Traceability in food processing: problems, methods, and performance evaluations-a review.

Processed food has become an indispensable part of the human food chain. It provides rich nutrition for human health and satisfies various other requirements for food consumption. However, establishing traceability systems for processed food faces a different set of challenges compared to primary agro-food, because of the variety of raw materials, batch mixing, and resource transformation. In this paper, progress in the traceability of processed food is reviewed. Based on an analysis of the food supply chain and processing stage, the problem of traceability in food processing results from the transformations that the resources go through. Methods to implement traceability in food processing, including physical separation in different lots, defining and associating batches, isotope analysis and DNA tracking, statistical data models, internal traceability system development, artificial intelligence (AI), and blockchain-based approaches are summarized. Traceability is evaluated based on recall effects, TRUs (traceable resource units), and comprehensive granularity. Different methods have different advantages and disadvantages. The combined application of different methods should consider the specific application scenarios in food processing to improve granularity. On the other hand, novel technologies, including batch mixing optimization with AI, quality forecasting with big data, and credible traceability with blockchain, are presented in the context of improving traceability performance in food processing.

Food cold chain management improvement: A conjoint analysis on COVID-19 and food cold chain systems.

Cold chains are effective in maintaining food quality and reducing food losses, especially for long-distance international food commerce. Several recent reports have demonstrated that frozen foods are serving as carriers of SARS-CoV-2 and transmitting the virus from one place to another without any human-to-human contact. This finding highlights significant difficulties facing efforts to control the spread of COVID-19 and reveal a transmission mechanism that may have substantially worsened the global pandemic. Traditional food cold chain management practices do not include specific procedures related to SARS-CoV-2-related environmental control and information warnings; therefore, such procedures are urgently needed to allow food to be safely transported without transmitting SARS-CoV-2. In this study, a conjoint analysis of COVID-19 and food cold chain systems was performed, and the results of this analysis were used to develop an improved food cold chain management system utilizing internet of things (IoT) and blockchain technology. First, 45 COVID-19-related food cold chain incidents in China, primarily involving frozen meat and frozen aquatic products, were summarized. Critical food cold chain control points related to COVID-19 were analyzed, including temperature and cold chain requirements. A conceptual system structure to improve food cold chain management, including information sensing, chain linking and credible tracing, was proposed. Finally, a prototype system, which consisted of cold chain environment monitoring equipment, a cold chain blockchain platform, and a food chain management system, was developed. The system includes: 1) a defining characteristic of the newly developed food cold chain system presented here is the use of IoT technology to enhance real-time environmental information sensing capacity; 2) a hybrid data storage mechanism consisting of off-chain and on-chain systems was applied to enhance data security, and smart contracts were used to establish warning levels for food cold chain incidents; and 3) a hypothetical food cold chain failure scenario demonstration in which information collection, intelligent decision making, and cold chain tracing were integrated and automatically generated for decision-making. By integrating existing technologies and approaches, our study provides a novel solution to improve traditional food cold chain management and thus meet the challenges associated with the COVID-19 pandemic. Although our system has been shown to be effective, subsequent studies are still required to develop precise risk evaluation models for SARs-CoV-2 in food cold chains and more precisely control the entire process. By ensuring food safety and reliable traceability, our system could also contribute to the formulation of appropriate mechanisms for international cooperation and minimize the effect of the COVID-19 pandemic on international food commerce.

Sustainable food cold chain logistics: From microenvironmental monitoring to global impact.

