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1.
BMC Nephrol ; 25(1): 157, 2024 May 07.
Article in English | MEDLINE | ID: mdl-38714960

ABSTRACT

BACKGROUND: This study aims to investigate the influencing factors of vascular calcification in peritoneal dialysis (PD) patients and its relationship with long-term prognosis. METHODS: This retrospective cohort study included chronic kidney disease patients undergoing peritoneal dialysis at the Peritoneal Dialysis Center of Beijing Luhu Hospital, Capital Medical University, from January 2019 to March 2019. Demographic and clinical laboratory data, including serum sclerostin (SOST), calcium (Ca), phosphate (P), serum albumin (ALB), and intact parathyroid hormone (iPTH) levels, were collected. Abdominal aortic calcification (AAC) was assessed using abdominal lateral X-ray examination to determine the occurrence of vascular calcification, and patients were divided into the AAC group and Non-AAC group based on the results. RESULTS: A total of 91 patients were included in the study. The AAC group consisted of 46 patients, while the Non-AAC group consisted of 45 patients. The AAC group had significantly older patients compared to the non-AAC group (P < 0.001) and longer dialysis time (P = 0.004). Multivariable logistic regression analysis indicated that risk factors for vascular calcification in PD patients included dialysis time, diabetes, hypertension, and SOST. Kaplan-Meier survival analysis showed that the AAC group had a significantly higher mortality rate than the non-AAC group (χ2 = 35.993, P < 0.001). Multivariable Cox regression analysis revealed that dialysis time, diabetes and AAC were risk factors for all-cause mortality in peritoneal dialysis patients. CONCLUSION: Longer dialysis time, comorbid diabetes, comorbid hypertension, and SOST are risk factors for vascular calcification in PD patients. Additionally, AAC, longer dialysis time, and comorbid diabetes are associated with increased risk of all-cause mortality in peritoneal dialysis patients.


Subject(s)
Peritoneal Dialysis , Vascular Calcification , Humans , Peritoneal Dialysis/adverse effects , Male , Female , Vascular Calcification/epidemiology , Vascular Calcification/diagnostic imaging , Vascular Calcification/etiology , Middle Aged , Retrospective Studies , Prognosis , Risk Factors , Aged , Renal Insufficiency, Chronic/therapy , Renal Insufficiency, Chronic/complications , Cohort Studies , Parathyroid Hormone/blood , Adult , Aorta, Abdominal/diagnostic imaging , Serum Albumin/metabolism , Serum Albumin/analysis , Calcium/blood
2.
Langmuir ; 2024 May 13.
Article in English | MEDLINE | ID: mdl-38738776

ABSTRACT

Layered transition metal oxides are commonly used as the cathode materials in sodium-ion batteries due to their low cost and easy manufacturing. However, the application is hindered by poor rate performance and complex phase transitions. To address these challenges, a new seven-component high-entropy layered oxide cathode material, O3-NaNi0.25Fe0.15Mn0.3Ti0.1Sn0.05Co0.05Li0.1O2 (HEO) has been developed. The entropy stabilization effect plays a crucial role in improving the performance of electrochemical systems and the stability of structures. The HEO exhibits a specific discharge capacity of 154.1 mA h g-1 at 0.1 C and 94.5 mA h g-1 at 7 C. In-situ and ex-situ XRD results demonstrate that the HEO effectively retards complex phase transitions. This work provides a high-entropy design for the storage materials with a high energy density. Meanwhile, it eliminates industry doubts about the performance of sodium ion layered oxide cathode materials.

