to an efficient end joining of the nick substrate with a 3'-ribonucleotide by LIG1. Finally, our results demonstrate that mutations at the active site residues of the ligase and LIG1 disease-associated variants significantly impact the ligation efficiency of RNA-DNA heteroduplexes harboring "wrong" sugar at 3'- or 5'-end of nick. Collectively, our findings provide a novel atomic insight into proficient sugar discrimination by LIG1 during processing of the most abundant form of DNA damage in cells, genomic ribonucleotides, during initial step of the RER pathway.

Inhibition of XPR1-dependent phosphate efflux induces mitochondrial dysfunction: A potential molecular target therapy for hepatocellular carcinoma?

Xenotropic and polytropic retrovirus receptor 1 (XPR1) is the only known transporter associated with Pi efflux in mammals, and its impact on tumor progression is gradually being revealed. However, the role of XPR1 in hepatocellular carcinoma (HCC) is unknown. A bioinformatics screen for the phosphate exporter XPR1 was performed in HCC patients. The expression of XPR1 in clinical specimens was analyzed using quantitative real-time PCR, Western blot analysis, and immunohistochemical assays. Knockdown of the phosphate exporter XPR1 was performed by shRNA transfection to investigate the cellular phenotype and phosphate-related cytotoxicity of the Huh7 and HLF cell lines. In vivo tests were conducted to investigate the tumorigenicity of HCC cells xenografted into immunocompromised mice after silencing XPR1. Compared with that in paracancerous tissue, XPR1 expression in HCC tissues was markedly upregulated. High XPR1 expression significantly correlated with poor patient survival. Silencing of XPR1 leads to decreased proliferation, migration, invasion, and colony formation in HCC cells. Mechanistically, knockdown of XPR1 causes an increase in intracellular phosphate levels; mitochondrial dysfunction characterized by reduced mitochondrial membrane potential and adenosine triphosphate levels; increased reactive oxygen species levels; abnormal mitochondrial morphology; and downregulation of key mitochondrial fusion, fission, and inner membrane genes. This ultimately results in mitochondria-dependent apoptosis. These findings reveal the prognostic value of XPR1 in HCC progression and, more importantly, suggest that XPR1 might be a potential therapeutic target.

The association between statin use and diabetic nephropathy in US adults: data from NHANES 2005 - 2018.

Background: A serious consequence of diabetes is diabetic nephropathy (DN), which is commonly treated by statins. Studies evaluating the effects of statin medication have yielded inconsistent results regarding the potential association with diabetic nephropathy. To manage diabetic nephropathy's onset and improve the quality of life of patients, it is imperative to gain a comprehensive understanding of its contributing factors. Data and methods: Our study was conducted using the National Health and Nutrition Examination Survey (NHANES) as well as weighted multivariate logistic regression models to determine the odds ratio (OR) and 95% confidence intervals (95%CI) for diabetic nephropathy. We conducted stratified analyses to examine the impact of statins and the duration of their usage on diabetic nephropathy in different subgroups. A nomogram model and the receiver operating characteristic (ROC) curve were also developed to predict DN risk. Results: Statin use significantly increased the incidence of DN (OR=1.405, 95%CI (1.199,1.647), p<0.001). Individuals who used statins for 5 to 7 years were more likely to develop diabetic nephropathy (OR=1.472, 95%CI (1.057,2.048), p=0.022) compared to those who used statins for 1-3 years (OR=1.334, 95%CI (1.058,1.682), p=0.015) or <1 year (OR=1.266, 95%CI (1.054,1.522), p = 0.012). Simvastatin has a greater incidence of diabetic nephropathy (OR=1.448, 95%CI(1.177, 1.78), P < 0.001). Conclusion: Taking statins long-term increases the risk of DN. Statin use is associated with an increased risk of DN. Caution should be exercised when prescribing atorvastatin and simvastatin for long-term statin therapy.

Structural and biochemical characterization of LIG1 during mutagenic nick sealing of oxidatively damaged ends at the final step of DNA repair.