Food cold chain logistics (FCCL) is a systematic engineering process involving the use of a low-temperature environment to maintain the quality and safety of perishable food and reduce food loss and waste (FLW). From a mechanism perspective, FCCL must balance resource costs for a required level of food quality and safety with the costs of greenhouse gas (GHG) emissions. In the context of global warming, the sustainability trade-off between FLW and environmental impact has recently become an important topic in research on efficient, green FCCL. This is mainly reflected in technological innovation, management optimization, and policy responses. With a focus on three levels (micro, meso, macro), this review analyzes current research areas and the gaps and challenges of FCCL in microenvironmental monitoring, life cycle assessment (LCA), and global impact. Future trends pertaining to FCCL in technology, management, and industry and sustainable development are also summarized. Future trends involving sustainable FCCL must be intelligent, systematic, and low carbon. Industry empowerment through next-generation information technologies (e.g., IoT, AI, big data, blockchain) will promote the multidimensional perception, real-time information transmission, and sustainable control of microenvironmental monitoring, as well as support LCA management transformation from fragmentation to system integration. From a macro level, due to the serious global loss of perishable food, the FCCL scale demand is growing greatly, causing a huge environmental burden. Global cooperation, low-carbon consensus, and appropriate policies will become the basis for promoting sustainable FCCL development.

Electrolyte disorders are ERAS-associated in patients undergoing hepato-pancreato-biliary surgery.

PURPOSE: Emerging evidences have raised concerns about electrolyte disorders caused by restrictive fluid management in the enhanced recovery after surgery (ERAS) protocol. This study aims to investigate the morbidity and treatment of electrolyte disorders associated with ERAS in patients undergoing hepato-pancreato-biliary (HPB) surgery. METHODS: Clinical data from 157 patients under the ERAS program and 166 patients under the traditional (Non-ERAS) program after HPB surgery were retrospectively analyzed. Risk factors and predictive factors of postoperative electrolyte disorders were analyzed by logistic regression analysis and receiver operator characteristic (ROC) curve analysis, respectively. RESULTS: The average of intravenous fluid, sodium, chloride, and potassium supplementation after surgery were significantly lower in the ERAS group. Hypokalemia was the most common type of electrolyte disorders in the ERAS group, whose incidence was substantially increased compared to that in the Non-ERAS group [28.77% vs. 8.97%, p < 0.001, on postoperative (POD) 5]. Logistic regression analysis identified the ERAS program and age as independent risk factors of hypokalemia. ROC curve analysis identified serum potassium levels below 3.76 mmol/L on POD 3 (area under curve 0.731, sensitivity 58.54%, specificity 82.69%) as a predictive factor for postoperative hypokalemia in ERAS patients. Oral supplementation at an average of 35.41 mmol potassium per day was effective in restoring the ERAS-associated hypokalemia. CONCLUSIONS: ERAS procedures were particularly associated with a lower supplementation of potassium and a higher incidence of hypokalemia in patients after HPB surgery. Oral potassium supplementation could be an adopted ERAS program for the elderly undergoing HPB surgery.

Food Packaging: A Comprehensive Review and Future Trends.

Innovations in food packaging systems will help meet the evolving needs of the market, such as consumer preference for "healthy" and high-quality food products and reduction of the negative environmental impacts of food packaging. Emerging concepts of active and intelligent packaging technologies provide numerous innovative solutions for prolonging shelf-life and improving the quality and safety of food products. There are also new approaches to improving the passive characteristics of food packaging, such as mechanical strength, barrier performance, and thermal stability. The development of sustainable or green packaging has the potential to reduce the environmental impacts of food packaging through the use of edible or biodegradable materials, plant extracts, and nanomaterials. Active, intelligent, and green packaging technologies can work synergistically to yield a multipurpose food-packaging system with no negative interactions between components, and this aim can be seen as the ultimate future goal for food packaging technology. This article reviews the principles of food packaging and recent developments in different types of food packaging technologies. Global patents and future research trends are also discussed.

Metabolomic profiles delineate the effect of Sanmiao wan on hyperuricemia in rats.

A serum metabolomic method based on ultra-high-performance liquid chromatography coupled with mass spectrometry was developed to characterize hyperuricemia-related metabolic profiles and delineate the mechanism of Sanmiao wan (SMW), a traditional Chinese medicine (TCM), in treating hyperuricemic rats. With partial least-squares discriminant analysis for classification and selection of biomarkers, 13 potential biomarkers in mouse serum were identified in the screen, primarily involved in purine metabolism, arginine and proline metabolism, citrate cycle, phenylalanine metabolism, tryptophan metabolism and glycerophospholipid metabolism. Taking these potential biomarkers as screening indexes, SMW could reverse the pathological process of hyperuricemia through partially regulating the perturbed metabolic pathway except for glycerophospholipid metabolism. Our results showed that a metabolomic approach offers a useful tool to identify hyperuricemia-related biomarkers and provides a new methodological cue for systematically dissecting the underlying efficacies and mechanisms of TCM in treating hyperuricemia.