3.
J Cardiothorac Surg ; 19(1): 278, 2024 May 06.
Article in English | MEDLINE | ID: mdl-38711077

ABSTRACT

OBJECTIVE: To evaluate the efficacy and safety of intrapleural perfusion with hyperthermic chemotherapy (IPHC) in treating malignant pleural effusion (MPE). METHODS: PubMed, Embase, Cochrane Library, Chinese National Knowledge Infrastructure (CNKI), Chinese Biomedical Literature Database (CBM), VIP Chinese Science and Technology Journal Full-text Database (VP-CSJFD), and Wanfang database were searched by computer from database establishment to January 17, 2024. Relevant randomized controlled articles with IPHC as the observational group and intrapleural perfusion chemotherapy (IPC) as the control group for MPE were included. Then, the methodological quality of the included articles was evaluated and statistically analyzed using Stata 16.0. RESULTS: Sixteen trials with 647 patients receiving IPHC and 661 patients receiving IPC were included. The meta-analysis found that MPE patients in the IPHC group had a more significant objective response rate [RR = 1.31, 95%CI (1.23, 1.38), P < 0.05] and life quality improvement rate [RR = 2.88, 95%CI (1.95, 4.24), P < 0.05] than those in the IPC group. IPHC and IPC for MPE patients had similar incidence rates of asthenia, thrombocytopenia, hepatic impairment, and leukopenia. CONCLUSION: Compared with IPC, IPHC has a higher objective response rate without significantly increasing adverse reactions. Therefore, IPHC is effective and safe. However, this study is limited by the quality of the literature. Therefore, more high-quality, multi-center, large-sample, rigorously designed randomized controlled clinical studies are still needed for verification and evaluation.


Subject(s)
Hyperthermia, Induced , Pleural Effusion, Malignant , Humans , Pleural Effusion, Malignant/therapy , Hyperthermia, Induced/methods , Treatment Outcome , Chemotherapy, Cancer, Regional Perfusion/methods , Chemotherapy, Cancer, Regional Perfusion/adverse effects , Antineoplastic Agents/administration & dosage , Antineoplastic Agents/adverse effects
4.
Plant Physiol Biochem ; 210: 108643, 2024 May.
Article in English | MEDLINE | ID: mdl-38653097

ABSTRACT

Drought priming is known to enhance plant low temperature tolerance, whereas polystyrene nanoplastic contamination exerts detrimental effects on plant growth. This study investigates the less-explored influence of nanoplastic contamination on cold stress tolerance in drought-primed plants. We compared the photosynthetic carbon assimilation, carbohydrate metabolism, reactive oxygen species metabolism, and grain yield between the non-primed and drought-primed wheat grown in both nanoplastic-contaminated and healthy soils. Our results reveal that the beneficial effects of drought priming on photosynthetic carbon assimilation and the efficiency of the "water-water" cycle were compromised in the presence of nanoplastics (nPS). Additionally, nPS exposure disturbed carbohydrate metabolism, which impeded source-to-sink transport of sugar and resulted in reduced grain yield in drought-primed plants under low temperature conditions. These findings unveil the suppression of nPS on drought-primed low-temperature tolerance (DPLT) in wheat plants, suggesting an intricate interplay between the induction of stress tolerance and responses to nPS contamination. The study raises awareness about a potential challenge for future crop production.


Subject(s)
Cold Temperature , Droughts , Polystyrenes , Triticum , Triticum/drug effects , Triticum/metabolism , Triticum/physiology , Triticum/growth & development , Soil/chemistry , Photosynthesis/drug effects , Reactive Oxygen Species/metabolism , Soil Pollutants/toxicity , Nanoparticles
5.
Bioorg Chem ; 147: 107384, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38643568

ABSTRACT

Esophageal squamous cell carcinoma (ESCC) is a malignant tumor that is highly susceptible to metastasis, recurrence and resistance, and few therapeutic targets have been identified and proven effective. Herein, we demonstrated for the first time that Rap1b can positively regulate ESCC cell stemness, as well as designed and synthesized a novel class of Pt(IV) complexes that can effectively inhibit Raplb. In vitro biological studies showed that complex-1 exhibited stronger cytotoxicity than cisplatin and oxaliplatin against a variety of ESCC cells, and effectively reversed cisplatin-induced resistance of TE6 cells by increasing cellular accumulation of platinum and inhibiting cancer cell stemness. Significantly, complex-1 also exhibited strong ability to reversal cisplatin-induced cancer cell resistance and inhibit tumor growth in TE6/cDDP xenograft mice models, with a tumor growth inhibition rate of 73.3 % at 13 mg/kg and did not show significant systemic toxicity. Overall, Rap1b is a promising target to be developed as an effective treatment for ESCC. Complex-1, as the first Pt(IV) complex that can strongly inhibit Rap1b, is also worthy of further in-depth study.