DNA ligase 1 (LIG1) joins broken strand-breaks in the phosphodiester backbone to finalize DNA repair pathways. We previously reported that LIG1 fails on nick repair intermediate with 3'-oxidative damage incorporated by DNA polymerase (pol) ß at the downstream steps of base excision repair (BER) pathway. Here, we determined X-ray structures of LIG1/nick DNA complexes containing 3'-8oxodG and 3'-8oxorG opposite either a templating Cytosine or Adenine and demonstrated that the ligase active site engages with mutagenic repair intermediates during steps 2 and 3 of the ligation reaction referring to the formation of DNA-AMP intermediate and a final phosphodiester bond, respectively. Furthermore, we showed the mutagenic nick sealing of DNA substrates with 3'-8oxodG:A and 3'-8oxorG:A by LIG1 wild-type, immunodeficiency disease-associated variants, and DNA ligase 3α (LIG3α) in vitro . Finally, we observed that LIG1 and LIG3α seal resulting nick after an incorporation of 8oxorGTP:A by polß and AP-Endonuclease 1 (APE1) can clean oxidatively damaged ends at the final steps. Overall, our findings uncover a mechanistic insight into how LIG1 discriminates DNA or DNA/RNA junctions including oxidative damage and a functional coordination between the downstream enzymes, polß, APE1, and BER ligases, to process mutagenic repair intermediates to maintain repair efficiency.

High-performance carboxymethyl starch/PVA based intelligent packaging films engineered with Cu-Trp nanocrystal as functional compatibilizer.

A spindle-like Cu-based framework (Cu-Trp, Trp = L-Tryptophan) nanocrystal with ammonia-responsiveness was fabricated via simple aqueous solution approach, and it was subsequently explored as a functional compatibilizer of carboxymethyl starch/polyvinyl alcohol (CMS/PVA) blend toward constructing high-performance intelligent packaging films. The results showed that incorporation of Cu-Trp nanocrystal into CMS/PVA blend resulted in significant promotions regarding to the compatibility, mechanical strength (42.92 MPa), UV-blocking (with UV transmittance of only 2.4%), and water vapor barrier effectiveness of the blend film. Besides, the constructed CMS/PVA/Cu-Trp nanocomposite film exhibited superb long-term color stability, favorable antibacterial capacity (over 98.0%) toward both E. coli and S. aureus bacteria, as well as color change ability under ammonia environment. Importantly, the application trial confirmed that the CMS/PVA/Cu-Trp nanocomposite film is capable of visually monitoring shrimp spoilage during storage. These results implied that the CMS/PVA/Cu-Trp nanocomposite film holds tremendous potential as an intelligent active packaging material.

Antimicrobial activity and structure-activity relationships of molecules containing mono- or di- or oligosaccharides: An update.

Bacterial infections are the second leading cause of death worldwide, and the evolution and widespread distribution of antibiotic-resistance elements in bacterial pathogens exacerbate the threat crisis. Carbohydrates participate in bacterial infection, drug resistance and the process of host immune regulation. Numerous antimicrobials derived from carbohydrates or contained carbohydrate scaffolds that are conducive to an increase in pathogenic bacteria targeting, the physicochemical properties and druggability profiles. In the paper, according to the type and number of sugar residues contained in antimicrobial molecules collected from the literatures ranging from 2014 to 2024, the antimicrobial activities, action mechanisms and structure-activity relationships were delineated and summarized, for purpose to provide the guiding template to select the type and size of sugars in the design of oligosaccharide-based antimicrobials to fight the looming antibiotic resistance crisis.

Impact of DNA ligase 1 and IIIα interactions with APE1 and polß on the efficiency of base excision repair pathway at the downstream steps.

Base excision repair (BER) requires a tight coordination between the repair enzymes through protein-protein interactions and involves gap filling by DNA polymerase (pol) ß and subsequent nick sealing by DNA ligase (LIG) 1 or LIGIIIα at the downstream steps. Apurinic/apyrimidinic-endonuclease 1 (APE1), by its exonuclease activity, proofreads 3' mismatches incorporated by polß during BER. We previously reported that the interruptions in the functional interplay between polß and the BER ligases result in faulty repair events. Yet, how the protein interactions of LIG1 and LIGIIIα could affect the repair pathway coordination during nick sealing at the final steps remains unknown. Here, we demonstrate that LIGIIIα interacts more tightly with polß and APE1 than LIG1, and the N-terminal noncatalytic region of LIG1 as well as the catalytic core and BRCT domain of LIGIIIα mediate interactions with both proteins. Our results demonstrated less efficient nick sealing of polß nucleotide insertion products in the absence of LIGIIIα zinc-finger domain and LIG1 N-terminal region. Furthermore, we showed a coordination between APE1 and LIG1/LIGIIIα during the removal of 3' mismatches from the nick repair intermediate on which both BER ligases can seal noncanonical ends or gap repair intermediate leading to products of single deletion mutagenesis. Overall results demonstrate the importance of functional coordination from gap filling by polß coupled to nick sealing by LIG1/LIGIIIα in the presence of proofreading by APE1, which is mainly governed by protein-protein interactions and protein-DNA intermediate communications, to maintain repair efficiency at the downstream steps of the BER pathway.