Role of IL-10-Producing Regulatory B Cells in Chronic Hepatitis B Virus Infection.

BACKGROUND: A subset of interleukin (IL)-10-producing regulatory B (Breg) cells that suppress T-cell-mediated immunity was recently identified; however, their role in chronic hepatitis B (CHB) remains elusive. AIM: To explore the possible role of Breg in the interaction with Th cells and consequent pathogenesis of CHB. METHODS: The prevalence of Breg as well as 3 major effector T-cell subsets--CD4(+)CD25(high)Foxp3(+) regulatory T (Treg) cells, T helper 1 cells (Th1), and T helper 2 cells (Th2)--was assessed in the peripheral blood of 31 patients with CHB, 28 patients with acute hepatitis B (AHB), and 25 healthy controls (HC). RESULTS: Compared to patients with AHB and HC, the prevalence of Breg and Treg cells and the concentration of IL-10 in the supernatant of cultured peripheral blood mononuclear cells (PBMCs) were greatly increased in patients with CHB. A significantly decreased proportion of Th1 cells was also observed in patients with CHB and was demonstrated to have a negative correlation with the prevalence of Breg. Furthermore, depletion of Treg cells in the PBMCs of patients with CHB did not alter the frequency of Breg cells or their ability to produce IL-10, indicating little, if any, impact of Treg cells on the generation and maintenance of Breg cells. CONCLUSIONS: Our data indicate that increased Breg cells might be a major source of elevated IL-10 in CHB and represent a critical and independent regulatory force in the development of impaired anti-HBV immunity, consequently contributing to the pathogenesis of CHB.

Identification of risk and prognostic factors for patients with clonorchiasis-associated intrahepatic cholangiocarcinoma.

BACKGROUND: Intrahepatic cholangiocarcinoma caused by clonorchiasis (CICC) has a poor prognosis, and there have been insufficient studies regarding risk and prognostic factors. We aimed to identify CICC-associated factors. METHODS: A retrospective analysis of 127 eligible patients with CICC was performed with 254 clonorchiasis cases used as matched controls to identify risk factors for CICC. The main outcomes analyzed included overall survival (OS) and disease-free survival (DFS). RESULTS: Out of 127 surgeries, R0 resection was performed in 61 patients, R1 in 32 patients, and R2 in 22 patients; nonresection surgery was performed in 12 patients. Median OS for the entire cohort was 29.5 months. Median OS and DFS for 61 patients with R0 resection were 52.4 months and 41.5 months, respectively. We found independent risk factors for CICC were duration of raw fish consumption of ≥28 years (p < 0.001) and hepatitis B virus infection (p = 0.040). R0 resection (p < 0.001), well or moderately differentiated tumor (p = 0.019), and stage I to II tumor (p < 0.001) predicted improved OS for CICC. Serum carcinoembryonic antigen level of ≤5 ng/ml (p = 0.029) and stage I to II tumor (p < 0.001) predicted improved DFS. CONCLUSIONS: Duration of raw fish consumption ≥28 years and hepatitis B virus infection were significant risk factors for CICC in patients with clonorchiasis. For patients with CICC, curative resection is an effective treatment. Higher tumor differentiation and earlier American Joint Committee on Cancer stage predicted good prognosis. Serum carcinoembryonic antigen level was found to predict the possibility of recurrence after curative resection.

Analysis of risk factors for pancreatic duct stones formation in patients with alcoholic chronic pancreatitis.