Subject(s)
Antineoplastic Agents , Cell Proliferation , Cisplatin , Drug Resistance, Neoplasm , Drug Screening Assays, Antitumor , Esophageal Neoplasms , Esophageal Squamous Cell Carcinoma , Humans , Cisplatin/pharmacology , Esophageal Squamous Cell Carcinoma/drug therapy , Esophageal Squamous Cell Carcinoma/pathology , Esophageal Squamous Cell Carcinoma/metabolism , Antineoplastic Agents/pharmacology , Antineoplastic Agents/chemistry , Antineoplastic Agents/chemical synthesis , Esophageal Neoplasms/drug therapy , Esophageal Neoplasms/pathology , Animals , Drug Resistance, Neoplasm/drug effects , Mice , Cell Proliferation/drug effects , Neoplastic Stem Cells/drug effects , Neoplastic Stem Cells/pathology , Structure-Activity Relationship , Molecular Structure , Dose-Response Relationship, Drug , Ligands , Mice, Nude , rap GTP-Binding Proteins/metabolism , rap GTP-Binding Proteins/antagonists & inhibitors , Mice, Inbred BALB C , Organoplatinum Compounds/pharmacology , Organoplatinum Compounds/chemistry , Organoplatinum Compounds/chemical synthesis , Cell Line, Tumor , Neoplasms, Experimental/drug therapy , Neoplasms, Experimental/pathology , Neoplasms, Experimental/metabolism , Coordination Complexes/pharmacology , Coordination Complexes/chemistry , Coordination Complexes/chemical synthesis
8.
Micromachines (Basel) ; 15(4)2024 Apr 21.
Article in English | MEDLINE | ID: mdl-38675363

ABSTRACT

Physically unclonable functions (PUFs) are crucial for enhancing cybersecurity by providing unique, intrinsic identifiers for electronic devices, thus ensuring their authenticity and preventing unauthorized cloning. The SRAM-PUF, characterized by its simple structure and ease of implementation in various scenarios, has gained widespread usage. The soft-decision Reed-Muller (RM) code, an error correction code, is commonly employed in these designs. This paper introduces the design of an RM code soft-decision attack algorithm to reveal its potential security risks. To address this problem, we propose a soft-decision SRAM-PUF structure based on the elliptic curve digital signature algorithm (ECDSA). To improve the processing speed of the proposed secure SRAM-PUF, we propose a custom ECDSA scheme. Further, we also propose a universal architecture for the critical operations in ECDSA, elliptic curve scalar multiplication (ECSM), and elliptic curve double scalar multiplication (ECDSM) based on the differential addition chain (DAC). For ECSMs, iterations can be performed directly; for ECDSMs, a two-dimensional DAC is constructed through precomputation, followed by iterations. Moreover, due to the high similarity of ECSM and ECDSM data paths, this universal architecture saves hardware resources. Our design is implemented on a field-programmable gate array (FPGA) and an application-specific integrated circuit (ASIC) using a Xilinx Virtex-7 and an TSMC 40 nm process. Compared to existing research, our design exhibits a lower bit error rate (2.7×10-10) and better area-time performance (3902 slices, 6.615 µs ECDSM latency).

9.
Sci Total Environ ; 929: 172626, 2024 Jun 15.
Article in English | MEDLINE | ID: mdl-38657823

ABSTRACT

Despite the wide acknowledgment that plastic pollution and global warming have become serious agricultural concerns, their combined impact on crop growth remains poorly understood. Given the unabated megatrend, a simulated soil warming (SWT, +4 °C) microcosm experiment was carried out to provide a better understanding of the effects of temperature fluctuations on wheat seedlings exposed to nanoplastics (NPs, 1 g L-1 61.71 ± 0.31 nm polystyrene). It was documented that SWT induced oxidative stress in wheat seedlings grown in NPs-contaminated soil, with an 85.56 % increase in root activity, while decreasing plant height, fresh weight, and leaf area by 8.72 %, 47.68 %, and 15.04 % respectively. The SWT also resulted in reduced photosynthetic electron-transfer reaction and Calvin-Benson cycle in NPs-treated plants. Under NPs, SWT stimulated the tricarboxylic acid (TCA) metabolism and bio-oxidation process. The decrease in photosynthesis and the increase in respiration resulted in an 11.94 % decrease in net photosynthetic rate (Pn). These results indicated the complicated interplay between climate change and nanoplastic pollution in crop growth and underscored the potential risk of nanoplastic pollution on crop production in the future climate.