Novel intelligent packaging films based on starch/PVA with Cu-ICA nanocrystal as functional compatibilizer for monitoring food freshness.

Considering public health and environmental safety, the development of reliable and efficient monitoring methods is essential to ensure food quality and safety. Herein, a new Cu-based metal organic framework (Cu-ICA) nanocrystal with ammonia-sensitive performance was built up and then introduced as a functional compatibilizer of starch/polyvinyl alcohol (STA/PVA) blend to develop high-performance intelligent packaging films for food freshness monitoring. The introduction of Cu-ICA upgraded the compatibility, mechanical strength (42.9 MPa), UV-protection (with UV transmittance of only 2.8 %), and moisture/oxygen barrier performances of STA/PVA film. Furthermore, the developed STA/PVA/Cu-ICA films presented long-term colour stability, outstanding antibacterial efficacy (over 99.5 %) toward both Escherichia coli and Staphylococcus aureus bacteria, as well as remarkable ammonia-sensitive discoloration capability. The STA/PVA/Cu-ICA films possessed visually identifiable colour change during the monitoring of shrimp spoilage. These findings indicate that the developed STA/PVA/Cu-ICA film possesses tremendous potential as an intelligent active packaging material.

Panax notoginseng saponins improve oral submucous fibrosis by inhibiting the Wnt/ß-catenin signal pathway.

OBJECTIVE: Oral submucous fibrosis (OSF) is a chronic, insidious, progressive mucosal disease that may be affected by mutations in the Wnt/ß-catenin signaling pathway. Panax notoginseng saponins (PNS) is a powerful anti-fibrosis agent; however, its effect and mechanism in treating OSF remain unclear. This study investigated the effect and mechanism of PNS treatment for OSF. STUDY DESIGN: Arecoline was used to induce OSF models in vivo and in vitro, which were then treated with PNS. Hematoxylin-eosin (HE) and Masson trichrome staining were used to observe histopathology changes; E-cadherin and ß-catenin were detected by Immunohistochemical assay, and type Ⅰ collagen (CollA1) and ß-catenin were detected by immunofluorescent staining. The Wnt/ß-catenin pathway and fibrosis signs were assessed using Western Blot and real-time quantitative polymerase chain reaction (RT-qPCR). RESULTS: The expression of CollA1, Wnt1, and ß-catenin were increased, and E-cadherin, GSK-3ß, and ß-catenin expression were decreased in OSF models. PNS and inhibitor intervention increased E-cadherin, Wnt1, and ß-catenin and decreased CollA1 and GSK-3ß in a dose-dependent manner. CONCLUSION: PNS can improve OSF by inhibiting the Wnt/ß-catenin signal pathway and thus may be used as a potential medicine for the treatment of OSF.

Sevelamer reverses liver fibrosis by deactivation of hepatic stellate cells.

Liver fibrosis is a chronic liver disease characterized by a progressive wound healing response caused by chronic liver injury. Currently, there are no approved clinical treatments for liver fibrosis. Sevelamer is used clinically to treat hyperphosphatemia and has shown potential therapeutic effects on liver diseases. However, there have been few studies evaluating the therapeutic effects of sevelamer on liver fibrosis, and the specific mechanisms are still unclear. In this study, we investigated the antifibrotic effects of sevelamer-induced low inorganic phosphate (Pi) stress in vitro and in vivo and analyzed the detailed mechanisms. We found that low Pi stress could inhibit the proliferation of activated hepatic stellate cells (HSCs) by promoting apoptosis, effectively suppressing the migration and epithelial-mesenchymal transition (EMT) of hepatic stellate cells. Additionally, low Pi stress significantly increased the antioxidant stress response. It is worth noting that low Pi stress indirectly inhibited the activation and migration of HSCs by suppressing transforming growth factor ß (TGF-ß) expression in macrophages. In a rat model of liver fibrosis, oral administration of sevelamer significantly decreased blood phosphorus levels, improved liver function, reduced liver inflammation, and increased the antioxidant stress response in the liver. Our study revealed that the key mechanism by which sevelamer inhibited liver fibrosis involved binding to gastrointestinal phosphate, resulting in a decrease in blood phosphorus levels, the downregulation of TGF-ß expression in macrophages, and the inhibition of HSC migration and fibrosis-related protein expression. Therefore, our results suggest that sevelamer-induced low Pi stress can attenuate hepatic stellate cell activation and inhibit the progression of liver fibrosis, making it a potential option for the treatment of liver fibrosis and other refractory chronic liver diseases.