BACKGROUND: Alcoholic chronic pancreatitis (ACP) is the dominant cause of chronic pancreatitis (CP). As a main complication of CP, the formation of pancreatic duct stones (PDS) compromises pancreatic function and symptomatic patients are often subjected to aggressive treatments. The present study aimed to identify PDS risk factors in patients with ACP. METHODS: A retrospective analysis of 93 ACP patients was performed; patients were divided into two groups: ACP with PDS (n = 48) and ACP without PDS (n = 45). Fourteen potential factors were analyzed by univariate and multivariate analyses to identify independent risk factors of PDS formation in ACP patients. A comparison of demographic and clinical characteristics between ACP patients with PDS and non-ACP patients with PDS (n = 43) was also carried out. RESULTS: ACP accounted for 47.7% (93/195) of CP in this cohort. Among ACP patients, the morbidity of PDS was 51.6% (48/93). Significant risk factors of PDS formation for ACP patients included duration of drinking ≥24.7 years (OR, 9.036; 95% CI, 2.737-29.837; p < 0.001); daily alcohol consumption ≥147.0 g (OR, 3.147; 95% CI, 1.040-9.522; p = 0.042); and MPD narrowing (OR, 7.245; 95% CI, 2.205-23.811; p = 0.001). Shorter periods between diagnosis and PDS formation (PDP) were observed in ACP patients than non-ACP patients. CONCLUSIONS: Alcohol consumption accelerates the progression of PDS formation in patients with CP.

Identification of prognostic factors and the impact of palliative resection on survival of patients with stage IV hepatolithiasis-associated intrahepatic cholangiocarcinoma.

BACKGROUND: Hepatolithiasis-associated intrahepatic cholangiocarcinoma (IHHCC) has a poor prognosis, because of lower curative resection rate when diagnosed in the advanced stage. There has been insufficient data regarding prognostic factors and the impact of palliative resection on its outcome. METHODS: A retrospective analysis of 78 eligible patients with stage IV IHHCC was performed. The potential prognostic factors were assessed by univariate and multivariate analyses. Patients were divided into groups A (margin positive) and B (nonresection) based on surgical methods. Demographic and operative data were compared. RESULTS: Of 78 surgeries, R1 was achieved in 11, R2 in 21 and nonresection in 46 patients. Median overall survival (OS) of the entire cohort was 10.5 months. Surgery (P < 0.01), tumor differentiation (P = 0.03), AJCC stage (P < 0.01), and serum CEA levels (P < 0.01) were independent prognostic factors. Significant differences were achieved in OS (P < 0.01), operation time (P < 0.01), estimated blood loss (P < 0.01), and postoperative complications (P = 0.02) between groups A and B. CONCLUSIONS: For patients with stage IV IHHCC, palliative resection is a rational and effective treatment. Normal serum CEA levels, higher tumor differentiation, and stage IVa predict good prognosis in stage IV IHHCC.

Enhanced proliferation and defective activation-induced cell death of CD4+ T cells in childhood asthma.

BACKGROUND: Hyperactivation of CD4+ T cells in peripheral blood and airway tissues has been suggested to play a key role in the development and maintenance of chronic inflammation in childhood asthma. However, the underlying mechanisms are not yet clear. OBJECTIVE: To investigate alterations in serum levels of T helper cell-related cytokines, mitogen-stimulated CD4+ T cell proliferation and activation-induced cell death (AICD) in childhood asthma. METHODS: 21 children with untreated asthma and 21 healthy volunteers (age and gender matched) participated in this study. Th1/Th2/Th17 cytokines in serum were analyzed by flow cytometry. CD4+ T cells were isolated from participants by using immuno-magnetic beads and were stimulated by phytohemagglutinin (PHA). Cell proliferation was evaluated with a Cell Counting Kit-8 (CCK-8). Activation induced cell death (AICD) of CD4+ T cells was also induced by PHA and apoptosis was assayed by annexin V/PI staining. Quantitative RT-PCR was carried out to analyze Fas and FasL mRNA expression. FLIPL, caspase-8 and Bcl-2 were detected by western blot analysis. RESULTS: In children with asthma, the proliferative capacity of CD4+ T cells was enhanced and AICD was inhibited significantly, while serum IL-4, IL-10 and TNF were markedly higher compared with the control group. Fas mRNA expression in the asthma group was obviously lower than that in the control group, while no change was detected in FasL mRNA expression. Western blot analysis showed that the levels of the anti-apoptotic proteins, FLIPL and Bcl-2 in CD4+ T cells of the asthma group were significantly higher than in the control group. Spearman's correlation tests showed that only IL-4 correlated positively with FLIPL and Bcl-2 expression, while IL-10 and TNF were unrelated to FLIPL and Bcl-2 expression. CONCLUSIONS: These results indicate that enhanced proliferation and defective AICD of CD4+ T cells influence the T cell-mediated inflammatory reaction in childhood asthma and that increased IL-4, FLIPL and Bcl-2 expression and decreased Fas expression jointly participate in these changes in cell proliferation and apoptosis.ression and decreased Fas expression jointly participate in these changes in cell proliferation and apoptosis.

