Evaluation of the extended Japan NBI expert team classification of subtype 2B in laterally spreading colorectal tumors based on blue laser imaging.

OBJECTIVES: The Japan NBI Expert Team (JNET) classification has good diagnostic potential for colorectal diseases. We aimed to explore the diagnostic value of the JNET classification type 2B (JNET2B) criteria for colorectal laterally spreading tumors (LSTs) based on magnifying endoscopy with blue laser imaging (ME-BLI) examination. METHODS: Between January 2017 and June 2023, 218 patients who were diagnosed as having JNET2B-type LSTs using ME-BLI were included retrospectively. Endoscopic images were reinterpreted to categorize the LSTs as JNET2B-low (n = 178) and JNET2B-high (n = 53) LSTs. The JNET2B-low and JNET2B-high LSTs were compared based on their histopathological and morphological classifications. RESULTS: Among the 178 JNET2B-low LSTs, 86 (48.3%) were histopathologically classified as low-grade intraepithelial neoplasia, 54 (30.3%) as high-grade intraepithelial neoplasia (HGIN), 37 (20.8%) as intramucosal carcinoma (IMC), and one (0.6%) as superficial invasive submucosal carcinoma (SMC1). Among the 53 JNET2B-high LSTs, five (9.4%) were classified as HGIN, 28 (52.9%) as IMC, 15 (28.3%) as SMC1, and 5 (9.4%) as deep invasive submucosal carcinoma. There were significant differences in this histopathological classification between the two groups (P < 0.001). However, there was no significant difference between JNET2B-low and JNET2B-high LSTs based on their morphological classification (granular vs nongranular) or size (<20 mm vs ≥20 mm). Besides, the κ value for JNET2B subtyping was 0.698 (95% confidence interval 0.592-0.804) between the two endoscopists who reassessed the endoscopic images. CONCLUSION: The JNET2B subtyping of LSTs has a diagnostic potential in the preoperative setting, and may be valuable for treatment decision-making.

PIP family-based association studies uncover ZmPIP1;6 involved in Pb accumulation and water absorption in maize roots.

Excessive lead (Pb) in the soil affects crop growth and development, thus threatening human beings via food chains. Plasma membrane intrinsic proteins (PIPs) facilitate the transport of substrates across cell membranes. Herein, we characterized maize PIPs and identified eight Pb accumulation-associated PIP genes using association studies. Among these, ZmPIP1;6 was simultaneously correlated with root Pb concentrations under various Pb treatment stages. Significant correlations were observed between the ZmPIP1;6 expression abundance and Pb accumulation in maize roots. Ectopic expression in yeast showed that ZmPIP1;6 conferred Pb accumulation in the cells and affected Pb tolerance in yeast. Overexpression in maize demonstrated that ZmPIP1;6 altered the Pb concentration performance and root moisture content under Pb stress. Meanwhile, protein interaction analyses suggested that ZmPIP1; 6 and three PIP2 members formed isoforms and facilitate water uptake in maize roots. However, ZmPIP1; 6 improved Pb absorption in maize roots probably by interacting with CASP-like protein 2C3 and/or another metal transporter. Moreover, the significant variants in the ZmPIP1;6 promoter caused the variations in ZmPIP1;6 expression level and Pb accumulation among various maize germplasms. Our study will contribute to understanding of PIP family-mediated Pb accumulation in crops and bioremediation of Pb-polluted soils.

A phased small interfering RNA-derived pathway mediates lead stress tolerance in maize.

Phased small interfering RNAs (phasiRNAs) are a distinct class of endogenous small interfering RNAs, which regulate plant growth, development and environmental stress response. To determine the effect of phasiRNAs on maize (Zea mays L.) tolerance to lead (Pb) stress, the roots of 305 maize lines under Pb treatment were subjected to generation of individual databases of small RNAs. We identified 55 high-confidence phasiRNAs derived from 13 PHAS genes (genes producing phasiRNAs) in this maize panel, of which 41 derived from nine PHAS loci were negatively correlated with Pb content in the roots. The potential targets of the 41 phasiRNAs were enriched in ion transport and import. Only the expression of PHAS_1 (ZmTAS3j, Trans-Acting Short Interference RNA3) was regulated by its cis-expression quantitative trait locus and thus affected the Pb content in the roots. Using the Nicotiana benthamiana (N. benthamiana) transient expression system, 5'-rapid amplification of cDNA ends, and Arabidopsis heterologously expressed, we verified that ZmTAS3j was cleaved by zma-miR390 and thus generated tasiRNA targeting ARF genes (tasiARFs), and that the 5' and 3' zma-miR390 target sites of ZmTAS3j were both necessary for efficient biosynthesis and functional integrity of tasiARFs. We validated the involvement of the zma-miR390-ZmTAS3j-tasiARF-ZmARF3-ZmHMA3 pathway in Pb accumulation in maize seedlings using genetic, molecular, and cytological methods. Moreover, the increased Pb tolerance in ZmTAS3j-overexpressed lines was likely attributed to the zma-miR390-ZmTAS3j-tasiARF-ZmARF3-SAURs pathway, which elevated indole acetic acid levels and thus reactive oxygen species scavenging capacity in maize roots. Our study reveals the importance of the TAS3-derived tasiRNA pathway in plant adaptation to Pb stress.