Diagnostic performance of 18F­DCFPyL PET vs. 68Ga­PSMA PET/CT in patients with suspected prostate cancer: A systemic review and meta­analysis.

In this systematic review and meta-analysis, the diagnostic performance of 68Ga-prostate-specific membrane antigen (PSMA) positron emission tomography (PET)/CT was compared with that of 18F-DCFPyL PET for patients with suspected prostate cancer (PCa). Up to September 2023, the PubMed, Embase and Web of Science databases were thoroughly searched for relevant papers. Studies examining the diagnostic performance of 18F-DCFPyL PET and 68Ga-PSMA PET/CT in patients with suspected PCa were included in the present review. The Quality Assessment of Diagnostic Performance Studies-2 tool was used to rate the diagnostic performance of each study. The diagnostic performance of 18F-DCFPyL PET and 68Ga-PSMA PET/CT for primary PCa was examined by 13 studies included, comprising 1,178 patients. The pooled sensitivity and specificity of 18F-DCFPyL PET were 0.92 (95% CI, 0.85-0.96) and 0.59 (95% CI, 0.08-0.96), respectively. For 68Ga-PSMA PET/CT, the pooled sensitivity and specificity were 0.96 (95% CI, 0.88-0.99) and 0.71 (95% CI, 0.57-0.82), respectively. 18F-DCFPyL PET and 68Ga-PSMA PET/CT both had an area under the receiver operating characteristic curve of 0.92 (95% CI, 0.89-0.94). In addition, the Fagan nomogram revealed that the post-test probabilities for 18F-DCFPyL PET and 68Ga-PSMA PET/CT could rise to 69 and 77% when the pre-test probability was set at 50%. In conclusion, a comparable diagnostic performance for patients with suspected PCa was determined for 18F-DCFPyL PET and 68Ga-PSMA PET/CT. However, it is crucial to keep in mind that the findings of the present meta-analysis come from investigations with modest sample sizes. Therefore, more extensive research is required to obtain more solid data.

Smart packaging films based on corn starch/polyvinyl alcohol containing nano SIM-1 for monitoring food freshness.

There is at present an acute need for the construction of biopolymer-based smart packaging material that can be applied for the real-time visual monitoring of food freshness. Herein, a nano-sized substituted imidazolate material (SIM-1) with ammonia-sensitive and antibacterial ability was effectively manufactured and then anchored within corn starch/polyvinyl alcohol (CS/PVA) blend to construct biopolymeric smart active packaging material. The structure, physical and functional performances of CS/PVA-based films with different content of SIM-1 (0.5, 1.0 and 2.0 wt% on CS/PVA basis) were then explored in detail. Results revealed that the incorporated SIM-1 nanocrystals were equally anchored within the CS/PVA matrix owing to the establishment of potent hydrogen-bonding interactions, which produced an obvious improvement in the compatibility of CS/PVA blend film, as well as its mechanical strength, water/oxygen barrier and UV-screening performances. The constructed CS/PVA/SIM-1 blend films further demonstrated superior long-term color stability property, ammonia-sensitive and antibacterial functions. Furthermore, the CS/PVA/SIM-1 blend films were utilized for effectively monitoring the deterioration of shrimp via observable color alteration. The above findings suggested the potential applications of CS/PVA/SIM-1 blend films in smart active packaging.

Design, synthesis and biological evaluation of the positional isomers of the galactose conjugates able to target hepatocellular carcinoma cells via ASGPR-mediated cellular uptake and cytotoxicity.