Finding Traceability Granularity Influencing Factors Using Rough Set Method: An Empirical Analysis of Vegetable Companies in Tianjin City, China.

The effectiveness evaluation of the traceability system (TS) is a tool for enterprises to achieve the required traceability level. It plays an important role not only for planning system implementation before development but also for analyzing system performance once the system is in use. In the present work, we evaluate traceability granularity using a comprehensive and quantifiable model and try to find its influencing factors via an empirical analysis with 80 vegetable companies in Tianjin, China. We collect granularity indicators mostly through the TS platform to ensure the objectivity of the data and use the TS granularity model to evaluate the granularity score. The results show that there is an obvious imbalance in the distribution of companies as a function of score. The number of companies (21) scoring in the range (50,60) exceeded the number in the other score ranges. Furthermore, the influencing factors on traceability granularity were analyzed using a rough set method based on nine factors pre-selected using a published method. The results show that the factor "number of TS operation staff" is deleted because it is unimportant. The remaining factors rank according to importance as follows: Expected revenue > Supply chain (SC) integration degree > Cognition of TS > Certification system > Company sales > Informationization management level > System maintenance investment > Manager education level. Based on these results, the corresponding implications are given with the goal of (i) establishing the market mechanism of high price with high quality, (ii) increasing government investment for constructing the TS, and (iii) enhancing the organization of SC companies.

An improved YOLOv5s model for assessing apple graspability in automated harvesting scene.

Introduction: With continuously increasing labor costs, an urgent need for automated apple- Qpicking equipment has emerged in the agricultural sector. Prior to apple harvesting, it is imperative that the equipment not only accurately locates the apples, but also discerns the graspability of the fruit. While numerous studies on apple detection have been conducted, the challenges related to determining apple graspability remain unresolved. Methods: This study introduces a method for detecting multi-occluded apples based on an enhanced YOLOv5s model, with the aim of identifying the type of apple occlusion in complex orchard environments and determining apple graspability. Using bootstrap your own atent(BYOL) and knowledge transfer(KT) strategies, we effectively enhance the classification accuracy for multi-occluded apples while reducing data production costs. A selective kernel (SK) module is also incorporated, enabling the network model to more precisely identify various apple occlusion types. To evaluate the performance of our network model, we define three key metrics: APGA, APTUGA, and APUGA, representing the average detection accuracy for graspable, temporarily ungraspable, and ungraspable apples, respectively. Results: Experimental results indicate that the improved YOLOv5s model performs exceptionally well, achieving detection accuracies of 94.78%, 93.86%, and 94.98% for APGA, APTUGA, and APUGA, respectively. Discussion: Compared to current lightweight network models such as YOLOX-s and YOLOv7s, our proposed method demonstrates significant advantages across multiple evaluation metrics. In future research, we intend to integrate fruit posture and occlusion detection to f]urther enhance the visual perception capabilities of apple-picking equipment.

The role and application of fibroblast activating protein.