The Neutrophil-to-Albumin Ratio (NAR): A Novel Index in Relation to Clinical Symptoms, Quality of Life, and Psychological Status in Diarrhea-Predominant Irritable Bowel Syndrome (IBS-D).

Introduction: Irritable bowel syndrome (IBS) is a common gastrointestinal disorder characterized by chronic abdominal pain and alterations in bowel habits. Despite the importance of biomarkers in disease management, the quest for precise and non-invasive biomarkers for IBS continues. Methods: This study focuses on investigating the clinical significance of the neutrophil-to-albumin ratio (NAR) as a potential biomarker in IBS. A cohort of 86 patients diagnosed with diarrhea-predominant IBS (IBS-D) and 106 healthy individuals were assessed for clinical symptoms, quality of life (QOL), psychological status, as well as serum and mucosal cytokine production. Results: Our findings revealed that NAR levels were notably elevated in patients with IBS-D compared to healthy controls. Positive correlations were observed between NAR levels and IBS clinical symptoms, while negative correlations were noted with QOL. Additionally, NAR showed positive associations with anxiety and depression scores, along with significant relationships with cytokine production (serum IL-6, TNF-α, IL-1ß, IL-17A, GM-CSF, IFN-γ, MCP-1; mucosal IL-6, TNF-α, IL-1ß, IL-17A) in IBS-D. Interestingly, patients with lower baseline NAR levels demonstrated potentially better clinical outcomes. Conclusion: The study underscores the potential utility of NAR as a novel biomarker in IBS, emphasizing its role in enhancing disease monitoring, understanding disease pathophysiology, and tailoring treatment strategies for patients with IBS-D.

Combining genome-wide association study and linkage mapping in the genetic dissection of amylose content in maize (Zea mays L.).

KEY MESSAGE: Integrated linkage and association analysis revealed genetic basis across multiple environments. The genes Zm00001d003102 and Zm00001d015905 were further verified to influence amylose content using gene-based association study. Maize kernel amylose is an important source of human food and industrial raw material. However, the genetic basis underlying maize amylose content is still obscure. Herein, we used an intermated B73 × Mo17 (IBM) Syn10 doubled haploid population composed of 222 lines and a germplasm set including 305 inbred lines to uncover the genetic control for amylose content under four environments. Linkage mapping detected 16 unique QTL, among which four were individually repeatedly identified across multiple environments. Genome-wide association study revealed 17 significant (P = 2.24E-06) single-nucleotide polymorphisms, of which two (SYN19568 and PZE-105090500) were located in the intervals of the mapped QTL (qAC2 and qAC5-3), respectively. According to the two population co-localized loci, 20 genes were confirmed as the candidate genes for amylose content. Gene-based association analysis indicated that the variants in Zm00001d003102 (Beta-16-galactosyltransferase GALT29A) and Zm00001d015905 (Sugar transporter 4a) affected amylose content across multi-environment. Tissue expression analysis showed that the two genes were specifically highly expressed in the ear and stem, respectively, suggesting that they might participate in sugar transport from source to sink organs. Our study provides valuable genetic information for breeding maize varieties with high amylose.

Incorporation of PD-1 blockade into induction chemotherapy improved tumor response in patients with locoregionally advanced nasopharyngeal carcinoma in a retrospective patient cohort.

OBJECTIVE: To investigate the short-term efficacy and safety of induction chemotherapy (IC) combined with anti-PD-1 immunotherapy in locoregionally advanced nasopharyngeal carcinoma (LA-NPC). METHODS: A total of 217 patients diagnosed with LA-NPC at the First Affiliated Hospital of Nanchang University, including 67 who received IC combined with anti-PD-1 and 150 who received IC, were retrospectively enrolled. Efficacy was evaluated at the end of the IC cycles and one month after radiotherapy based on RECIST v1.1 criteria. Acute toxicities were graded based on the CTCAE v5.0 criteria. Quantitative variables were compared by unpaired t-tests, and categorical variables were evaluated by Fisher Freeman-Halton test or Pearson Chi-square test. RESULTS: At the end of all induction therapy cycles, the objective response rate (ORR) of the IC + anti-PD-1 group was 88.1 % (59/67) as opposed to 70.0 % (105/150) in the IC group. Subgroup analysis showed that patients in both stage Ⅲ and ⅣA achieved a significant improvement in ORR with the inclusion of anti-PD-1 therapy. Patients with T3-4 or N2-3 category appeared to benefit more from anti-PD-1 compared to patients with T1-2 or N0-1 category. However, neither ORR nor the complete response (CR) rate was significantly different between the two treatment groups one month after the end of radiotherapy. In addition, the frequency of Grade 3-4 adverse events were also similar in both groups. CONCLUSIONS: IC combined with anti-PD-1 immunotherapy significantly improved the ORR of LA-NPC patients after induction therapy compared to IC alone.