Subject(s)
Photosynthesis , Soil Pollutants , Soil , Temperature , Triticum , Triticum/physiology , Triticum/drug effects , Soil/chemistry , Soil Pollutants/toxicity , Photosynthesis/drug effects , Global Warming , Climate Change , Seedlings/drug effects , Seedlings/physiology , Plastics/toxicity
10.
Langmuir ; 40(18): 9556-9562, 2024 May 07.
Article in English | MEDLINE | ID: mdl-38666374

ABSTRACT

Direct regeneration has gained much attention in LiFePO4 battery recycling due to its simplicity, ecofriendliness, and cost savings. However, the excess carbon residues from binder decomposition, conductive carbon, and coated carbon in spent LiFePO4 impair electrochemical performance of direct regenerated LiFePO4. Herein, we report a preoxidation and prilling collaborative doping strategy to restore spent LiFePO4 by direct regeneration. The excess carbon is effectively removed by preoxidation. At the same time, prilling not only reduces the size of the primary particles and shortens the diffusion distance of Li+ but also improves the tap density of the regenerated materials. Besides, the Li+ transmission of the regenerated LiFePO4 is further improved by Ti4+ doping. Compared with commercial LiFePO4, it has excellent low-temperature performance. The collaborative strategy provides a new insight into regenerating high-performance spent LiFePO4.

11.
Front Oncol ; 14: 1347282, 2024.
Article in English | MEDLINE | ID: mdl-38595815

ABSTRACT

Given their good antitumor effects, epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) are standard first-line therapy for EGFR-sensitive mutations, including exon 19 deletions and exon 21 L858R mutations. EGFR fusion mutations and EGFR amplification are very rare in non-small cell lung cancer (NSCLC). We describe 2 patients with NSCLC harboring EGFR fusion mutations (EGFR-MACF1 and EGFR-GNAT3) combined with EGFR amplification. Both patients received EGFR-TKI treatment, and 1 of them showed an antitumor response.

12.
iScience ; 27(3): 109318, 2024 Mar 15.
Article in English | MEDLINE | ID: mdl-38482499

ABSTRACT

Janus textiles with asymmetric wettability have shown great potential in wearable applications due to their ability to manage biofluids efficiently. This review summarizes recent advances in smart Janus textiles for biofluid control and monitoring, focusing on wearable technologies. We first introduce the design configurations and fabrication approaches of Janus textiles, including asymmetric generation and asymmetric decoration strategies. We then highlight their diverse wearable applications spanning personal thermal management textiles, sweat sensors, hemostatic wound dressings, and protective equipment. These textiles offer innovative solutions for directional sweat transport, enhancing cooling and humidity control, and providing antibacterial properties. Finally, we discuss current limitations in durability, biocompatibility, and manufacturing scalability, alongside emerging opportunities in the field of smart Janus textiles.

13.
Int J Mol Sci ; 25(5)2024 Feb 26.
Article in English | MEDLINE | ID: mdl-38473927

ABSTRACT

Mouse embryonic stem cells (ESCs) and epiblast stem cells (EpiSCs) are derived from pre- and post-implantation embryos, representing the initial "naïve" and final "primed" states of pluripotency, respectively. In this study, novel reprogrammed pluripotent stem cells (rPSCs) were induced from mouse EpiSCs using a chemically defined medium containing mouse LIF, BMP4, CHIR99021, XAV939, and SB203580. The rPSCs exhibited domed clones and expressed key pluripotency genes, with both X chromosomes active in female cells. Furthermore, rPSCs differentiated into cells of all three germ layers in vivo through teratoma formation. Regarding epigenetic modifications, the DNA methylation of Oct4, Sox2, and Nanog promoter regions and the mRNA levels of Dnmt3a, Dnmt3b, and Dnmt1 were reduced in rPSCs compared with EpiSCs. However, the miR-290 family was significantly upregulated in rPSCs. After removing SB203580, an inhibitor of the p38 MAPK pathway, the cell colonies changed from domed to flat, with a significant decrease in the expression of pluripotency genes and the miR-290 family. Conversely, overexpression of pri-miR-290 reversed these changes. In addition, Map2k6 was identified as a direct target gene of miR-291b-3p, indicating that the miR-290 family maintains pluripotency and self-renewal in rPSCs by regulating the MAPK signaling pathway.