Galactose as a recognizing motif for asialoglycoprotein receptor (ASGPR) is a widely accepted vector to deliver cytotoxic agents in the therapy of hepatocellular carcinoma (HCC), however, the individual hydroxyl group of galactose (Gal) contributed to recognizing ASGPR is obscure and remains largely unanswered in the design of glycoconjugates. Herein, we designed and synthesized five positional isomers of Gal-anthocyanin Cy5.0 conjugates and three Gal-doxorubicin (Dox) isomers, respectively. The fluorescence intensity of Gal-Cy5.0 conjugates accumulated in cancer cells hinted the optimal modification sites of positions C2 and C6. Comparing to the cytotoxicity of other conjugates, C2-Gal-Dox (11) was the most potent. Moreover, Gal-Dox conjugates significantly the toxicity of Dox. A progressively lower internalization capacity and siRNA technology implied the cellular uptake and cytotoxicity directly related to the ASGPR expression level. Accordingly, position C2 of galactose may be the best substitution site via ASGPR mediation in the design of anti-HCC glycoconjugates.

Impact of polß/XRCC1 Interaction Variants on the Efficiency of Nick Sealing by DNA Ligase IIIα in the Base Excision Repair Pathway.

Base excision repair (BER) requires a coordination from gap filling by DNA polymerase (pol) ß to subsequent nick sealing by DNA ligase (LIG) IIIα at downstream steps of the repair pathway. X-ray cross-complementing protein 1 (XRCC1), a non-enzymatic scaffolding protein, forms repair complexes with polß and LIGIIIα. Yet, the impact of the polß mutations that affect XRCC1 interaction and protein stability on the repair pathway coordination during nick sealing by LIGIIIα remains unknown. Our results show that the polß colon cancer-associated variant T304 exhibits a reduced interaction with XRCC1 and the mutations in the interaction interface of V303 loop (L301R/V303R/V306R) and at the lysine residues (K206A/K244A) that prevent ubiquitin-mediated degradation of the protein exhibit a diminished repair protein complex formation with XRCC1. Furthermore, we demonstrate no significant effect on gap and nick DNA binding affinity of wild-type polß by these mutations. Finally, our results reveal that XRCC1 leads to an efficient channeling of nick repair products after nucleotide incorporation by polß variants to LIGIIIα, which is compromised by the L301R/V303R/V306R and K206A/K244A mutations. Overall, our findings provide insight into how the mutations in the polß/XRCC1 interface and the regions affecting protein stability could dictate accurate BER pathway coordination at the downstream steps involving nick sealing by LIGIIIα.

NOD-like receptors mediate homeostatic intestinal epithelial barrier function: promising therapeutic targets for inflammatory bowel disease.

Inflammatory bowel disease (IBD) is a chronic gastrointestinal inflammatory disease that involves host genetics, the microbiome, and inflammatory responses. The current consensus is that the disruption of the intestinal mucosal barrier is the core pathogenesis of IBD, including intestinal microbial factors, abnormal immune responses, and impaired intestinal mucosal barrier. Cumulative data show that nucleotide-binding and oligomerization domain (NOD)-like receptors (NLRs) are dominant mediators in maintaining the homeostasis of the intestinal mucosal barrier, which play critical roles in sensing the commensal microbiota, maintaining homeostasis, and regulating intestinal inflammation. Blocking NLRs inflammasome activation by botanicals may be a promising way to prevent IBD progression. In this review, we systematically introduce the multiple roles of NLRs in regulating intestinal mucosal barrier homeostasis and focus on summarizing the activities and potential mechanisms of natural products against IBD. Aiming to propose new directions on the pathogenesis and precise treatment of IBD.

Novel ammonia-sensitive sodium alginate-based films containing Co-Imd microcrystals for smart packaging application.

Currently, there is an urgent requirement for the fabrication of smart packaging materials that can be applied for the real-time visual monitoring of food freshness. In this research, cubic Co-MOF (Co-Imd) microcrystal with ammonia-sensitivity and antibacterial activity was manufactured and then anchored within sodium alginate (NaAlg) matrix to construct smart packaging materials. The structure, physical and functional performances of NaAlg-based films with different content of Co-Imd (0.5, 1.0 and 2.0 wt% on NaAlg basis) were then evaluated in detail. Results reveal that the incorporated Co-Imd fillers are equally anchored within the NaAlg matrix due to the generation of new hydrogen-bonding interaction, which make an obvious improvement in mechanical strength, toughness, oxygen/water barrier, and UV-blocking ability of the NaAlg film. Moreover, the constructed NaAlg/Co-Imd blend films show superior antibacterial capability, ammonia-sensitivity function as well as color stability. Ultimately, the NaAlg/Co-Imd blend films were successfully utilized for indicating the deterioration of shrimp based on noticeable color alteration, suggesting their tremendous prospects for utilization in smart active packaging. This work offers a facile and efficient method for fabricating novel ammonia-sensitive and long-term color-stable NaAlg-based film materials with improved mechanical strength, toughness, oxygen/water barrier, UV-blocking, and antibacterial performances for smart active packaging application.