Fibroblast activation protein-α (FAP), a type-II transmembrane serine protease, is rarely expressed in normal tissues but highly abundant in pathological diseases, including fibrosis, arthritis, and cancer. Ever since its discovery, we have deciphered its structure and biological properties and continue to investigate its roles in various diseases while attempting to utilize it for targeted therapy. To date, no significant breakthroughs have been made in terms of efficacy. However, in recent years, several practical applications in the realm of imaging diagnosis have been discovered. Given its unique expression in a diverse array of pathological tissues, the fundamental biological characteristics of FAP render it a crucial target for disease diagnosis and immunotherapy. To obtain a more comprehensive understanding of the research progress of FAP, its biological characteristics, involvement in diseases, and recent targeted application research have been reviewed. Moreover, we explored its development trend in the direction of clinical diagnoses and treatment.

Nonalcoholic steatohepatitis critically rewires the ischemia/reperfusion-induced dysregulation of cardiolipins and sphingolipids in mice.

Background: Lipid dysregulation plays a fundamental role in nonalcoholic steatohepatitis (NASH), which is an emerging critical risk factor that aggravates hepatic ischemia/reperfusion (I/R) injury. However, the specific lipids that mediate the aggressive I/R injury in NASH livers have not yet been identified. Methods: The mouse model of hepatic I/R injury on NASH was established on C56B/6J mice by first feeding the mice with a Western-style diet to induce NASH, then the NASH mice were subjected to surgical procedures to induce hepatic I/R injury. Untargeted lipidomics were performed to determine hepatic lipids in NASH livers with I/R injury through ultra-high performance liquid chromatography coupled with mass spectrometry. The pathology associated with the dysregulated lipids was examined. Results: Lipidomics analyses identified cardiolipins (CL) and sphingolipids (SL), including ceramides (CER), glycosphingolipids, sphingosines, and sphingomyelins, as the most relevant lipid classes that characterized the lipid dysregulation in NASH livers with I/R injury. CER were increased in normal livers with I/R injury, and the I/R-induced increase of CER was further augmented in NASH livers. Metabolic pathway analysis revealed that the enzymes involved in the synthesis and degradation of CER were highly upregulated in NASH livers with I/R injury, including serine palmitoyltransferase 3 (Sptlc3), ceramide synthase 2 (Cers2), neutral sphingomyelinase 2 (Smpd3), and glucosylceramidase beta 2 (Gba2) that produced CER, and alkaline ceramidase 2 (Acer2), alkaline ceramidase 3 (Acer3), sphingosine kinase 1 (Sphk1), sphingosine-1-phosphate lyase (Sgpl1), and sphingosine-1-phosphate phosphatase 1 (Sgpp1) that catalyzed the degradation of CER. CL were not affected by I/R challenge in normal livers, but CL was dramatically reduced in NASH livers with I/R injury. Consistently, metabolic pathway analyses revealed that the enzymes catalyzing the generation of CL were downregulated in NASH-I/R injury, including cardiolipin synthase (Crls1) and tafazzin (Taz). Notably, the I/R-induced oxidative stress and cell death were found to be aggravated in NASH livers, which were possibly mediated by the reduction of CL and accumulation of CER. Conclusions: The I/R-induced dysregulation of CL and SL were critically rewired by NASH, which might potentially mediate the aggressive I/R injury in NASH livers.

Safety and efficacy of postoperative adjuvant therapy with atezolizumab and bevacizumab after radical resection of hepatocellular carcinoma.

BACKGROUND: The effects of postoperative adjuvant therapy for high-risk recurrent hepatocellular carcinoma (HCC) in immunotherapy are still under investigation. This study evaluated the preventive effects and safety of postoperative adjuvant therapy, including atezolizumab, and bevacizumab, against the early recurrence of HCC with high-risk factors. METHODS: The complete data of HCC patients who underwent radical hepatectomy with or without postoperative adjuvant therapy after two-year follow-up were analyzed retrospectively. The patients were divided into high-risk or low-risk groups based on HCC pathological characteristics. High-risk recurrence patients were divided into postoperative adjuvant treatment and control groups. Due to the difference in approaches in postoperative adjuvant therapies, they were divided into transarterial chemoembolization (TACE), atezolizumab, and bevacizumab (T + A), and combination (TACE+T + A) groups. The two-year recurrence-free survival rate (RFS), overall survival rate (OS), and associated factors were analyzed. RESULTS: The RFS in the high-risk group was significantly lower than that in the low-risk group (P = 0.0029), and the two-year RFS in the postoperative adjuvant treatment group was significantly higher than that in the control group (P = 0.040). No severe complications were observed in those who received atezolizumab and bevacizumab or other therapy. CONCLUSION: Postoperative adjuvant therapy was related to two-year RFS. TACE, T + A, and the combination of these two approaches were comparable in reducing the early recurrence of HCC without severe complications.