Subject(s)
MicroRNAs , Pluripotent Stem Cells , Animals , Mice , Female , Pluripotent Stem Cells/metabolism , Cell Differentiation/genetics , Signal Transduction , MAP Kinase Signaling System , MicroRNAs/metabolism , Germ Layers/metabolism , MAP Kinase Kinase 6
14.
Microbiol Spectr ; 12(4): e0314223, 2024 Apr 02.
Article in English | MEDLINE | ID: mdl-38385646

ABSTRACT

Previous studies have shown that the gut microbiota and its metabolites are associated with the success of organ transplantation. However, the specific changes in the gut microbiota of lung transplant patients remain unclear. Hence, this study aimed to elucidate the interplay between the gut microbiota, metabolome, and lung transplantation outcomes. Using 16S metagenomics sequencing and untargeted metabolic profiling, we conducted a comprehensive analysis of gut microbial and metabolic alterations in lung transplant recipients relative to non-transplant group. Our findings revealed the predominance of Enterococcus and Streptococcus genera within the lung transplant cohort, accompanied by the significant reduction in Bacteroides, Epulopiscium, Faecalibacterium, and Prevotella abundance. In addition, a significant reduction in ATRA (all-trans retinoic acid) levels and suppression of IgA production were observed in lung transplant recipients, which were found to be closely associated with the Enterococcus genus. It was speculated that the association might have implications for the prognosis of lung transplant patients. Notably, the differences in gut microbial composition and metabolomic profiles between successful transplant recipients and those experiencing chronic rejection were not statistically significant. These novel insights shed light on the putative implications of the gut microbiota and metabolome in shaping lung transplantation outcomes, and provide a foundation for future investigations and targeted therapeutic interventions. IMPORTANCE: This study has profound implications for lung transplantation as it uncovers the important role of gut microbiota and metabolome in shaping transplantation outcomes. The identification of dominant bacterial genera, such as Enterococcus and Streptococcus, within the lung transplant cohort, along with the significant decrease in Bacteroides, Epulopiscium, Faecalibacterium, and Prevotella abundance, reveals potential microbial imbalances associated with lung transplantation. In addition, a significant reduction in ATRA (all-trans retinoic acid) levels and suppression of IgA production were observed in lung transplant recipients, which were found to be closely associated with the Enterococcus genus. It was speculated that the association might have implications for the prognosis of lung transplant patients. These findings hold immense clinical significance as they lay the groundwork for future research and targeted therapeutic interventions. Understanding the impact of the gut microbiota and metabolome on lung transplantation outcomes offers promising avenues for improving transplantation patient prognosis.


Subject(s)
Gastrointestinal Microbiome , Lung Transplantation , Humans , Metabolome , Enterococcus , Tretinoin , Immunoglobulin A , RNA, Ribosomal, 16S
15.
Int J Mol Sci ; 25(3)2024 Feb 05.
Article in English | MEDLINE | ID: mdl-38339174

ABSTRACT

The extensive utilization of zinc oxide nanoparticles in consumer products and the industry has led to their substantial entry into the soil through air and surface runoff transportation, which causes ecotoxicity in agro-ecosystems and detrimental effects on crop production. Nanobubbles (diameter size < 1 µm) have many advantages, such as a high surface area, rapid mass transfer, and long retention time. In this study, wheat seedlings were irrigated with a 500 mg L-1 zinc oxide nanoparticle solution delivered in the form of nanobubble watering (nanobubble-ZnO-NPs). We found that nanobubble watering improved the growth and nutrient status of wheat exposed to zinc oxide nanoparticles, as evidenced by increased total foliar nitrogen and phosphorus, along with enhanced leaf dry mass per area. This effect can be attributed to nanobubbles disassembling zinc oxide aggregates formed due to soil organic carbon, thereby mitigating nutrient absorption limitations in plants. Furthermore, nanobubbles improved the capability of soil oxygen input, leading to increased root activity and glycolysis efficiency in wheat roots. This work provides valuable insights into the influence of nanobubble watering on soil quality and crop production and offers an innovative approach for agricultural irrigation that enhances the effectiveness and efficiency of water application.