GPX4 inhibits apoptosis of thyroid cancer cells through regulating the FKBP8/Bcl-2 axis.

GPX4 has attracted much attention as a key molecule of cell ferroptosis, but its role in cell apoptosis is rarely reported, and its role in apoptosis of thyroid cancer (TC) cell has not been reported. The analysis of TCGA database showed that both GPX4 and FKBP8 were highly expressed in TC tumor tissues; The expression of GPX4 and FKBP8 were positively correlated. The immunohistochemical analysis further confirmed that GPX4 and FKBP8 were highly expressed in TC tumor tissues. In addition, the high expression of GPX4 and FKBP8 were both significantly correlated with the poor prognosis of TC. Silencing GPX4 significantly inhibited the proliferation, induced apoptosis of TC cells, and reduced tumor growth in mice. The co-immunoprecipitation assay revealed a physical interaction between GPX4 and FKBP8 observed in the TC cells. Knockdown of FKBP8 significantly inhibited the proliferation and induced apoptosis of TC cells. Rescue experiments suggested that knockdown of FKBP8 could reverse the strengthens of cell proliferation and apoptosis and the higher expression of FKBP8 and Bcl-2 caused by overexpression of GPX4. Our results suggest that the GPX4/FKBP8/Bcl-2 axis promotes TC development by inhibiting TC cell apoptosis, which provides potential molecular targets for TC therapeutic strategies.

CsA promotes trophoblast invasion accompanied by changes in leukaemic inhibitory factor and fibroblast growth factor in peri-implantation blastocysts.

During the early stages of human pregnancy, successful implantation of embryonic trophoblast cells into the endometrium depends on good communication between trophoblast cells and the endometrium. Abnormal trophoblast cell function can cause embryo implantation failure. In this study, we added cyclosporine A (CsA) to the culture medium to observe the effect of CsA on embryonic trophoblast cells and the related mechanism. We observed that CsA promoted the migration and invasion of embryonic trophoblast cells. CsA promoted the expression of leukaemic inhibitory factor (LIF) and fibroblast growth factor (FGF). In addition, CsA promoted the secretion and volume increase in vesicles in the CsA-treated group compared with the control group. Therefore, CsA may promote the adhesion and invasion of trophoblast cells through LIF and FGF and promote the vesicle dynamic process, which is conducive to embryo implantation.

Intelligent selection of healthcare supply chain mode - an applied research based on artificial intelligence.

Introduction: Due to the inefficiency and high cost of the current healthcare supply chain mode, in order to adapt to the great changes in the global economy and public health, it is urgent to choose an effective mode for sustainable development of healthcare supply chain. The aim of this paper is to use artificial intelligence systems to make intelligent decisions for healthcare supply chain mode selection. Methods: Firstly, according to the economic benefits, social benefits and environmental benefits of healthcare supply chain, this paper identifies different healthcare supply chain modes in combination with artificial intelligence technology. Secondly, this paper presents the intelligent choice optimization method of healthcare supply chain mode based on deep reinforcement learning algorithm. Finally, the effect of artificial intelligence in healthcare supply chain mode selection is verified by simulation experiment. Results and Discussion: The experimental results show that healthcare supply chain mode selected by artificial intelligence is basically consistent with the target mode, while healthcare supply chain mode selected by the basic selection method, BP neural network method and big data method is different from the target mode, which indicates that AI has more advantages in the selection of medical supply chain mode. Therefore, we recommend the application of artificial intelligence to healthcare supply chain management. This study not only makes up for the ineffective problems of existing methods, but also makes up for the gaps in the application of AI technology in the field of healthcare supply chain. The scientific value of this paper is that the proposed framework and the artificial intelligence algorithm enrich the relevant theories of healthcare supply chain research and provide methodological guidance for intelligent decision-making of healthcare supply chain. At the same time, for medical enterprises, this research provides a new practical guideline for the application of artificial intelligence in the sustainable development and modern management of healthcare supply chain.