Activation of Sphingomyelin Phosphodiesterase 3 in Liver Regeneration Impedes the Progression of Colorectal Cancer Liver Metastasis Via Exosome-Bound Intercellular Transfer of Ceramides.

BACKGROUND & AIMS: The machinery that prevents colorectal cancer liver metastasis (CRLM) in the context of liver regeneration (LR) remains elusive. Ceramide (CER) is a potent anti-cancer lipid involved in intercellular interaction. Here, we investigated the role of CER metabolism in mediating the interaction between hepatocytes and metastatic colorectal cancer (CRC) cells to regulate CRLM in the context of LR. METHODS: Mice were intrasplenically injected with CRC cells. LR was induced by 2/3 partial hepatectomy (PH) to mimic the CRLM in the context of LR. The alteration of corresponding CER-metabolizing genes was examined. The biological roles of CER metabolism in vitro and in vivo were examined by performing a series of functional experiments. RESULTS: Induction of LR augmented apoptosis but promoted matrix metalloproteinase 2 (MMP2) expression and epithelial-mesenchymal transition (EMT) to increase the invasiveness of metastatic CRC cells, resulting in aggressive CRLM. Up-regulation of sphingomyelin phosphodiesterase 3 (SMPD3) was determined in the regenerating hepatocytes after LR induction and persisted in the CRLM-adjacent hepatocytes after CRLM formation. Hepatic Smpd3 knockdown was found to further promote CRLM in the context of LR by abolishing mitochondrial apoptosis and augmenting the invasiveness in metastatic CRC cells by up-regulating MMP2 and EMT through promoting the nuclear translocation of ß-catenin. Mechanistically, we found that hepatic SMPD3 controlled the generation of exosomal CER in the regenerating hepatocytes and the CRLM-adjacent hepatocytes. The SMPD3-produced exosomal CER critically conducted the intercellular transfer of CER from the hepatocytes to metastatic CRC cells and impeded CRLM by inducing mitochondrial apoptosis and restricting the invasiveness in metastatic CRC cells. The administration of nanoliposomal CER was found to suppress CRLM in the context of LR substantially. CONCLUSIONS: SMPD3-produced exosomal CER constitutes a critical anti-CRLM mechanism in LR to impede CRLM, offering the promise of using CER as a therapeutic agent to prevent the recurrence of CRLM after PH.

ACOX2 is a prognostic marker and impedes the progression of hepatocellular carcinoma via PPARα pathway.

Hepatocellular carcinoma (HCC) has been extensively studied as one of the most aggressive tumors worldwide. However, its mortality rate remains high due to ideal diagnosis and treatment strategies. Uncovering novel genes with prognostic significance would shed light on improving the HCC patient's outcome. In our study, we applied data-independent acquisition (DIA) quantitative proteomics to investigate the expression landscape of 24 paired HCC patients. A total of 1029 differentially expressed proteins (DEPs) were screened. Then, we compared DEPs in our cohort with the differentially expressed genes (DEGs) in The Cancer Genome Atlas, and investigated their prognostic significance, and found 183 prognosis-related genes (PRGs). By conducting protein-protein interaction topological analysis, we identified four subnetworks with prognostic significance. Acyl-CoA oxidase 2 (ACOX2) is a novel gene in subnetwork1, encodes a peroxisomal enzyme, and its function in HCC was investigated in vivo and in vitro. The lower expression of ACOX2 was validated by real-time quantitative PCR, immunohistochemistry, and Western blot. Cell Counting Kit-8 assay, wound healing, and transwell migration assay were applied to evaluate the impact of ACOX2 overexpression on the proliferation and migration abilities in two liver cancer cell lines. ACOX2 overexpression, using a subcutaneous xenograft tumor model, indicated a tumor suppressor role in HCC. To uncover the underlying mechanism, gene set enrichment analysis was conducted, and peroxisome proliferator-activated receptor-α (PPARα) was proposed to be a potential target. In conclusion, we demonstrated a PRG ACOX2, and its overexpression reduced the proliferation and metastasis of liver cancer in vitro and in vivo through PPARα pathway.