Subject(s)
Nanoparticles , Soil Pollutants , Zinc Oxide , Triticum , Carbon , Ecosystem , Soil
16.
Biochem Biophys Res Commun ; 703: 149637, 2024 Apr 09.
Article in English | MEDLINE | ID: mdl-38354464

ABSTRACT

The normal development of pollen grains and the completion of double fertilization in embryos are crucial for both the sexual reproduction of angiosperms and grain production. Actin depolymerizing factor (ADF) regulates growth, development, and responses to biotic and abiotic stress by binding to actin in plants. In this study, the function of the ZmADF1 gene was validated through bioinformatic analysis, subcellular localization, overexpression in maize and Arabidopsis, and knockout via CRISPR/Cas9. The amino acid sequence of ZmADF1 exhibited high conservation and a similar tertiary structure to that of ADF homologs. Subcellular localization analysis revealed that ZmADF1 is localized mainly to the nucleus and cytoplasm. The ZmADF1 gene was specifically expressed in maize pollen, and overexpression of the ZmADF1 gene decreased the number of pollen grains in the anthers of transgenic Arabidopsis plants. The germination rate of pollen and the empty seed shell rate in the fruit pods of the overexpressing plants were significantly greater than those in the wild-type (WT) plants. In maize, the pollen viability of the knockout lines was significantly greater than that of both the WT and the overexpressing lines. Our results confirmed that the ZmADF1 gene was specifically expressed in pollen and negatively regulated pollen quantity, vigor, germination rate, and seed setting rate. This study provides insights into ADF gene function and possible pathways for improving high-yield maize breeding.


Subject(s)
Arabidopsis , Destrin , Pollen , Zea mays , Amino Acid Sequence , Arabidopsis/metabolism , Destrin/genetics , Destrin/metabolism , Gelsolin/metabolism , Gene Expression Regulation, Plant , Pollen/genetics , Pollen/growth & development , Zea mays/metabolism
17.
Heliyon ; 10(4): e26430, 2024 Feb 29.
Article in English | MEDLINE | ID: mdl-38404844

ABSTRACT

Objective: To describe our experience of reducing anastomotic leakage, a problem that has not been properly solved. Methods: Starting in January 2020, we began implementing our integrated strategy (application of an esophageal diameter-approximated slender gastric tube, preservation of the fibrous tissue around the residual esophagus and thyroid inferior pole anastomosis) in consecutive patients undergoing esophagectomy without a nasogastric tube or a nasal-jejunum feeding tube. Additionally, the blood supply at the site of the anastomosis was evaluated with a near-infrared fluorescence thoracoscope after the completion of esophagogastric anastomosis in the integrated strategy group. Results: Of 570 patients who were reviewed, 119 (20.9%) underwent the integrated strategy, and 451 (79.1%) underwent the conventional strategy. The rate of anastomotic leakage was 2.5% in the integrated strategy group and 10.2% in the conventional strategy group (p = 0.008). In the integrated strategy group, the site of most of the anastomotic blood supply was the residual esophagus dominant (82.4%), followed by the gastroesophageal dual-dominant (12.6%) and the gastric tube dominant (5.0%). The reconstruction route was more likely to be orthotopic in the integrated strategy group than in the conventional strategy group (89.9% vs. 38.6%, p = 0.004). Gastric dilation was identified in 3.4% of the patients in the integrated strategy group and in 21.1% in the conventional strategy group. Conclusions: Patients who underwent our proposed integrated strategy (Zhengzhou Strategy) during McKeown esophagectomy without a nasogastric tube or a nasal-jejunum feeding tube had a strikingly lower rate of anastomotic leakage and a relatively lower rate of postoperative complications, such as gastric tube dilation and delayed gastric emptying.