Irreversible repolarization of tumour-associated macrophages by low-Pi stress inhibits the progression of hepatocellular carcinoma.

Numerous studies have shown the positive correlation between high levels of Pi and tumour progression. A critical goal of macrophage-based cancer therapeutics is to reduce anti-inflammatory macrophages (M2) and increase proinflammatory antitumour macrophages (M1). This study aimed to investigate the relationship between macrophage polarization and low-Pi stress. First, the spatial populations of M2 and M1 macrophages in 22 HCC patient specimens were quantified and correlated with the local Pi concentration. The levels of M2 and M1 macrophage markers expressed in the peritumour area were higher than the intratumour levels, and the expression of M2 markers was positively correlated with Pi concentration. Next, monocytes differentiated from THP-1 cells were polarized against different Pi concentrations to investigate the activation or silencing of the expression of p65, IκB-α and STAT3 as well as their phosphorylation. Results showed that low-Pi stress irreversibly repolarizes tumour-associated macrophages (TAMs) towards the M1 phenotype by silencing stat6 and activating p65. Moreover, HepG-2 and SMCC-7721 cells were cultured in conditioned medium to investigate the innate anticancer immune effects on tumour progression. Both cancer cell lines showed reduced proliferation, migration and invasion, as epithelial-mesenchymal transition (EMT) was inactivated. In vivo therapeutic effect on the innate and adaptive immune processes was validated in a subcutaneous liver cancer model by the intratumoural injection of sevelamer. Tumour growth was significantly inhibited by the partial deprivation of intratumoural Pi as the tumour microenvironment under low-Pi stress is more immunostimulatory. The anticancer immune response, activated by low-Pi stress, suggests a new macrophage-based immunotherapeutic modality.

Quantification of ectopic fat storage in the liver and pancreas using six-point Dixon MRI and its association with insulin sensitivity and ß-cell function in patients with central obesity.

OBJECTIVES: To assess the association of ectopic fat deposition in the liver and pancreas quantified by Dixon magnetic resonance imaging (MRI) with insulin sensitivity and ß-cell function in patients with central obesity. MATERIALS AND METHODS: A cross-sectional study of 143 patients with central obesity with normal glucose tolerance (NGT), prediabetes (PreD), and untreated type 2 diabetes mellitus (T2DM) was conducted between December 2019 and March 2022. All participants underwent routine medical history taking, anthropometric measurements, and laboratory tests, including a standard glucose tolerance test to quantify insulin sensitivity and ß-cell function. The fat content in the liver and pancreas was measured with MRI using the six-point Dixon technique. RESULTS: Patients with T2DM and PreD had a higher liver fat fraction (LFF) than those with NGT, while those with T2DM had a higher pancreatic fat fraction (PFF) than those with PreD and NGT. LFF was positively correlated with homeostatic model assessment of insulin resistance (HOMA-IR), while PFF was negatively correlated with homeostatic model assessment of insulin secretion (HOMA-ß). Furthermore, using a structured equation model, we found LFF and PFF to be positively associated with glycosylated hemoglobin via HOMA-IR and HOMA-ß, respectively. CONCLUSIONS: In patients with central obesity, the effects of LFF and PFF on glucose metabolism. were associated with HOMA-IR and HOMA-ß, respectively. Ectopic fat storage in the liver and pancreas quantified by MR Dixon imaging potentially plays a notable role in the onset ofT2DM. CLINICAL RELEVANCE STATEMENT: We highlight the potential role of ectopic fat deposition in the liver and pancreas in the development of type 2 diabetes in patients with central obesity, providing valuable insights into the pathogenesis of the disease and potential targets for intervention. KEY POINTS: • Ectopic fat deposition in the liver and pancreas is associated with T2DM. • T2DM and prediabetes patients had higher liver and pancreatic fat fractions than normal individuals. • The results provide valuable insights into pathogenesis of T2DM and potential targets for intervention.