Integrated Proteomics and Bioinformatics to Identify Potential Prognostic Biomarkers in Hepatocellular Carcinoma.

BACKGROUND: Liver hepatocellular carcinoma (HCC) is the third most common cause of death by cancer and has a high mortality world-widely. Approximately 75-85% of primary liver cancers are caused by HCC. Uncovering novel genes with prognostic significance would shed light on improving the HCC patient's outcome. OBJECTIVE: In this research, we aim to identify novel prognostic biomarkers in hepatocellular carcinoma. METHODS: Integrated proteomics and bioinformatics analysis were performed to investigate the expression landscape of prognostic biomarkers in 24 paired HCC patients. RESULTS: As a result, eight key genes related to prognosis, including ACADS, HSD17B13, PON3, AMDHD1, CYP2C8, CYP4A11, SLC27A5, CYP2E1, were identified by comparing the weighted gene co-expression network analysis (WGCNA), proteomic differentially expressed genes (DEGs), proteomic turquoise module, The Cancer Genome Atlas (TCGA) cohort DEGs of HCC. Furthermore, we trained and validated eight pivotal genes integrating these independent clinical variables into a nomogram with superior accuracy in predicting progression events, and their lower expression was associated with a higher stage/risk score. The Gene Set Enrichment Analysis (GSEA) further revealed that these key genes showed enrichment in the HCC regulatory pathway. CONCLUSION: All in all, we found that these eight genes might be the novel potential prognostic biomarkers for HCC and also provide promising insights into the pathogenesis of HCC at the molecular level.

Ceramides and sphingosine-1-phosphate mediate the distinct effects of M1/M2-macrophage infusion on liver recovery after hepatectomy.

Post-hepatectomy liver dysfunction is a life-threatening morbidity that lacks efficient therapy. Bioactive lipids involved in macrophage polarization crucially regulate tissue injury and regeneration. Herein, we investigate the key bioactive lipids that mediate the cytotherapeutic potential of polarized-macrophage for post-hepatectomy liver dysfunction. Untargeted lipidomics identified elevation of ceramide (CER) metabolites as signature lipid species relevant to M1/M2 polarization in mouse bone-marrow-derived-macrophages (BMDMs). M1 BMDMs expressed a CER-generation-metabolic pattern, leading to elevation of CER; M2 BMDMs expressed a CER-breakdown-metabolic pattern, resulting in upregulation of sphingosine-1-phosphate (S1P). After infusing M1- or M2-polarized BMDMs into the mouse liver after hepatectomy, we found that M1-BMDM infusion increased M1 polarization and CER accumulation, resulting in exaggeration of hepatocyte apoptosis and liver dysfunction. Conversely, M2-BMDM infusion enhanced M2 polarization and S1P generation, leading to alleviation of liver dysfunction with improved hepatocyte proliferation. Treatment of exogenous CER and S1P or inhibition CER and S1P synthesis by siRNA targeting relevant enzymes further revealed that CER induced apoptosis while S1P promoted proliferation in post-hepatectomy primary hepatocytes. In conclusion, CER and S1P are uncovered as critical lipid mediators for M1- and M2-polarized BMDMs to promote injury and regeneration in the liver after hepatectomy, respectively. Notably, the upregulation of hepatic S1P induced by M2-BMDM infusion may have therapeutic potential for post-hepatectomy liver dysfunction.