18.
Br J Cancer ; 130(4): 694-700, 2024 03.
Article in English | MEDLINE | ID: mdl-38177659

ABSTRACT

BACKGROUND: Neoadjuvant chemo-immunotherapy combination has shown remarkable advances in the management of esophageal squamous cell carcinoma (ESCC). However, the identification of a reliable biomarker for predicting the response to this chemo-immunotherapy regimen remains elusive. While computed tomography (CT) is widely utilized for response evaluation, its inherent limitations in terms of accuracy are well recognized. Therefore, in this study, we present a novel technique to predict the response of ESCC patients before receiving chemo-immunotherapy by testing volatile organic compounds (VOCs) in exhaled breath. METHODS: This study employed a prospective-specimen-collection, retrospective-blinded-evaluation design. Patients' baseline breath samples were collected and analyzed using high-pressure photon ionization time-of-flight mass spectrometry (HPPI-TOFMS). Subsequently, patients were categorized as responders or non-responders based on the evaluation of therapeutic response using pathology (for patients who underwent surgery) or CT images (for patients who did not receive surgery). RESULTS: A total of 133 patients were included in this study, with 91 responders who achieved either a complete response (CR) or a partial response (PR), and 42 non-responders who had stable disease (SD) or progressive disease (PD). Among 83 participants who underwent both evaluations with CT and pathology, the paired t-test revealed significant differences between the two methods (p < 0.05). For the breath test prediction model using breath test data from all participants, the validation set demonstrated mean area under the curve (AUC) of 0.86 ± 0.06. For 83 patients with pathological reports, the breath test achieved mean AUC of 0.845 ± 0.123. CONCLUSIONS: Since CT has inherent weakness in hollow organ assessment and no other ideal biomarker has been found, our study provided a noninvasive, feasible, and inexpensive tool that could precisely predict ESCC patients' response to neoadjuvant chemo-immunotherapy combination using breath test based on HPPI-TOFMS.


Subject(s)
Esophageal Neoplasms , Esophageal Squamous Cell Carcinoma , Humans , Esophageal Squamous Cell Carcinoma/therapy , Esophageal Neoplasms/therapy , Esophageal Neoplasms/drug therapy , Retrospective Studies , Prospective Studies , Neoadjuvant Therapy , Breath Tests/methods , Biomarkers
20.
NPJ Precis Oncol ; 8(1): 24, 2024 Jan 30.
Article in English | MEDLINE | ID: mdl-38291241

ABSTRACT

Metabolic reprogramming has been observed in cancer metastasis, whereas metabolic changes required for malignant cells during lymph node metastasis of esophageal squamous cell carcinoma (ESCC) are still poorly understood. Here, we performed single-cell RNA sequencing (scRNA-seq) of paired ESCC tumor tissues and lymph nodes to uncover the reprogramming of tumor microenvironment (TME) and metabolic pathways. By integrating analyses of scRNA-seq data with metabolomics of ESCC tumor tissues and plasma samples, we found nicotinate and nicotinamide metabolism pathway was dysregulated in ESCC patients with lymph node metastasis (LN+), exhibiting as significantly increased 1-methylnicotinamide (MNA) in both tumors and plasma. Further data indicated high expression of N-methyltransferase (NNMT), which converts active methyl groups from the universal methyl donor, S-adenosylmethionine (SAM), to stable MNA, contributed to the increased MNA in LN+ ESCC. NNMT promotes epithelial-mesenchymal transition (EMT) and metastasis of ESCC in vitro and in vivo by inhibiting E-cadherin expression. Mechanically, high NNMT expression consumed too much active methyl group and decreased H3K4me3 modification at E-cadherin promoter and inhibited m6A modification of E-cadherin mRNA, therefore inhibiting E-cadherin expression at both transcriptional and post-transcriptional level. Finally, a detection method of lymph node metastasis was build based on the dysregulated metabolites, which showed good performance among ESCC patients. For lymph node metastasis of ESCC, this work supports NNMT is a master regulator of the cross-talk between cellular metabolism and epigenetic modifications, which may be a therapeutic target.

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